You are on page 1of 55

PHARMA CHRONICLE

AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS


R&C/AJ/PDS/1979

ISSUE 69

PHARMA C HRONICLE
Since 2009

July 2011

Readers Testimonials
I enjoyed reading it and more important I could get some very interesting information in our field It is always very interesting. Good continuation! It is very instructive and I think could be of interest to all of us. ...I like the new look! I always forward your chronicle to my colleagues. This effort is very informative and productive for Professional with special concern of up date for
Pharma Industries in the world; We are getting up date knowledge through this effort

Thanks for sharing such an informative & well-presented material to keep us updated about the
Pharma Industry. Keep it up!

PHARMA CHRONICLE

JULY 2011

For more information about PSI, please visit www.psiltd.com

PHARMA CHRONICLE

JULY 2011

For more information about PSI, please visit www.psiltd.com

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

CONTENTS
INSIDE THIS ISSUE:
CHRONICLE SPOTLIGHT NEWS FROM THE GULF INSIGHTS: Why Are Drug Prices Set So Unscientifically? P RODUCT LAUNCH F EATURE: Acquisitions, Not Research, Fuels New Drugs DRUGS ON THE WAY: Eli Lilly Plans 10 Drugs In Final-Stage Trials NEWS UPDATE F DA APPROVALS E MA NEWS F UNNY PHARMA CARTOON T IE-UPS & AGREEMENTS P HARMA ARTICLES UPCOMING FAIR INBANGKOK, THAILAND UPCOMING EVENT IN VIENNA, AUSTRIA

JULY 2011

515 16 17 19 20 21 22 2226 27 2729 30 31 32 33 3344 45 46 47 4750 51 5152 53


4

eyeforpharma ARTICLES
P HARMA ARTICLES BUT...MY PROJECTS ARE SPECIAL

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

CHRONICLE SPOTLIGHT
FDA APPROVES NOVARTIS ARCAPTA NEOHALER TO TREAT COPD

JULY 2011

The U.S. Food and Drug Administration on Jul. 1, 2011 approved Arcapta Neohaler (indacaterol inhalation powder) for the long term, once-daily
maintenance bronchodilator treatment of airflow obstruction in people with chronic obstructive pulmonary disease (COPD) including chronic bronchitis and/or emphysema. COPD is a serious lung disease that makes breathing difficult. Symptoms can include breathlessness, chronic cough and excessive phlegm. Cigarette smoking is the leading cause of COPD, and is the fourth leading cause of death in the United States, according to the Centers for Disease Control and Prevention. Arcapta Neohaler is a new molecular entity in the beta2-adrenergic agonist class that helps muscles around the airways of the lungs stay relaxed to prevent symptoms of COPD, such as wheezing and breathlessness. Arcapta Neohaler is not intended to treat asthma or sudden, severe symptoms of COPD. "The approval of new long-term drugs for COPD that relieve breathing difficulty by opening airways provides another treatment option for the millions of people, said Curtis Rosebraugh, M.D., M.P.H., director of the Office of Drug Evaluation II in the FDAs Center for Drug Evaluation and Research. The safety and efficacy of Arcapta Neohaler was demonstrated in six confirmatory clinical trials that included 5,474 patients ages 40 and older with a clinical diagnosis of COPD. Those treated had a smoking history of at least one pack a day for 10 years and exhibited moderate-to-severe decreases in lung function. Arcapta Neohaler carries a boxed warning that long-acting beta2 adrenergic agonists (LABA) increase the risk of asthma-related death. All LABA, including Arcapta Neohaler, should not be used in patients with asthma, unless used with a long-term asthma control medication. The FDA approved Arcapta Neohaler with a medication guide that includes instructions for use and information about the potential risks of taking the drug. The most common side effects reported by those using Arcapta Neohaler include runny nose,cough,sore throat,headache and nausea. Arcapta Neohaler is marketed by Novartis Pharmaceuticals Corp. of East Hanover,N.J. (Source: http://www.biospace.com/News/fda-approves-archimedes-pharmas-lazandar-first/225930/Source=TopBreaking FDA Approves Novartis Pharmaceuticals Corporation (NVS)'s Arcapta Neohaler to Treat Chronic Obstructive Pulmonary Disease Jul. 1, 2011)

N E W S T UDY:
A

ZIN C PREV E NT S DIABE TE S DAMAG E

new study led by an Indian professor has revealed that zinc keeps a protein called amylin in check and acts like a security guard in preventing major damage from diabetes. Ayyalusamy Ramamoorthy, a professor of chemistry and biophysics at the University of Michigan, and his colleagues explained that in type two diabetes, amylin forms dense clumps that shut down insulin-producing cells,wreaking havoc on the control of blood sugar. Amylin has been explained as something of a two-faced character. In healthy people who have normal levels of zinc in the insulin-producing islet cells of the pancreas, amylin actually pitches in to help with blood sugar regulation. This is because in molecular terms, zinc prevents amylin also known as Islet Amyloid Polypeptide (IAPP) from forming harmful clumps similar to those found in Alzheimer's, Parkinson's, Huntington's and various other degenerative diseases. However, in a zinc-starved cellular environment of someone with type two diabetes, amylin has no watchful guard. It is free to clump together with other amylin molecules in the molecular equivalent of a gang. This clumping eventually leads to the formation of ribbon-like structures called fibrils, and because fibril formation has been linked to a number of human diseases, it was long assumed that fibrils themselves were toxic. The study shows that the binding of zinc in the middle makes one end of the amylin molecule, called the N-terminus become more orderly. This is significant, because the N-terminus is very important in clump formation and amylin toxicity, said Ramamoorthy. The researchers also discovered that before amylin can begin forming fibrils, zinc must be rousted from its nesting place.

The study appears in the upcoming issue of the Journal of Molecular Biology.
(Source: http://timesofindia.indiatimes.com/life-style/health-fitness/health/Zinc-prevents-diabetes-damage/articleshow/9064976.cms Zinc prevents diabetes damage ANI Jul. 1, 2011)

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

CHRONICLE SPOTLIGHT
FDA APPROVES JANSSENS XARELTO TO HELP PREVENT DVT

JULY 2011

Janssen Pharmaceuticals,Inc. announced on Jul. 1,2011 that the U.S. Food and Drug Administration (FDA) has approved XARELTO (rivaroxaban
tablets), a novel, once-daily, oral anticoagulant for the prevention (prophylaxis) of deep vein thrombosis (DVT) which may lead to a pulmonary embolism (PE) in people undergoing knee or hip replacement surgery. The approval of once-daily XARELTO tablets will provide a new option to help protect patients from developing venous blood clots following knee or hip replacement surgery, said Louis M. Kwong, M.D., Professor of Orthopedic Surgery at Harbor-UCLA Medical Center, who was involved with the rivaroxaban clinical trials program in this indication. XARELTO has a proven clinical benefit over one of todays most widely used options in preventing these potentially life-threatening blood clots, and the use of a once-daily pill may play an essential role in helping to simplify clinical practice. According to the American Academy of Orthopedic Surgeons, more than 800,000 Americans undergo knee or hip replacement surgery each year. These procedures are associated with an increased risk for DVT, a blood clot that forms in a deep vein, usually in the leg. If all or part of a DVT breaks off, it can travel to the lungs and become a PE, where it may impact the flow of oxygenated blood and lead to potentially lifethreatening consequences. The American College of Chest Physicians recommends the use of blood thinners (anticoagulants) immediately following major orthopedic replacement surgery and extended use post-discharge (at least 10 days for knee replacement, and up to 35 days for hip replacement) to help reduce such risks; however, full compliance with these guidelines using previously available options has not been widely observed. DVT and PE are the leading causes of re-hospitalization following joint replacement surgery. The use of blood thinners has been shown to safely and effectively help keep people from developing preventable blood clots, said Alan Brownstein, Chief Executive Officer of the National Blood Clot Alliance. The FDA approval of a new blood thinner, XARELTO, offers a new option for patients seeking knee or hip replacement surgery, and we encourage people to discuss with their physicians the risk of blood clots and which blood thinner offers optimal protection as part of their presurgical consultation. Pivotal data from the XARELTO Phase 3 clinical development program reflected in the approved label showed significantly greater efficacy of rivaroxaban, both in head-to-head comparison with enoxaparin and when comparing extended-duration (5 weeks) rivaroxaban with shortduration (2 weeks) enoxaparin, followed by placebo. In these trials, rivaroxaban and enoxaparin demonstrated similar safety profiles including low rates of major bleeding. XARELTO is approved for use at a 10 mg dose, once-daily for 35 days following hip replacement and for 12 days following knee replacement surgery. To date, XARELTO is approved in more than 110 countries worldwide and has been successfully launched in more than 80 countries by Bayer HealthCare. Janssen Pharmaceuticals, Inc. holds marketing rights for XARELTO in the U.S. The U.S. Bayer HealthCare sales force will support the Janssen Pharmaceuticals, Inc. sales force by detailing XARELTO in designated hospital accounts. Shorter hospital stays following hip and knee replacement surgeries have made the prevention of venous blood clots an outpatient issue, and XARELTO provides a safe and effective oral treatment option that can be easily transitioned from use in hospital to home, said Paul Chang, M.D., Vice President, Medical Affairs, Internal Medicine, Janssen Pharmaceuticals, Inc. Were pleased to make XARELTO tablets available to physicians to help them better protect their patients from these highly preventable surgical complications.
Please see full Product Information, or visit www.XARELTOhcp.com

(Source: http://www.biospace.com/News/fda-approves-novartis-pharmaceuticals-corporations/226000/Source=TopBreaking FDA Approves Janssen Pharmaceutica N.V.'s XARELTO(R) (rivaroxaban tablets) to Help Prevent Deep Vein Thrombosis in Patients Undergoing Knee or Hip Replacement Surgery Raritan, New Jersey Jul. 1, 2011)

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

CHRONICLE SPOTLIGHT
ELECTROMAGNETIC FIELDS CAN DISTURB LEARNING, STUDY SUGGESTS

JULY 2011

The effects of high-frequency electromagnetic fields emitted by mobile phones on humans have been hotly debated for years. In a new study,
neuroscientists from Ruhr-Universitaet-Bochum (RUB) in Germany have shed light on this question. For the first time, they provide evidence that extremely high-powered electromagnetic fields can influence learning processes on the synaptic level within the brain, independent from other factors such as stress. However, such high levels are not encountered during typical use of mobile phones, the researchers note. "For this effect, very high values are necessary. These do not occur during the daily use of mobile phones," explains Dr. Nora Prochnow, with RUB's Medical Faculty.

Mobile phone derived non-ionizing radiation can produce heat


High-frequency electromagnetic fields (HEFs) are not only used in mobile phones, but also in a variety of other communication systems like radio, television or cordless telephone sets. Mobile phones of the so-called third generation utilize the UMTS technology (Universal Mobile Communication System) with a frequency of 1200 MHz and a relatively weak operating range (3.8-4.8 V/m). With increasing power, electromagnetic fields (EMFs) are able to elicit local warming of body tissues, being also described as a "thermal effect." Reportedly, mobile phones can cause local warming of the brain by less than 0.1C. The effect on function and structure of the brain during long term use of mobile phones (e.g. > 30 min) remains unexplained until now.

and might influence cellular activity


Furthermore, findings regarding the non-thermal effects of mobile phone emitted EMFs are unclear and contradictory. These comprise, for instance, an increase in permeability and fluidity of cellular membranes, which can be implicated in changes in ion-channel integration and metabolism, even without a detectable change in temperature. This may impair synaptic learning processes in the brain. Until now, experiments could not sufficiently answer the question of whether these effects are derived from non-thermal HEFs or from stress, as it can be induced by handling of the experimental animal (e.g. placing a rat into an unknown environment).

Stress or non-thermal EMF effect -- Scientists find out for the first time
To investigate this question, a new study was performed by scientists of the Department of Neuroanatomy and Molecular Brain Research (Professor Dr. med. Rolf Dermietzel) in cooperation with the Chair of Electromagnetic Theory of the University of Wuppertal. For the experiment, rats were placed into differently powered non-thermal HEFs in the UMTS operating range. Synaptic learning and memory formation were analyzed by electrophysiological methods. Furthermore, all animals were tested for stress hormone release immediately following the HEF exposure.

Mobile phone use seems to be harmless -- critical values for occupational use have to be controlled precisely
The results: Although there was daily training and effortless contact to the exposure environment, increases in blood derived stress hormone levels could be detected for all exposed groups. The stress clearly influences learning and memory formation on the synaptic level in the rat brain. Highpowered EMFs (SAR 10 W/kg) also have a significant effect on learning and memory formation. In contrast to this,weak EMFs (SAR 0 and 2 W/kg) lead to no detectable changes or impairments. "These results cannot directly be transferred to humans," says Nora Prochnow. "But in the animal model, it can be demonstrated that neuronal mechanisms of synaptic learning can serve as a target for high powered EMFs." However,there is no need for serious concerns: humans are not exposed to such high-powered EMFs during daily mobile phone use. Nevertheless,the matter has to be regarded differently in special occupational situations,for instance during the use of body worn antenna systems as it is common for security services or military purposes. Here,critical levels for occupational exposure may be reached more easily and have to be controlled carefully. (Source: http://www.sciencedaily.com/releases/2011/06/110630091657.htm Electromagnetic Fields Can Disturb Learning, Study Suggests, but Only at Very High Levels ScienceDaily Jul. 1, 2011 Story source: The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Ruhr-Universitaet-Bochum www.ruhr-uni-bochum.de via AlphaGalileo www.alphagalileo.org)

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

CHRONICLE SPOTLIGHT
M ERCK SAYS GARDASIL, CUBICIN APPROVED IN JAPAN
Merck says Japanese regulators cleared HPV vaccine Gardasil,an antibiotic,and a cancer drug

JULY 2011

Merck & Co. said on Jul. 1, 2011 that Japanese regulators approved three of its products, including the vaccine Gardasil, which protects against a virus that causes cervical cancer. Merck said Gardasil was approved for the prevention of cervical cancer and precancerous lesions caused by four types of human papillomavirus. Its use was approved in women and girls age 9 and older. The Ministry of Health, Labor and Welfare also approved Zolinza, an oral drug used for treatment of cutaneous T-cell lymphoma. The drug will be marketed in Japan by Taiho Pharmaceutical Co. The third approved was for Cubicin, an antibiotic that treats severe skin and bloodstream infections. Cubicin was developed by Cubist Pharmaceuticals Inc. Merck sells the drug outside the U.S. Japan is the world's second-largest drug market after the U.S. (Source: http://finance.yahoo.com/news/Merck-says-Gardasil-Cubicin-apf-2398153422.html?x=0&.v=1 Merck says Gardasil, Cubicin approved in Japan Associated Press Whitehouse Station, New Jersey Jul. 1, 2011)

A STRAZENECAS ENDING OF DOCTORS FREE TRIPS TO SPREAD


straZeneca PLC's decision to scrap payments for doctors to attend international medical congresses is ground breaking but necessary if the pharmaceutical industry wants to improve its tarnished image,said Richard Bergstrom,who heads the industry's European trade body. "I think others will follow," said Bergstrom, director general of the European Federation of Pharmaceutical Industries and Associations. AstraZeneca took the decision in April, partially in response to criticism of the pharma industry's potential influence on prescribers of medicines. "We just wanted to tighten things up even further than the industry codes currently required or voluntarily suggest, because we never want to do anything that can be misinterpreted," an AstraZeneca spokesperson said, adding: "I think we're the first to go to this extent." Congresses are held in Europe and the U.S. every year on subjects like diabetes, heart and lung disease and cancer, during which hundreds of specialist physicians are flown in at the expense of drug makers--a practice that has become increasingly criticized as healthcare costs have risen. "We probably need to find ways of interacting which is more acceptable to society at large," said Bergstrom. The pharma industry is also keen not to be seen breaching new anti-bribery laws. " AstraZenecas move probably reflects concern that such practices might run foul of legislation in the U.S., and now the new bribery act in the U.K., depending on how you do this, and depending on how you invite these physicians," said Bergstrom, a Swede and pharmacist by training. "This trend is a wake-up call for the medical community and healthcare professionals who have gotten used to the fact the industry is paying for all this." Bergstrom said that around half of all the congresses held around the world are related to life sciences. "Congress organizers realize that we're in this together, and realize we need to take away the unnecessary things that are still remaining--the unnecessary social activities, and the gala dinners--they're just giving the wrong impression of a high science meeting. But some of doctors associations are responding very negatively, suggesting they regard this as something that they have a right to--getting the pharmaceutical industry's money to pay for their education. So some of them are in denial." Britain's biggest drug maker, GlaxoSmithKline PLC,said it will continue funding trips for selected doctors to attend international medical congresses.

"Large, world-class, academic conferences such as ASCO [American Society of Clinical Oncology], ADA [American Diabetes Association] and ERS [European Respiratory Society] act as leading forums for discussion around serious diseases areas such as oncology, diabetes and respiratory disease. "Unfortunately, for many healthcare professionals the costs involved in attending these conferences may prove prohibitive without support," it added.
(Source: http://www.nasdaq.com/aspx/company-news-story.aspx?storyid=201106281208dowjonesdjonline000244&title=interview-astrazenecas-endingof-doctors-free-trips-to-spread#ixzz1QhLBC6u4 INTERVIEW: AstraZeneca's Ending Of Doctors' Free Trips To Spread by Sten Stovall Dow Jones Newswires London Jul. 1, 2011)

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

CHRONICLE SPOTLIGHT
CANADIANS WAIT MORE TO ACCESS LATEST DRUGS
Canada's federal and provincial governments are now taking more than two
and a half years, on average, to approve new prescription medicines, says a new report. The federal regulator, Health Canada, takes an average of nearly 16 months to approve new drugs as safe and effective, after which the provincial governments typically spend another 15 months or more to decide whether new drugs will be eligible for public reimbursement under their drug plans, says the report, from free-market think tank The Fraser Institute. This combination of federal and provincial decision-making creates delays or, more often, deprives patients of access to new medicines, it claims. The Institute's research found that only 23% of new drugs approved as safe and effective by Health Canada in 2004 had been approved for either full or partial reimbursement under provincial drug plans as of June 9, 2011, compared to 98% that had been covered by at least one private insurer. Moreover, Health Canada took longer to certify new drugs during 2006-2009 than the European Medicines Agency (EMA) and, during five of the last six years studied (2004-2009), its performance was worse than that of the US Food and Drug Administration (FDA). The report's authors suggest two specific policy changes to make new medicines available more quickly to Canadians. First, they say, Canada could speed up its regulatory processes by taking advantage of the knowledge and capacity of other jurisdictions, rather than attempting to duplicate the processes of the US FDA. If Canada entered into agreements of "mutual recognition" with other countries, new medications already approved in those jurisdictions could be introduced onto the Canadian market far more rapidly, and vice versa, they add.

JULY 2011

CORCEPT SAYS FDA ACCEPTS CORLUX APPLICATION


orcept Therapeutics says FDA will make decision on Cushing's Syndrome drug Corlux by Feb. 17 Corcept Therapeutics Inc. said on Jun. 30, 2011 that regulators accepted its application to market the drug Corlux as a treatment for the rare disease Cushing's Syndrome. Corcept said the Food and Drug Administration expects to decide whether to approve Corlux by Feb. 17. The company filed for approval on April 15, and FDA reviews usually take about 10 months. Cushing's Syndrome is caused when tumors cause a person's body to produce too much of the hormone cortisol. Its symptoms can include high blood sugar, high blood pressure, fatigue and muscle weakness. Corcept said about 20, 000 people in the U.S. have the condition. Earlier this month, Corcept reported results from late-stage testing that showed Corlux improved patients' blood sugar levels and blood pressure, and decreased body weight and waist circumference. If the drug is approved, Corcept will have seven years of marketing exclusivity because the FDA awarded Corlux orphan drug status, an incentive given to treatments for rare diseases. The company is also studying Corlux as a treatment for psychotic depression. Corcept shares fell 13 cents, or 3.1 percent, to $4.12 in premarket trading. The stock has traded between $2.76 and $5.07 in the last year.
(Source: http://finance.yahoo.com/news/Corcept-says-FDA-accepts-itsapf-38018945.html?x=0&.v=1 Corcept says FDA accepts its Corlux application Associated Press Menlo Park, California Jun. 30, 2011)

Second, government drug programmes could be replaced with means-tested subsidized access to private insurance, they suggest. A properlyregulated and competitive private-sector insurance market, in which universal access to catastrophic drug insurance would be facilitated through means-tested subsidies for those on low incomes, could make new medicines more readily available without increasing the burden on taxpayers, the report proposes. In fact, only a very small percentage of Canadians actually face exorbitant drug costs, says the Institute; during 1997-2002, only 3% of Canadian households spent more than 5% of their annual income on prescription drugs. Means-tested subsidies provided to those with low incomes, regardless of age, to purchase catastrophic drug insurance in a private, competitive insurance market benefits recipients by giving them the choice of selecting the drug plan that meets their individual medical needs and financial abilities," said Mark Rovere, study co-author and associate director of health policy studies at the Institute. Unlike the majority of public drug plans, which have small, flat co-payments, most private drug insurance plans include co-payments that are linked to the full cost of the prescription, and these encourage patients to make cost-efficient choices between alternative treatments, says the report. Consumer sensitivity to prices in turn creates incentives for physicians to prescribe treatment more efficiently and for drug manufacturers to invest efficiently in the development of new drugs, it adds. "Allowing the private insurance market to compete through prices and service, thus eliminating government monopolies on drug prices and coverage, is the best policy choice for improving access to the newest prescription drugs," according to Mr Rovere. (Source: http://www.pharmatimes.com/article/11-06-30/canadians_wait_more_than_30_months_to_access_latest_drugs.aspx Canadians wait more than 30 months to access latest drugs" by Lynne Taylor World News Jun. 30, 2011)

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

CHRONICLE SPOTLIGHT
JOHNSON & JOHNSON RECALLS EXTRA STRENGTH TYLENOL

JULY 2011

J ohnson & Johnson on announced another Tylenol recall due to a musty moldy odor linked to a trace chemical.
The company's McNeil Consumer Healthcare unit is recalling one product lot of Tylenol Extra Strength Caplets made in February 2009 and distributed in the U.S. The recall totals 60,912 bottles,each of which has 225 caplets. McNeil said it has received a small number of reports about the pills' odor, which has been linked in past J&J recalls to the presence of trace amounts of "2,4,6-tribromoanisole." TBA is a byproduct of a chemical preservative sometimes used on shipping pallets. Besides causing an unpleasant odor, TBA has been associated with temporary and non-serious gastrointestinal symptoms. Since September 2009, New Brunswick, N.J.-based Johnson & Johnson has had about two dozen recalls of prescription and nonprescription medicines, replacement hips, contact lenses and diabetes test strips, including tens of millions of bottles of children's and adult Tylenol and Motrin. The reasons have ranged from metal and other contaminants, to nauseating odors and packaging issues. Joint replacement systems so painful they required corrective surgery were also recalled, as were contact lenses that irritated eyes, along with potentially contaminated syringes full of the antipsychotic drug Invega. The high-profile lapses have tugged at J&J's revenue, profit and stock price, as well as its once-stellar reputation. J&J has said that it has inspected more than 100 plants around the world and invested millions to improve the quality of its manufacturing and satisfy federal regulators, who have three of its factories under scrutiny. The product lot number for the recalled Tylenol Extra Strength product can be found on the side of the bottle label - it is ABA619 300450444271. Customers should stop using the product from the lot immediately and contact McNeil at www.tylenol.com or by calling 1-888-222-6036 for instructions on receiving a refund or product coupon.
(Source: http://www.dddmag.com/news-JJ-Recalls-Extra-Strength-Tylenol-62911.aspx J&J Recalls Extra Strength Tylenol Drug Discovery & Development Jun. 29, 2011 Primary source: Associated Press - Fort Washington, Pa)

S TR IDES

TO SET UP MANUFAC TUR ING UNIT IN MALAY SIA

Bangalore-based Strides Arcolab on Jun. 29, 2011 signed an agreement to set-up biopharmaceuticals and sterile injectables manufacturing unit in a
biotechnology park in Malaysia. The financial details were yet to be disclosed. The company's subsidiary Agila Specialties will set up a customized facility in biotech park, Bio-XCell Ecosystem in Johor in Malaysia. "Malaysia provides us with a strategic location to expand our manufacturing operations. The attractive financial incentives by the Malaysian government and presence of a pharma and biotech ecosystem are catalysts to our decision," said Adam Levitt, CEO-Americas of Strides. The project will be built by Bio-XCell to the design requirements by Strides and leased out to the company on a long-term basis. The lease rentals are applicable from the date of commercialization, which supports the biotech strategy of Strides, where there is a long gestation period from development to commercialization, the company said. In addition to Strides, Indian biotech firm Biocon, Metabollic Explorer from France, and Glycos Biotechnologies of US are some of the other companies, which will set up manufacturing units in the Bio-XCell Ecosystem. (Source: http://www.business-standard.com/india/news/strides-to-setmanufacturing-unit-in-malaysia/139689/on Strides to set up manufacturing unit in Malaysia by BS Reporter Mumbai, INDIA Jun. 29, 2011)

10

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

CHRONICLE SPOTLIGHT
20 EXPENSIVE DRUGS THAT COULD BANKRUPT MEDICARE
THE 20 MOST EXPENSIVE DRUGS IN AMERICA:
1. 2. 3. 4. 5. 6. 7. 8. 9. 11. 12. 13. 15. 17.

JULY 2011

Soliris, Alexion Pharmaceutical, $409, 500 a year. Monoclonal antibody drug treats a rare disorder in which the immune system destroys red blood cells at night. Elaprase,Shire, $375, 000 per year. Treats Hunters syndrome,a metabolic disorder. Naglazyme,BioMarin,$365, 000 a year. Treats rare connective tissue disorder. Cinryze,ViroPharma, $350, 000 a year. Treats hereditary angioedema,a rare,life-threatening genetic disorder that causes painful swelling. Arcalyst,Regeneron, $250, 000 a year. An anti-inflammatory for patients with impaired immune systems. Myozyme,Sanofi,$300,000 per year. Treats Pompe disease. Cerezyme,Sanofi, $200, 000 per year. Treats Gaucher disease. Fabrazyme,Sanofi, $200, 000,per year. Treats Fabry disease. Aldurazyme,Sanofi,$200, 000,per year. Treats Hurler syndrome. Erbitux,Eli Lilly, $80, 000 per year. Treats lung cancer. Folotyn,Allos Therapeutics,$60, 000 per two-month treatment. Treats a rare type of lymphoma. Lemtrada (alemtuzumab),Sanofi,$60, 000.* Treats M.S. Jevtana,Sanofi, $48, 000 per year. Treats prostate cancer. Zytiga,J&J,$40, 000 per year. Treats prostate cancer.

10. Provenge,Dendreon $93, 000 per year. Treats prostate cancer.

14. Avastin, Roche, $50, 000 a year. Treats colon cancer. 16. Gilenya,Novartis,$40,000 per year. Treats multiple sclerosis. 18. Xgeva,Amgen,$21, 500 per year. Treats prostate cancer. 19. Tofacitinib,Pfizer $20, 000 a year.* An anti-inflammatory biologic. 20. Fuzeon,Roche, $20, 000 per year. Treats HIV.
Sources: Forbes,The New York Times,BNET,Bloomberg and the AP. *Not launched yet.

(Source: http://www.bnet.com/blog/drug-business/20-expensive-drugs-that-could-bankrupt-medicare/8885?pg=2&tag=content;drawer-container 20 Expensive Drugs That Could Bankrupt Medicare by Jim Edwards Jun. 29, 2011)

P FI Z ER

SUB MI TS AXI TI NIB FOR AD VANC ED R CC TO FD A

P fizer says that axitinib,for the treatment of advanced kidney cancer,has been accepted for review by the US Food and Drug Administration.
The drug, which was filed in Europe at the beginning of June, is for previously-treated patients with advanced renal cell carcinoma, the most prevalent form of kidney cancer. The US submission is based on Phase III data, which found that axitinib extended progression-free survival (PFS) by 6.7 months compared with Bayer/Onyx's Nexavar (sorafenib), which extended PFS by 4.7 months. Axitinib is an oral drug which inhibits vascular endothelial growth factor receptors 1,2 and 3,which can influence the spread and growth of tumors. Garry Nicholson, head of the drug giant's Oncology Business Unit, said the filing represents "a significant step towards accomplishing Pfizer's goal of bringing axitinib to advanced RCC patients who are in need of additional, effective treatment options". The company already has two kidney cancer treatments on the market - Sutent (sunitinib) and Torisel (temsirolimus). Pfizer noted that some 210,000 people worldwide are diagnosed with kidney cancer every year, and about 102,000 patients die of the disease. While "great advances have been made", five-year survival rates for patients with advanced RCC remain low, at around 20%. (Source: http://www.pharmatimes.com/Article/11-06-29/Pfizer_submits_axitinib_for_advanced_RCC_to_FDA.aspx Pfizer submits axitinib for advanced RCC to FDA by Kevin Grogan World News Jun. 29, 2011)

11

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

CHRONICLE SPOTLIGHT
H YDERABAD FIRM LAUNCHES TRACKING TOOL FOR PHARMA INDUSTRY
G

JULY 2011

oose, a city-based business re-engineering solutions provider, on Jun. 28, 2011 announced the launch of an indigenously developed product to help pharma industry meet the new regulatory packaging guideline,detect counterfeit drugs and protect their brand reputation. 'Procon Tracker' is a new addition to Goose's wide range of solutions adopted by several leading global pharma companies to increase business process efficiency, Goose said in a statement here. Deb Pattnaik, Founder of Goose, said the recent directive from the government to pharma industry to implement track and trace automatic identification process to offset counterfeits opens an opportunity for his firm's new product. "We found the pharma industry is eager to meet the new regulatory compliance norms deadline without disrupting packaging quality process and Procon Tracker is designed precisely to meet these expectations." A Centre for Medicines in the Public Interest report has estimated that globally counterfeit pharmaceutical commerce will grow to become 16% of the aggregate size of the legitimate industry, a 6 percentage point rise from 2004. This illegal business will generate $75 billion in revenues for its owners in 2010, a 92% increase from 2005, Pattnaik said, quoting the report. "We are excited about the potential of Procon Tracker and its addition to a wide range of high performance solutions we offer to the global pharma industry," he said. According to him, Goose expects wide acceptance and adoption of Procon Tracker in the industry. (Source: http://www.business-standard.com/india/news/hyderabad-firm-launches-tracking-tool-for-pharma-industry/139657/on launches tracking tool for pharma industry Press Trust of India Hyderabad, INDIA Jun. 28, 2011) Hyderabad firm

NUTRA PHARMA ANNOUNCES JORDAN DISTRIBUTOR FOR NYLOXIN PAIN RELIEVERS


utra Pharma Corp., a biotechnology company that is developing treatments for Multiple Sclerosis (MS), Human Immunodeficiency Virus (HIV), Adrenomyeloneuropathy (AMN) and Pain, announced on Jun. 28, 2011 that it has selected Medicinesconsult to serve as the exclusive distributor in Jordan for its Nyloxin-branded pain relievers. Nutra Pharma continues to increase awareness internationally and while we are establishing the framework for international distribution of our pain relievers, commented Rik J Deitsch, Chairman and CEO of Nutra Pharma Corporation. "Medicinesconsult has already begun the registration process for our Nyloxin products in Jordan and will begin an aggressive marketing campaign throughout the Middle East once they have regulatory clearance, he added. Medicinesconsult is known for their highly experienced management and consultant marketers who have broad experience in the medical field, including: prescription and OTC drugs, biotech products, medical equipment and medical devices. Medicinesconsult works directly with the Jordanian Ministry of Health, Military and Governmental Hospitals, private hospitals, and other health institutions in Jordan with the mission to provide the Jordanian market, as well as the Middle East and North Africa markets, with high quality medical products for human use. Recently, the Jordan Food and Drug Administration (JFDA) have warned the public against extensive use of painkillers containing paracetamol (acetaminophen) because of the associated risk of liver damage. Additionally, it was reported in the November 1, 2010 issue of The Jordan Times that although Jordanians consume the most painkillers in the region, more needs to be done to improve access to necessary drugs. According to the Jordanian Pain Society (JPS),Jordan was ranked 59th internationally and first regionally in the consumption of painkillers in 2008. According to JPS Secretary General Ahmad Khatib, more efforts are needed to improve access to painkillers in Jordan to reach international averages. General Khatib noted that the sub-average rates are due to the belief of health institutions and physicians that the use of painkillers leads to addiction and their related refusal to prescribe the drugs to their patients -- hence the necessity for a non-addictive alternative. Nyloxin is an over-the-counter (OTC) pain reliever clinically proven to treat moderate to severe (Stage 2) chronic pain. Nyloxin is currently available in the United States as an oral spray for treating back pain, neck aches, headaches, joint pain, migraines, and neuralgia, and as a topical gel for treating joint pain, neck pain, arthritis pain, and pain from repetitive stress. In addition to its everyday strength formulation, Nyloxin is also offered in an extra strength formula for more advanced, Stage 3, chronic pain. Previously, Nutra Pharma announced agreements with distributors in Mexico, Colombia, Venezuela and Lebanon. The drug registration process for both Cobroxin and Nyloxin are currently being pursued in more than 20 countries. For additional information about Nutra Pharma, visit: http:// www.NutraPharma.com (Source: http://www.nutrapharma.com/newsroom/display.php?newsid=181 Nutra Pharma Announces Jordan Distributor for Their Nyloxin Pain Relievers Coral Springs, Florida Jun. 28, 2011)

12

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

CHRONICLE SPOTLIGHT
FOR
J
J APANE S E M & A, I NT E GRAT I ON IS T H E KE Y

JULY 2011

apan has about 2,400 drug manufacturers. Sounds like an industry ripe for consolidation? But Japanese drugmakers with the resources to snap up smaller companies don't want domestic buyouts. They're looking overseas for deals. Take Takeda Pharmaceutical, which recently agreed to buy the Swiss drugmaker Nycomed for $13.7 billion. As the Financial Times reports, CEO Yasuchika Hasegawa dislikes the idea of buying a fellow Japanese pharma. "We are not interested," he told the newspaper. "I'd rather spend my time on a more rewarding opportunity [overseas] in terms of return on investment. I don't see [opportunities] domestically." One reason is government regulation. Were Takeda to buy up some smaller Japanese drugmakers, it would find its freedom to integrate operations rather limited. It's tough to lay off redundant staff, for instance, the FT notes. So,restructuring to cut costs and generate the ROI Hasegawa cites just isn't as straightforward as it can be when buying an overseas firm. Not that it's easy; just listen to Takeda EVP Frank Morich, who's charged with bringing Nycomed into the fold. The two companies are very different, and Takeda wants to keep Nycomed's more entrepreneurial-minded managers to handle its far-flung operations with a high degree of local autonomy. "The vital condition for achieving this is to have enough trust between where those other decisions are made and Tokyo," Morich says. "I see that as my main role. That these guys get the trust, that they get enough freedom from Tokyo--and that I ensure that is not read the wrong way in Tokyo."
(Source: http://www.fiercepharma.com/story/japanese-ma-integrations-key/2011-06-28 | For Japanese M&A, integration's the key by Tracy Staton | Jun. 28, 2011)

M EDPRO S AFE TY INTRODUCES


M

HYPODE RMIC S AFE TY S YRIN GE

edPro Safety Products, Inc., a leading developer of transformational technologies that enable safer medication delivery and blood collection, on Jun. 27, 2011 announced the introduction of its hypodermic safety syringe. The device incorporates a proprietary safety shield that is automatically released during the administration of medicine,covering the needle as it is removed,and thereby enhancing patient and operator safety. The passive (automatic) hypodermic safety syringe provides unique features and benefits. The passive safety mechanism is integrated into the syringe and is activated through the normal process of medication delivery. The shield is automatically deployed over the contaminated needle,reducing the chances of a needlestick injury. It prevents recapping, removal and reuse of the syringe with the engagements of its auto-disable feature and reduces the chance of blood or drug splatter. The device is easy to use and provides an unobstructed view of the patient during an injection. "The passive hypodermic safety syringe is the latest offering in our efforts to expand our patented passive safety technology across a broad range of products," said Craig Turner, CEO of MedPro Safety Products. "This development demonstrates the strength of our research and development effort. We are in various stages of discussions with several potential partners to explore the commercialization of the hypodermic safety syringe
(Source: http://www.marketwatch.com/story/medpro-safety-products-introduces-passive-hypodermic-safety-syringe-2011-06-27? r e f lin k = M W _ n e w s _ s t m p MedPro Safety Products Introduces Passive Hypodermic Safety Syringe Lexington, Kentucky BusinessWire Jun. 27, 2011 Primary source: MedPro Safety Products, Inc. - http://www.medprosafety.com)

S UN PHARMA GETS FDA APPROV AL F OR MIG RAINE IN JECT ION


U.S. largest regional market for contract manufacturing.
Drug firm Sun Pharma on Jun. 23, 2011 said it has received the US health regulator's approval for the launch of its generic Sumatriptan Succinate injections, used in the treatment of migraines and headaches, in the American market. The Mumbai-headquartered firm's US subsidiary has received approval from the US Food and Drug Administration (USFDA) to market Sumatriptan Succinate injections in strength of 6 mg (base)/0.5ml, Sun Pharmaceutical Industries said in a statement. "Annual sale for Sumatriptan Succinate injections in the US is approximately USD 190 million, the company said. Generic Sumatriptan Succinate " injections are equivalent to GlaxoSmithKline's Imitrex Stat dose system in the same strength,it added. "Sumatriptan Succinate injection is indicated for the acute treatment of migraine attacks with or without aura and the acute treatment of cluster headache episodes," it said.
(Source: http://articles.economictimes.indiatimes.com/2011-06-23/news/29690320_1_usfda-approval-injections-treatment-of-migraine-attacks Sun Pharma gets USFDA approval for migraine injection PTI New Delhi, INDIA Jun. 23, 2011)

13

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

CHRONICLE SPOTLIGHT
ORCHID CHEMICALS, PHARMA LTD CLEAR U.S. FDA INSPECTION
C

JULY 2011

hennai-based pharma company Orchid Chemicals and Pharmaceuticals Ltd has said its Cephalosporin API manufacturing (antibiotic) complex in Alathur, Chennai,has successfully cleared the USFDA inspection that it went through. The company announced this to the stock exchanges on Jun. 22, 2011. "This test is conducted to show that our products and plant meet the required global standards," the company spokesperson told ET. The facility has a capacity of 800 tonnes per annum. The oral and sterile Cephalosporin APIs produced here cater to developed markets such as the US, Europe and Japan. This mandatory and routine test would enable Orchid continue with its supplies to those markets. (Source: http://articles.economictimes.indiatimes.com/2011-06-22/news/29689999_1_orchid-chemicals-cephalosporin-apis-chennai-based-pharma Orchid Chemicals, Pharmaceuticals Ltd clear USFDA inspection ET Bureau Chennai, INDIA Jun. 22, 2011)

N OW CHECK GENUINENESS OF PHARMA PRODUCTS THROUGH SMS


US-based Sproxil on Jun. 21,2011 announced the launch of its operations in India and unveiled a product to check the drug counterfeit market.
Mobile Product Authentication (MPA) enables consumers to verify the authenticity of a pharmaceutical product by sending the unique code on the drug as a free text message to the manufacturers in real time,Sproxil CEO Ashifi Gogo told reporters. Sproxil established the first national mobile-based anti-counterfeit service in Africa and has already sold millions of anti-counterfeit labels which provide services to several global pharmaceutical companies, the company said. India has one of the largest pharmaceutical markets in the world, but is plagued by counterfeit (spurious) medicines made elsewhere that tarnish brand India, Gogo said. "Our services enable Indian companies to reduce the presence of counterfeit medicines by connecting companies directly to their consumers in a scalable manner, using mobile phones", he added. Sproxil recently received $1.8 million from Acumen Fund, a non-profit global venture fund, to expand operations in India (which would get the lion's share) and Eastern African countries such as Kenya,Tanzania and Uganda. The company said MPA product delivers automatic protection,simple labels and back-end analytics,and enables consumers to SMS an item-unique code for a rapid response that confirms a brand's genuineness. (Source: http://articles.economictimes.indiatimes.com/2011-06-21/news/29683507_1_sms-anti-counterfeit-labels Now check genuineness of pharma products through SMS PTI Bangalore, India Jun. 21, 2011)

EU REGULATORS APPROVE MARKETING OF DIABETES DRUG BYDUREON


European Union regulators have approved the first once-per-week diabetes medication, the companies that developed the drug said on Jun. 21,2011.
Eli Lilly and Co., Amylin Pharmaceuticals Inc. and Alkermes Inc. said they received marketing approval for Bydureon, a drug that is intended to help patients control their blood sugar in combination with other diabetes medications. The drug is designed to increase the bodys insulin production. Bydureon is a version of Lilly and Amylins diabetes drug Byetta, which was approved in the U.S. in April 2005 and in Europe in November 2006. Byetta, or exenatide, is taken twice a day. Alkermes, based in Waltham, Mass., created the technology that gradually releases the drug over the course of a week. Common side effects of Bydureon included mild to moderate nausea, vomiting, diarrhea, and constipation. The companies have not received approval to sell Bydureon in the U.S. The Food and Drug Administration declined to approve Bydureon in October, asking the companies to run a thorough study that evaluated effects of bigger doses of Bydureon on patients heart rates. The agency also requested results from a study intended to evaluate the efficacy, and labeling of the safety and effectiveness, of the commercial formulation of Bydureon. Lilly,Amylin and Alkermes plan to submit that information in late 2011. Lilly is based in Indianapolis,and Amylin is headquartered in San Diego. (Source: http://www.washingtonpost.com/business/lilly-and-partners-say-eu-regulators-approved-marketing-of-once-a-week-diabetes-drugbydureon/2011/06/21/AGMbQAeH_story.html Lilly and partners say EU regulators approved marketing of once-a-week diabetes drug Bydureon Associated Press New York, USA Jun. 21, 2011)

14

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

CHRONICLE SPOTLIGHT
SANOFI ENTERS INTO RESEARCH COLLABORATION WITH AUDION THERAPEUTICS
Over 500 Million Patients Suffer from Hearing Loss Worldwide with No Currently Available Disease-Modifying Treatments

JULY 2011

Sanofi announced on Jun. 17,2011 that it has entered into a two-year research collaboration with the biopharmaceutical company Audion Therapeutics (Audion) to develop potential treatments for hearing loss through the optimization of small molecules by using a regenerative medicine approach. This collaborative research will utilize technology developed at the Massachusetts Eye and Ear Infirmary in the Eaton-Peabody Laboratory, one of the world's largest basic research facilities dedicated to the study of hearing and deafness, by investigator and Audion co-founder Dr. Albert Edge, who has strong expertise in stem cells and inner ear biology. Audion licensed Dr. Edge's technology from Mass Eye and Ear. Under the terms of the agreement, Sanofi has an option to license technology rights from Audion related to research conducted under the collaboration. "We are very excited about this collaboration with Sanofi that validates our thinking around developing small molecule regenerative drugs for the treatment of hearing loss," said RolfJan Rutten and Helmuth van Es, founders of Audion Therapeutics. "Sanofi's interest in the hearing loss field plus its vast experience and infrastructure in small-molecule drug discovery make them the perfect partner to move this program forward as diligently as possible." "Our new relationship with Audion demonstrates our commitment to work with partners on conditions with unmet and growing medical needs, such as hearing loss," said Elias Zerhouni, M.D., President, Global Research & Development, Sanofi. "This collaboration is a multi-disciplinary approach with our internal Aging Therapeutic Strategic Unit and our Early-to-Candidate Unit working together to advance novel therapies in the field of otolaryngology using the most advanced technologies available to study cochlear biology." (Source: http://www.pharmaceuticalonline.com/article.mvc/Sanofi-Enters-Into-Research-Collaboration-0001 Sanofi Enters Into Research Collaboration With Biopharmaceutical Company Audion Therapeutics To Develop Potential Treatments For Hearing Loss PRNewswire Paris Jun. 17, 2011)

N OVARTIS BEGINS CONSTRUCTION OF

PHARMA FACILITY IN ST. PETERSBURG, RUSSIA

Novartis held a groundbreaking ceremony to announce the start of construction of a pharmaceutical manufacturing plant in St. Petersburg, Russia.
The construction of this facility represents the most significant Novartis investment in Russia to date. This facility will further expand the company's capabilities to produce and deliver both innovative pharmaceuticals and high-quality generics to Russian patients. The new greenfield facility will be built in the Novoorlovskaya Special Economic Zone (SEZ), located to the north of the St. Petersburg city center. Once completed and approved for commercial production, which is expected in 2014, the state of-the-art facility will use cutting-edge technologies to produce approximately 1.5 billion units per year. It will also be an attractive workplace for local talent, employing more than 350 highly qualified professionals who will have access to world-class training and development programs at Novartis. "The establishment of the new Novartis manufacturing facility demonstrates our commitment to invest in the Russian healthcare infrastructure and to contribute to the long-term goals of improving healthcare in Russia, set by the government", said Joseph Jimenez, CEO, Novartis AG. "The plant in St. Petersburg is the latest step in our strategy to bring both innovative pharmaceuticals and low cost, high quality generics closer to patients and customers in Russia." The groundbreaking ceremony was attended by Minister of Economic Development of the Russian Federation, E. Nabiullina, Governor of St. Petersburg V. Matvienko, Novartis AG CEO Joseph Jimenez and other Novartis collaborators and key representatives from the Russian government and the Swiss embassy. Novartis decision to launch drug production in Saint-Petersburg is an outstanding example of a successful collaboration between Russia and foreign investors in the high-technology and innovation sphere, creating new job opportunities for local talent", said Valentina Matvienko, Governor of St. Petersburg. "We're looking forward to help Novartis in solving one of the key challenges on the government agenda - modernization of healthcare". This facility is part of a USD 500 million five-year investment into Russian healthcare infrastructure announced by Novartis in December 2010. This comprehensive partnership addresses three core areas, which are local manufacturing, R&D collaborations and public health development in Russia. Novartis and its predecessors have been active in Russia since the 1860s, and today the company is one of the key players in the Russian pharmaceuticals market. Novartis currently employs over 2,000 professionals in Russia across all business divisions, spanning Pharmaceuticals, Alcon, Sandoz, Consumer Health and Vaccines & Diagnostics. (Source: http://www.pharmanews.eu/novartis/831-novartis-begins-construction-of-new-state-of-the-art-pharmaceutical-manufacturing-plant-in-stpetersburg-russia Novartis begins construction of new state-of-the-art pharmaceutical manufacturing plant in St. Petersburg, Russia Jun. 17, 2011)

15

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

NEWS FROM THE GULF


PRICES OF 565 VITAL MEDICINES REDUCED

JULY 2011

Patients suering from a range of serious illnesses,including diabetes and anxiety disorders,will benet from a 20 per cent reduction in costs.
Patients suffering from a range of serious illnesses, including diabetes and anxiety disorders, will benefit from a 20 per cent reduction in costs on an average for their medication from September 1. This follows a Ministry of Health directive to make 565 pharmaceutical drugs cheaper and more accessible to the public. Our adoption of the decision to approve the reduction of the prices of the pharmaceutical drugs is a practical step towards providing comprehensive health care to all members of our society. This is part of the ministrys vision and mission to put health, disease prevention and treatment as our national priorities, UAE Health Minister Dr Hanif Hassan said at a Press conference on Jun. 27, 2011. He said the price reduction was a result of a fruitful cooperation between the Ministry of Health and pharmaceutical companies to provide patients with care and support. Sixty-seven drugs by pharmaceutical majors like Pfizer and Merck Sharp & Dohme are part of the first batch of roughly 20 per cent of a price cuts across the board, eective from July 1. The price cut on the remaining 498 drugs will be effective from September. Al Baraha Pharmacys Assistant Pharmacist, Mohanan T, commented on the potential impact the reduced prices may have on pharmacies across the UAE. This initiative is a breakthrough for patients, even though it may mean less of a profit for pharmacies, he said. After working in the field for the past 12 years, Mohanan noted the relatively costly nature of medicines in the UAE. Compared to other countries, medicines in the UAE are still on the higher side, but that is because almost all drugs are imported from all over the world. With the Ministry of Health tying up with international drug companies, prices can steadily be decreased with time, which is good for patients who dont have insurance. An average type-2 diabetes patient can spend more than Dh500 a month on medication alone, so these kinds of price reductions can really make a difference, he said. According to Mohanan, the most popular prescription drugs include Lipitor by Pfizer aimed at patients with heart disease and high cholesterol levels; Xanax by Pfizer, used to treat moderate to severe anxiety disorders and panic attacks; and Januvia by Merck Sharp & Dohme, used in conjunction with exercise and dietary restrictions to lower blood sugar levels in adults with type-2 diabetes. All three of the top-sellers will sell cheaper from July.
From September, 103 drugs under GlaxoSmithKline, will be available at reduced prices for the general public. Other firms supporting price reductions include Alcon Pharmaceuticals Ltd,

AstraZeneca, Bayer Schering, Boehringer Ingelheim, Bristol-Myers Squibb, Chauvin Pharmaceuticals Ltd., Eli Lilly,Ferring Pharmaceuticals,H. Lundbeck A/S, Hoffmann-La Roche Ltd., Janssen-Cilag, Les Laboratories Servier, Merck Serono, Novartis Pharma AG,Sanofi Aventis,and Valeant Pharmaceuticals.

Once the directive by the Ministry of Health is announced to all pharmacies and hospitals, price stickers and inventory lists will need to be revised. We will need to wait for official instructions on how to treat old stock ordered before the directive. Some pharmacies may choose to absorb 20 per cent of the price until new shipments come in, but it depends on a lot of factors and we cannot be sure, Mohanan added.
( S o u r c e : http://www.khaleejtimes.com/DisplayArticleNew.asp? section=theuae&xfile=data/theuae/2011/june/theuae_june782.xml | Prices of 565 vital medicines reduced by Praseeda Nair | Khaleej Times Jun. 28, 2011)

Pharmaceutical Solutions Industry Tel: +966 2 6361383 Fax: 966 2 6379460 P.O. Box 17476 Jeddah 21484 Kingdom of Saudi Arabia. For more info, visit www.psiltd.com

16

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

INSIGHTS
WHY ARE DRUG PRICES SET SO UNSCIENTIFICALLY?
For an industry rooted in science,why are drug prices set so unscientifically?

JULY 2011

The pharmaceutical market does not follow the basic laws of economics. If it did, there would be, at least in each country, one set, limited price range for each drug,dictated by supply, demand and other market fundamentals. Instead, we seem to have chaos. Prices that U.S. consumers pay for name-brand and generic drugs vary widely depending on ones insurance carrier. I tested this recently by trying to use two different insurance cards to order an asthma inhaler: in one case,the cost was $250, in the other,$46. (It would have cost even more than $250 without insurancea sobering thought.) U.S. prices remain far above those in other countries. Can the U.S. consumers willingness to pay more for pharmaceuticals, indefinitely, be assumed? But variability is also seen outside the U.S. A recent European Union study found that prices for 150 name brand medications varied by 24% across member states, and that generic drug prices could vary by a factor of 16! In May, a group of pharma CEOs spoke candidly about drug pricing at the Reuters Health Summit. After reading a report on it, blogger Jim Edwards take on the meeting Four Pharma CEOs Admit They Jack Up Prices For the Hell of Itdidnt seem far from the truth. AstraZeneca CEO David Brennan noted the lack of transparency on pricing in the U.S., Reuters reported. Shire CEO Angus Russell was quoted as saying, Prices were just shoved up every year to make more money and meet earnings. The industry has been in volume decline for three yearsits been propped up on price, said Tim van Biesen, head of Bain & Cos healthcare practice, as quoted by Reuters. You have to ask how long that can continue. There is a call for more transparency about all things, but particularly drug pricing. Last month, UNICEF began to publish the prices that drug manufacturers quote for vaccines. In addition, in the U.S., a group of Democratic Congressmen wrote to drug manufacturers asking them to clarify the means by which they are establishing prices for new drugs. One of the two drugs targeted is Avanir Pharmaceuticals neurological treatment, Nuedexta. Nuedexta is reportedly a combination of quinidine and dextromethorphan, both inexpensive ingredients, and the lawmakers asked why a product made with $20 worth of ingredients was being sold for $600. They demanded cost figures for clinical trials and post-market studies, marketing budgets,and details on how the price was established. Newspapers and blogs also discussed the high prices for some newly approved drugs, including Optimers Dificid and Vertexs Incivid, and the fact that price isnt being openly shared, up front, with the groups who need that information most: physicians and patients. As consumers become better educated about drug effects,how willing will they be to pay much more for a drug that may, in some cases, provide only marginally better performance? In Europe, the move is toward Value Based Pricing. This approach,critics argue, is keeping the latest innovations from patients. Others say it is keeping prices,and manufacturer hype,down to manageable levels. Last year, in the U.K., the National Institute for Health and Clinical Excellence (NICE) failed to recommend three new cancer drugs because the treatments were too expensive relative to the benefit they offered. NICE is said to be working on a value-based approach, set to take shape by 2014. Germany has also drafted a value-based set of requirements for drug manufacturers. Can the U.S. be far behind? Undoubtedly, this developing trend will add to the challenges of getting new drugs approved. However, it will also force drugmakers to ensure that new drugs convey additional value to physicians and patients to justify a higher price.
(Source: http://www.pharmamanufacturing.com/articles/2011/091.html Drug prices? eenie meenie miney mo by Agnes Shanley, Editor-in-Chief)

17

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

ANALYSIS
M ENS WAIST LINES COULD BE KEY T O HEALTH
Men can gain significant health benefits
from watching their waist size and, if necessary, losing some flab around the middle, the American Dietetic Association says. Just as its important to know your blood pressure, cholesterol, blood sugar and weight numbers, men need to know their waist circumference. So, get out the tape measure, registered dietitian and ADA spokesman Jim White said in an ADA news release. For an average male, a waistline of 40 inches puts him into the disease-risk zone, the experts warned. Excess abdominal fat, as opposed to fat elsewhere on the body, increases mens risk for health problems such as diabetes, heart disease and some types of cancer. This fat around internal organs is known as visceral fat. To correctly measure your waist size, wrap the tape measure over bare skin on your natural waistline, a little above the belly button at the narrowest part of your torso. Dont hold the tape measure too loose or too tight, White said. Eating better, decreasing stress levels, engaging in physical activity and getting at least seven to nine hours of sleep every day can help keep a mans midsection under control, registered dietitian and ADA spokesman Manuel Villacorta said in the news release. Villacorta suggested reducing portion sizes, cutting back on alcohol and exercising regularly.
(Source: http://news.health.com/2011/06/20/mens-waistlines-could-be-key-tohealth/#more-46431 Mens Waistlines Could Be Key to Health HealthDay News Jun. 20, 2011 Primary source: American Dietetic Association, news release Jun. 15, 2011)

JULY 2011

QUOTE & UNQUOTE


To me, the most important part of intelligence is being able to recognize and acknowledge what you dont know and what is possibly unknown by anyone. I think that understanding my own limits and acknowledging the things that I dont knowas well as being able to discuss and interact with scientists to determine the extent of our current knowledge and understanding on a particular topichas served me well as both an entrepreneur and life science executive.

Randal J. Kirk Sr. Managing Director & CEOThird Security, LLC www.thirdsecurity.com
(Abstract from the source: Through The Eyes Of A Billionaire Life Sciences Investor by Cliff Mintz, Ph.D. Life Science Leader www.LifeScienceLeader.com June 2011)

For our industry to regain public trust, we must constantly examine how we interact with our customers, how we communicate with patients and providers, how we fund activities, and how we share information. We also need to do a better job of informing those we serve about how we operate now. We also need others in healthcare to stand with us and embrace a values-based approach to our interactions and recognize and respond to how we've changed. By doing these things, we can assure the public that our industryan industry that has brought so much benefit to so manyis conducting its business with focus on the patient, with transparency, with integrity, and with respect. In this way we will be worthy of trust.
(Abstract from the source: http://pharmexec.findpharma.com/ pharmexec/Commentary/Restoring-Public-Trust-in-Pharma/ ArticleStandard/Article/detail/716295? contextCategoryId=48158 Restoring Public Trust in Pharma by Deirdre Connelly, President, North American Pharmaceuticals at GlaxoSmithKline Pharmaceutical Executive Apr. 1, 2011) Strategic alliances are an important area for improving pharma R&D and bringing medicines to patients. The pharmaceutical industry needs to go through this transformation. There are huge pressures facing pharma now, such as increasing costs and development times. Strategic alliances are one of the ways were fixing R&D, so we can speed the delivery of novel medicines to patients.

DID YOU KNOW?


b o u t Hearing Loss: Hearing loss is the most prevalent inner ear disorder and the World Health Organization estimates that 500 million people worldwide have a mild to moderate to severe or greater hearing loss. Of people aged 65 to 74, nearly 33 percent have hearing loss and close to 50 percent of people over the age of 75 are affected. Of people over the age of 85, almost everyone is affected to some extent.
Estimates are that the number of people in the world with age-related hearing loss is expected to increase to 900 million by 2050. However, the incidence is rising rapidly among younger people as well, due to frequent exposure to excessive noise. Estimates from the National Institutes of Health and the Centers for Disease Control and Prevention place the total annual costs of hearing loss at approximately $50 billion per year in the U.S. alone. There are currently no prescription products for a disease modifying treatment for hearing loss.

Adrienne Takacs, Ph.D., Senior Advisor & Alliance ExecutiveEli Lilly and Company.
(Source: http://www.lifescienceleader.com/index.php? option=com_jambozine&layout=article&view=page&aid=4276&It emid=56 Strategic Alliances: The Cure For What Ails Pharma? by Sara Gambrill Life Science Leader May 2011)

18

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

PRODUCT LAUNCH
BAUSCH
& LOMB TO LAUNCH OPHTHALMIC DROPS IN INDIA

JULY 2011

Bausch + Lomb,through a strategic agreement with Micro Labs,is set to launch ophthalmic pharmaceutical business in India.
The agreement will provide the Rochester-based global eye health company with manufacturing capabilities in India to accelerate the launch of new prescription and over-the-counter ophthalmic drops including Moxisurge,Aquasurge,Aquasurge Max,Bromvue, Ketovue and Moxisurge-KT. Bausch + Lomb will also set up sales and marketing teams,and deliver practitioner and patient education programs in relation to eye care. As part of the agreement,Bausch + Lomb will source ophthalmic solution products from Micro Labs and,market and sell them in Asia Pacific. The companies will partner over manufacturing technology for the production of eye drops. They will also conduct ophthalmic pharmaceutical products research and development for emerging markets. (Source: http://www.pharmaceutical-business-review.com/news/bausch-lomb-partners-with-micro-labs-to-establish-pharma-business-in-india-010711 |Bausch + Lomb partners with Micro Labs to establish pharma business in India by PBR Sta Writer |Pharmaceutical Business Review Jul. 1, 2011)

M EDPRO SAFETY INTRODUCES PRE-FILLED SAFETY SYRINGE


M edPro Safety Products, Inc.,a leading developer of transformational technologies that enable safer medication delivery and blood collection,
on Jun. 28, 2011 announced the introduction of its pre-filled safety syringe (PFSS). The device contains a precise dose of pharmaceutical stored within a syringe system equipped with MedPro's unique, fully passive safety mechanism that reduces and potentially eliminates the risk of needlestick injury. Pre-lled syringes represent an approximately 2.6 billion unit annual market growing at approximately 14% (Pre-lled Syringes, Greystone Associates, February 2008). There is no fully passive pre-filled safety syringe currently commercially available in the U.S. and the MedPro product represents the first truly passive market entry. Current estimates indicate that only 15% of the pre-filled market segment has converted to any type of safety solution. The PFSS is comprised of two unique parts: (a) A standard glass or plastic cartridge that will act as both a pre-filled medicament reservoir and syringe plunger, and (b) A plastic safety syringe that incorporates a fully passive (or automatic) safety deployment system. The PFSS device offers significant benefits to healthcare safety, both for the patient and the healthcare professional. The automatic activation of a safety shield as a needle is removed protects the operator from the contaminated needle and prevents a needlestick injury. The shield also reduces the chance of blood or drug splatter. The prefilled cartridge offers patient safety through exact dosage control and the theoretical reduction of medicine delivery errors. It also saves time in drug preparation and delivery. The PFSS is designed to be compatible with existing pharmaceutical filling technology for ease of adoption and operational efficiencies, and the glass cartridge is consistent with current industry standards. "The pre-filled safety syringe is another example of the Company's strategy to expand our unique patented passive safety technology across platforms," said Craig Turner, CEO of MedPro Safety Products. "The PFSS can deliver a wide range of biotech and pharmaceutical products. We are currently in various stages of discussions with several potential partners to explore the commercialization of the PFSS in several markets
(Source: http://www.marketwatch.com/story/medpro-safety-products-introduces-pre-filled-safety-syringe-2011-06-28?reflink=MW_news_stmp MedPro Safety Products Introduces Pre-filled Safety SyringeLexington, Kentucky BusinessWire Jun. 28, 2011 Primary source: MedPro Safety Products, Inc. - http://www.medprosafety.com)

19

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

FEATURE
ACQUISITIONS, NOT RESEARCH, FUELS NEW DRUGS

JULY 2011

Outside business deals rather than internal research projects are stocking the new drug cabinets of major pharmaceutical companies,analysts
for Fitch Ratings said on Jun. 27, 2011 in a global health care business report. Thanks to acquisition and licensing deals, the multinational drug makers, taken as a whole, are on pace to meet last years level of 21 new drug approvals by the end of the year in the United States and Europe,the Fitch report said. But at the same time, 15 possible new drugs have hit major hurdles since the beginning of the year, mostly because of unfavorable clinical trials, the analysts said. The largest drug companies started at least 22 new projects in their late-stage pipelines since the beginning of the year, Fitch said, but mostly from business deals rather than internal R&D. The companies setbacks in their own labs are well known in the industry, notably at Pfizer, which has announced plans to slash research by as much as $2.9 billion the next two years. Pfizer, Eli Lilly and Johnson & Johnson have each added three or more new experimental drugs to their late-stage development plans since the beginning of the year, Fitch said. Two of Lillys were diabetes drugs licensed from Boehringer Ingelheim in January. Pfizer acquired three new pain medicine candidates called Remoxy,Oxecta, and ALO-02 when it bought King Pharmaceuticals for $3.6 billion in October 2010. J&J acquired a yellow fever vaccine in late development with the $2.4 billion takeover of the Dutch biotechnology company Crucell and licensed another experimental drug from Swedens Medivir. In another analyst report with a broad view of the industry recently, Dr. Timothy Anderson of Bernstein Research looked at the prospects for nine major pharmaceutical companies to 2020. His June 16 investor note found some companies with good long-term prospects from existing products, while others fall off the patent cliff as generic competition is expected to pound their sales. The three companies with the best sales prospects to 2020 are GlaxoSmithKline, Novartis and Bristol-Myers Squibb,Bernstein reported. Those with the most troubling revenue outlook are, by far, Eli Lilly and AstraZeneca. This chart from Bernstein shows base pharmaceutical revenues to 2020, normalized to 2010:
Source: Bernstein Research, based on company reports and Bernstein estimates and analysis

(Source: http://prescriptions.blogs.nytimes.com/2011/06/27/acquisitions-not-research-fuels-new-drugs/?scp=8&sq=drug&st=cse Acquisitions, Not Research, Fuels New Drugs by Du Wilson Prescriptions The Business of Health Care Jun. 27, 2011)

20

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

DRUGS ON THE WAY


ELI LILLY PLANS 10 DRUGS IN FINAL-STAGE TRIALS BY YEAR END

JULY 2011

Eli Lilly & Co., the drugmaker slated to lose U.S. patent protection on its biggest-selling medicine Zyprexa in October, said it will have at least 10 new
therapies in final-stage studies by years end. Lilly has 33 drugs in the second and third stages of clinical trials, including medicines for cancer, diabetes and Alzheimers disease, up from seven in 2005, the Indianapolis- based company said on Jun. 30,2011 in a statement. The drugmaker confirmed its forecast of at least $20 billion in annual revenue and $3 billion in full-year net income from 2011 to 2014. Lillys 2010 net income was $5.07 billion with sales of $23.1 billion. Patent expirations on Zyprexa and other drugs are estimated to reduce annual sales by about $7 billion from 2010 to 2014, Lilly said in the statement released before its investor meeting in New York. New products will help growth return after 2014,the company said. Zyprexa had $5.03 billion in sales last year. With our pipeline maturing,we will be in a position where we will resume a good growth trajectory as we come out of the patent-expiration period, Chief Executive Ocer John C. Lechleiter said in an interview on Jun. 30,2011. Growth in the emerging markets, Japan and in Lillys Elanco animal-health unit may generate more than $4 billion of additional revenue by 2015, the company said. Earnings per share are expected to decline from 2011 to 2012,rise in 2013 and decline again in 2014,the company said.

NEGATIVE VIEW
Expectations are pretty low, said Les Funtleyder, a portfolio manager with Miller Tabak & Co., in a telephone interview on Jun. 29, 2011. The street is about as negative as you are going to get for a pharma company. Lilly rose 19 cents to $37.46 at 9:43 a.m. in New York Stock Exchange composite trading. The shares had gained 6.4 percent in trading this year before Jun. 30,2011. Growth-oriented investors have a hard time reconciling Lillys strategy of shrinking first and growing later, he said. I am looking for an articulation of their strategy. Lilly faces generic competition in 2013 for the antidepressant Cymbalta, the companys second-biggest seller at $3.46 billion,and in 2014 to its $1 billion osteoporosis drug,Evista.

$34 BILLION
U.S. drugmakers face patent losses this year to products with $34 billion in yearly sales. Sales at risk from generic rivals will increase to $147 billion by 2015, according to Bloomberg data. In the statement, Lilly said it had fully enrolled patients in two final-stage trials of solanezumab, the companys experimental Alzheimers drug. The company expects to complete the studies in the rst half of 2012. Three phases of clinical trials are generally required for U.S. regulatory approval of new drugs. Lechleiter reiterated the companys opposition to a large merger and said Lilly is seeking smaller deals that would complement or supplement assets we already have. The CEO cited Lillys January partnership with German drugmaker Boehringer Ingelheim GmbH to develop and sell diabetes treatments as the type of deals the company favors. We see these large-scale combinations as solving short- term problems, Lechleiter said. We think they are a distraction.
(Source: http://www.bloomberg.com/news/2011-06-30/eli-lilly-plans-10-drugs-in-final-stage-trials-by-end-of-2011.html?cmpid=yhoo |Eli Lilly Plans 10 Drugs in Final-Stage Trials by Year End by Robert Langreth |Story Editor: Reg Gale |Bloomberg New York |Jun. 30, 2011)

21

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

NEWS UPDATE
PHARMA TRADERS MUST FOLLOW INTL STANDARDS: TDAP CHIEF
Pakistani Pharma traders should follow
industry.

JULY 2011

international standards in terms of products acceptability in global market to boost pharmaceutical

Tariq Iqbal Puri, Chief Executive Trade Development Authority of Pakistan (TDAP) addressing 1st Pharma Summit on Jun. 15, 2011 said the role of PPMAs leadership in awakening the need to revamp the pharma industry is laudable. He informed the audience about the role being played by TDAP for the growth of export from pharma industry by extending different subsidies. He said realizing the importance of international accreditation, TDAP approved subsidy for UK MHRA Gap-Analysis at the behest of PPMA. TDAP created a Pharma Cell in TDAP for the promotion of export from the pharma industry. Prompted by this realization, Pharma Cell of TDAP has organized two workshops on WHO Pre-Qualification Program and Export Opportunities in Karachi and Lahore. We have to remain globally competitive by revamping the industry to meet international standards, he said. Sindh Health Minister, Dr Saghir Ahmad assured government support for establishment of FDA-approved drug manufacturing plants in the province. He said government was committed to assisting industries creating employment opportunities and earning foreign exchange for the country. Talking about devolution of health sector to the provinces, with specific reference to registration of drugs, their licensing, pricing and quality control, he said these issues have been discussed with the federal government and a clear picture would appear in the next few months. Saghir Ahmed offered to facilitate PPMA in issues that were believed to be hindering progression and strengthening of local pharmaceutical industry. About Appellate Board handling complaints against drug industry and regarding matters related to pricing of drugs, he said there has to be a balanced representation of all the provinces in boards to be established in each province. Mirza Ikhtiar Baig, advisor to Prime Minister said the conference would be helpful for the growth and development of pharma industry. He asked the PPMA to provide him with the list of pharmaceutical products intended for zero-rating for export to China. This list, he said was being currently prepared by the government. He mentioned there were good opportunities for pharmaceutical exports to Yemen and Morocco. He asked the PPMA to procure government support and capture this big market share. Dr Shahzeb Akram, Vice Chairman of PPMA suggested pharma family to join hands in procurement of FDA and WHO approved plants. He mentioned the country was about to have a WHO approved Drug Testing Lab in Lahore at its Sunder Industrial Estate. He said this lab would become functional in 2012. Haroon Qasim Chairman PPMA appreciated the role played by TDAP for the support of pharma industry of Pakistan. (Source: http://www.dailytimes.com.pk/default.asp?page=2011\06\16\story_16-6-2011_pg5_6 Pharma traders must follow intl standards: TDAP chief Sta Report Jun. 16, 2011 Karachi, PAKISTAN)

Pharmaceutical Solutions Industry


Tel: +966 2 6361383 - Fax: 966 2 6379460 Kingdom of Saudi Arabia. For more info, visit www.psiltd.com

22

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

NEWS UPDATE
STUDY: CANCER DRUGS APPROVED IN U.S. BEFORE EUROPE

JULY 2011

New cancer medicines typically reach the U.S. market several months before they go on sale in Europe,according to a study published amid a debate
about access to new drugs. The findings released on Jun. 16, 2011 counter a common belief among doctors, academics and investors that new oncology drugs often win approval in Europe first, said researchers from the nonprofit advocacy group Friends of Cancer Research. Each of the 23 cancer drugs cleared by the United States and Europe over a seven-year period debuted in the U.S. market, the study found. Drugmakers usually submitted their medicines to the U.S. Food and Drug Administration first, and the FDA review period was generally shorter at around six months. In Europe, the median review time was nearly a year, at 350 days. "To patients battling cancer, with no treatment options, access to new medicines five-and-a-half months sooner is a very important and potentially lifesaving difference," said Ellen Sigal, who chairs and founded the cancer group. The findings were published online in the journal Health Affairs. The researchers analyzed regulatory review times for 35 new cancer drugs approved in either the United States, Europe or both between 2003 through 2010. Twenty-three medicines won clearance in both regions. Europe cleared three medicines the FDA did not approve. The FDA gave a green light to nine drugs that did not reach the European market. The researchers did not analyze the reasons for the conflicting decisions. FDA Commissioner Margaret Hamburg, in a statement, said the findings "reflect FDA's commitment to foster access to effective therapies in a responsive and timely manner." The agency has drawn fire from some manufacturers as being too cautious in analyzing cancer and other drugs as well as medical devices. Some critics say the FDA is harming innovation and U.S. competitiveness with unnecessarily tough requirements. The medical device industry has argued vocally that the FDA is driving companies to Europe where developers see a quicker path to the market. Consumer advocates and others, meanwhile, argue that the FDA may sacrifice safety for speed and should demand more data from companies. Dr. Janet Woodcock, the FDA's top drug official, said the agency was "not in a race with other regulatory agencies." But she said the cancer drug findings could help dispel an "urban myth" that the United States was routinely falling behind Europe on approval decisions. "FDA review of cancer drugs is efficient. It is rapid. The real problems are in the scientific development programs and scientific uncertainty" about how to attack cancer, she said. For investors, the findings show "there are certain things that are working quite well" in the United States, said Jonathan Leff, managing director of healthcare at private equity firm Warburg Pincus. He pointed to the FDA's accelerated approval process, a program designed to bring new drugs for serious diseases to the market quickly based on early data. Investors worry, however, that the FDA will require companies to produce more data to show safety and effectiveness for cancer drugs as the agency has in other areas. "The fear this is bleeding over into oncology is palpable," Leff said. The study's authors said their results showed the need for Congress to adequately fund the FDA. They planned a briefing for congressional staff on the findings on Jun. 16, 2011. Republican lawmakers in the U.S. House of Representatives have proposed steep cuts to the FDA's budget. "Strong public and congressional support is desperately needed for the FDA to continue this trend and to improve its scientific foundation," Sigal said.
The study was published online by Health Affairs at

http://content.healthaffairs.org/cgi/content/abstract/hlthaff.2011.0231

(Source: http://www.chicagotribune.com/business/yourmoney/sns-rt-us-cancer-drugs-apptre75f1cd-20110616,0,7505467.story Study: Cancer drugs approved in U.S. before Europe by Lisa Richwine Edited by Tim Dobbyn Reuters Washington Jun. 16, 2011)

23

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

NEWS UPDATE
CADILA TO BUY ASSETS OF U.S. - BASED NESHER

JULY 2011

Cadila Healthcare Ltd., a part of the Zydus Group, on Jun. 17, 2011 said its U.S. unit has agreed to acquire the assets of U.S.-based pharmaceutical
company Nesher Pharmaceuticals Inc. for an undisclosed amount. Cadila Healthcare said the acquisition of Nesher--the generic unit of KV Pharmaceutical--will allow its U.S. unit to make and sell generic controlled substances in the country, which otherwise cannot be imported. The acquisition includes Nesher's existing and future portfolio of generic drugs, certain manufacturing facilities and a research and development laboratory, Cadila Healthcare said in a statement. The company said the deal entails the assumption of certain liabilities of Nesher, but didn't elaborate. Cadila Chairman Pankaj Patel said the development gives the company access to a "difficult-to-develop product pipeline, expertise and infrastructure that will add value to our operations in the U.S." Nesher's pipeline of generic drugs include eight existing filings with the U.S. drug regulator and five products under development. The deal also includes supply and technical services agreements whereby certain products of KV Pharmaceutical will be manufactured by Zynesher Pharmaceuticals USA LLC, a unit of Zydus Pharmaceuticals USA Inc. Annual sales of controlled substances medications in the U.S. are estimated at $7 billion,the statement added. (Source: http://www.marketwatch.com/story/cadila-to-buy-assets-of-us-based-nesher-2011-06-17 Cadila to buy assets of U.S.-based Nesher by Rumman Ahmed MarketWatch Bangalore, INDIA Jun. 17, 2011)

A S T RAZEN E CA

G RABS RUSS IAN OPPORT UN IT Y

Question: When does a threat become an opportunity?


Answer: When it is in your interests. That is how AstraZeneca interpreted Russias past warnings that global pharmaceutical companies would be punished if they didnt build operations inside Russia and transfer technology there. I was here a couple of years ago and had that conversation with a couple of ministers and ultimately we came back with a plan on how to do it. We recognized that would be an opportunity for us, AstraZenecas CEO David Brennan said in an exclusive interview about the drug makers strategy for Russia, which was unveiled on Jun. 16, 2011. AstraZeneca announced that it plans to build a research and development hub in St. Petersburg in the coming year. The move by the U.K.s secondlargest drug maker strengthens its investments in Russianow targeted at $1.2 billion over the next five yearsand supports the Russian governments strategy to modernize and develop the countrys pharmaceutical sector. The company has already begun building a new $150 billion manufacturing facility in the countrys central Kaluga region to supply Russia with locally manufactured medicines. That looks like a win-win proposition for a company that sees Russia, Brazil and China as key to growing its revenue and business base. It will position us well, said Mr. Brennan. Were not the leading foreign drug company in Russia but we will certainly be very active on the ground, with a couple of hundred new employees with our new manufacturing facilities, some research activities, as well as a strong marketing and sales organization. From my perspective, thats a pretty complete picture for a country like this. Given that the Russian government plans to invest heavily in the pharmaceuticals industry and sees the sector as a key one for restoring the countrys industrial strength, AZs move looks pretty smart. But it isnt alone in spotting the opportunity Russia offers. Several pharmaceutical companies have already pledged to build manufacturing plants in Russia over the past 18 months including Sanofi,Nycomed and Novo Nordisk. This is essentially a land grab by drug makers, said Peter Cartwright, an associate with Fiske. Everyone has already piled into China and Brazil. Russia, by comparison, is more or less untouched by big drug makers despite the countrys many attractions: a relatively receptive government, an ageing population and a huge need for quality medicines. There is also much to be gained from establishing greenfield sites with your own locally-based management. That is much easier than having to work with a local partner who might not do what you want all the time. (Source: http://blogs.wsj.com/source/2011/06/16/astrazeneca-grabs-russian-opportunity/?mod=yahoo_hs AstraZeneca Grabs Russian Opportunity by Sten Stovall Jun. 16, 2011)

24

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

NEWS UPDATE
APP PHARMA TO PLUG $38M INTO EXPANDING NY MANUFACTURING SITE
A

JULY 2011

PP Pharmaceuticals plans on investing $38 million to expand a manufacturing facility in Grand Island, NY, to increase its production of injectable genetic drugs. It will thus add 90 jobs to its existing workforce of 580 at the plant. APP, a wholly owned subsidiary of Fresenius Kabi Pharmaceuticals Holding, will expand its production site by 13,000 square feet and add six new production lines for injectable products. The expansion is anticipated to begin this month and take two years to complete. At Grand Island, APP manufactures a variety of injectable pharmaceutical products for the North America market. The products encompass four therapeutic areas: anti-infectives, critical care, analgesia/anesthesia, and oncology. Through the expansion, the site will significantly contribute to the continuous local supply of high-quality injectable generics for the U.S. and Canada, states Michael Schnhofen, president, science, production, and technology for Fresenius Kabi. Based on its promise of the new and retained jobs, APP has won nearly $1.2 million in tax credits over five years through New York states Excelsior Jobs Program; 2,000 kW of lower-cost power through the state Power Authority; and local property tax, sales tax, and mortgage tax abatements through the Erie County Economic Development Corp. APP owns two manufacturing plants in Grand Islandone of 210, 000 square feet, the other 148, 000 square feetas well as 120, 000 square feet of warehouse and administrative space. (Source: http://www.genengnews.com/gen-news-highlights/app-pharma-to-plug-38m-into-expanding-ny-manufacturing-site/81245307/ APP Pharma to Plug $38M into Expanding NY Manufacturing Site GEN News Highlights Jun. 15, 2011)

V IR OP HARMA S

CIN R YZE G E T S N OD F R OM E U RO PE AN COM MIS S ION

Biotechnology company ViroPharma Inc. said on Jun. 15, 2011 it received European approval for Cinryze, an intravenous treatment for a genetic
disease that can cause dangerous swelling in the throat and extremities. The company said the European Commission approved Cinryze for the prevention and treatment of angioedema attacks in adults and adolescents. The commission also authorized properly trained patients to administer Cinryze to themselves. Hereditary angioedema, or HAE, affects at least 10,000 people in Europe. Patients with it can experience unpredictable and potentially deadly swelling attacks that can affect the larynx, abdomen and face. Many patients experience frequent or severe attacks that are not only disabling and potentially fatal, but also lead to constant anxiety about when an attack will occur significantly impacting patients ability to conduct normal and productive lives, Konrad Bork of the Department of Dermatology of Johannes Gutenberg University in Mainz, Germany, said in a prepared statement. The approval of Cinryze in Europe provides a very important new option to meet the needs of these severely afflicted HAE patients. Cinryze is already approved in the United States and generated $57 million in sales during the first quarter. HAE is a variable disease due to a deficiency of C1 inhibitor, a human plasma protein that prevents swelling. Cinryze helps to control HAE by increasing functional C1 inhibitor activity. ViroPharma said Cinryze is the first and only FDA-approved C1 inhibitor approved on clinical data supporting its effectiveness in the prevention of attacks of this potentially dangerous genetic disease. The approval of Cinryze follows the positive opinion adopted by the Committee for Medicinal Products for Human Use in March. Cinryze is now approved throughout all the member states of the European Union as well as in the European Economic Area, namely Norway, Iceland and Liechtenstein. The approval of Cinryze throughout Europe is an important milestone for ViroPharma in our evolution as an international biopharmaceutical company that delivers novel solutions that address the unmet medical needs of patients living with few, if any, clinical treatment options, said Vincent Milano, ViroPharmas president and chief executive. (Source: http://www.pennlive.com/newsflash/index.ssf/story/viropharma-drug-gets-ok-from-europe/d61345adcf0a4c6a83472c6e3e0d1a15 ViroPharma drug gets OK from Europe by Gretchen Metz Daily Local News Uwchlan Jun. 15, 2011)

25

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

NEWS UPDATE
MERCK TEAMS WITH HANWHA TO DEVELOP BIOSIMILAR ENBREL

JULY 2011

Merck & Co. is teaming up with Korean firm Hanwha Chemical to develop a biosimilar form of Pfizer and Amgens TNF-blocker,Enbrel (etanercept),
which has a patent expiry date looming in October 2012. The collaboration will focus on Hanwhas HD203 candidate, which is currently undergoing a Phase III trial in Korea. The study is comparing HD203 with Enbrel as combination therapy with methotrexate in the treatment of rheumatoid arthritis. Clinical trials with HD203 have yet to be initiated in the U.S. Under terms of the deal Merck will carry out clinical development and manufacturing of HD203, and has rights to commercialize the drug globally, except in Korea and Turkey, where Hanwha has retained marketing rights. Korea-based Hanwha will also receive an up-front payment from Merck, along with technology transfer and regulatory-associated milestones, plus tiered sales royalties. Enbrel is currently approved in various markets globally for the treatment of rheumatoid arthritis and polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis. Originally developed by Immunex, Enbrel is marketed by Amgen in the U.S. and Canada, and by Pfizer in all other approved markets. For the three months ended March 31 2011 Amgen reported Enbrel sales of $875 million, up 9% on equivalent 2010 sales. The drug is Amgens second biggest sales earner, behind Neulasta/Neupogen. Sales of Enbrel by Pfizer in non-U.S./Canadian markets were also up 9% during Q1 2011, at $870 million. The drug is currently Pfizers third highest-ranking in terms of global sales, even excluding the U.S. and Canadian markets. (Source: http://www.genengnews.com/gen-news-highlights/merck-co-teams-with-hanwha-to-develop-biosimilar-enbrel/81245290/ Merck & Co. Teams with Hanwha to Develop Biosimilar Enbrel GEN News Highlights Jun. 13, 2011)

US

ADDS FORMALDEHYDE T O LIST OF CARCINOGENS

The government on Jun. 10, 2011 added formaldehyde, a substance found in plastics and other commonly used products, to a list of known
carcinogens and warned that the chemical styrene might cause cancer. In a report prepared for the Secretary of the Department of Health and Human Services (HHS), scientists warned that people with higher exposure to formaldehyde were more at risk for nasopharyngeal cancer, myeloid leukemia and other cancers. "There is now sufficient evidence from studies in humans to show that individuals with higher measures of exposure to formaldehyde are at increased risk for certain types of rare cancers ...," the Report on Carcinogens said. Formaldehyde is a colorless, flammable,strong-smelling chemical widely used to make resins for household items,such as composite wood products, paper product coatings, plastics, synthetic fibers, and textile finishes. It is also commonly used as a preservative in medical laboratories, mortuaries, and some consumer products, including hair-straightening products. The report, produced by the National Toxicology Program (NTP), also added styrene to the list of substances that were reasonably anticipated to be human carcinogens. Styrene is a synthetic chemical used in the manufacture of products such as rubber, plastic, insulation, fiberglass, pipes, automobile parts, food containers, and carpet backing. The greatest exposure to styrene in the general population is through cigarette smoking, the report said. The American Chemistry Council (ACC), an industry group, lashed out at the report, saying it was concerned that politics may have hijacked the scientific process. "Today's report by HHS made unfounded classifications of both formaldehyde and styrene and will unnecessarily alarm consumers," Cal Dooley, president and CEO of the ACC, said in a statement. Jennifer Sass of the National Resources Defense Council, a U.S. environmental group, praised the government for publishing the report in the face of what she described as pressure by chemical companies to prevent its release. "The chemical industry fought the truth, the science, and the public -but, in the end our government experts came through for us, giving the public accurate information about the health risks from chemicals that are commonly found in our homes, schools, and workplaces," Sass wrote in a blog. The report also listed aristolochic acids, found in some plants, as a known carcinogen and added the fungicide captafol, some inhalable glass wool fibers, cobalt-tungsten carbide, riddelliine and o-Nitrotoluene to the list of substances reasonably anticipated to be carcinogens. It, however, said listing the substances did not in itself mean they would cause cancer. Amount and duration of exposure,and susceptibility to a substance were among the many factors that affected whether a person developed cancer,it said. The report is available at ntp.niehs.nih.gov/go/roc12 (Source: http://www.reuters.com/article/2011/06/11/us-usa-health-cancer-idUSTRE75A0KN20110611 U.S. adds formaldehyde to list of carcinogens by Paul Simao, Americas Desk Reuters Washington Jun. 11, 2011)

26

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

FDA APPROVALS
FDA APPROVES RECTIV FOR PAIN ASSOCIATED WITH ANAL FISSURES
P

JULY 2011

roStrakan Group plc,a subsidiary of Kyowa Hakko Kirin Co. Ltd.,and an international specialty pharmaceutical company,today announces that it has received approval from the U.S. Food and Drug Administration (FDA) for Rectiv (nitroglycerin) Ointment 0.4 % for the treatment of moderate to severe pain associated with chronic anal fissures. Rectiv will be the only FDA approved prescription product for patients with this condition. "The pain associated with anal fissures can be unrelenting and debilitating. Prompt initiation of treatment by primary care practitioners, gynecologists, gastroenterologists and surgeons alike is critical to a patient's wellbeing," said Scott Berry MD, FACS, colorectal surgeon and the principal investigator on one of Rectiv's clinical trials. "Now we have an effective and easy-to-use topical ointment which allows grateful patients to resume their daily lives." Anal fissures are fairly common, with approximately 700, 000 people in the U.S. receiving a diagnosis or treatment for an episode each year. An anal fissure is a small tear in the skin that lines the anus, and can occur in a number of ways such as passing large or hard stools, straining during a bowel movement, or following an episode of diarrhea. When an anal fissure occurs, it typically causes severe pain and bleeding with bowel movements. Chronic anal fissure has been shown to impact significantly on patients' quality of life. An episode can take six to eight weeks to heal; and if healing does not occur then surgery may be required. Peter Allen, Chairman of ProStrakan, said: "The market in the U.S. for a prescription medicine to treat chronic anal fissure pain is significant and, having successfully marketed this product in Europe for some years, we are pleased that it will now be made available to patients in the U.S." "We will now evaluate the most efficient way of bringing this product to market and making it available as widely as is necessary."

ProStrakan expects Rectiv to be available in the U.S. in the rst quarter of 2012. Marketed under the name Rectogesic, the product is already approved in the EU and marketed by ProStrakan in all major European countries, where sales grew by 15% in 2010 to $14.4 million (9.3 million Pounds Sterling). The product has also been out-licensed outside Europe by ProStrakan to commercial partners in 34 countries worldwide.
(Source: http://www.news-medical.net/news/20110622/FDA-approves-ProStrakans-Rectiv-for-pain-associated-with-anal-fissures.aspx FDA approves ProStrakan's Rectiv for pain associated with anal fissures Jun. 22, 2011)

LUPIN GETS FDA NOD TO MARKET GENERIC LEVAQUIN TABLETS IN US MARKET


harma major, Lupin Ltd. said its US subsidiary Lupin Pharmaceuticals, Inc. had obtained final approval from the United States Food and Drugs Administration (US FDA) for its abbreviated new drug application (ANDA) to market a generic version of Ortho McNeil's Levaquin (levofloxacin) tablets. The company said the commercial shipment of the product had commenced. Lupin's levooxacin 250mg,500mg and 750mg tablets are the AB-rated generic equivalent of Levaquin,a synthetic broad spectrum antibacterial agent used to treat or prevent infections that are proved or strongly suspected to be caused by susceptible bacteria. As per IMS Health sales data,Levaquin tablets had annual sales of around $1.6 billion for the twelve months ended March 31 this year. (Source: http://www.rttnews.com/Content/IndianNews.aspx?Id=1651268&SM=1 Lupin Gets US FDA Final Nod To Market Generic Levaquin Tablets In US Market by RTT Staff Writer Jun. 22, 2011)

WATS ON LABORAT ORIES GETS F DA N OD F OR N ABUMET ONE T ABLETS


Watson Pharmaceuticals,Inc. on Jun. 17,2011 announced that its subsidiary, Watson Laboratories,Inc.,has received approval from the United States
Food and Drug Administration (FDA) for Nabumetone Tablets USP,500 mg and 750 mg. Watson expects to launch the product shortly. Nabumetone had total U.S. sales of $58 million for the twelve months ending April 30,2011,according to IMS Health. Nabumetone is indicated for the relief of signs and symptoms of osteoarthritis and rheumatoid arthritis. (Source: http://ir.watson.com/phoenix.zhtml?c=65778&p=irol-newsArticle&ID=1575067 Watson's Nabumetone Tablets Receive FDA Approval PARSIPPANY, N.J., - Jun. 17, 2011 PRNewswire via COMTEX Primary source: Watson Pharmaceuticals www.watson.com)

27

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

FDA APPROVALS
FDA
fibrosis.

JULY 2011

A P P R OVES I NF A NT DOS E OF D RU G FO R CY S T I C FI B R OS IS

The FDA has approved the first infant-specific dosage of pancrelipase (Creon) to treat exocrine pancreatic insufficiency (EPI) common in cystic
The new dosage of Creon Delayed-Release Capsule contains 3, 000 units of lipase, which allows for more precise dosing at feeding, a statement from manufacturer Abbott said. Pancrelipase is indicated to improve food digestion in patients who cannot digest food properly because of EPI and should be taken with each meal and snack. EPI is common among patients with cystic fibrosis but is also associated with pancreatic cancer, gastrointestinal surgery, and chronic pancreatitis. "We know that the need for consistent, precise dosing of pancreatic enzyme replacement therapy is critical for infants and children living with cystic fibrosis," Eugene Sun, MD, vice president of Abbott, said in the statement. The original FDA approval for Creon in 2009 was based on the results of three clinical studies of 103 patients with EPI to an endpoint of coefficient of fat absorption. Studies one and two measured drug effects in patients with EPI due to cystic fibrosis, while the third study examined patients with EPI due to chronic pancreatitis and pancreatectomy. In the first two studies, those in the pancrelipase group had average coefficients of fat absorption of 89% and 83%, versus 47% in the placebo group. In the third study, average change in coefficient of fat absorption was greater in patients with lower run-in period coefficient of fat absorption values than in those with higher run-in period values. Adverse events related to pancrelipase include fibrosing colonopathy, flatulence, headache, stomach pain, dizziness, hyperglycemia, and hypoglycemia. The drug may cause an allergic reaction, including severe stomach pain, worsening of gout, swollen joints, troubled breathing, skin rash, or swollen lips. The capsules should not be crushed or chewed, as they may cause mouth irritations. (Source: http://www.medpagetoday.com/PublicHealthPolicy/FDAGeneral/27094FDA Okays Infant Dose of Drug for CF by Cole Petrochko, Associate Staff Writer MedPage Today Washington - Jun. 16, 2011)

FDA APPROVES NDA FOR TWO HYDROCODONE COUGH AND COLD MEDICATIONS
The U.S. Food and Drug Administration (FDA) has approved Optimer Pharmaceuticals' antibacterial drug DIFICID (fidaxomicin) tablets for the
treatment of Clostridium dicile-associated diarrhea (CDAD) in adults 18 years of age and older. Cypress Pharmaceutical announced recently that the Food and Drug Administration (FDA) approved a new drug application (NDA) for Zutripro (hydrocodone bitartrate, chlorpheniramine maleate and pseudoephedrine HCl) Oral Solution (CIII) and Rezira (hydrocodone bitartrate and pseudoephedrine HCl) Oral Solution (CIII). Both products are indicated for the relief of cough and symptoms associated with the common cold. Zutripro and Rezira Oral Solutions are the only FDA approved hydrocodone cough and cold combinations containing a nasal decongestant. The approval of Zutripro and Rezira Oral Solutions marks the first NDA approval by the FDA for a liquid hydrocodone cough medication since 1990. These products will be marketed by Hawthorn Pharmaceuticals,a subsidiary of Cypress Pharmaceutical,Inc. "Currently, there are very few prescription products for patients suffering from cough and the symptoms associated with the common cold," said Chris Smith, EVP of Sales for Hawthorn Pharmaceuticals. "With Zutripro and Rezira Oral Solutions, healthcare practitioners finally have more options when treating patients suffering from a cough and symptoms associated with the common cold. Additionally, Zutripro and Rezira both contain a decongestant which is very beneficial considering the fact that one of the most common symptoms of the common cold is nasal congestion. Zutripro and Rezira Oral Solutions are available through all national drug wholesalers, as well as chain drug stores and other distribution channels and will begin shipping immediately. Zutripro and Rezira Oral Solutions are available by prescription only in the United States. ZUTRIPRO (hydrocodone bitartrate,chlorpheniramine maleate and pseudoephedrine hydrochloride) Oral Solution (CIII) is indicated for the relief of cough and nasal congestion associated with common cold and relief of upper respiratory allergy symptoms including nasal congestion in adults 18 years of age and older.
Visit www.hawthornrx.com for complete prescribing information on both products.

(Source: http://www.pharmaceuticalonline.com/article.mvc/FDA-Approves-NDA-For-Two-Hydrocodone-Cough-0001? sectionCode=Freeform1&templateCode=LifeScienceSponsor&user=20&source=nl:31109 FDA Approves NDA For Two Hydrocodone Cough And Cold Medications Primary source: Cypress Pharmaceutical Jun. 15, 2011)

28

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

FDA APPROVALS
B RISTOL-MYERS GETS FDA OK ON NEW T RANS PLANT DRUG

JULY 2011

The first new type of drug in more than a decade for keeping transplanted kidneys functioning won approval from federal regulators on Jun. 15,2011.
The Food and Drug Administration approved Nulojix, developed by Bristol-Myers Squibb Co., for preventing rejection of a transplanted kidney in adult patients, despite concerns about serious possible side effects. It was approved for use along with other medicines that suppress the immune system, including corticosteroids. Without immune suppressants, a patient's body would reject the new kidney as a foreign object and attack it. If other drugs can't counteract that rejection, the kidney could stop its crucial job of filtering toxins from the blood, and the patient would have to undergo hours-long dialysis three times a week. Even with the best care, about half of patients either die or have their new kidney stop working in roughly 8 to 10 years, said Dr. Brian Daniels, senior vice president for global development and medical affairs at New York-based Bristol-Myers. "This is the first meaningful alternative in over a decade for patients, and one that provides potential for long-term survival" of transplanted kidneys, Daniels told The Associated Press in an interview. Besides having a new mechanism of action, Daniels said Nulojix kept kidneys functioning better over three years in the company's two large, final-stage studies, compared to the standard treatment, cyclosporine. He said in a small number of patients getting Nulojix in a separate study and followed for up to eight years, kidney function had yet to decline significantly. Nulojix, given through 30-minute intravenous infusions once a month for life, works by inhibiting the activation of T cells, which are key to triggering an immune system response to a perceived invader. Bristol-Myers said it expects to launch the drug in early July. So far, it is not disclosing the expected price. Nulojix, also known by the chemical name belatacept, is an alternative to some older immune suppressants, which cause headaches and nausea and, occasionally, kidney toxicity. The approval comes 3 1/2 months after a panel of FDA advisers voted 13-5 to approve Nulojix despite concerns about higher rates of severe kidney rejection than older drugs have. The drug carries a boxed warning, the most serious type, that it can increase risk of a type of cancer in which white blood cells grow out of control after an organ transplant, a condition called post-transplant lymphoproliferative disorder. There is a second boxed warning that Nulojix, as well as other immune suppressants, increases risk of other cancers and serious infections. Nulojix can also cause other side effects. Common reactions in studies that included more than 1,200 patients included anemia, constipation, kidney and bladder infections, and swollen legs, ankles or feet. In addition, all transplant patients are at risk of infection, so they should not get live vaccines. Those taking Nulojix also should limit time spent in sunlight because of the risk of skin cancer. More than 89, 000 patients in the United States are waiting for a kidney transplant,according to the Organ Procurement and Transplantation Network. (This version to kidney toxicity in 9th paragraph. Corrects to 13-5 in 10th paragraph) (Source: http://finance.yahoo.com/news/BristolMyers-gets-FDA-OK-on-apf-591147682.html?x=0&.v=6 Bristol-Myers gets FDA OK on new transplant drug by Linda A. Johnson, AP Business Writer Associated Press Trenton, N.J. Jun. 15, 2011)

AUROBINDO PHARMA GETS US FDA NOD FOR RAMPIRIL CAPSULES


Aurobindo Pharma has obtained the approval from the US drug regulator to make and market Ramipiril capsules,a company statement said.
The drug used for the treatment of congestive heart failure (CHF) and hypertension (high blood pressure) will be available in 1.25mg, 2.5mg, 5mg and 10mg strengths. Ramipiril is remake of Altace manufactured by American drug maker King Pharmaceuticals. Ramipiril falls under the Cardiovascular ( CVS) therapeutic segment and its market size is estimated at $95 million for the 12 months ending September 2010, according to IMS data. Cardiovascular disease is still the world's leading cause of death, even after a couple of decades of declining death rates. Expenditures for cardiovascular drugs account for about one-fifth of total expenditures for all types of drugs. Aurobindo now has a total of 138 ANDA approvals (108 Final approvals and 30 tentative approvals) from US Food and Drug regulator. Over the last one year,the company filed 1270 formulations dossiers across several therapeutic segments in other key regulated markets including multiple registrations in European Union. (Source: http://articles.economictimes.indiatimes.com/2011-06-10/news/29643102_1_usfda-nod-final-approvals-tentative-approvals Pharma gets USFDA nod for Rampiril Capsules by Deepika Amirapu ET Bureau Hyderabad, INDIA Jun. 10, 2011) Aurobindo

29

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

EMA NEWS
CHMP RECOMMENDS NOVARTIS DRUG VOTUBIA FOR APPROVAL IN EU

JULY 2011

If approved, Votubia (everolimus) will be first medication in EU for subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC) CHMP opinion based on Phase II study of 28 patients showing 33% experienced a SEGA tumor reduction of 50% or greater at six months relative to baseline Brain surgery is only treatment option in EU for growing SEGAs, benign brain tumors that primarily affect children and adolescents Worldwide regulatory submissions for everolimus to treat this patient population are under way; rst approval received in the US in 2010 as Afinitor Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Votubia (everolimus) tablets for the treatment of patients aged 3 years and older with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC), who require therapeutic intervention but are not amenable to surgery. If approved, Votubia will be the first medication available for these patients in the European Union (EU). Tuberous sclerosis complex,also known as tuberous sclerosis (TS), may cause benign tumors to form in vital organs and can affect many different parts of the body, most commonly the brain. Signs of TSC vary depending on which system and which organs are involved. SEGAs,or benign brain tumors,occur in up to 20% of patients with TSC. Tuberous sclerosis complex is also associated with a variety of resulting disorders including seizures, swelling in the brain (hydrocephalus), developmental delays and skin lesions. Currently, brain surgery is the only treatment option for patients in the EU with growing SEGAs associated with TSC. The CHMP positive opinion is for a conditional approval based on a prospective, open-label, single-arm, Phase II study of 28 patients. Results showed that 78% of patients (21 of 27) experienced a reduction of 30% or greater in the size of their largest SEGA and 33% (9 of 27) experienced a reduction of 50% or greater at six months relative to baseline. "The positive CHMP opinion for Votubia is encouraging as it may lead to the approval of the first medication in the European Union for patients with this challenging disease," said Herv Hoppenot, President of Novartis Oncology. "Our focus on tuberous sclerosis complex research reflects the commitment Novartis has made to develop innovative therapies to help address unmet medical needs." The European Commission generally follows the recommendations of the CHMP and delivers its final decision within three months of the CHMP recommendation. The decision will be applicable to all 27 EU member states plus Iceland and Norway. Regulatory approvals have already been granted for SEGA associated with TSC in the United States,Switzerland,Brazil, Colombia, Guatemala, the Philippines and South Korea. Additional submissions to global regulatory agencies are under way worldwide. Everolimus targets mTOR, a protein that acts as an important regulator of tumor cell division, blood vessel growth and cell metabolism. Tuberous sclerosis complex is caused by defects in the TSC1 and/or TSC2 genes. When these genes are defective, mTOR activity is increased, which can cause uncontrolled tumor cell growth and proliferation, blood vessel growth and altered cellular metabolism, leading to the formation of benign tumors throughout the body, including the brain. By inhibiting mTOR activity in this protein pathway, everolimus may reduce cell proliferation, blood vessel growth and glucose uptake related to SEGA associated with TSC. Tuberous sclerosis complex is a genetic disorder affecting approximately one to two million people worldwide. In Europe, the prevalence in the general population is estimated to be nearly nine cases per 100,000.
(Source: http://www.novartis.com/newsroom/media-releases/en/2011/1525934.shtml Novartis drug Votubia recommended by CHMP for approval in the EU for children and adults with SEGA associated with tuberous sclerosis Basel - Jun. 24, 2011)

The

30

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

FUNNY PHARMA CARTOON

JULY 2011

I s that a controlled document?


(Source: http://www.pharmamanufacturing.com/articles/2010/155.html Submitted by Dominic Tunzi)

ANSWER

FROM T HE EXPERT

Q: When a high-visibility project is not going according to plan, how do you get leaders to talk about it?
The secret is amazingly simple: Be candid. Get the stakeholders together, and lead an honest discussion of the circumstances. Sometimes it helps to have each stakeholder take a quiet moment before the discussion begins to write a brief description of the problem along with an assessment of exactly what they could do make a contribution to the issue. Then have each person sequentially read their comments aloud for the group. It is important for the facilitator of this kind of meeting to call this tactical session as early as possible, make sure that all stakeholders are in attendance, and then keep the discussion moving. It is also important in critical situations to avoid blaming and to seek constructive solutions. Many times, the simple act of articulating the problem can quickly lead to a situation. In real-life situations, long delays, avoidance, and interpersonal triangulation are the poison trilogy for problem solving.

David Frew
Dr. David Frew is a visiting professor at Mercyhurst College in the Graduate Organizational Leadership (MSOL) Program. He has served as a consultant to GE Crotonville, NASA, and dozens of other regional, national, and international clients. (Source: Ask The Board Life Science Leader www.LifeScienceLeader.com June 2011)

C OMPAN Y PROF IL E :

WHO S WHO?

About Boehringer Ingelheim: The Boehringer Ingelheim group is one of the worlds 20 leading pharmaceutical companies. Headquartered in
Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine. As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheims endeavors. In 2010, Boehringer Ingelheim posted net sales of about 12.6 billion euro while spending almost 24% of net sales in its largest business segment Prescription Medicines on research and development. For further information, please visit www.boehringer-ingelheim.com 31

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

TIE-UPS & AGREEMENTS


LUPIN, NATCO TIE UP TO MARKET BREAST CANCER TABLETS

JULY 2011

Drug firms Lupin Ltd and Natco Pharma on Jun. 23, 2011 said that they have entered into an alliance to jointly market generic Lapatinib
Ditosylate tablets, used for treating breast cancer, in the American market. Natco has filed an abbreviated new drug application (ANDA) seeking United States Food and Drug Administration ( USFDA) approval for marketing these tablets in the strength of 250 mg, Natco and Lupin Ltd said in separate statements. "Natco has partnered with Lupin for marketing of the product," Natco Pharma said in a filing to the Bombay Stock Exchange (BSE). Lapatinib Ditosylate tablets are sold under the brand name Tykerb in the American market. The patent of Tykerb is with Glaxo. "Tykerb had sales of USD 113.6 million as of March, 2011, according to IMS health," Lupin said. "Natco and Lupin believe that they are the first to file an ANDA containing a paragraph IV certification for Lapatinib," it added. This means that once their ANDA is approved, the rms could have 180 days' exclusivity for the product in the US.
(Source: http://articles.economictimes.indiatimes.com/2011-06-23/news/29694483_1_natco-pharma-breast-cancer-tablets Lupin, Natco tie up to market breast cancer tablets New Delhi, INDIA Jun. 23, 2011)

LIGAND ENTERS INTO CAPTISOL SUPPLY AGREEMENT WITH MERCK


L igand Pharmaceuticals Incorporated announced on Jun. 20,2011 that it has entered into a Captisol supply agreement with Merck & Co.,Inc. for
an undisclosed program. Ligand will supply clinical and commercial supplies of Captisol and, if the program is approved for commercialization, expects to deliver multiple metric tons of Captisol annually. Financial terms of the deal were not disclosed. We are extremely pleased to enter into a long-term commercial supply agreement for this Captisol-enabled program, said Matt Foehr, Executive Vice President and Chief Operating Officer of Ligand Pharmaceuticals. This collaboration with Merck is a good example of the type of relationships we try to build with our partners. Merck used Captisol to reformulate a drug in their portfolio and performed initial proof of concept under a research use agreement. This announcement marks the natural transition of the program to a full commercial supply relationship as commercialization approaches, added Mr. Foehr. This deal has the potential to add meaningful revenue to the Ligand business in the coming years and extends the already significant partnering relationship that we have developed with Merck over the past few years. About Captisol : Captisol is a patent protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. This unique technology was originally developed by Ligands subsidiary company CyDex Pharmaceuticals and has enabled five FDA approved products, including Pfizers VFEND IV and Prism Pharmaceuticals NEXTERONE. There are currently over twenty Captisol-enabled products in development, including Onyx pharmaceuticals carfilzomib program. About Ligand: Ligand Pharmaceuticals is located in La Jolla, California on the cliffs just above Torrey Pines Beach. Founded in 1987, Ligand is a biotech company with a rich heritage in drug discovery and development. Ligand has used its drug development expertise to produce over 40 clinical candidates, 22 INDs, and 5 approved drugs. That's a level of productivity that ranks near the top of the biotech industry. Today, Ligand is operating with a business model that is based upon the concept of developing or acquiring royalty revenue generating assets and coupling them to an efficiently lean corporate cost structure. Ligand's goal is to produce a bottom line that supports a sustainably profitable business.
For more information, visit www.ligand.com

(Source: http://www.istockanalyst.com/business/news/5240600/ligand-enters-into-captisol-r-commercial-supply-agreement-with-merck Ligand Enters into Captisol Commercial Supply Agreement with Merck Business Wire Jun. 20, 2011)

32

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

PHARMA ARTICLES
QbD FOR BETTER METHOD VALIDATION AND TRANSFER
Just as process validation can benefit from a QbD and a product lifecycle approach,so can analytical method validation and transfer

JULY 2011

More companies in the pharmaceutical industry today are adopting the principles of Quality by Design (QbD) for pharmaceutical development and manufacturing. Described in ICH Q8,Q9 and Q10 guidance documents, QbD enables enhanced process understanding, and a more systematic and scientific approach to development, so that better controls may be implemented. The end goal is more robust manufacturing processes than those that typically result from traditional approaches to drug development. The QbD framework has many implications for manufacturers and regulators alike. This article describes how analytical methods can be viewed as "processes" and QbD concepts applied, to improve both method validation and transfer. Its goal is to stimulate thinking and discussion on how analytical method validation and transfer could evolve as industry increasingly adopts Quality by Design concepts. But QbD cannot be considered without examining validation within a product lifecycle framework. The U.S. Food and Drug Administration (FDA) attempted to do just that in a recent draft guidance designed to help achieve the goals of its Pharmaceutical GMP's for the 21st Century A Risk Based Approach. This guidance addresses some of the problems with traditional approaches to process validation, which were articulated by Moheb Nasr nearly five years ago. Too narrow a focus on a "three-batch" approach to validation has encouraged a "don't rock the boat" mindset within the industry that can fail to foster continuous improvements in quality or efficiency.

The Need for Real World Verification


The same problems can be seen in analytical method validation and transfer, where the focus often shifts from ensuring the robustness of the method itself to ensuring the robustness of the documentation,and how well it will withstand regulatory scrutiny. Methods for pharmaceutical products are normally validated by experts who have developed the method in accordance with ICHQ2 guidance (Validation of Analytical Procedures: Text and Methodology) or USP <1225> (Validation of Compendial Procedures). However, validation can be treated as a one-off event, with little consideration given to verifying how well the method will perform at everyday, "real world" operating conditions. All too often, regulators and industry use ICH Q2 or USP <1225> in a check box manner without considering the intent of these guidances, or the philosophy of method validation.

Continued on page 34 33

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

PHARMA ARTICLES
Continued from page 33. . QbD For Better

JULY 2011 Method Validation And Transfer

These issues continue after the method has been validated, when it is transferred to another laboratory. This transfer step requires that the knowledge of how to operate the method be transferred to those who will use it routinely, and that an exercise be performed, documenting that similar results have been obtained by both parties. The transfer exercise is usually performed by the most competent analytical staff in the receiving laboratory, yet it may have little relationship with how the method will be used in routine, day to day operations. It may come as little surprise, then, that most methods fail to perform as intended in the receiving laboratory, triggering efforts to identify variables that are causing the discrepancies,and repeated,costly testing and documentation. The roots of method transfer failures can usually be traced to insufficient consideration of the routine operating environment during the method validation exercise, and lack of an effective process for capturing and transferring the tacit knowledge of the development analysts.

A QbD Framework for Analytical Method Life Cycle Management


If an analytical method is viewed, simply, as a process, whose output is data of acceptable quality, QbD concepts designed for manufacturing processes can be applied to analytical methods. Thus, the concepts of lifecycle validation that are being developed for manufacturing processes might also be applied to analytical methods. Quality by Design (QbD) is defined as a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding based on sound science and quality risk management. And FDA has proposed a definition for process validation that is the collection and evaluation of data,from the process design stage throughout production,which establishes scientific evidence that a process is capable of consistently delivering quality products. When considering a lifecycle approach to method validation, a similar definition could be adopted The collection and evaluation of data and knowledge from the method design stage throughout its lifecycle of use which establishes scientific evidence that a method is capable of consistently delivering quality data. From these definitions,it can be seen that there a number of key factors that are important in a QbD\Lifecycle approach. These include: The importance of having predefined objectives The need to understand the method,or being able to explain the method performance as a function of the method input variables The need to ensure that controls on method inputs are designed such that the method will deliver quality data consistently in all the intended environments in which it is used The need to evaluate method performance from the method design stage throughout its lifecycle of use. In alignment with the approach proposed in the draft FDA guidance for process validation, a three-stage approach could be taken with method validation. (See chart.)

Continued on page 35 34

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

PHARMA ARTICLES
Continued from page 34. . QbD For Better

JULY 2011 Method Validation And Transfer

Stage 1 Method Design: Define method requirements and conditions and identify critical controls Stage 2 Method Qualification: Confirm that the method is capable of meeting its design intent. Stage 3 Continued Method Verification: Gain ongoing assurance to ensure that the method remains in a state of control during routine use.

STAGE 1 - METHOD DESIGN


The Method Design stage includes establishing the method performance requirements, developing a method that will meet these requirements and then performing appropriate studies to understand the critical method variables that must be controlled to assure the method is robust and rugged. The method design stage can be an iterative process,which is repeated as required in accordance with the lifecycle phase of the product.

Method Performance Requirements


Utilizing a QbD approach, it is essential at this stage that sufficient thought be given to the intended use of the method and that the objectives or performance requirements of the method be fully documented. This represents the Analytical Target Profile (ATP) for the method. To draw a parallel to qualification of new analytical equipment, the ATP for the method is effectively the equivalent of a User Requirement Specification that would be produced to support qualification of new analytical equipment (or the Design Qualification as defined in USP <1058>). To build the ATP,it is necessary to determine the characteristics that will be indicators of method performance. Typically, these characteristics will be a subset of those described in ICH Q2, such as accuracy or precision. It is important, however, not to use the ICH Q2 characteristics in a check box manner but to consider the method's intended use. For example, the characteristics that are critical to the performance of an HPLC assay method intended to be used to quantify the active ingredient within a tablet might be quite different from those of an NIR method intended to be used to measure the end point of a blending operation. In the second case, accuracy may not be a critical method performance requirement in determining homogeneity. Once the important method characteristics are identified, the next step is to define the target criteria- in other words, how accurate or precise the method should be. A key factor in choosing the appropriate criteria is the impact of method variation on the overall manufacturing process capability. Knowledge of the proposed specification limits and the expected process mean and variation is helpful in setting meaningful criteria.

Method Development
Once the ATP has been defined, an appropriate technique and method conditions must be selected in order to meet the requirements of the ATP. While method development is a very important part of the method lifecycle, it is not necessary to elaborate here since it has been extensively addressed in the literature.

Method Understanding
Based on an assessment of risk (i.e. the method complexity and the potential for robustness and ruggedness issues) one can perform an exercise focused on understanding the method to better understand what key input variables might have an impact on the method's performance characteristics. From this, one can identify a set of operational method controls. Experiments can then be run to understand the functional relationship between method input variables and each of the method performance characteristics. Knowledge accumulated during the development and initial use of the method provides input into a risk assessment (using tools such as the Fishbone diagram and FMEA), which may be used to determine which variables need studying and which require controls. Robustness experiments are typically performed on parametric variables using Design of Experiments (DoE) to ensure that maximum understanding is gained while minimizing the total number of experiments. Depending on the type of method,surrogate measures of characteristics such as accuracy or precision may be evaluated. An example might be peak resolution in a chromatographic method. It follows that well designed System Suitability requirements can be a valuable tool for assuring that a method is operating in a region where the ATP requirements will be met. When developing an understanding of the methods ruggedness,it is important to consider variables that the method is likely to encounter in routine use,such as in situations involving different analysts and different instruments. Tools such as measurement system analysis can be useful in providing a structured experimental approach to examining such variables.

Method Design Output


A set of method conditions will have been developed and defined which are expected to meet the ATP. Those conditions will have been optimized based on an understanding of their impact on method performance.

Continued on page 36 35

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

PHARMA ARTICLES
Continued from page 35. . QbD For Better

JULY 2011 Method Validation And Transfer

STAGE 2 - METHOD QUALIFICATION


Once a set of operational method controls has been determined during the design phase, the next step is to qualify that the method will operate as intended. In a similar manner to equipment qualification,method qualification can be broken down into the stages of method installation qualification (MIQ),method operational qualification (MOQ),and method performance qualification (MPQ).

Method Installation
Qualification focuses on ensuring that the facility where the method will be used is prepared to use it. This process includes ensuring that the analytical equipment is qualified and that appropriate knowledge transfer and training of analysts has been performed. The method conditions and detailed operating controls, along with all the knowledge and understanding generated during the design phase, must be conveyed to staff at the facility in which the method will be used. Performing a method walkthrough exercise with both the development and routine analytical teams can be extremely valuable in ensuring all tacit knowledge about the method is communicated and understood. The extent of the IQ phase may vary depending on the level of pre-existing knowledge of the routine testing laboratory with the product,method or technique. For example, the laboratory that originally developed the method may merely ensure that other personnel who will use the method are trained. The Method Operational Qualification phase is focused on demonstrating that the method meets its design intent. It is similar to traditional method validation. In the lifecycle approach, however, the focus is not about performing the traditional check box exercise to demonstrate compliance with ICH Q2. Instead,it is about demonstrating that the method meets the specific requirements that have been pre-defined in the Analytical Target Profile. A fundamental principle of this stage is that it should build on information that may have been generated in experiments already performed; for example,evidence of the selectivity or limit of quantification of a method may already exist from studies performed as part of method design. The final stage in the qualification phase is to perform a MPQ exercise. At this stage, the actual manufactured supply samples are tested in facility, equipment and by personnel that will be used for routine analysis. The method should be operated exactly in accordance with the defined method controls and local operating procedures. As with the IQ stage above, the extent of the PQ exercise could vary, and would include for example confirming system suitability criteria are being routinely met.

STAGE 3 - CONTINUED METHOD VERIFICATION


The goal of this stage of the method lifecycle is to continually assure that the method remains in a state of control. This should include an ongoing program to collect and analyze data that relate to method performance---for instance,by setting criteria for replication of samples or standards during the analysis,by trending system suitability data or by trending the data from the regular analysis of a reference lot. This activity aligns with the guidance in USP chapter 1010 on system performance verification. Close attention should also be given to any out of specification (OOS) or out of trend (OOT) results generated by the method once it is being operated in its routine environment. Ideally,using the new approach,laboratories should encounter fewer OOS results. If they do,it will be easier for staff to determine their root cause.

Change Control
During the lifecycle of a product, both the manufacturing process and the method are likely to experience a number of changes brought through unintentional deviations, continuous improvement activities or the need to operate the method and\or process in a different environment. It is essential that all changes to the method operating conditions be considered in light of the knowledge and understanding that exists on the method performance. If the method operating conditions are modified such they fall outside the known method operable region (determined as part of method understanding during the original design phase) then the Method Qualification should be revisited. Likewise if the process changes and samples contain analytes at levels outside those covered in the method operational qualification exercise or have new interferences, a new ATP would need to be generated and a partial re-qualification exercise will be required to ensure the method is still capable of producing consistent and reliable results for the extended range or modified sample. Where a method needs to be transferred to new location, appropriate Method Installation Qualification activities (including knowledge transfer) will need to be performed in addition to a Method Qualification exercise. Consistent with QbD principles, the extent of re-qualification should be driven

by scientific principles,as described previously. Continued on page 37 36

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

PHARMA ARTICLES
Continued from page 36. . QbD For Better Other Scenarios

JULY 2011 Method Validation And Transfer

The approach to method qualification described above focuses on the activities that would typically be performed when a method is developed and used within a single company. Other scenarios exist where a laboratory may need to use a method for which it has no access to the original method design or qualification information such as in a contract testing laboratory. In these situations,it is important that an ATP is defined and documented. An appropriate qualification study is then performed to demonstrate that the method meets its ATP. This approach could also be applied to qualification of a pharmacopoeia method. By applying the lifecycle approach to pharmacopoeia methods it is envisaged that there would be no need for a separate USP chapter on method verification (USP <1226> Verification of Compendial Procedures). Another scenario that needs to be considered is when a method is used to support drug development rather than drug manufacturing activities. In this case, the method will still need to produce data that is scientifically sound - particularly as it may be used to release material for clinical supplies, support stability studies or support the development of process understanding. At this point, in the product lifecycle, however the focus is on understanding the method performance rather than demonstrating that it meets predefined acceptance criteria. A key advantage of this approach for the above scenarios is the flexibility to perform a qualification against the specific ATP defined for the intended use of the method. This eliminates the current desire to create a qualification document against ICHQ2 in a check box manner, which can lead to unnecessary headaches and additional work. Since there is the potential for this approach to be adopted for all users of analytical methods,it also offers the potential to standardize the multiple, misrepresented terminology, which currently exists within the industry. It would result in a harmonized method qualification approach with standardized terminology which would remove the current state of confusion between the terms; method validation transfer and verification and the many interpretations as to what is actually required for each. In short,adopting a QbD approach to analytical method lifecycle management would have some significant implications for analytical scientists in the pharmaceutical industry. First, ICH Q2 and pertinent USP chapters would need to be revised to align with the lifecycle validation concepts described above. (The need for a revision of ICH Q2 as a consequence of increasing adoption of QbD concepts and use of PAT has also been identified. The activities that were previously defined as method transfer (that is, knowledge transfer and confirmation of equivalence) would become a central component of the lifecycle validation approach (in other words, they would be described as method qualification activities) rather than being treated as distinct from validation. Likewise, method validation as described in USP chapter <1225>, method verification as described in USP chapter 1226 and the proposed USP chapter on Transfer of Analytical Procedures would be encompassed within the lifecycle approach and it may be logical to combine those chapters. The CMC section of regulatory submissions may also need to change. In a Quality by Design rather than Quality by Testing paradigm, it seems inappropriate that the validation details of the test methods should fill such a large proportion of a submission. With a lifecycle approach to method validation the submission would see an increased focus on the method design aspects and demonstration of the work performed to arrive at method understanding. This would parallel the increasing focus on process understanding in submission,which has arisen since the introduction of ICH Q8. Review of formal method qualification activity would become an inspection issue rather than a registration issue. Underpinning this approach is the need for effective lifecycle management of knowledge and understanding of the analytical method.

In summary, the switch to a QbD approach to method development is already beginning to bring improvements to the performance of analytical methods. It is now time to look to modernize and standardize industrys approach to method validation and transfer. By aligning method validation concepts and terminology with those used for process and equipment qualification, there is an opportunity to both reduce confusion and complexity for analytical scientists as well as to ensure that efforts invested in method validation truly add value, rather than simply being a check box exercise.

GLOSSARY:
Analytical Target Profile (ATP): The combination of all method performance criteria that direct the method development process. An ATP would be
developed for each of the attributes defined in the control strategy and defines what the method has to measure (i.e. acceptance criteria) and to what level the measurement is required (i.e. performance level characteristics: e.g. precision, accuracy, working range, sensitivity and the associated performance criterion).

Continued on page 38 37

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

PHARMA ARTICLES
Continued from page 37. . QbD For Better

JULY 2011 Method Validation And Transfer

Method Development: The collection of activities performed to select an appropriate technique and method conditions that should have the
capability to meet the ATP requirements.

Method Understanding (MU): The knowledge gained from the collection of activities performed to understand the relationship between variation in
method parameters and the method performance characteristics.

Method Installation Qualification (MIQ): The collection of activities necessary to ensure a method is properly installed in its selected environment. This will include the knowledge transfer activities such that the laboratory understand the critical control requirements of the method and the activities required to ensure the laboratory can meet these requirements e.g. purchasing of appropriate consumables such as columns, and reagents, ensuring reference standards are available,ensuring appropriate equipment is available and appropriate training is given to personnel. Method Operational Qualification (MOQ): The collection of activities necessary to demonstrate that a method can meet its ATP. Experiments
performed as part of the OQ exercise must be appropriate for the specific intended use as defined in the ATP. This may involve demonstrating the method has adequate precision and accuracy over the intended range of analyte concentrations for which it will be used. Method Performance Qualification (MPQ): The activities that demonstrate that a method performs as intended when used with the actual samples, facilities,equipment and personnel that will routinely operate the method. (Source: http://www.pharmamanufacturing.com/articles/2010/060.html QbD for Better Method Validation and Transfer by Phil Nethercote, Head of the Analytical Centre of Excellence in GSKs manufacturing division; Phil Borman, Manager in Analytical Sciences, Chemical Development within GSK; Tony Bennett, Project Leader for Laboratory Support in Quality Analytical Sciences, Existing Product Support, Global Manufacturing Supply at GSK; Gregory Martin, President of Complectors consulting LLC, in Pottstown, Pennsylvania; and Pauline McGregor, Analytical Method Support Specialist for PMcG Consulting of Oakville, Ontario)

INNOVATION AT THE INTERSECTION OF


death imperative.

CREATIVITY AND AUTOMATION

In the same way that the guillotine concentrates the senses, the need to improve productivity in the pharmaceutical industry has become a life-orImproving productivity does not mean working harder and faster while doing the same job as before. Improving productivity lies in innovationin the technology and processes that clever minds bring into existence. Moreover,what this innovation must accomplish is vividly clear. We must

Reduce the time and cost of drug development Increase the probability of successful experiments and Bring better drugs to the marketplace.

I believe that this current crisis demands we pursue innovations that will give scientists time to think. The insight and intuition we need for big leaps in productivity will come in creative thought,not in the details of executing manual and sometimes mundane day-to-day tasks. To find the time for creative thought,scientists and project managers must come to grips with several important issues. First,we need to free scientists time by assigning tasks to people at the appropriate skill level. Second,we need to understand those tasks so that proper work instructions can be communicated. Third,we need to define and harness the data flow to allow for automation where it is achievable. Imagine a system in which data are available in the needed format without requiring a scientist to spend 50% of his or her overall project time on dataset creation. Imagine graphical display tools that present smart display options by anticipating results. Put this system in the hands of trained scientists and suddenly they are no longer hunched over their computers crunching numbers. Suddenly, they have time to think, and most importantly,they have time to think about solutions to the questions plaguing drug development projects.

Continued on page 39 38

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

PHARMA ARTICLES
Continued from page 38. . . Innovation At The Intersection Of Creativity And Automation

JULY 2011

This system is not a pipe dream; in fact, the organizing principlethe idea of workflowsis already available. Workflows are a new idea in pharma R&D. The work of scientists has been viewed as more of an art than a process, so it can be difficult to imagine how one would go about identifying and defining a scientists tasks so that at least some of the common and repetitive elements are amenable to automation. An understanding of those repetitive elements and definition of the accompanying metadata provide the underpinnings for automation. That is how systems can be made to seemingly think with you. And the richer the metadata, the smarter the system. (For more about metadata, read Understanding Metadata from the National Information Standards Organization by following the link http://www.niso.org/publications/press/UnderstandingMetadata.pdf) Of course, considerable effort will be required to study what needs to be done and how to do it. And we need to develop complete and clear requirements for each task in the execution of a workflow. But the time and effort expended to develop a workflow will ultimately save even more time and effort. Plus, each run through the workflow allows us to learn even more about the tasks and provides the input for a continuous quality improvement process that can improve the speed,efficiency and effectiveness of the workflow. So what will we do with all that extra time to think? Here are some suggestions. First,spend as much time as possible with scientists from other specialties. Second, talk to those other scientists about the problems they are facing in their work. Third, ask whether you could do something different that would make someone elses job easier or your results more informative. This is especially important when your data is going to be used by someone else downstream. Fourth,work to develop a common understanding of the disease process or drug effects of interest and systematically discuss what is known versus unknown. Fifth,consider whether data collected for other purposes or reported in the literature might be relevant and useful for addressing a particular challenge. Finally,use some of the time left over to have some fun. The imperative to improve the productivity of the pharma R&D effort cannot be ignored. The only choice is in how to respond. For the unlucky, this will mean working harder and faster while doing the same job as before. For the lucky, and hopefully most of us will fall into this category,it will mean taking a long hard look at what we do and figuring out how to do it better and faster with smarter tools and automated workflows. (Source: http://www.cognigencorp.com/index.php/cognigen/comments/innovation_at_the_intersection_of_creativity_and_automation/ Innovation at the intersection of creativity and automation May 25, 2011)

S CIE NT IF IC WORKFL OWS T HE KN OWLE DGE-GE NERAT ING ENG IN ES OF R&D


Scientific research requires two kinds of effort.

One is the generation and synthesis of original ideas by skilled practitioners. This is a desirable and often lauded talent that can spawn remarkable innovations in science and medical care. The second kind of effort is less visible, but equally importantthe hard work required to turn an idea into reality. Executing the experiments, analyzing the data, and developing presentations of results are examples of this work. Although these latter efforts are necessary,and even enjoyable,they nonetheless can be tedious,time-consuming,and expensive.

In model-based research and development (MBR&D), turning an idea into reality includes creating analysis-ready datasets, managing analysis processes,and preparing work products, such as tables and graphs. The idea of automating these and the other tasks required for MBR&D may seem preposterous. The fact is that some companies have already made strides in automating various recurring tasks,such as creating graphs and managing the results from statistical analyses. Other tasks still require a scientists careful scrutiny and judgment, however. To achieve the degree of rigor required to adequately support these more complicated tasks,a more sophisticated and higher order of automation is necessary. The challenge is huge, but I think automation is overdue in pharmacometricsautomation is needed so that we can achieve the productivity gains we desperately need in the Pharma of the Future.

Continued on page 40 39

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

PHARMA ARTICLES
Continued from page 39. . . Scientific

JULY 2011 WorkflowsThe Knowledge-Generating Engines Of R&D

Over the last few years,my colleagues and I have been working to understand the obstacles that must be addressed in order to improve productivity in the pharmacometrics enterpriseto industrialize it,if you will. A major obstacle we had to address early on was the belief that automation is the first step in an undesirable transition to hands-off, machinedominated science. In fact,our efforts at industrialization have led to remarkable improvements in the consistency and quality of our work products and to a greater emphasis on thinking instead of doing. Specifically, formalization and automation are required for what is now a largely hands-on, ad hoc process. The manual approach is problematic for several reasons. 1. First, creating analysis-ready datasets, managing analysis processes, and preparing work products are time-consuming and error-prone when done manuallyand as the size of datasets and the complexity of models increase, these tasks may become impossible to do without automation. 2. Second, archiving each of the steps in the modeling and simulation process, including both high-level scientific results and low-level details about the hardware and software environment, is tedious. Without this information, however, it is difficult to re-generate the results. Reproducibility of results is a cornerstone of the scientific methodthe scientific soundness and integrity of the computational efforts at the center of MBR&D will be questioned without the ability to reproduce results. Workflows have recently emerged as a paradigm for representing and managing complex distributed scientific computational processes. A workflow is a computerized facilitation or automation of a business process,in whole or part. Scientific workflows capture individual data transformations and analysis steps in addition to the mechanisms to carry them out in a distributed environment. Each step in the workflow specifies a process or computation to be executed (for example, a software program to be executed, a web service to be invoked, datasets to be assembled, and exploratory graphical displays to be generated). The steps are linked according to dependencies among the data and workflow tasks. The schematic for these workflows must contain the many details required to carry out each analysis step,including the use of specific execution and storage resources in distributed environments. The details of computational processes captured within workflow systems can be exploited to automate the execution of steps in the workflow. Workflows can also provide the provenance information necessary for scientific reproducibility, publication of results, and sharing among collaborators. By providing formalism and supporting automation, workflows have the potential to accelerate and transform the modeling and simulation efforts required for MBR&D. Much research is currently underway in the cyber-infrastructure community to address issues of creation, reuse, provenance tracking, performance optimization, and reliability of workflows. To fully realize the promise of workflow technologies in MBR&D, many additional requirements and challenges must be met. Workflows must be able to track the evolution of models from their origins in early discovery to the mature and comprehensive models used for clinical trial simulations,for design of clinical trials,and for making informed predictions of clinical and commercial performance. Workflows must be able to support dynamic, event-driven analyses, handle streaming data, accommodate interaction with users, give intelligent assistance,and allow collaborative support for workflow design,to enable sharing of results across functional areas. Meeting the workflow challenge head-on has a benefit that is more important than just speeding up the doing. A robust and useful workflow can only be conceived and implemented with the explicit cooperation of the many functional areas involved in generating the requisite data. The interdisciplinary collaboration needed to specify workflow requirements, to achieve consensus on study methods,and to detail how to interpret and present results is sorely missing in many companies. This collaboration is surely the most critical step for improving the productivity of the pharmaceutical research and development enterprise. (Source: http://www.cognigencorp.com/index.php/cognigen/comments/scientific_workflows--the_knowledge-generating_engines_of_rd/ workflowsthe knowledge-generating engines of R&D Apr. 14, 2011) Scientific

40

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

PHARMA ARTICLES
PHARMACOMETRICS: A NEW DRUG DEVELOPMENT PARADIGM

JULY 2011

While the term pharmacometrics has become fashionable since the start of the 21st century, the methods it encompasses have evolved from early
pharmacokinetics (PK) work (circa 1920) to full-blown clinical trial simulation, thanks largely to enhanced computational capability and the work of many insightful minds. Whatever the computational intensity or method, the purpose of pharmacometrics is best expressed in the International Conference on Harmonization (ICH)-E4 Guideline titled, Dose-Response Information to Support Drug Registration: Knowledge of the relationships among dose, drug concentration in blood, and clinical response (effectiveness and undesirable effects) is important for the safe and effective use of drugs in individual patients. This information can help identify an appropriate starting dose, the best way to adjust dosage to the needs of a particular patient, and a dose beyond which increases would be unlikely to provide added benefit or would produce unacceptable side effects. In todays fast-paced drug development environment, data is produced at an exponential rate. Efficient extraction of knowledge from the data to support development and decision-making is becoming a cornerstone of success. Pharmacometrics specifically aims at extracting this knowledge and identifying the degree of uncertainty associated with it through the use of quantitative methods. Armed with such knowledge, pharmaceutical companies can make enlightened decisions regarding the next development steps. At the regulatory level, this knowledge is helping to render decisions on approval, make dosing recommendations on the product label, and evaluate the need for further studies.

PHARMACOMETRICS DEFINED
Although there is no one universal definition of pharmacometrics, all definitions currently in use emphasize the application of quantitative methods to characterize and predict a systems behavior, whether at the individual, disease, or clinical trial level. Perhaps a good description of pharmacometrics,if not a formal definition,is one offered by the FDA: Pharmacometrics is an emerging science defined as the science that quantifies drug, disease,and trial information to aid efficient drug development and/or regulatory decisions. The FDAs description has the advantage of clearly emphasizing pharmacometrics role in drug development and is not limiting in scope. Nevertheless, pharmacometrics is generally understood as a collection of model-based approaches used to Extract from data and organize our understanding of a systems behavior in a concise manner and Do so in a language (i.e. mathematics) that allows simulation of the system output. These models can be divided into three broad classes: 1. 2. 3. Exposure-response models that specifically describe the relationships among dose, drug concentration in blood (or another matrix), and clinical response (effectiveness and undesirable effects), as stated in the ICH-E4 guidance document; Disease models that,as the name implies,aim to describe disease progression; Clinical trial models that describe patient demographics,adherence,dropout rates,trial structure,and so on.

While exposure-response models are by far the most commonly used pharmacometrics applications in the pharmaceutical industry today, the future should see greater use of clinical trial simulation applications.

PHARMACOMETRICS IN THE REGULATED INDUSTRY


Although from the above discussion it may sound as if pharmacometrics is something brooding deep within universities walls, it is, in fact, a lively discipline both at the regulatory level and within pharmaceutical companies. Several regulatory documents address the use and need of pharmacometrics in drug development. The ICH, followed by the FDA, produced scientific guidance on exposure-response studies emphasizing the use of concentration-effect relationship modeling in individualizing therapy, in preparing dosage instructions, and in providing primary evidence of effectiveness. The FDA and European Medicines Agency (EMA) guidances on population pharmacokinetics outline specific provisions on the conduct, context, and use of nonlinear mixed-effect modeling in drug development and regulatory submissions. One pertinent document is the FDA guidance titled, Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products, published after the Food and Drug Administration Modernization Act (FDAMA) of 1997 to clarify what constitutes confirmatory evidence of effectiveness. The guidance makes provisions for the use of extrapolation from existing studies to support effectiveness. In this regard,pharmacometrics is an undeniably potent tool.

Continued on page 42 41

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

PHARMA ARTICLES
Continued from page 41. . . Pharmacometrics: A New Drug Development

JULY 2011 Paradigm

Finally, the 2009 FDA guidance on the end-of-Phase 2A (EOP2A) meetings for sponsors of investigational new drug applications (INDAs) closes the loop by unequivocally advocating the use of pharmacometrics n drug development and regulatory evaluation: The purpose of an EOP2A meeting is to facilitate interaction between FDA and sponsors who seek guidance related to clinical trial design employing clinical trial simulation and quantitative modeling of prior knowledge (e.g. drug, placebo group responses, disease), designing trials for better dose response estimation and dose selection, and other related issues.

PHARMACOMETRICS IN THE DEVELOPMENT PHASES


While it is not uncommon for late-phase trials to incorporate pharmacometrics analyses, the full potential of pharmacometrics is achieved when data is modeled from the start of development at the non-clinical level, up to the confirmatory phase 3 and post-marketing trials. During the non-clinical development phase, a major concern is the prediction of human exposure-response behavior from animal data. Two modeling strategies often applied to circumvent this problem are allometric scaling and physiologically based modeling.

The former approach is based on the relationship that exists between animal size and metabolic rate and is generally used to extrapolate appropriate doses to humans from other species data. The second strategy, physiologically based modeling, works by dividing the system into organized anatomical compartments and using physiologically oriented parameterization; this approach has intrinsic, between-species, scaling proprieties that allow for exposure-response modeling in various species.

In early clinical trials (e.g. Phases 1 and 2A), several doses will generally be tested, and safety data will be collected as well as preliminary efficacy data. This stage often involves the quantification of dose dependence in PK, along with the effects of food, concomitant drugs, and exposure in certain populations. Exposure-response modeling should be performed to relate blood concentration to safety outcomes of interest such as QT interval prolongation and relevant biomarkers, if available. The resulting model, along with appropriate trial model components, can be used prospectively to simulate later-phase trial designs and predict drug exposure,adverse events expectancy, and efficacy. In fact,the FDA had this very intention in mind when it issued the EOP2A meeting guidance. Late-stage trials also benefit from pharmacometrics integration, not only to extract knowledge from observational data (as is often the case for latestage PK sampling,for example),but also to confront the early-phase models to the more diverse patient population encountered in those trials. Only with a thorough knowledge of the dose-response behavior in specific patient populations can adequate dosing recommendations be made. Having an incomplete characterization of the shape and location of the exposure-response profile can lead to significant dosing errors. For example, in a 2002 paper by Cross et al.,it was found that of 499 new molecular entities approved by the FDA from 1980 to 1999,one in five had a post-marketing dosage change,and for four out of five,the change resulted in a decrease in dose.

A ROLE FOR CROS


Until recently,pharmacometrics was seldom heard of as a service provided by CROs. The reasons for this are twofold: 1. 2. CROs do not usually have access to the entire body of data from sponsors,and Typically only big pharmas had the means to assemble pharmacometrics teams within their organizations.

However, the situation is changing rapidly. The pressure to reduce development costs within pharmaceutical companies, the increasing interest from the FDA in predictive (as opposed to descriptive) analysis methods, and the existence of commercially available analysis tools are making the offering of pharmacometrics services attractive to CROs. CROs now offer a full range of pharmacometrics services, from non-clinical to post-marketing applications. Being relatively new, current pharmacometrics service providers are best used for circumscribed analyses that require handling data from one or a few selected trials. When deciding to outsource pharmacometrics services to a CRO, some aspects should be taken into consideration. First is the CROs ability to handle data. pharmacometrics typically involves analysis data sets that will be built from one or several study databases. It represents a challenge because study databases are typically class-oriented (e.g. interventions,events,findings),while pharmacometrics analysis data sets are subject- and chronology-oriented.

Continued on page 43

42

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

PHARMA ARTICLES
Continued from page 42. . . Pharmacometrics: A New Drug Development

JULY 2011 Paradigm

Second is the scope of work. The modeling tasks to be undertaken by the CRO are to be clearly established from the start and ideally should not be modified too much in the course of work. This is because in the modeling process,timelines tend to elongate significantly,as the tasks at hand become more complex or diverse. Of course, additional tasks or changes in orientation may arise, but to the extent possible, they should be covered in the initial contract by allowing for changes in timelines and scope. Third,the type and level of quality control for the data and the model(s) should be clearly stated in the contract. Because pharmacometrics analysis is typically not a linear process,the quality of inputs and outputs should be reviewed regularly in the process. The level of quality control will depend on the task (descriptive vs. predictive modeling) and the intended use (internal vs. submission). As contractual pharmacometrics services mature,it will also become possible to enter into functional service partnerships. While a few CROs can offer pharmacometrics partnerships,it is not yet a common practice. For it to be a viable alternative to in-house pharmacometrics groups,service providers need to have appropriate data management capabilities,a sufficient number and diversity of personnel (e.g.,data management,biostatistics, clinical pharmacology, programming), and the ability to provide independent quality assurance. The requirement for clear-cut deliverables, although always important, may be relaxed to accommodate stakeholders priorities, since a drug development program is not, incidentally, a very linear process, either. Indeed,pharmacometrics often deals with,and evolves within,largely nonlinear processes.

THE FUTURE OF PHARMACOMETRICS


Even if some may argue that clinical trial simulation (CTS) is a well-implemented practice,it remains a challenging and resource-intensive endeavor at all levels. CTS requires computational capabilities, demonstrated expertise, and diversity in personnel backgrounds, making it an activity essentially reserved to a few well-organized pharmaceutical heavyweights. In addition, access to the critical data required to simulate some components of clinical trials (i.e. data on the natural progression of diseases) are often not easily accessible. However, with the advent of concerted efforts aimed at making disease data and models publicly available, it now becomes possible to envision a broad use of CTS in drug development. One has only to think about the Alzheimers disease model from the Coalition Against Major Diseases (CAMD), the OpenDiseaseModels.org initiative of the Metrum Institute, or the FDAs Specific Disease Model Library. With the continued development and sharing of such models amongst the industry and regulatory stakeholders, it will become easier for scientists to build and for regulatory bodies to review larger,more complex trial simulations that may eventually replace some of todays live clinical trials. (Source: http://www.lifescienceleader.com/index.php?option=com_jambozine&layout=article&view=page&aid=4277&Itemid=56 Pharmacometrics: A Drug Development Paradigm by Pierre-Olivier Tremblay Life Science Leader May 2011)

BREAKING

DOWN S IL OS: A Q&A WIT H J OHN KOTT E R

What are some risks silos pose to an organization?


Silos can occur in global corporations or start-up ventures with 15 employees or more. And no matter the size, they are detrimental to an organizations ability to succeed in a rapidly changing world. It is also important to note that silos can be vertical or horizontal. Individual units can have high barriers between them or senior leadership can be completely isolated from lower management levels. A siloed organization cannot act quickly on opportunities that arise in a fast-paced business landscape, nor is it able to make productive decisions about how to change in order to seize these opportunities. Consider the following consequences of organizational silos: Destroy Trust: People who spend significant time in a single department or division often develop loyalty to their immediate group and distrust in the motives of others, even if they are in the same firm. Product development may view sales with suspicion, a global subsidiary looks at the American parent with great disdain, and so on. Without trust, you cannot create teamwork across an organization, and without a team that moves quickly, organizations fall behind their competitors. Cut off Communication: Silos cut off clear communication between different business units or managerial levels. People can fall easily into only communicating with those directly around them or those who are at the same level in the organization. When there is little or unclear communication between groups, the right hand doesnt know what the left hand is doing. As a leader, you fall out of touch with employee sentiment, lose track of important resources at your fingertips and dont hear crucial feedback.

Continued on page 44 43

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

PHARMA ARTICLES
Continued from page 43. . . Breaking Down Silos: A Q&A

JULY 2011 With John Kotter

Foster Complacency: In an organization where people in different divisions have little contact with one another, it is easy to become inwardly focused and complacent with the status quo. It will cause them to miss new opportunities and hazards coming from competitors or customers and changes in the regulatory environment. For example, if R&D has little communication with sales, research employees will never know end customers changing preferences, and your organization could lose out to another competitor that meets customer needs better and faster. How can you recognize when silos are forming in your organization? There are several signs. First,are you surprised to hear about projects taking place in other divisions? Are these projects well underway,without your ever knowing about them? Second,do you communicate infrequently with other leaders around the organization? Finally,have you been championing an opportunity or project for a while, and a large subset of the organization doesnt know about it or understand why you are pursuing it? Ask yourself these questions. If you are finding the answers are yes,there is a good chance that silos are present in your organization. To eliminate silos you must bring people across the organization together. There are several ways you can do this: Bring the outside in: Make divisions share data with one another so people understand how each division is performing, what customer or external stakeholder complaints are, and where this room for improvement. Make it clear this is an important opportunity to galvanize action, but it is not a blame game. Frame changes that must be made as organizational,not divisional. Focus on opportunity,not crisis: While crisis can be a catalyst for action,fear also can send people running for the door. If you frame the organizations need to break down silos as a positive opportunity,you will see more people raising their hand to do it. Help people in different divisions understand how they have a chance to make the organization better and more powerful by eliminating the barriers between divisions or management levels. Create a guiding coalition that breaks down barriers: Bring together a team of people committed to changing the way the organization operates, composed of people from all levels, divisions and locations. Dont pick this team; require people to apply for it to gauge their level of commitment. Ensure this team has enough:

Key players on it so those left out cannot block change People who represent all relevant points of view in the organization Credibility so that the groups pronouncements will be taken seriously Skilled managers and proven leaders to drive the change process

Once formed,hold an inaugural in-person meeting that allows members to connect to each other with both hearts and minds as a way to build trust among them. Set regular meetings, such as quarterly in-person gatherings and bi-weekly conference calls, to maintain momentum. Encourage group members to communicate outside of organized meetings and, more importantly, filter messages about the groups activities to others in their respective divisions or offices. Finally,ensure senior leadership stays closely involved with the guiding coalition without this involvement, the group cannot make needed change happen. John Kotter is the chief innovation ocer for Kotter International, a leadership organization that helps Global 5000 company leaders develop the practical skills and implementation methodologies required to lead change in a complex, large-scale business environment. He is also the Konosuke Matsushita Professor of Leadership,Emeritus at the Harvard Business School and a graduate of MIT and Harvard. (Source: http://www.lifescienceleader.com/index.php?option=com_jambozine&layout=article&view=page&aid=4280&Itemid=56 Breaking Down Silos: A Q&A With John Kotter Life Science Leader May 2011 Written by John Kotter, Chief Innovation Officer, Kotter International)

44

PHARMA CHRONICLE

JULY 2011

U PCOMING FAIR IN BANGKOK, T HAILAND

INTERNATIONAL EXHIBITION ON HOSPITAL, DIAGNOSTIC, PHARMACEUTICAL, MEDICAL & REHABILIATION EQUIPMENT & SUPPLIES
1416 September 2011 at Queen Sirikit National Convention Center, Bangkok, THAILAND

5th

A B OU T M ED I C A L F A I R T H A I L A N D 20 1 1 : The exhibition will provide vital access for companies trying to penetrate the
Southeast Asian markets. The combined population of Southeast Asia which is in excess of 540 million people, the changing demographics, longer life expectancy and the aging population will have an enormous impact on the need for better healthcare. In addition, with the increase in foreign patients, particularly in Thailand, many of the healthcare institutions are in need of new equipment, devices, solutions and better technologies to serve the medical and healthcare needs. MEDICAL FAIR THAILAND is pleased to bring together the best in the business of hospital, diagnostic, pharmaceutical, medical and rehabilitation equipment and supplies to Thailand and the neighboring Southeast Asian countries. MEDICAL FAIR THAILAND will also serve as a platform for medical suppliers, industry professionals, government bodies, hospital administrators, doctors, nurses and other healthcare professionals. 5,000 trade visitors and buyers from the region are expected to visit the 3-day exhibition. Join us in bringing global and healthcare technologies to one of the most dynamic regions in the world.

Strong showing for Thailands leading medical and health care exhibitionMEDICAL FAIR THAILAND 2011

A COMPREHENSIVE SHOWCASE OF. . .


Accident and Emergency Equipment Fabrics / Laundry Building Technology and Services Laboratory Equipment Catering and Kitchen Equipment Medical Furniture and Equipment Communication and Information Technology Medical Consumables Dental Equipment and Supplies Ophthalmic Supplies Diagnostic Pharmaceutical Supplies Disinfection and Disposal Systems Rehabilitation Equipment / Orthopedic Supplies Electro-medical Equipment / Medical Technology Services and Publication

For registration please visit www.medicalfair-thailand.com For more information, please contact Project Team Shirley Lim, General Manager Tel: +65 6332 9626 Michelle Leona, Project Manager Tel: +65 6332 9682 Email: shirley@mda.com.sg Email: michelle@mda.com.sg

45

PHARMA CHRONICLE

JULY 2011

U PCOMING EVENT IN VIENNA, AUST RIA

E URO CANCERTECH E XPO


Innovative Research R&D TechnologiesServices & Solutions

1314 October 2011 in Vienna, AUSTRIA E V E N T O V E R V I E W : The EuroCANCERTECHexpo will be a great chance for anyone who is involved in small & large molecule

cancer R&D (discovery, pre-clinical, translational and early-phase clinical research) to meet with other oncology-focused pharmaceutical and biotech companies, renowned and up and coming academic research institutes, as well as expert service providers. The ultimate aim is to ensure a large number of experts in cancer R&D and licensing are in the one place at the one time, to forge closer relationships and partnerships and to encourage and enhance more early-phase innovation. Are you looking to enhance your alliances in oncology research & early-phase clinical development? Then this is a must attend event! T Y PE S O F C AN C E R T E C H N O L O GI E S & SE R V I C E S W I L L I N C L U D E :
Small pharma, biot echs, universit ies & research inst it ut es in areas such as: small, large molecules & cancer va ccines in discovery/pre -clinical early clinical) immunot herapeutics, t herapeut ic ant ibodies Platform t echnologies Biomark ers, t ranslational medicine, cancer diagnost ics Drug delivery syst ems Services & t ools-discovery, p re- clinical & early clinical cont ract research Cont ract manufact uring of early-phase clinical supplies Consulting and cont ract research in areas su ch as Modeling and simulat ion expertise in areas such as pharmacology, modeling & simulation, t ranslational medicine. Laborat ory service s, supplies, equipment & reagent s

To Request the full agenda please follow the link: http://www.nextlevelpharma.com/events/request_agenda/euro_cancertech_expo For Booking Information Contact: Erika Vavrovicova Tel: +421 232 660 382 Fax: +421 2 3301 0331 Email: erika@nextlevelpharma.com Website: www.nextlevelpharma.com

46

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

eyeforpharma ARTICLES
DOCTORS VIEWS ON ONLINE NETWORKS AND E-DETAILING

JULY 2011

T he Internet has become an integral part of the healthcare conversation,presenting opportunities for sharing,developing and educating. Pharma,
while somewhat impeded by ambiguous regulation,is exploring how to take advantage of these opportunities. A recent report by Gerson Lehrman Group (GLG),which taps into the company's unique database of doctor partners,provides pharma with interesting research as to how these channels can be used effectively and how to maximize doctors' receptivity. Readers get a fly on the wall' perspective through GLG's live conversations with doctors. Interestingly, while the report acknowledges that doctors still struggle with the volume of information thrown at them versus the time they have available, most participants seemed satisfied with their pharmaceutical relationships. However, physicians still see communication with sales reps as adding unnecessary stress to their schedules. So,many doctors seek out added rewards or incentives for participating. Perhaps unsurprisingly, doctor respondents enjoy the social interaction with and perks from their pharma reps more than the direct benefits to their practice and patients. There is obviously a fundamental paradox here and it highlights the difficulty for pharma,which is increasingly scrutinized for offering such perks. Key resources for learning about new solutions for patients are conferences and meetings (e.g., ASCO), and industry literature and journals. Communication with pharma companies is still primarily through the traditional rep. But some doctors are delegating these relationships to office management,a development that is a cause of concern for pharma. The report explores doctor opinions on the various online routes available to them, finding which they prefer and which they simply don't like using. For example,e-Detailing seems rather unpopular,with respondents citing "not enough of an incentive" and "annoying ads" as some of the negatives. Though online promotion offers convenience,participants overwhelmingly prefer to learn about medical products directly from medical experts. Are doctors simply more resistant to change or too busy to break from tradition?
You can download the full report (free of charge) here at http://www.eyeforpharma.com/glg/eDetailingReport.pdf

(Source: http://social.eyeforpharma.com/story/doctors-views-online-networks-and-e-detailing Doctors views on online networks and e-Detailing by Alexandra Uprichard, Editorial Manager Eyeforpharma Jun. 21, 2011)

N EW MODELS FOR DR UG DISCOVERY AND MARKETING

A ngelo DePalma investigates how emerging collaborative partnerships could alter how drug firms manage innovation and market new medicines.
To value concretely the pharmaceutical industrys reliance on drug discovery collaborations, it pays to pause and estimate the economic magnitude of such deals. Quantifying outlays for discovery is hampered by the industrys habit of reporting R&D or research spending, which includes almost everything that occurs in a laboratory or clinic, but does not include financial terms for discovery-stage deals,in-licensing,mergers,and acquisitions. The US drug industry spends about $45 billion yearly on R&D. By applying commencement of human studies (approximately one-third of the development cycle) as a cutoff, and approximating a cost-weighting factor of one-and-a-half to two for clinical (vs. preclinical) activities, one arrives at a figure of approximately $8 billion to $12 billion for what might be reasonably termed drug discovery. The diminishing return on this ongoing investment as measured by approved innovative drugs, and looming expirations of lucrative patents, have spawned numerous calls for big pharma to reinvent its business model.

PRE-COMPETITIVE COLLABORATION
In its 2011 report, Progressions: Building Pharma 3.0 Ernst and Young outlines the evolution of the pharmaceutical industry from Pharma 1.0 (vertically integrated blockbuster model) through Pharma 2.0 (the current model characterized by diversification, flexible R&D, specializations, partnerships) to 3.0, where companies will succeed based on their ability to improve health outcomes. That this denition of 3.0 should represent revolutionary,or even evolutionary,thinking in an industry traditionally dedicated to human health is quite remarkable. Nevertheless, the report proposes some interesting thoughts on collaboration. For example, It will be imperative to learn how to

contribute assets and IP into new models [pharmaceutical firms] do not entirely control. Continued on page 48 47

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

eyeforpharma ARTICLES
Continued from page 47. . . New

JULY 2011

Models For Drug Discovery And Marketing

PRE-COMPETITIVE COLLABORATION
In its 2011 report, Progressions: Building Pharma 3.0 Ernst and Young outlines the evolution of the pharmaceutical industry from Pharma 1.0 (vertically integrated blockbuster model) through Pharma 2.0 (the current model characterized by diversification, flexible R&D, specializations, partnerships) to 3.0, where companies will succeed based on their ability to improve health outcomes. That this denition of 3.0 should represent revolutionary,or even evolutionary,thinking in an industry traditionally dedicated to human health is quite remarkable. Nevertheless, the report proposes some interesting thoughts on collaboration. For example, It will be imperative to learn how to contribute assets and IP into new models [pharmaceutical firms] do not entirely control. This represents a sharp departure from the culture of exclusivity and secrecy that dominates the collaborative landscape today. In fact, it describes a new model,pre-competitive collaboration,which is currently all the rage among consultants but has yet to catch on. In a contributed sidebar to Progressions, Procter & Gamble managing director Chris Thoen urges readers to only do what you can do and not to engage in reinventing wheels. Thoen claims his companys open innovation strategy has resulted in more than 1, 000 active agreements with external parties, which has led to such innovations as Tide dry cleaners and Mr. Clean car washes (laundry and household cleaning products,respectively). One can only imagine the regulatory hurdles awaiting cholesterol-lowering milkshakes on tap at baseball games and antifungal cream paintball contests Perhaps the most revealing pronouncement in the Ernst and Young report came from Jackie Hunter, a psychologist by training, former top-pharma executive, and current consultant. Hunter wrote, Firms will have to dedicate some of their best people to managing relationships and encouraging] collaborative behaviors. Hunter is a proponent of open innovation, a variation on the pre-competitive collaboration theme. Pre-competitive collaboration has become a significant driver for innovation and productivity in drug development, says Maria Vassileva, scientific program manager at the Biomarkers Consortium in Bethesda, Maryland. Yet the Consortiums initial project suffered from lengthiness,lack of collaboration tools,disagreements on biomarker qualification,and reluctance to share data. One could expect such misgivings with new drugs, but biomarkers are not drugs. They are surrogates for clinical outcomes, discovery tools, like microplate readers or tissue-based assays. The chasm between biomarkers and potential blockbuster drugs, from the perspective of intellectual property and investment, presents a very high hurdle for open innovation.

PUBLIC-PRIVATE COLLABORATIONS
For the foreseeable future, collaboration will be of the more traditional type, Ernst and Youngs recommendations notwithstanding. Public-private collaborations, in particular, seem to be gaining steam. In late 2010, the Obama Administration funded the National Center for Advancing Translational Sciences (NCATS), an offshoot of the US National Institutes of Health (NIH) dedicated to drug discovery. NCATS will incorporate some existing NIH functions and receive additional (and as yet undisclosed) US federal funding. News reports refer to NCATS as a billion-dollar initiative but much of its projected funding will come from existing appropriations. No one seems to know exactly how much more the Center will receive. Critics lost no time criticizing NCATS. Budget hawks excoriated yet another taxpayer bailout of an industry that privatizes profits but increasingly seeks to collectivize risk. In a New York Times interview, Mark Lively of Wake Forest University noted, the NIH is not likely to be very good at drug discovery. In the same article, Thomas R. Insel, who heads the National Institute of Mental Health, says that something must be done to mitigate the pharmaceutical industrys abdication of its traditional research role, but admits that NIH has never developed drugs and actually doesnt know how to do therapeutics that well.

Continued on page 49 48

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

eyeforpharma ARTICLES
Continued from page 48. . . New

JULY 2011

Models For Drug Discovery And Marketing

Chas Bountra, who heads Oxford Universitys Structural Genomics Consortium, has proposed a $200 million international drug discovery consortium funded by corporations, governments, and charities. Like pharma consultant Hunter, Boutra is a proponent of pre-competitive collaboration,

specifically open and freely accessible data up to phase 3 human testing.


What were trying to do is reduce duplication associated with multiple companies working simultaneously on the same drug target, he told NatureNews in February. While $200 million may seem like a triflePfizers current round of layoffs seeks to trim $2 billion from just that companys R&D budgetit may be a start,or model for future discovery efforts. GlaxoSmithKlines twist on public-private collaboration is more direct. In February, GSK announced that it was partnering with ten leading academicians in an attempt to reduce its drug discovery risk. The deals are nothing unusual: ongoing research funding and milestone payments in return for exclusivity. GSKs announcement came on the heels of the November, 2010 deal between Pfizer and the University of California, San Francisco. This $85-million collaboration, for biological drug discovery, preceded by just a few weeks Pfizers announcements to close its Sandwich, UK and Groton, Connecticut drug discovery centers.

PRIVATE-PRIVATE DISCOVERY DEALS


While public-private collaborations are well established, the fruits of such deals are not always obvious, and at best cast doubt on the proper role of universities and public funding. Much less controversial are private-private discovery deals,which a simple newswire scan shows are still very much in vogue. The last few months have seen discovery-related announcements from

Ingenuity/Covance on next-generation sequencing, Phylogica/Isogenica (peptide discovery and engineering), Elan/PPD (early development services), Xenthion/Grnenthal (ion channel modulators), Receptos/Lilly (GPCR agents), Sanofi/Avila (oncology drugs), BioRelix/Merck (antimicrobials), Incyte/Novartis (kinase inhibition),and Envoy/Merck (diabetes/obesity).

With two ongoing discovery deals with Merckone with Merck acquisition Schering-Ploughand one with Canadas National Research Council, Helix Biopharma in Aurora, Ontario understands the value of both public-private and industry-industry collaborations. The firm has spent 60% of the more than $50 million it has raised on drug development. 2009 was a terric year,relative to 2010,for oncology collaborations, says company president John Docherty. There have been some fairly lucrative terms for licenseers, including some for hundred-million-dollar up-front and milestone payments, not to mention royalties. Docherty estimates that costs for conducting clinical trials of its phase 3 interferon cream for cervical dysplasia would have exceeded $16 million; instead, Merck picked up the tab.

Continued on page 50 49

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

eyeforpharma ARTICLES
Continued from page 49. . . New

JULY 2011

Models For Drug Discovery And Marketing

Add to that the costs of an imminent phase 1/2 trial of L-DOS-47, an immunoconjugate lung cancer agent, and it is evident how even modest success can overwhelm the resources of development-stage companies. Docherty describes Helixs strategy as value-added development, which, if conducted properly, provides relatively equal benefits to licensee and licenser (or discoverer/marketer).

HYBRID MODELS
Achieving the goal of rapid progression to proof-of-concept has not been easy within a traditional collaborative discovery environment. Failure rates still suggest unsustainability, according to Salim Shah, chief scientist at Georgetown University Medical Center in Washington, DC, who terms this as the discovery dilemma. What is holding everything back are costly,lengthy animal and early-stage human studies and the difficulty translating preclinical to clinical results. Without robust surrogates for clinical testing, discovery efforts will forever languish in the current paradigm regardless of how collaborations are structured. The answer, Shah says, lies in biomarkers and phase zero clinical trials that could replaceit is hoped, at little risktraditional development stages where most drugs fail. Phase 0, a recent FDA designation, seeks metabolism, toxicology, and other data from microdoses administered to very small (10-15) groups of patients. Shah believes that direct deals between industry and academe,which push professors to be business people, are not ideal. The late-stage failure rate achieved through these collaborations is no different from the more traditional model, he says. He proposes a hybrid model for future collaborations between companies and non-profits, taking only do what you can do to a more refined level. He sees the proper venue for discovery at universities and government labs,provided they enjoy complete freedom to conduct basic research. The translational agents would be small companies specializing in specific development tasks like lead optimization or preclinical studies, which, in turn,funnel into early clinical development firms and,finally,to a sponsor for late-stage development and marketing. While the failure rate may be the same,prevailing wisdom holds that collaborations allow sponsors to fail more cheaply,with lower risk. Smaller firms, and particularly university groups, operate much leaner than big pharma R&D units, but whether these deals bring about significant savings compared with the older model,no one can say, Helix Biopharmas Docherty admits. Cost and risk-mitigation cannot by themselves explain the significance of discovery deals. The emergence of biologicals, the eventual approval of biosimilars, and the explosion in new targets and pathways are pushing traditional drug firms into unfamiliar territory,leading to a combination of risk mitigation and the need for specialized expertise. For example, L-DOS-47 combines not just a pharmacologically active antibody-enzyme combination, but it draws on Helixs experience in altering tumor microenvironments. We expect that pharmaceutical firms,which have derived so much of their innovation from outside their corporate walls,will continue to externalize R&D, says Gautam Jaggi, senior manager at Ernst and Young. But they will never completely abandon [internal] R&D. According to Jaggi,the impetus is not direct cost savings,but improved efficiencies related to doing what companies do best. (Source: http://social.eyeforpharma.com/story/new-models-drug-discovery-and-marketing New models for drug discovery and marketing by Angelo DePalma, Writer & Consultant Jun. 6, 2011)

50

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

PHARMA ARTICLES
PHARMA MUST ACT AGAINST PATIENT NON-COMPLIANCE
T

JULY 2011

he pharmaceutical industry has been called to action by a new report that highlights the health and cost repercussions of patient noncompliance. According to Capgeminis report, Patient Adherence: The Next Frontier in Patient Care (http://www.capgemini.com/services-and-solutions/by-industry/ life-sciences/vision-and-reality/) patient adherence to medications for chronic conditions,such as HIV and Arthritis,averages at only 50%. Almost all chronic conditions face high rates of non-adherence and those with no visible symptoms, such as depression, have the lowest adherence rates. The problem even extends to oral formulation chemotherapy drugs, where one would not expect to encounter patient adherence issues due to the seriousness of the condition. As much as 40% of cancer patients are non-adherent in this case, says the report. The report estimates that patient non-adherence to prescribed medicine courses is responsible for 194, 500 deaths per year in the European Union (EU) and 131, 400 deaths per year in the United States. Non-adherence results in annual costs of close to EUR 125 billion in the EU and $300 billion in the US, according to the report. The report makes several recommendations to improve patient adherence. However, the report also explains that it is a difficult issue to tackle,even with patient-adherence programs. Patient adherence is difficult to address because each situation is specific, based on patient behaviors, or the condition he or she is being treated for, says the report. The healthcare system does not have aligned incentives for all stakeholders to monitor and improve treatment adherence. Poor understanding of patient needs and behaviors, insufficient prioritization or siloed approaches can hold back programs helping patients undergo complete, on-time, and at-prescribed-dosage courses of medication. One of the recommendations is for the healthcare industry to take advantage of new digital health media tools, such as digitalized patient records and information sharing through the Internet, which will enable healthcare stakeholders to manage information effectively, identify points where adherence ceases, and help create programs to address them. The pharmaceutical industry has also been urged to take action. The report suggests considering patient adherence early in development as a strategic issue that is part of the product-value proposition. The pharmaceutical industry needs to address patient adherence in a more strategic and integrated part of its activities, which will be good for the patients and for the industry overall, Jean-Marc Neimetz, global leader of the life-sciences practice at Capgemini Consulting, said in a statement. Thomas Forissier, a principal of the life-sciences practice, Capgemini Consulting, added, Pharmaceutical companies need to design and deploy programs targeted to the very specific patient situations and leverage both traditional and digital approaches to do so. (Source: http://biopharminternational.findpharma.com/biopharm/News/Capgemini-Pharma-Must-Act-Against-Patient-Noncompl/ArticleStandard/Article/ detail/725709?contextCategoryId=435 Capgemini: Pharma Must Act Against Patient Noncompliance by Stephanie Sutton, Assistant Editor, Pharmaceutical Technology Europe BioPharm Bulletin Jun. 7, 2011)

P ROFESSIONAL PHARMA REPRESENTATIVE COMPENSATION


nless you really understand and appreciate the mindset difference between that of the professional representative compared with that of the traditional pharmaceutical sales representative, this compensation discussion will not make sense to you. As GlaxoSmithKline discovered, a change in sales compensation structure, especially incentive compensation,away from traditional sales and prescription volume model will take an organizational and perhaps even industry realignment of pharmaceutical sales compensation philosophy. Most pharmaceutical companies,their commercial management teams,and many representatives are not ready for this. In fact, I predict that sales organizations will be most resistant to this change as most pharmaceutical sales representatives and managers are too grounded in the traditional sales mentality. Many sales people are just going to see this as a take-away and will want nothing to do with the job. It will also be hard for managers to get their arms around how to manage sales (drive sales) and evaluate performance without sales quotas and other activity based numbers.

They will complain about the inability to fairly and consistently assess performance if they dont have hard numbers. They ignore the fact that todays prescription data and sales volumes are not accurate and are filled with national, regional, district, and territory caveats. They also like to think that todays sales goals and territory alignments are fairly distributed and accurately reflect potential.

And when was the last time we correlated the number of territory activities to sales results? Continued on page 52 51

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

PHARMA ARTICLES
Continued from page 51. . . Professional

JULY 2011 Pharma Representative Compensation

In the end, none of this matters because incentive compensation is not a performance driver for professional representatives the way it is for traditional sales representatives. Incentive pay is not a scorecard like it is for traditional sales reps. In fact, if the lack of incentive pay is the reason for a representative to quit, you really didnt lose a professional representative, you lost a sales representative and this is fine because they wouldnt be happy or satisfied trying to make it work. This is the hardest concept to get comfortable with if you have a traditional sales and sales incentive mentality. Professional representatives want to be paid for their expertise, their stature in their medical community, and recognized for their personal performance excellence. They prove their expertise and the effectiveness of that expertise by the business health of their territory in terms of how their products are perceived, formulary and reimbursement status, their access to key decision makers, and the professional respect those decision makers have of them personally. They appreciate that actual sales of their product depends on a number of factors,some they can influence while for others it would be inappropriate to influence (e.g.,encouraging the use of their product for patients who are not good candidates or where there is a better product available). Sales and prescriptions are merely surrogate markers for a lot of things going on,not just their performance. So how do you compensate the professional representative? You pay them relatively high base salaries (compared to traditional sales representatives) consistent with their expertise and ability to create or maintain a healthy market environment for your products. How many people can you hire with that level of expertise and ability to keep a territory healthy? If you think you can find a lot of these people,you dont have much for expectations and you are probably not looking beyond physician prescribing.

Are the people you are talking about able to hold their own in a scientific discussion with the Medical Director of an insurance company or pharmacy benefits manager that is considering how your product should be used in their patient population?

Can your representative cite the scientific literature to support their claims and recommendations for appropriate use? Is your professional representative so knowledgeable and good at their job that the insurance company Medical Director wants to hire them?

As for incentive pay, you might as well save it or better yet, invest it in your professional representatives development. You would be better off spending the $20, 000 per year on training, development, or sending them to more scientific meetings not to stand in an exhibit but to go to sessions and interact with their professional and academic colleagues. If you still feel compelled to provide incentive pay,test them regularly on their expertise and give cash awards for testing performance. You have to remember,professional representatives dont do things because there is an additional pay opportunity associated with it. They inherently want to do it because they see it as their responsibility. Their job is a big part of who they are and they take pride in themselves and the work they do. They view their compensation as a reflection of the level of expertise they have and the value they bring to the company when they apply that expertise. They get more job satisfaction out of applying their expertise than any incentive pay could possibly achieve. In fact,they would rather have a pay raise as recognition of their advanced expertise than an incentive to drive sales. The industrys strong sales mentality will make it difficult to embrace the professional representative concept and even more challenging to formulate sales compensation plans that are not tied to sales and prescription volume. You have to start somewhere so perhaps this at least has got you thinking about it philosophically. (Source: http://www.pharmareform.com/2010/09/22/professional-pharmaceutical-representative-compensation/ Professional Pharmaceutical

Representative Compensation by Mike Wokasch Sep. 22, 2010)

52

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

PHARMA ARTICLES
BUT.
S
. . . . MY PROJECTS ARE SPECIAL

JULY 2011

cientists in the field of pharmaceutical research and development face a most daunting challenge. Our understanding of the diseases we work to treat grows more complex and perplexing with each new published study. Take, for example, the gusher of information coming out on Alzheimers disease. How can research findings from genetics, neurology, nutrition, protein chemistry,pharmacology,and epidemiology (just to name a few) be tracked,sorted,and used? Interdisciplinary R&D needs a conceptual synthesis to bridge the disciplines and allow research results from one discipline to be applied to the questions of other disciplines. Disease-drug models can provide this conceptual synthesis. The predictive power of disease-drug models is likely to become the key determinant,and measure,of interdisciplinary research effectiveness. Currently, creating a model is mostly an ad hoc process that is dependent on special interests of project team members, previous experience of pharmacometricians, and current understanding of the disease process and drug pharmacology. Models are managed informally,with no established process of maintenance and storage. The result is that crucial information-bearing relationships represented in the model may go unnoticed. This hampers information flow across disciplinary groups and delays recognition of the need for critical studies that would inform the model and improve predictability. Consequently,harvesting the efficiencies that can come from recognizing and exploiting these commonalities are lost to the furious and time-consuming activities of specialty-focused research projects. A systematic process for envisioning,developing, and maintaining disease-drug models has to be developed before these models can take their place at the center of drug development. This process will become more important and difficult as the models become more mechanistic. The transition to mechanistic models is necessary if the models are going to provide much needed insight into the determinants of drug efficacy and safetya prerequisite for improving the chances of success in clinical trials. Only then will disease-drug models become a conceptual framework that can be used to inform experimentation strategies and to render research results. Developing a process for establishing and maintaining disease-drug models will likely take a substantial investment in time, money, patience, and persistence. As a preliminary effort, I have been spending much of my time recently considering the nature of communications among pharmacometricians at the technical level and between pharmacometricians and other members of a development team at the strategic and tactical level. I look for common patterns that emerge in these communications because I believe the patterns hold the key to more efficient and relevant communications across stakeholders and to a strategy on how discipline-specific research results can be more properly incorporated into disease-drug models. Ultimately, the goal is to improve productivity of pharmaceutical research and development programs, a goal that has proved more elusive than understanding the implications of variability in the universal constant. (Source: http://www.cognigencorp.com/index.php/cognigen/comments/but._._.my_projects_are_special/ ButMy Projects Are Special September 15, 2010)

Pharmaceutical Solutions Industry


Tel: +966 2 6361383 - Fax: 966 2 6379460 Kingdom of Saudi Arabia. For more info, visit www.psiltd.com

53

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

JULY 2011

Tel: +966 2 6361383 - Fax: 966 2 6379460 P.O. Box 17476 Jeddah 21484 Kingdom of Saudi Arabia. For more info about PSI, please visit www.psiltd.com

54

PHARMA CHRONICLE
AN ESSENTIAL SOURCE FOR PHARMA PROFESSIONALS

JULY 2011

Tel: +966 2 6361383 - Fax: 966 2 6379460 P.O. Box 17476 Jeddah 21484 Kingdom of Saudi Arabia. For more info about PSI, please visit www.psiltd.com

55