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Index, February, 2017

Government to monitor National Deworming Day for drug reactions

NEETU CHANDRA SHARMA
10 Feb 2017
http://www.dnaindia.com/health/report-government-to-monitor-national-deworming-day-for-drug-
reactions-2318237
In a bid to manage instances of adverse drug reactions that may be caused by deworming tablets
administered to kids on National Deworming Day on Friday, the Union Health Ministry has established
over 210 Adverse Drug Reaction Monitoring Centres (AMCs) across the country. "Each year, news of
kids falling ill after having the deworming tablet is reported. This year we have looped in the Indian
Pharmacopoeia Commission (IPC) to monitor and manage adverse events," said Dr Ajay Khera, Deputy
Commissioner, Child Health and Immunisation, Ministry of Health and Family Welfare (MoHFW).

"In case of any adverse effect, states are instructed to contact the nearest AMC," he said.

Also, for the time 7.8 crore children in private schools across the country will be part of the Deworming
Day. The overall target this year is to cover 34 crore children. About 4.3 crore out-of-school children
will be covered through Anganwadi workers and ASHAs. The MoHFW has also developed a National
Deworming Day app to facilitate quick and easier data collection. The auto-validation of data will also
help reduce the probability of reporting errors. "NDD is being implemented through combined efforts of
Department of School Education and Literacy under Ministry of Human Resource and Development,
Ministry of Women and Child Development, and Ministry of Drinking Water and Sanitation," said CK
Mishra, Secretary, Union Health Ministry.

Infections due to Soil Transmitted Helminths (STH) or worms cause morbidity by adversely affecting
nutritional status; impairing cognitive processes and causing complications that may require surgical
intervention. The association of worms' infestation with school performance and absenteeism is also
noted. As per World Health Organisation, STH, or worms infection is considered a public health
problem when the prevalence of any of the three worms is more than 10 per cent after two to three years
of deworming. To eliminate the public health problem, WHO advises mass administration of
albendazole tablets. "Albendazole is very safe drug. It's been in use for decades by millions around the
world with no or minimal side effects. It's chewable and kids like it. As per studies, there is a probability
of 1-2 per cent of adverse events during the deworming campaign. Side effects such as nausea and

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vomiting can manifest in the children with high worm load," said Dr Khera. WHO, under its free drug
donation programme, has supplied around 18 crore albendazole tablets to the government. These tablets
have been supplied to 17 states and UTs facing procurement challenges. Remaining states have procured
drugs through the funding under Programme Implementation Plan (PIP) of National Health Mission.

National Deworming Day was first observed in February 2015, and 8.9 crore children were administered
the tablet across 11 states and UTs on a single day. Building on this success, the programme was scaled
up to all 36 states and union territories in 2016, and over 17.9 crore children were dewormed.

No more worms

In one of India's largest single-day public health initiatives, an estimated 34 crore children in the age
group of 1-19 years, will be administered deworming tablets today to reduce worm infestation that can
stifle physical and intellectual growth. India has the highest burden of worm infections in the world,
with the WHO estimating in 2014 that over 22 crore Indian children aged between one and 14 years are
at risk

Uflex develops special polyester film for pharma packaging

MATTHEW FUTTERMAN
BS B2B Bureau
February 15, 2017
http://www.business-standard.com/content/b2b-plastics-polymers/uflex-develops-special-polyester-film-
for-pharma-packaging-117021500672_1.html

Conventionally polyvinyl chloride (PVC) and bi-axially oriented polyamide (BOPA) - commonly known
as BON - films have been extensively used in cold formed pharma packaging industry. A typical Alu-
Alu blister laminate comprises three layers - 25 micron BOPA, 60 micron soft aluminium foil and 60
micron PVC. Eliminating BOPA and PVC films in the cold formed Alu-Alu laminate blister pack for
pharmaceuticals has for long remained a daunting task for packaging experts.

A conventional cold formed pharmaceutical blister back when dumped in the land fill gives away
chlorine upon coming in contact with sunlight. This is extremely harmful for the environment. PVC also
contains plasticisers with phthalates linked to a host of health disorders that can damage the liver,
kidneys, lungs and reproductive system. PVC film leaves high carbon footprint making it further
undesirable from the environmental perspective besides exhibiting very low temperature resistance
which is yet another shortcoming. BOPA (BON) on the other hand is also fraught with challenges like
high moisture absorption to the tune of 8-10 percent making its processing difficult; leading to de-
lamination and impairing the ability of the film to be chemically primed.

Keeping these challenges of BOPA and PVC substrates in mind, Uflex Ltds films business has
developed a special polyester film that obviates the problems posed by BON and PVC. The special
polyester film is all set to replace the top and bottom substrates of the conventional cold formed Alu
Alu laminate to a whole new structure comprising 36 micron special polyester, 50 micron soft
aluminium foil and 36 micron special polyester.

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Polyester is a para-crystalline material which possesses excellent barrier, clarity, printability, and
hardness properties. Film forming and orientation of polyester augurs well for the creation of thin profile
webs with excellent properties for use in flexible packaging.

This specialty film that has been developed by Uflex can be laminated on both sides of the aluminium
foil without any problem quite like the laminate comprising BOPA, aluminium foil and PVC films. The
engineers at Uflex have been successfully able to bring metaphase morphology which has made it
possible to form the film in Z direction which happens to be a pre-requisite for blister packaging.

Getting better functionalities as compared to the Alu-Alu laminate structure comprising BOPA-
aluminium foil-PVC, Uflex has come up with a special polyester film that will have significant and
substantial benefits for the converters catering to pharmaceutical brands. If we talk about India, BOPA
(BON) is imported from countries like China, Korea and Taiwan. More over the convertors are left with
no option other than managing varied inventories of BON and PVC films separately. With the
introduction of our specialised Polyester film that will now be laminated on both the sides of aluminium
foil, the logistical hassles for convertors will surely go down. The dependency on import of BOPA will
also go down as the converting industry gradually switches over to our new specialised polyester film
for cold forming the blister packs. This film therefore makes a strong case for import substitution in
India, said Dr Sudhir Naik, senior general manager, corporate technical services at films business of
Uflex.

Pramod Sirsamkar, president - technical & new product development (films), Uflex Limited, added,
The introduction of specialised polyester film in Alu-Alu blister packaging as a replacement for BON
and PVC films has also opened up avenues for us to come up with biodegradable and oxo-degradable
variants further minimising the carbon foot prints. We are also working on developing such speciality
films using recycled polyester and green PET that will bolster our commitment towards the
environment.

The World Wakes Up to the Danger of Superbugs

The Editorial Boardsept. 28, 2016
https://www.nytimes.com/2016/09/28/opinion/the-world-wakes-up-to-the-danger-of-superbugs.html?
rref=collection%2Ftimestopic%2FMicrobiology&_r=0

Tuberculosis. Malaria. Syphilis. Gonorrhea. The microbes that cause these diseases are increasingly
resistant, and sometimes even impervious, to antibiotics that worked in the past. Last week, amid other
pressing business, 193 nations at the United Nations General Assembly signed a declaration summoning
each of them to a war against a powerful and resourceful enemy: superbugs that have learned to evade
sciences last remaining defenses.

These bacteria, viruses and other microbes are responsible for 700,000 deaths a year, according to a
2014 British study. In the United States alone, says the Centers for Disease Control and Prevention, at
least 23,000 people die annually from drug-resistant infections that could once be easily cured. Given
current trends, these numbers are likely to rise. Two forces are at work. Excessive and improper use of

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existing drugs by doctors, patients and farmers has hastened the natural process through which microbes
develop immunity. And scientists and pharmaceutical companies are not developing new medicines fast
enough to replace ineffective treatments. A successful counterattack will involve multiple strategies.
Through regulation and educational campaigns, doctors need to be instructed in the dangers of
prescribing antibiotics for viral flus and other common infections for which they are largely useless. The
C.D.C. estimates that at least 30 percent of antibiotic prescriptions in the United States are unnecessary.

In addition, doctors and nurses need to take practices like hand washing and equipment sterilization
much more seriously to reduce widespread drug-resistant infections in hospitals. Consumers must make
sure they and their children are vaccinated, which helps prevent infections in the first place. More than
70 percent of the antibiotics used in the United States are given to livestock. Because the indiscriminate
use of drugs in animals can destroy the drugs effectiveness for humans, the Food and Drug
Administration has issued regulations that it says will reduce antibiotic use in livestock. The agency will
need to monitor farms closely to make sure the rules are working.

Increasing the supply of new drugs and vaccines is another challenge. Many companies find it more
profitable to produce drugs for cancer and other chronic diseases that patients battle for months or years
at a time. Just two new classes of antibiotics have been brought to market in the last 50 years, Dr.
Margaret Chan, the director-general of the World Health Organization, told the U.N. This puts a burden
on governments to invest more in research and development. Governments could also offer incentives
prizes have been suggested, for instance to companies that develop new vaccines and antibiotics,
and they could contractually agree to buy medicines to assure companies that they will have a market for
their products. The United Nations was right to ring the alarm about superbugs, a growing danger that
requires a global response.

Govt plans to establish pharma & medical technology zone at Bengaluru

BS B2B Bureau
February 14, 2017
http://www.business-standard.com/content/b2b-pharma/govt-plans-to-establish-pharma-medical-
technology-zone-at-bengaluru-117021400755_1.html

The government is planning to establish an exclusive zone for pharmaceuticals and medical technology
(Med Tech) at Bengaluru to give a boost to domestic production of these products under the Make in
India initiative. Bengaluru, being the hub of information technology and skilled manpower, will prove
to be the ideal location to set up a pharma and Med Tech zone and the Ministry will work with the State
Government to establish it soon, said Ananth Kumar, Minister for Chemicals & Fertilizers, while
inaugurating the India Pharma & India Medical Device International Conference in Bengaluru on
Saturday. Concurring with the views of Kumar, Mansukh Lal Mandaviya, Minister of State for
Chemicals & Fertilizers, said that the recent approval of the pharma and Med Tech zone in Andhra
Pradesh has attracted over 30 investment proposals from domestic and international pharma companies
which has the potential to reduce the manufacturing cost of drugs and medical devices by around 30
percent as compared to global prices.

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Talking about the achievements of the pharma sector, Ananth Kumar said that the industry has achieved
a compounded annual growth rate (CAGR) of over 15 percent and expressed confidence that the sector
would be worth $ 55 billion by 2020 from the present $ 32 billion. India accounts for around 20 percent
of the worlds generic medicine supply chain, exporting to over 250 countries globally. Indian pharma
industry provides over 60 percent of global vaccines. In this fiscal year, the Indian Pharma sector has
received Foreign Direct Investment (FDI) close to $14 billion and has generated employment for over
2.5 million people across India, informed Ananth Kumar.

Highlighting the long pending issues addressed by the government to promote Ease of Doing Business
in pharma and medical devices sector, he said, Correction of the inverted duty structure for medical
devices, withdrawal of extension duty on imports to promote domestic manufacturing of bulk drugs and
bringing about a fair, transparent, predictable and level playing field in the sector etc, has been done by
the government. The government will maintain this stability for the sector in the future as well.

Siddaramaiah, Karnataka Chief Minister, said, This is the second time Karnataka is hosting this
conference on medical device & pharmaceutical sector, thus giving the state an opportunity to emerge as
the desired destination for investments under pharma & medical devices sector and give a boost to
Make in India mission in this sector. The state pharma industry constitutes 264 manufacturing units that
include small-medium, large, public sector and multinational companies. The state stands fifth in
pharmaceuticals exports with 40 percent of its pharma produce being exported overseas, he added.

The Free Market Is Coming for Pharma

February 13, 2017
https://spectator.org/the-free-market-is-coming-for-pharma/

Scratch a conservative defender of the pharmaceutical industry on the topic of drug prices, and youll
generally hear an argument formulated something like the following: High drug prices are just the free
market at work. Who are we to judge how much a piece of life-saving technology is worth?

Were the market for drugs truly free and competition open, this line of reasoning would be hard to argue
with, at least from the Right. However, as anyone with a basic understanding of pharmas abuse of the
patent system, or of the anti-competitive ban on drug importation, or any of a number of other policies
will tell you, nothing of the sort is true. If anything, high drug prices are a result of specific government
policy: something that decisively argues against the notion that the market for drugs is in any way free.

But fortunately, after this week, it just might get closer to being free. Thats because this week, Sen.
Mike Lee (R-UT) will take the first step to curtail drug prices using the very thing that big pharma fears
most: competition. Specifically, Lee is going to introduce a bill that takes square aim at pharmas
capacity to shut generic drugs out of the marketplace: something that has been integral to its
anticompetitive business model for eons. To explain the bill, known as the Creating and Restoring Equal
Access to Equivalent Samples (CREATES) Act, a quick thought experiment is necessary: Imagine that
you wanted to open a hamburger joint. However, the only way you could get a recipe for the sandwich
was for your would-be restaurant to pass a health inspection conducted not by the government but by the
head of McDonalds.

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It doesnt take a market forecaster to predict how many hamburger chains would open (aside from
McDonalds) under such a regime. Yet this is precisely this Kafkaesque situation that would-be generic
drug manufacturers face when trying to manufacture generic versions of existing drugs. This is because,
under a little-known government program called the Risk Evaluation and Mitigation Strategies (REMS)
program, the FDA basically outsources the job of figuring out which generic drug manufacturers are
planning on making safe products to the very pharmaceutical companies whose formulas those
manufacturers will need to start production.

Granted, the program explicitly forbids companies from denying access to their formulas solely on the
basis of stopping lower-cost alternatives from entering the market. However, this ban is hard to enforce,
and its no stretch to imagine pharmaceutical companies concocting spurious reasons to deny access to
their formulae, just as they concoct spurious reasons to extend their patents. And as it stands, the only
remedy that possibly exists is antitrust litigation, which is almost no solution at all, since many cases are
difficult-to-impossible to prove.

Enter Mike Lees version of the CREATES Act, which sets out specific and much easier conditions for
generic manufacturers to meet when crying foul over anticompetitive behavior by Big Pharma, while
offering a means of resolving the dispute that is less costly than antitrust suits for everyone involved.
Pharma, of course, howled bloody murder about the bill, claiming it would permit rogue snake oil-style
generic manufacturers to gain access to their formulas with the threat of lawsuits and regulatory
interference. And to be fair to the industry, a previous version of the bill introduced last year was
vulnerable to these charges.

However, where that bill went after REMS abuses with a hammer, Lees targets them with a scalpel. For
example, Lees bill explicitly limits the extent to which brand name pharmaceutical companies can be
sued in cases where their generic accusers can be proven not to have used adequate safety measures.
Pharmaceutical companies can also escape liability, if they can prove that generic companies couldve
gotten access to formulae through other, commercially viable means. In other words, this is a bill aimed
at increasing competition with pharma but only provided that the would-be competitors are playing by
the rules, not cutting corners, and acting in good faith.

Not only is such an approach commonsensical; it is deeply, unquestionably conservative. The balancing
act in Lees bill between ensuring that generic manufacturers meet the standards to produce the drugs
and also making sure that Pharma follows the rules and permits competition when they do is emblematic
of a timeless tension within conservative thought. That is, it pays special attention to balancing the free
market (by encouraging competition) with the rule of law (by curtailing abuses by all sides). Granted,
pharma will likely still oppose the bill, and one probably shouldnt have expected anything else from the
architects of Obamacare, which wasnt exactly a strong bill for either freedom or the rule of law. And in
that regard, Lees bill is also doing an important service: It is smoking out the anticonservative nature of
an industry that conservatives have been willing to accept uncritically as an ally for far too long.

A more prudent iteration of pharma might understand this and support the bill. However, if they prove
unlikely to be so prudent, then one can thank Mike Lee and the CREATES Act for destroying not only

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pharmas credibility but the corporate welfare-driven pricing regime with which they have held so much
of America hostage.

Indias Aurobindo plans second pharma plant in US as Trump calls for local production
Feb 10, 2017
http://www.hindustantimes.com/business-news/india-s-aurobindo-plans-second-pharma-plant-in-us-as-
trump-calls-for-local-production/story-yBmqvBKBuoEHacp7w7mP4O.html

Indian drugmaker Aurobindo Pharma plans to set up a factory in the United States for injectable
products, it said on Friday, days after US President Donald Trump called on pharmaceutical companies
to make more drugs locally. Trump urged US drug industry executives at a meeting last month to
increase local manufacturing and to bring down medicine prices. He also proposed to impose a penalty
in the form of a border tax on US imports, a move criticised by several import-dependant industries.
His comments have worried some in Indias roughly $15 billion pharmaceutical industry which supplies
about 30% of the medicines sold in the United States and relies on the country for the bulk of its export
revenue. With the current landscape of whats happening with the US White House administration, and
some of the things that may change there, clearly, we dont think having capacity in the US would be
detrimental at this point, Aurobindos US chief, Bob Cunard, told an earnings briefing.

Trumps push for lower drug prices to benefit Indian pharma Severely obese people more likely to die
at home than in a hospice care Aurobindo, Indias fourth biggest drugmaker by sales, makes more than
half its revenue in the United States selling everything from HIV/AIDS medicines to anti-bacterials to
schizophrenia drugs. It makes tablets in New Jersey but much of its US supply still comes from its six
factories in India. Cunard said the company was planning to put the injectable drugs factory at its New
Jersey site. Aurobindo also reported lower than expected profit in the final quarter of 2016 on Friday as
it was hurt by price erosion in the United States.

Trump is also looking to repeal the Affordable Care Act, a move that would leave some Americans
without insurance and make them more reliant on cheap generics, said DG Shah, secretary general of the
Indian Pharmaceutical Association that represents 20 large generic drugmakers. While not all Indian

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drug makers are looking to boost their US manufacturing presence just yet, most are watching closely
for any policy changes. We are extremely vigilant, said Nilesh Gupta, managing director of Indias
third biggest drugmaker Lupin, which made its biggest US investment in 2015 through a $880 million
deal to buy generic drug assets there.

No time for gym? Try short, intense stair climbing for a healthy heart

Night shifts, manual labour affect womans capacity to have babies: Study In an interview on Thursday,
Gupta said Lupin had no plans to scale up its US manufacturing but cautioned: If there is ever a border
tax or something, then obviously, we will need to revisit the whole situation. Lupins CEO Vinita Gupta
said the cost of such a tax would have to be passed on to patients and the US healthcare system, meaning
this would go against Trumps goal to lower drug prices. Rival Cipla, which made a $550 million
acquisition in the US last year in its biggest boost to business there, said it did not plan on changing its
strategy just yet. We will watch the evolving regulatory aspects in the US, but its unlikely that generics
will get impacted, said Kedar Upadhye, Ciplas chief financial officer.

Inauguration of Regional Office of IPC at Hyderabad

http://ipc.nic.in/printcont.asp?lid=678&EncHid=
With a vision to promote the highest standards of drugs for use in human and animals, Indian
Pharmacopoeia Commission (IPC) initiated steps to open its extended arm across multiple cities in the
country as well as in other countries. This move is in line with our commitment to strengthen the
standard setting body at national and international level by providing doorstep interaction with
stakeholders and to establish global harmonization with international standards. Due to on-going
parliament session and other commitments, Dr. G. N. Singh, Drug Controller General of India DCG(I)
& Secretary-Cum-Scientific Director, IPC, Ministry of Health & Family Welfare, Government of India
could not participate in the inaugural function. In this connection, he had deputed Dr. P. L. Sahu,
Principal Scientific Officer, Head, R & D, IPC and Dr. P.B.N. Prashad DDC (I), Hyderabad to
inaugurate the function and to coordinate other activities. Dr. G. N. Singh conveyed his best wishes on
this occasion. A team of renowned industrialists, academicians & stakeholders along with the team of
regulators and IPC team consisting of Dr. Robin Kumar, Pr. Scientific Officer, Dr. Anuj Prakash, Sr.
Scientific Officer, Dr. Meenakshi Dahiya, Sr. Scientific Officer, Dr Sucheta, Senior Scientific Officer
and Prof. Prakash Diwan, Technical Advisor, IPC, witnessed the occasion. With a dream of spreading
wings of IPC across India and world, Dr. P.L Sahu and Dr. P.B. N. Prasad inaugurated the first regional
office of IPC at Hyderabad on 1st Feb in the campus of CDTL, Hyderabad. In fact, IPC is also planning
to set up Regional offices in Mumbai, Chennai and Kolkata. He said that if things go as planned, other
offices of IPC will be coming up in the near future in other countries. Inauguration ceremony was
followed by interaction session between Sh. P.B.N. Prasad, DDC (I), Hyderabad, Shri Uday Bhaskar,
DG, Pharmexcil, Sh. Amruth Rao, DCA, AP & Scientists of IPC with the distinguished delegates from

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various Pharma Industries in which various issues related to Pharma activities with regulatory bodies &
updates on IPC were discussed.

Discovering Novel Antibiotics

Sandeep Ravindran, February 1, 2017
http://www.the-scientist.com/?articles.view/articleNo/48069/title/Discovering-Novel-Antibiotics/

Antibiotic resistance is a major threat to global health, and researchers have struggled to identify new
antimicrobial compounds. By the late 1990s, the bacterial reservoirs from which almost all clinically
useful antibiotics had sprung appeared to run dry. As bacterial genome sequencing became more
widespread in the last decade, however, researchers discovered many potential sources of new drugs
hidden in these genomes. Now they just need to learn how to mine them.

MIXING IT UP: The bacterium Streptomyces coelicolor produces a variety of novel compounds when grown in
combination with other bacterial species, and these interspecies interactions result in differences in colony
development and pigment production when viewed under a microscope.mBio, doi:10.1128/mBio.00459-13,
2013

Most antibiotics are derived from small molecules produced by bacteria, and the genes that synthesize,
regulate, and export these molecules typically occur together in groups called biosynthetic gene clusters,
which range in size from just a handful to several dozen genes. Sequencing efforts have revealed that the

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genomes of antibiotic-producing organisms, such as Streptomyces coelicolor, contained a large number
of gene clusters that were silent or cryptic and were not expressed under laboratory conditions. We
were culturing these bacteria for decades, and we had only found a handful of compounds in each of
these key, industrially relevant strains, says Mohammad Seyedsayamdost, an assistant professor of
chemistry at Princeton University. It was just remarkable that they had so much more potential that we
hadnt tapped into.

Bioinformatic tools can now identify many silent biosynthetic gene clusters in bacterial genomes. The
next step is figuring out how to activate them. That would profoundly change natural product
discovery, and also drug discovery, says Seyedsayamdost. Researchers have tried many approaches,
such as expressing these gene clusters in other bacterial species, modifying their promoters or regulators,
and changing how the bacteria are cultured. Many of these strategies are not scalable or generally
applicable, says Huimin Zhao, a professor of chemical and biomolecular engineering at the University
of Illinois at Urbana-Champaign. Theres a lot of luck involved.

But that may be changing, as more reliable and high-throughput methods to activate these clusters come
online. Advances in synthetic biology, small-molecule screening, and mass spectrometry have led to
promising new ways to induce gene clusters and identify their products. Some hurdles remain
scientists are still trying to develop better ways to pinpoint the clusters that will yield new and useful
compounds, as well as methods to more quickly and accurately identify the molecules produced by
individual clusters. In addition, the new approaches for turning on gene clusters may help elucidate how
this activation is regulated.

The Scientist talked with researchers about some of these new approaches. Heres what we learned.

HARNESSING MICROBIAL INTERACTIONS

Investigators: Matt Traxler, Assistant Professor, Department of Plant & Microbial Biology, University of
California, Berkeley, and Roberto Kolter, Professor of Microbiology and Immunobiology, Harvard
Medical School

Project: Take advantage of the natural interactions between bacteria to activate silent gene clusters.

Approach: Past work has shown that bacteria undergo very different physiological changes when grown
in the presence of other microbes than when theyre grown by themselves. Kolter and Traxler wondered
if they could harness the crosstalk between different bacterial species to activate silent gene clusters.
They systematically tested this hypothesis by growing different combinations of bacteria together and
using mass spectrometry to identify and compare the compounds produced. It became very clear that
many very different metabolites get made when things are grown in co-culture, says Kolter. When they
paired one species of actinobacterium (Streptomyces coelicolor) with five others, the researchers further
found that the set of compounds that were produced were different for each of the five co-cultures
(mBio, doi:10.1128/mBio.00459-13, 2013). We can see a lot of interactions that lead to antibiotic
biosynthesis, says Traxler. That suggested to us that there is still some deep potential here for drug
discovery.

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Advantages: This approach is relatively simple to implement and doesnt require any prior knowledge of
the bacterial genomes. In addition, its linked directly to the ecology of these organisms, and I see that
as a major strength, says Traxler. He suggests that co-cultures replicate some of the complex ecological
interactions that bacteria face in their natural habitats, which might force them to activate more novel
gene clusters than methods that rely only on single-species bacterial cultures. There may be a limit to
what were able to find in single culture, and we may only be able to cross that by going to co-culture or
even in situ, to find antibiotics we may never find otherwise, he says.

Limitations: The main drawback of the method is that it can be slow and labor-intensive, especially
when trying out many different combinations of bacteria. High-throughput for us means a hundred
combinations, not hundreds of thousands or millions of combinations, says Kolter. In addition, once the
researchers identify interesting compounds being produced by bacteria in co-culture, they still need to
comb through the bacterial genomes to try to figure out which gene clusters they came from. We have
to work backwards to identify which processes we have woken up, says Kolter.

Looking ahead: Traxler is trying to use microfluidics to make this approach higher-throughput, and
hopes to eventually test tens of thousands of combinations using this setup. He is also planning to go
from looking at simple binary interactions to looking at more-complex interactions in natural settings.
How to use: Its pretty cheap and easy to do this, says Traxler. Just set up your co-cultures and watch
them grow.

Looking For Activating Signals

ELICiTING A SIGNAL: Researchers insert a reporter gene inside a silent gene cluster of interest (white
arrows), then screen a small-molecule library for signals that can turn on the cluster (colored arrows).
When this approach was used in Burkholderia thailandensis, the antibiotic trimethoprim was found to
activate the silent gene cluster that produces the cytotoxin malleilactone B.

FEMS Microbiology Reviews, doi:10.1093/femsre/fuw035, 2016

Investigator: Mohammad Seyedsayamdost, Assistant Professor, Department of Chemistry, Princeton

University

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Project: Screen a small-molecule library for compounds that activate silent gene clusters.

Approach: Seyedsayamdost and his team postulated that certain natural compounds turn on biosynthetic
gene clusters, so they developed a high-throughput screen to search out these elicitor molecules.
Seyedsayamdosts group first inserts a genetic reporter, such as lacZ, into a gene cluster of interest. They
then expose the bacteria to a large library of natural products and bioactive small molecules, looking for
those that induce the expression of the gene cluster. The approach can pinpoint molecules that activate a
specific silent gene cluster as well as global elicitors that activate many different clusters (PNAS,
111:7266-71, 2014). Interestingly, it turned out that antibiotics in these compound libraries in many
cases turn out to be the elicitors, Seyedsayamdost says. This suggests that old antibiotics could be used
to find new antibiotics.

Advantages: One of the advantages of our method is that we can find naturally occurring inducers,
says Seyedsayamdost. Identifying global elicitors that activate many gene clusters could also help
researchers identify common regulatory mechanisms that could be deployed to activate silent clusters. In
addition, the approach can be used to screen tens of thousands of small-molecule elicitors at the same
time.

Limitations: The main challenge of the system lies in genetically modifying the bacteria with a suitable
reporter, which can be difficult and time-consuming depending on the species. Seyedsayamdost has
successfully applied the technique to the gram-negative soil bacterium Burkholderia thailandensis, but
getting it to work in less genetically tractable species will require more time and effort, he says.

Looking ahead: Seyedsayamdost is expanding the technique to different bacterial species. Were now
getting it to work in Actinomycetes, which are responsible for many antibiotics, says Seyedsayamdost.
In organisms where its difficult to insert a genetic reporter, he envisions using mass spectrometry as a
readout for bacterially produced small molecules. He is also trying to use more than one reporter to
simultaneously assay multiple gene clusters, and eventually hopes to use RNA-seq to monitor an
elicitors effects on an organisms entire transcriptome.

How to use: The approach involves standard microbiology and genetics techniques. The main expense
comes from the small-molecule screening. Each screen may cost something like $500 to $5000 with a
5,000- to 10,000-compound library, says Seyedsayamdost. For the amount of data you get, its
actually fairly affordable. Once the screen is done, youre off to the races.

PLUG-AND-PLAY GENE EXPRESSION

EASY ASSEMBLY: A silent biosynthetic gene cluster of interest (genes 1 to n) is reconstructed in a

vector (orange, top) and integrated into a yeast chromosome through recombination at the d site
(bottom). The assembled biosynthetic cluster can then be isolated from yeast and transferred into a
heterologous host, where it is expressed and its products analyzed by mass spectrometry and nuclear
magnetic resonance spectroscopy.

Adapted from Nucleic Acids Res, doi:10.1093/nar/gkn991, 2009

12
Investigator: Huimin Zhao, Professor, Department of Chemical and Biomolecular Engineering,
University of Illinois at Urbana-Champaign

Project: Use synthetic biology to re-create and express silent gene clusters.

Approach: Zhaos team uses bioinformatics to home in on a gene clusters structural genesthose that
dont encode regulatory proteins but are instead directly involved in the synthesis of the compound. The
researchers then either amplify these genes using PCR or synthesize them anew. They clone these genes
into a previously developed plug-and-play scaffold with standardized promoters for expressing
biosynthetic pathway genes (Nucleic Acids Res, doi:10.1093/nar/gkn991, 2009; Mol Biosyst, 7:1056-59,
2011). Finally, they express the genes in a nonnative, or heterologous, host. The whole idea is to
basically rebuild the pathway from scratch, Zhao says. The researchers used this method to activate a
silent biosynthetic gene cluster from Streptomyces griseus and identify potential antibiotic compounds
(Nat Commun, 4:2894, 2013).

Advantages: By focusing on the structural genes from the biosynthetic cluster, Zhaos approach aims to
circumvent the expression of any regulatory genes that might repress the gene cluster. Using well-
characterized and standardized promoters and heterologous hosts, the technique also reduces the number
of variables that researchers need to troubleshoot in order to activate a particular cluster. The method
also makes it easy to delete or alter specific genes in a cluster; by deleting different genes, Zhao was
able to dissect the individual steps of a Streptomyces biosynthetic pathway. By tweaking the scaffold
and changing the heterologous host used, the technique could be extended to other species of bacteria
and eukaryotes. You cannot just work on one organism; you have to work on many different ones,
Zhao says.

Limitations: Gene clusters from some bacteria, such as Streptomyces, can be hard to amplify using PCR.
Synthesizing the gene cluster is an alternative, but could get expensive if the cluster has a lot of genes.
In addition, the host used may lack some of the precursors necessary to create the final product of the
cluster. Looking ahead: Zhaos eventual goal is to automate the synthetic expression of silent gene
clusters. In order to make an impact, we have to scale up the process, he says. Given the recent
progress, Im very optimistic. How to use: The protocols used in Zhaos technique have been published
and all the necessary tools are commercially available. [Researchers] just need to follow the protocols,
theyre all very straightforward, he says. He estimates that it should cost a few hundred dollars to
synthetically construct and express a particular gene cluster.

End of fillings in sight as scientists find Alzheimer's drug makes teeth grow back
Sarah Knapton, science editor
9 JANUARY 2017
Fillings could be consigned to history after scientists discovered that a drug already trialled in
Alzheimer's patients can encourage tooth regrowth and repair cavities. Researchers at King's College
London found that the drug Tideglusib stimulates the stem cells contained in the pulp of teeth so that
they generate new dentine the mineralised material under the enamel. Teeth already have the capability
of regenerating dentine if the pulp inside the tooth becomes exposed through a trauma or infection, but

13
can only naturally make a very thin layer, and not enough to fill the deep cavities caused by tooth decay.
But Tideglusib switches off an enzyme called GSK-3 which prevents dentine from carrying on forming.
Scientists showed it is possible to soak a small biodegradable sponge with the drug and insert it into a
cavity, where it triggers the growth of dentine and repairs the damage within six weeks. The tiny
sponges are made out of collagen so they melt away over time, leaving only the repaired tooth. This is
an extremely interesting and novel approach which shows great promise and we will look forward to it
being translated into clinical application
Dr Nigel Carter, CEO of the Oral Health Foundation

Professor Paul Sharpe, lead author of the study, of the Dental Institute, from Kings College London,
said: The simplicity of our approach makes it ideal as a clinical dental product for the natural treatment
of large cavities, by providing both pulp protection and restoring dentine.

In addition, using a drug that has already been tested in clinical trials for Alzheimers disease provides
a real opportunity to get this dental treatment quickly into clinics.Currently dentists use man-made
cements or fillings, such as calcium and silicon-based products, to treat larger cavities and fill holes in
teeth.But this cement remains in the tooth and fails to disintegrate, meaning that the normal mineral
level of the tooth is never completely restored.However the new technique could reduce the need for
fillings of cements, which are prone to infection and often need replacing a number of times.When
fillings fail or infection occurs, dentists have to remove and fill an area that is larger than what is
affected, and after multiple treatments the tooth may eventually need to be extracted.Dr Nigel Carter,
CEO of the Oral Health Foundation: This is an extremely interesting and novel approach which shows
great promise and we will look forward to it being translated into clinical application that could
undoubtedly be a progressive step in the treatment of dental disease.While fillings have remained
highly effective in repairing large cavities, they are susceptible to wear-and-tear and can occasionally be
in need of repair and replacement. This presents problems as the dentist could have to remove and fill a
larger area each time and after numerous treatments the tooth may then have to be extracted.Creating a
more natural way for the tooth to repair itself could not only eliminate these issues, but also be a far less
invasive treatment option for patients. With dental phobia still being very common, using a natural way
to stimulate the renewal of dentine could be an especially comforting proposal for these groups, for
which undergoing treatment can often be a cause great anxiety.The procedure has so far only been used
in mouse teeth, but it was shown to 'fill the whole injury site'.And Tideglusib has already been shown to
be safe in clinical trials of patients with Alzheimer's disease so scientists say that the treatment could be
fast-tracked into dental practices. The research was published in the journal Scientific Reports.

Superbug death spurs drug regulator warning

Sushmi Dey
Jan 18 2017: The Times of India (Delhi)
http://timesofindia.indiatimes.com/india/superbug-death-spurs-drug-regulator-
warning/articleshow/56634853.cms

In the wake of the recent death of an American woman after contracting an infection resistant to
antibiotics, the drug regulator has directed the pharma supply chain, including retailers, chemists and
drug makers, to strictly follow norms while selling antibiotics. The Drugs Controller General of India

14
(DCGI) has also asked companies to carry specified warnings to avoid antimicrobial resistance. To
contain anti-microbial resistance, the office has been advising the supply chain system in India to follow
strict requirements of Schedule H and H1 for sale of medicines, DCGI G N Singh said in a notice
issued to all state regulators and other stakeholders. The Centre has also asked state drug regulators to
take strong policy measures including stringent regulatory action on the over-the-counter (without
prescription) sale of high-end antibiotics.
An American woman, who contracted an infection while being treated for a thigh bone fracture in India
two years ago, died recently . CDC Atlanta, which houses one of world's most advanced laboratories,
conducted tests on the wound specimen later and confirmed the presence of New Delhi Metallo-Beta-
Lactamase (NDM) --a superbug that makes bacteria resistant to antibiotics. The incident has triggered a
lot of concerns among health experts.Though antibiotic resistance is a global public health threat, misuse
of antibiotics is rampant in India. According to a 2016 report in international journal PLOS, the
infectious disease mortality rate in India is 416.75 per 100,000 persons and is twice the rate prevailing in
the United States when antibiotics were introduced.

Experts blame poor public health systems, hospital infection, high rates of infectious disease,
inexpensive antibiotics, and rising incomes for the increasing prevalence of resistant pathogens.
Antimicrobial resistance has resulted in striking rise in the burden of untreatable neonatal sepsis and
health-care-associated infections. To check irrational use of antibiotics, the government has already
introduced a `red line' differentiating highend antibiotics from other drugs. The move is aimed at
discouraging unnecessary prescription and over-thecounter sale of antibiotics causing drug resistance for
several critical diseases including TB, malaria, urinary tract infection and even HIV .

High-end antibiotics are used for critical diseases and in serious infection cases.This also include some
new and innovative medicines used in cancer treatments.However, misuse of such an tibiotics for
common health conditions help bacteria develop resistance. The government is running campaigns
against irrational prescriptions and over the counter sale of antibiotics. The World Health Organisation
has also created pressure on India seeking urgent and concrete measures to arrest the reducing
effectiveness of antibiotics. It has cautioned the government and public health experts that if enough was
not done now, common bacterial infections such as skin sores or diaorrhea would become untreatable
and fatal.

15
 Indian generic drug players unlikely to be affected by Trump attacks
Sohini Das
Ahmedabad January 13, 2017
http://www.business-standard.com/article/companies/indian-generic-drug-players-unlikely-to-be-
affected-by-trump-attacks-117011300077_1.html
The Indian pharma industry, which account for nearly 40 per cent of the generic drugs in the US, is
unlikely to come under pressure after US President-elect Donald Trump attacked the pharmaceutical
industry for high drug prices and overseas manufacturing, felt industry here. Speaking at the sidelines of
the Vibrant Gujarat Global Summit, Pankaj Patel, chairman of Federation of Indian Chambers of
Commerce and Industry (FICCI) and also chairman and managing director of Cadila Healthcare Ltd said

16
that generic drug industry in India which supplies to the US is unlikely to be affected. His own firm
draws around 35-40 per cent of its revenues from the US markets.

He explained that the generic drug industry in India, in fact, has saved revenues to the tune of $40
billion dollar by supplying cheaper yet quality drugs to the US last year. Shares of Indian pharma
companies, however, fell on Thursday with companies like Aurobindo Pharma, Cadila Healthcare, Dr.
Reddys Laboratories, Lupin Ltd, Cipla etc witnessing a fall in the range of 1-2 per cent on the Bombay
Stock Exchange (BSE). As such generic drug companies are already under pricing pressure in the US
thanks to rising competition as well as price erosion of 8-9 per cent in base business. However, analysts
too felt that while there would be some short term pressure on the industry as a whole, there is hardly
any incremental risk. G N Singh, Drug Controller General of India (DCGI) also said that Indian pharma
companies are known for supplying quality generic drugs to the US as reasonable prices. He added that
there was hardly any incremental risk posed at generic pharma companies exporting to the US. India is
the largest provider of generic drugs globally with the Indian generics accounting for 20 per cent of
global exports in terms of volume.

US president-elect Donald Trump on Wednesday attacked the pharmaceutical industry for high drug
prices and for manufacturing overseas. He also said that he will create new procedures for bidding on
drugs. The US is the largest buyer of drugs in the world, Trump had said adding that it, however, does
not bid properly. With changes in bidding procedures, Trump feels that the US would be able to save
billions of dollars.

Health ministry asks states to screen antibiotics sale

Sun, 22 Jan 2017
NEETU CHANDRA SHARMA
http://www.dnaindia.com/health/report-health-ministry-asks-states-to-screen-antibiotics-sale-2294881

Asks for strict monitoring on sale of schedule H and H1 drugs sale without prescription, and also directs
pharmacies, consumer bodies to adhere to laws related to medicine In reaction to the reports of death of
a 70-year-old woman from US, who al-legedly contracted New Delhi metallo-beta-lactamase (NDM-1)
strain infection superbug from India a drug control department has alerted the States to strictly
keep a check on sale of antibiotics without prescription. The Central Drugs Standards Control
Organization (CDSCO) under Ministry of Health and Family Welfare has also directed pharmaceutical
companies and consumer associations to strictly adhere to laws and regulations regarding sale of
medicines in India and spread awareness about hazards of antibiotic abuse. To contain anti-microbial
resistance, we have been advising the supply chain system in India to follow strict requirements of
Schedule H and H1 for sale of medicines, said Dr GN Singh, Drugs Controller General of India in his
letter to all the Drugs Controllers of the State and Union Territories, Pharmaceutical companies and
Consumer Associations.

Stakeholders have been advised for strict compliance of the requirement of the Drugs & Cosmetics Act
and Rules made thereunder by taking strong policy measures including stringent regulatory action on the
over the counter (without prescription) sale of high end antibiotics included in the above Schedules,
said Dr Singh. The law may also be complied by raising awareness through consumer associations

17
about the side effects of taking antibiotics without pre-scription, so that the antibiotic microbial
resistance could be avoided for pa-tient safety, their well-being and protection of their health, he said.

Antimicrobial resistance is closely linked to inappropriate antibiotic use. It is estimated that 50 per cent
or more of hospital antimicrobial use is inappropri-ate in India. Published reports in India reveal an
increasing trend of drug re-sistance in common diseases of public health importance. It has been
reported that cholera is now showing high level of resistance to commonly used antim-icrobials like
Furazolidone (60-80 per cent), Cotriamoxazole (60-80per cent) and Nalidixic Acid (80-90per cent).
Resistance is also seen in Meningococcal infections, malaria, leprosy, kala-azar, TB, Enteric fever,
Meningococcal infec-tions, Gonococcal infections and HIV. In wake of increasing antibiotic resistance
across the globe, the National Centre for Disease Control (NCDC) also set to formulate a National
Action Plan to curb it. NCDC said it would soon submit the plan to Union Health Ministry for
incorporating it into the national policy.

Trump victory to maintain status quo for Indian pharma

AVEEK DATTA
Nov 9, 2016
http://www.forbesindia.com/article/trump-presidency-india-impact/trump-victory-to-maintain-status-
quo-for-indian-pharma/44755/1
The Republican candidate's surprise victory in the US presidential elections have helped allay concerns
over curbs on pricing power for pharma companies feared if Hillary Clinton came to power Despite the
initial skepticism visible in the stock markets with respect to the future perform-ance of Indian
pharmaceutical companies, industry insiders say that Donald Trumps presi-dency will not have much
impact on their fortunes. By Wednesday afternoon, construction tycoon and Republican candidate
Donald Trump was announced as US President-elect, as his opponent and Democrat Hillary Clinton
conceded defeat. In the analysis and speculation that had built up till Wednesdays verdict, it was widely
anticipated that Secretary of State in the current Barack Obama administration, Clinton will be US next
President. But as the re-sults of the polls from various US states started pouring in, the tide increasingly
turned in Trumps favour.

Pharma sector experts were of the opinion that a potential government with Clinton at the helm may
have sought to curb the profits raked in by generic pharma companies that cater to the US market, the
worlds largest for generic drugs, which are versions of innovator medi-cines that lose patent protection.
This, analysts believed, would lead to a pressure on the pric-ing power that drug-makers enjoy in the
US. Indian pharma companies comprise the largest set of generic drug suppliers to the US, accounting
for as much as 40 percent of the supply of such medicines. A major development in recent times that led
to this line of thought was news of the US beginning a grand jury probe into instances of possible price
cartelization by pharma companies the fallout of an anti-trust investigation being conducted by the US
De-partment of Justice (DoJ), which began around two years ago. As a part of this investigation, several
marquee global pharma companies like Teva Pharmaceutical Industries, Allergan (acquired by Teva
Pharmaceutical Industries from Actavis in August), and Mylan, among others, have been served
subpoenas demanding explanation for price hike actions taken. In-dian companies that fall within the

18
ambit of the DoJ investigation include Sun Pharmaceutical Industries and Dr. Reddys Laboratories.
Trump, a successful businessman in his own right, is expected to be more business-friendly given his
own entrepreneurial experience and belief in free market dynamics, which could work to the benefit of
pharma companies. In his victory speech on Wednesday, Trump, 70, said that his presidency will focus
on creating in-frastructure and generating employment for the people of the US. He is also in a good
posi-tion to do so since his Republican Party will also control the US Senate, which could facilitate
smoother decision-making. Consequently, if Trump incentivizes manufacturing of drugs in the US, it
may work to the benefit of Indian pharma companies like Sun Pharmaceutical Industries, Cipla, Dr.
Reddys Laboratories and Lupin, which have a manufacturing presence in the US.

In Wednesdays trade on the bourses, the S&P BSE Healthcare Index tanked sharply to factor in
concerns facing pharma companies that constitute this index emanating from the likelihood of a Clinton
victory. The index, which opened at 15,247.07 points, soon tanked 8.27 percent to 13,993.33 points at
9:16 am. The index recovered from this low to inch marginally higher than the opening value to trade at
15,489.58 points at 3:17 pm. The S&P BSE Sensex also pared losses as trade progressed through the day
and was trading 1.22 percent lower at 3:17 pm at 27,254.41 points. Pharma majors that are a part of the
30-share index like Dr. Reddys, Sun Pharma and Lupin were trading in the green; while IT companies
like Tata Consultancy Services and Infosys were trading in the red. Unlike in India, a change of guard
in the US administration may not entail any drastic measures, says Pranav Amin, joint MD of
Vadodara-based pharma company Alembic Pharmaceuticals Ltd. Yes, there is some amount of
unpredictability at present, but Indian pharma is the largest supplier of generic drugs to the US, and the
new government will be aware of that.

Commenting on the DoJ investigation, Amin said that it was very hard to prove collusion be-tween
market players to increase prices. It is a free market and there is nothing illegal in price hikes, he says.
The generic drugs market in the US is very competitive with pricing pressure on all companies, so price
hikes are not a norm, but few and far in between.Analysts opinion reflects Amins understanding. We
do believe that while the generic industry is facing growth challenges in US, it is unlikely that players
have orchestrated pricing coordination, says a November 4 research report by Edelweiss Securities Ltd.
Our view is that it may be an uphill task for the Department of Justice to prove that these companies
have colluded in taking price hikes and the case may take years to reach any conclusion.

Kiran Mazumdar-Shaw, chairperson and MD of Indias largest biotech company Biocon says that she
doesnt expect any negative impact on healthcare sector on account of Trumps vic-tory. She points out
to the possibility of Trump moving towards scrapping ObamaCare, an initiative of the outgoing
Democrat President that aims at expanding the overage of health insurance and providing affordable
healthcare to the American masses. But she adds that Trump will have to replace ObamaCare, the
official name for which is the Patient Protection and Affordable Care Act, with some other form of
healthcare initiative. The US healthcare sectors dependence on generics will continue and there may
not be much to be concerned about as far as the Indian pharma sector is concerned, since it is in the Us
best interest to bring down costs, Mazumdar-Shaw told Forbes India over the phone from New York.
The pharma industry is already facing a lot of challenges, even without Hillary as President, said
Vinita Gupta, Lupins CEO at the Forbes India Leadership Awards function on Tuesday eve-ning in

19
Mumbai, where she and her brother and Lupin MD, Nilesh Gupta won the Entrepre-neur for the Year
award. A lot of what happens in the future will depend on whether we Have a Democratic Senate and
Congress in the US.

To be sure, the expectation on Tuesday evening was that Clinton will come to power. But it was Trump
instead and the Senate is also a Republican-controlled one. The industry has al-ready faced a lot of
pressure and survived and I dont see much changing, Vinita said. Speaking at the same forum, YK
Hamied, Ciplas non-executive chairman who was conferred the Lifetime Achievement Award
presented a contrarian view. In his opinion a Clinton administration would have been good for
indigenous Indian pharma, since prices of the generic drugs that they supplied to the US was already
very low; and it would be so-called big pharma, comprising some US drug-makers who would have
been forced to bring down their prices. Though Trumps presidency may not change much for Indian
pharma, there have been structural challenges that companies have been facing in the US and they
continue. In short, these challenges include a consolidation in the supply chain of drug distributors and
retailers, and increased competition that has led to pricing pressure for Indian pharma companies active
in the US.

In the last one year, the S&P BSE Healthcare Index has declined 10 percent, while the benchmark S&P
BSE Sensex has risen five percent over the same period. Given the chal-lenges in the US market and
the size of the base business, companies need to transition to-ward more innovative and complex
portfolios, says an August 21 research note by Jefferies. This is already visible with companies
spending around 10 percent of sales on R&D [(re-search and development) versus six percent three
years back]. Success in these would drive sharp valuation distinction over the next three years in our
view.Another Jefferies research report dated November 9 states that while a Trump victory is largely
neutral for the Indian pharma sector, unlike the large negative from a Clinton victory, we expect
scrutiny on pric-ing and the DoJ case overhangs to continue for the sector.

Catalyst adds fluorine-containing groups to make new compounds

January 23, 2017
Christine Daniloff/MIT
https://www.sciencedaily.com/releases/2017/01/170123162312.htm

Drugs that contain one or more fluorine atoms tend to be more stable, more powerful, and easier for the
body to absorb. For those reasons, drug developers would like to be able to incorporate fluorine or a
fluorine-containing unit known as trifluoromethyl into new experimental drugs, but this has been very
difficult to do. Now, a team of chemists at MIT and Boston College has discovered a new type of
catalyst that can incorporate a trifluoromethyl group within a variety of organic molecules. The
availability of these exceptionally efficient and selective catalysts should allow researchers to rapidly
generate potential new fluorinated drugs, including antibiotics and anticancer agents, for testing.

The new catalysts use a nontoxic foam-blowing agent (which is conventionally used to spread
insulation) as the source of fluorine atoms. "The fact that this fluorinated compound behaves in this

20
reaction like its nonfluorinated analog is really amazing," says Richard Schrock, the Frederick G. Keyes
Professor of Chemistry at MIT and one of the senior authors of the paper, which appears in the Jan. 23
issue of Nature.

Amir Hoveyda, the Vanderslice Millennium Professor of Chemistry at Boston College, is also a senior
author of the paper. The paper's lead author is Boston College graduate student Ming Joo Koh. Other
authors include MIT postdoc Jonathan Lam, former MIT postdoc Jakub Hyvl, Boston College graduate
student Thach Nguyen, and Boston College senior research fellow Sebastian Torker.

Making and breaking bonds

Schrock has spent much of his career developing catalysts that break and make double bonds between
carbon atoms to produce new types of carbon-carbon double bonds. In 2005, he won the Nobel Prize in
chemistry for designing the first catalyst that could perform this type of reaction, known as olefin
metathesis.

This reaction allows chemists to attach various chemical groups to the carbon atoms that form the
double bond, which is an important step in manufacturing pharmaceuticals, fuels, and other chemicals.
For the new Nature study, the Schrock/Hoveyda team was able to discover and demonstrate the
usefulness of a family of catalysts containing molybdenum, a metal often used in steel. The
molybdenum in the new catalysts is bound to four other chemical groups (five in its inactive resting
state), and changing those chemical groups influences the catalysts' activity.

Subsequent examination of these catalysts led the MIT/BC team to discover that they could be used to
perform a certain reaction involving a carbon-carbon double bond in which one carbon is also attached
to a trifluoromethyl group -- a carbon bound to three fluorine atoms. When the catalyst is added to a
compound containing this chemical structure, it can transfer the double bond and trifluoromethyl group
into another organic molecule.

Furthermore, they discovered that the new complexes are capable of promoting reactions that generate
alkenes (molecules with a carbon-carbon double bond) containing a single halogen atom with a
particular configuration more effectively than catalysts previously discovered by the same team.

Through the use of these catalysts, the researchers were able to introduce trifluoromethyl groups into a
variety of organic molecules, in reactions that took between two and 12 hours. Catalysts in which
molybdenum was bound to a chlorine atom proved to be particularly effective.

"These catalysts are very reactive for reasons we are beginning to understand, and they do reactions that
have never been done before," Schrock says.

More potent drugs

21
Many potent drugs contain trifluoromethyl groups, so scientists are very interested in adding these
groups to existing drugs to see if they make the drugs more powerful or give them new functions.

"There are cases where by substituting an organic group like a methyl group with a trifluoromethyl
group, it completely changes the mode of action, so this reaction allows easy access to a much larger
variety of potential drug candidates," Hoveyda says. "A lot of these compounds are unknown because
people didn't know how to make them."

To demonstrate the potential usefulness of this approach, the researchers showed that they could add
trifluoromethyl groups to several drugs, including antibiotics, an antimalarial drug, a diabetes drug, and
a topical painkiller.

Schrock now hopes to develop new catalysts that are more stable and will perform the same type of
reaction at lower concentrations. In 2010, he and Hoveyda started a company called XiMo to develop
molybdenum and tungsten catalysts for metathesis reactions to make compounds including plastics,
pharmaceuticals, and fragrances. The research was funded by the National Institutes of Health and the
John LaMattina Fund.

FDA: Toxic Belladonna In Homeopathic Teething Product

Bruce Y. Lee
JAN 28, 2017
http://www.forbes.com/sites/brucelee/2017/01/28/fda-toxic-belladonna-in-homeopathic-teething-
products/#5591ed56a586
Here's a way to stop your baby from having teething pain. Give your baby some potential poison. The
Food and Drug Administration (FDA), you know that government agency that is there to protect you,
has urged parents not to use certain homeopathic teething tablets because they may contain higher than
safe levels of belladonna, a toxic substance. Belladonna means beautiful lady but it ain't a lady and
there's nothing beautiful about giving it to babies. Belladonna, which comes from the deadly nightshade
plant, can be poisonous. The FDA found that Hyland's homeopathic teething products in some cases had
belladonna levels far exceeding the amount claimed on the label and asked the Standard Homeopathic
Company in Los Angeles recall their product. (Of course, not every tablet may have toxic levels of
belladonna but the risk is there.) However, the company has not yet agreed to recall the product,
according to the FDA. Nice. As the National Library of Medicine (NLM) explains, belladonna's
components can inhibit the nerv-ous system, which can lead to dry mouth, enlarged pupils, blurred

22
vision, red dry skin, fever, fast heartbeat, inability to urinate or sweat, hallucinations, spasms, mental
problems, convulsions, sei-zures, coma, and death. But at least your baby won't have teething pain. But
wait, the FDA has never evaluated, tested, or approved homeopathic teething products. So who knows
how effective they really are in helping with teething pain?

This is not the first time the FDA has had to push for a recall of homeopathic teething products. In
November 2016, as the FDA reports, "Raritan Pharmaceuticals (East Brunswick, New Jersey) agreed to
recall three belladonna-containing homeopathic products, two of which were marketed by CVS." The
FDA already warned against the use of homeopathic teething tablets and gels in September 2016. As
CNN reports, the FDA originally recommended against Hyland's Teething Tablets in 2010 and since that
warning fielded more than 400 reports of adverse events associated with belladonna-containing teething
products. CNN also quotes Lyndsay Meyer, FDA spokeswoman, as saying, "Most describe serious
adverse events, like seizures. We are also aware of reports of 10 deaths during that time period that
reference homeopathic teething products." Hmmm, teething pain versus seizures and death. Decisions,
decisions.

Hyland did discontinue the homeopathic teething product in October 2016. However, Mary C.
Borneman, Hyland's spokeswoman, told CNN that Hyland's Teething Tablets "are a top-selling product
and a consumer favorite, and sadly it resulted in the loss of 24 jobs", meaning from the discontinuation
of the teething product line and not the use of the product.

Why use this homeopathic product? There are certainly alternatives for teething pain. As the Mayo
Clinic suggests, you can rub your baby's gums, change the food that your baby is eating, apply a cool
wash cloth or teething ring, or use something actually approved by the FDA such as acetominophen or
ibuprofen. Moreover, teething is not a life threatening condition, unless the teeth are enormous. Sure
your baby is uncomfortable. But is it really worth trying something that may not be safe?

Risking your health is one thing. Putting your baby (who has no say in the matter) at risk is an en-tirely
different level. Also, while some have called for reducing the FDA's oversight, imagine if the FDA were
indeed weakened to the point that it could no longer catch potentially harmful or even deadly products.
With all the talk of vaccine safety (when vaccines have undergone extensive scientific testing and
approval by the FDA), why isn't there as much talk about the safety of homeopathic remedies that have
not really been scientifically tested?

Indian pharma likely to report tepid earnings growth for Q3 FY17

AVEEK DATTA Forbes India Staff
PUBLISHED: Jan 25, 2017
http://www.forbesindia.com/article/q3-earnings-2017/indian-pharma-likely-to-report-tepid-earnings-
growth-for-q3-fy17/45565/1

The Indian pharmaceutical sector has seen a significant share of market value erode over the last couple
of years owing to multiple challenges, most notably those faced in the US, the largest market for generic
drugs in the world. The two main hurdles faced by Indian pharma companies catering to the US are

23
pricing pressure in the due to increased competition and a consolidation in the supply chain, and
regulatory scrutiny of the Indian manufacturing units of these drugmakers by the US Food and Drug
Administration (USFDA).

These factors are expected to weigh down on the earnings of Indian pharma companies for the October-
December quarter of fiscal 2017. Though turnover and profitability may increase for some of Indias
biggest drugmakers, the rate of growth is unlikely to match with what has been seen historically. Indian
pharma companies are expected to report a 12 percent increase in their aggregate turnover for the period
under review, but their profit margins are estimated to take a 100 basis points hit, according to a Jefferies
research report. US business will remain the key focus given regulatory and pricing headwinds. In
India, we expect limited impact from demonetisation for pharma, the report authored by Piyush Nahar
and Anurag Mantry said. The key focus in the results and commentary will be the pricing erosion faced
by Indian companies in US and outlook going forward. Some global peers have indicated that pricing is
likely to remain under pressure in 2017 also.

Another report by domestic brokerage Anand Rathi expects a more modest year-on-year revenue growth
of 6 percent for pharma companies in its coverage universe. The collective profit after tax of these
companies, according to Anand Rathi, is estimated to decline 28 percent year-on-year, accentuated by a
higher base effect due to blockbuster sales of the generic version of a drug called Abilify by companies
Alembic Pharmaceuticals and Torrent Pharmaceuticals in the third quarter of the previous fiscal.
Moreover, the drugmakers that Anand Rathi tracks have also not had any meaningful launches in the
third quarter of the current fiscal, the report states. The larger generic drugmakers that are in Jefferies
coverage universe Sun Pharmaceutical Industries, Lupin, Cipla, Dr. Reddys Laboratories, Aurobindo
Pharma, Natco Pharma and Strides Shasun are expected to post a combined turnover of Rs25,356
crore in the December 2016 quarter. Their combined net profit is expected to come in at Rs4,078.50
crore, up 16 percent.

Sun Pharma is expected to report healthy increase in turnover and profit margins aided by the launches
of generic versions Glivec and Olmesartan. Analysts will be looking forward to management
commentary on the expected timelines for resolution of challenges at its Halol unit, which has come
under USFDA scrutinty. Lupin is expected to report a 200 basis points year-on-year decline in margin
due to pricing pressure and new competition in the sale of a diabetes drug that it sells in the US. Cipla
and Aurobindo are expected to have stable quarterly earnings, while analysts are expecting further
clarity from Dr. Reddys on steps being taken to address the warning letter received from the US drug
regulator. It is the relatively smaller pharma companies, such as Natco and Ajanta Pharma, which are
expected to do well in the December quarter. Ajanta announced its earnings on January 24 and reported
a revenue of Rs530 crore, up 12 percent over the year-ago period, and an 18 percent rise in net profit to
Rs134 crore. Growth was driven by new launches in the US, a market where the Mumbai-based
company is looking to aggressively ramp up and robust sales of branded formulation drugs in India, says
the Anand Rathi report.

Natco is expected to post a 63 percent year-on-year jump in revenue to Rs450.50 crore for the third
quarter of FY2016-17, and an 81 percent growth in profitability to Rs67.20 crore, spurred by earnings

24
from the generic version of Tamiflu. With the new presidency in the US in place, Indian pharma
companies will also be eagerly watching out for announcements coming from US President Donald
Trump, who has vowed to bring manufacturing back to the country by imposing prohibitive taxes on
imports. Generic drugs made in India account for as much as 40 percent of such drugs consumed in the
US. Senior executives of the Indian pharma sector, however, think that Trump, who assumed office on
January 20, is unlikely to create disincentives for the export of generic medicines from India to the US,
since such exports help keep the prices of such drugs in check, leading to lower government spending.

Someday Your Doctor Will Sniff You (And You'll Be Good With It)
David DiSalvo
http://www.forbes.com/sites/daviddisalvo/2017/01/26/someday-your-doctor-will-sniff-you-and-youll-be-
good-with-it/#12b5813b57ef

Imagine instead of having your blood drawn, your doctor tells you that your symptoms will be evaluated
with a thorough, non-invasive sniffing. Sounds strange, sure, but the technology to identify what ails us
via smell is comingat least smell through amplifying tools, if not a regular human nose. Much can be
learned sniffing someones breath, for example, assuming the sniffer knows what its sniffing for. One
day before long, your doctor may examine you just like that. A team of researchers recently showed
impressive progress in that direction using a high-tech nose made of carbon nanotubes. The tiny
cylindrical carbon sheets, tipped with gold, were de-signed to sniff the breath of patients suffering from
an array of serious illnesses, including Parkin-sons, multiple sclerosis, hypertension and cancer. Unlike
a human nose, however, this electrode nose was outfitted with layers of organic film designed to detect
compounds associated with a range of diseases.

The team tested the nose on the breath of about 1,400 patients, each suffering from at least one of 17
illnesses. The results werent perfect. The nose had some trouble distinguishing between closely related
forms of cancer, although it still did better than chance. But it scored almost flawlessly in other cases
between less closely related diseases. Overall the success rate was 86%.

For an initial test, thats not bad at all. Unlike breath analyzers designed to find one disease (or, for that
matter, dogs trained to identify particular ailments), this one can potentially pick a needle from the
enormous haystack of things that infect our bodies. Analysis at that level would be a major leap forward
if it helps avoid blood tests and other invasive screenings. Were not close to being there just yet, but
with time and adjustment, disease sniffers may become a standard go-to in your family docs office.
Quoting the researchers from the study, This approach has the potential to support detection of many
diseases in a direct harmless way, which can reassure patients and prevent numerous unpleasant
investigations. And avoiding unpleasant investigations in a doctors office, I'm guessing you'll agree,
has a lot of upside.

High Anxiety Among Partners Of Young Breast Cancer Survivors, Study Finds
Elaine Schattner
http://www.forbes.com/sites/elaineschattner/2017/01/24/partners-of-young-breast-cancer-survivors-
suffer-from-high-anxiety-study-finds/#789c8241c6e6

25
Among partners of young women with breast cancer, anxiety is commonaffecting over 42% of survey
respondentsand may occur years after diagnosis. Thats according to a new study of partners of
women who received a breast cancer diagnosis before age 40. This report is one of the first to examine
the psychological and social issues affecting family members of people with cancer. Nancy Borstelmann
MPH, LICSW, directs the department of social work at Bostons Dana Farber Cancer Institute, will
present the findings this week at the 2017 Cancer Survivorship Symposium in San Diego.

"Breast cancer is one of the most common cancers in young women, Borstelmann said in a press
conference yesterday. This study supports that the long-term effects of a cancer diagnosis on pa-tients
families can be profound. Cancer doesnt just happen to one person; it has an impact on the entire
family, she stated. The researchers invited partners of women with breast cancer to respond to a one-
time survey about their lives, coping behavior, social support systems, financial stability, concerns about
their partnership and about parenting, anxiety and depression. Of 289 respondents, 284 were male. The
age range was 27 to 65 years; the median age was 43 years. Nearly 75% had children under the age of
18 years living in the home. Approximately half of the surveys were completed five years after the
partners breast cancer diagnosis.

The study is limited by its survey nature, and by its demographic narrowness: 93% or respondents were
white, according to the paper; 94% were working full-time, and 78% were college-educated. It did not
include partners of men with breast cancer, or breast cancer patients who were older than age 40 at
diagnosis. The researchers asked patients partners about what Borstelmann referred to as maladaptive
coping behaviors. Those would include withdrawing emotionally (from the relationship), drinking
more, blaming others for problems and behaving in an aggressive manner. Although the proportion of
patients partners who admitted negative coping strategies was not detailed, Borstelmann indicated that
these maladaptive behaviors were one of two factors associated with anxiety. Partners with maladaptive
coping strategies were more than twice as likely as those without to report anxiety, she indicated.

The other risk factor identified, based on correlations found in this study, is having a lower level of
education. But having less education may not be a true risk factor for anxiety, Borstelmann sug-gested in
discussion during the press meeting. It could be that lower education correlates with eco-nomic
problems, and so could be a surrogate marker for financial stress, which can cause anxiety. Also,
patients' partners with less education may be less likely to speak up and ask questions, or ask for support
if they need that, she considered.

Improved Semisynthetic Organism Created

Abby Olena January 23, 2017
The Scientist

26
 http://www.the-scientist.com/?articles.view/articleNo/48114/title/Improved-Semisynthetic-Organism-
Created/
In 2014, scientists generated a semisynthetic organism that harbored an unnatural base pair, ex-panding
its genetic alphabet from four letters to six. But the organism grew poorly and lost the un-natural base
pairs over time and under less-than-optimal conditions. Now, in a study published to-day (January 23) in
PNAS, the researchers have generated a healthier version of the semisynthetic organism that grows
robustly and retains the unnatural base pairs indefinitely.

See Augmenting the Genetic Alphabet

Pursuit of a grand challengehere, to create artificial life based on different molecular compo-nents
forces scientists across uncharted terrain where they must solve unscripted problems, Steven Benner of
the Foundation for Applied Molecular Evolution in Alachua, Florida, who did not participate in the
work, wrote in an email to The Scientist. This paper is an excellent example of what pursuits of that
grand challenge can do for you by way of discovery. What we did a couple of years ago is we threw
the switch, and the light bulb flashed on for a sec-ond, said coauthor Floyd Romesberg of the Scripps
Research Institute in La Jolla, California. It had never flashed on before and that was really exciting,
but then it went off. What weve done now is weve set up an organism that, when you turn the light
switch on, the light bulb goes on and stays on. As in their previous study, Romesberg and colleagues
worked with Escherichia coli, to which they added a transporter that moves unnatural triphosphates
which are broken down and incorporated into the DNAinto the cells. The researchers truncated the
transporter to make it less toxic, which led to better retention of the unnatural base pair. They also
improved retention by trading one of the bases in the unnatural base pair for a different one.

Despite these improvements, the semisynthetic organism still lost the unnatural base pair when it was
present in some sequence contexts and when the organism grew in certain culture conditions. To address
this problem, the researchers took advantage of the CRISPR system to immunize the semisynthetic
organism against the loss of the unnatural base pair, Romesberg explained. The team introduced
plasmids containing both the unnatural base pair and guide sequences that facilitate the plasmids
cleavage by endonuclease Cas9 should the unnatural base pair be lost. Using this system, they achieved
minimal loss of the unnatural base pair in all culture conditions and across the majority of sequence
contexts tested. The CRISPR-based strategy is really clever, said Nigel Richards of Cardiff University
in Wales and the Foundation for Applied Molecular Evolution, who also did not participate in the work.
Now the way forward is really to be able to control gene expression containing these unnatural bases
and to go to the next step which is to make the messenger RNA and then make proteins with new amino
acids using these base pairs, he added. Romesberg said the team is moving in that direction, and that
the potential applications of this strategy are vast. You could produce artificial proteins with unnatural
amino acids, he proposed. But the artificial proteins could be not just to prep, pull out the cell, and
purify as a drug, but to work within the cell to bestow it with new functions, he added. I think theyre
moving towards a place where we are able to ask questions that weve never asked before, said Eugene
Wu of the University of Richmond in Virginia, who did not participate in the study. There may be some
genetic questions and fundamental origin of life questions that an organism like this might help answer.

27
 No new antidepressants likely in next decade, say scientists
Sarah Boseley Health editor
Wednesday 11 January 2017 17.30 GMT
https://www.theguardian.com/science/2017/jan/11/no-new-antidepressants-likely-next-decade-say-
scientists
No new drugs for depression are likely in the next decade, even though those such as Prozac work for
little more than half of those treated and there have been concerns over their side-effects, say scientists.
Leading psychiatrists, some of whom have been involved in drug development, say criti-cism of the
antidepressants of the Prozac class, called the SSRIs (selective serotonin reuptake inhibitors), is partly
responsible for the pharmaceutical industrys reluctance to invest in new drugs even though demand is
steadily rising. But the main reason, said Guy Goodwin, professor of psychiatry at Oxford University, is
that the the NHS and healthcare providers in other countries do not want to pay the bill for new drugs
that will have to go through expensive trials. The antidepressants that GPs currently prescribe work for
only about 58% of people, but they are cheap because they are out of patent. We are not going to get
any more new drugs for depression in the next decade simply because the pharmaceutical industry is not
investing in research, said Goodwin. It cant make money on these drugs. It costs approximately $1bn
to do all the trials before you launch a new drug.There is also a failure of the science. It has to get more
understanding of how these things work before they can improve them.

Andrea Cipriani, an associate professor of psychiatry at Oxford who works on reviews of the evi-dence
of the effects of the drugs, said at a briefing in London that 58% of patients in clinical trials responded to
them, while 40% responded to a placebo. A review of the effects in children found that only one of the
SSRIs worked: fluoxetine, better known as Prozac. But, say the experts, the drugs help people cope with
the acute stage of depression, when they feel unable to carry out their daily activities. They help them
overcome their negative thoughts and give them a more positive outlook. Recovery, however, takes
much longer and involves counselling and other therapy.

Prescription rates have steadily climbed in spite of the limited efficacy and reports of side-effects
including suicidal thoughts in young people. The number of prescriptions for antidepressants has risen
quite dramatically since the 1990s, said Glyn Lewis, professor of psychiatric epidemiology at
University College London. The SSRIs were safer than previous antidepressants, so they began to be
prescribed in increasing numbers by GPs and the rate was now rising by 6-7% a year, he said. There
were 61m prescriptions a year in England last year, compared with 31m a decade earlier in 2005. The
bill was 285m in 2015. It was not about increasing numbers of people getting depressed, he said.
There is a slight increase in men and women of reports of depression, but thats not the explanation, he
said. The increase seems to be about people staying on them for longer. But it was still not entirely
clear whether there was over-prescription or under-prescription, he said.

Only about 20% of people reporting a lot of symptoms are taking antidepressants. Why not the other
80%? They might have tried them in the past and they didnt work or they had lots of symp-toms.
Lewis is now engaged in research to find out what is happening and potentially give guidance to GPs on
when to prescribe. Maintenance therapy staying on the drugs for nine months or even longer does

28
prevent relapses and is helpful, say the experts. But many people then found it hard to come off the
drugs, Lewis said. Counselling and in particular cognitive behaviour therapy have been shown to make
people well and are recommended by the National Institute for Health and Care Excellence, while
antidepressants are only recommended for moderate to severe cases of depression. There can be long
waits for treatment, however, which leads GPs to prescribe antidepressants and patients to take them to
alleviate the symptoms while they are waiting.

The Conversation Placebo

DANIELLE OFRIJAN. 19, 2017
https://www.nytimes.com/2017/01/19/opinion/sunday/the-conversation-placebo.html

In my daily work as a primary care internist, I see no letup from pain. Every single patient, it seems, has
an aching shoulder or a bum knee or a painful back. Our bodies evolved to live about 40 years, I
always explain, and then be finished off by a mammoth or a microbe. Thanks to a century of
staggering medical progress, we now live past 80, but evolution hasnt caught up; the cartilage in our
joints still wears down in our 40s, and we are more obese and more sedentary than we used to be, which
doesnt help. So its no surprise that chronic arthritis and back pain are the second and third most
common non-acute reasons that people go to the doctor and that pain costs America up to $635 billion
annually. The pain remedies developed by the pharmaceutical industry are only modestly effective, and
they have side effects that range from nausea and constipation to addiction and death.

Whats often overlooked is that the simple conversation between doctor and patient can be as potent an
analgesic as many treatments we prescribe. In 2014, researchers in Canada did an interesting study about
the role of communication in the treatment of chronic back pain. Half the patients in the study received
mild electrical stimulation from physical therapists, and half received sham stimulation (all the
equipment is set up, but the electrical current is never activated). Sham treatment placebo worked
reasonably well: These patients experienced a 25 percent reduction in their levels of pain. The patients
who got the real stimulation did even better, though; their pain levels decreased by 46 percent. So the
treatment itself does work.

Each of these groups was further divided in half. One half experienced only limited conversation from
the physical therapist. With the other half, the therapists asked open-ended questions and listened
attentively to the answers. They expressed empathy about the patients situation and offered words of
encouragement about getting better. Patients who underwent sham treatment but had therapists who
actively communicated reported a 55 percent decrease in their pain. This is a finding that should give all
medical professionals pause: Communication alone was more effective than treatment alone. The
patients who got electrical stimulation from engaged physical therapists were the clear winners, with a
77 percent reduction in pain. This type of study provides hard evidence for what shamans, witch doctors
and assorted mystics have known for millenniums: A substantial portion of healing comes from the
communication and connection with the patient. Before we had treatments that could actually counteract
the pathology of disease antibiotics, chemotherapy, stents, organ transplants, transfusions placebo
was the mainstay of medical care, and in many cases it was remarkably effective.

29
A good example is patients suffering from vague diffuse pains with no discernible cause. Frequently my
patients ask if a multivitamin will give them more energy. In the past I would say no, because there are
no significant scientific studies to demonstrate this, and also because in the absence of a vitamin
deficiency theres not much for a basic multivitamin pill to do. Now I take a different approach. I say
something along the lines of Many of my patients find that they have more energy when they take a
multivitamin. Im not lying, because many have indeed said so. Without fail, there are always a few
patients who come back at the next visit and swear they feel much better.

There are some who argue that it is unethical to promote placebos to patients. But increasingly, many
say it would be unethical not to give placebos a try in situations where patients are not getting relief
from traditional means (and where it would not cause harm or replace a necessary treatment). Its clear
that how doctors and nurses communicate their treatment can have profound effects on how patients
experience the results of that treatment. Yet the conversation between doctors and patients is one of the
least valued aspects of medical care. Insurance reimbursements for tests and medical procedures dwarf
reimbursements for talking to patients or spending time thinking about what ails them. And the
pharmaceutical industry, with its direct-to-consumer advertising, has promulgated the fallacy that every
ailment must be met with a pill brand name, of course.

As health care faces its latest overhaul, its crucial for the medical profession, as well as insurance
companies and decision makers in government, to recognize the power of the doctor-patient con-
versation. Its the most valuable diagnostic tool we have and can be remarkably effective as a treatment
tool as well. Training for doctors and other medical professionals should emphasize communication
skills with the same rigor that it does for other clinical skills. Call conversation a placebo if you like, but
if it helps without causing harm, then its legitimate medicine. Relieving suffering, after all, is what the
Hippocratic oath is all about. Danielle Ofri is an associate professor of medicine at N.Y.U., the editor in
chief of the Bellevue Literary Review and the author of the forthcoming What Patients Say; What
Doctors Hear, from which this essay was adapted.

We Will Miss Antibiotics When Theyre Gone

Nicholas Bagley And Kevin Outtersonjan.
https://www.nytimes.com/2017/01/18/opinion/how-to-avoid-a-post-antibiotic-world.html

On Friday, the Centers for Disease Control and Prevention released a disturbing report about the death
of an elderly woman in Washoe County, Nev. What killed her wasnt heart disease, cancer or pneumonia.
What killed her were bacteria that were resistant to every antibiotic doctors could throw at them. This
anonymous woman is only the latest casualty in a war against antibiotic-resistant bacteria a war that
we are losing. Although most bacteria die when they encounter an antibiotic, a few hardy bugs survive.
Through repeated exposure, those tough bacteria proliferate, spreading resistance genes through the
bacterial population. Thats the curse of antibiotics: The more theyre used, the worse they get,
especially when theyre used carelessly.

Already, more than 23,000 people in the United States are estimated to die every year from resis-tant
bacteria. That death toll will grow as microbes develop new mechanisms to defeat the drugs that, for

30
decades, have kept infections at bay. We are on the cusp of what the World Health Organization calls a
post-antibiotic era. And we will miss antibiotics when theyre gone. Minor scrapes and routine
infections could become life threatening. Common surgeries would start looking like Russian roulette.
Gonorrhea and other sexually transmitted infections might become untreatable. Diseases that our parents
defeated like tuberculosis could come roaring back. The economic costs would be staggering: In
September, the World Bank estimated that between 1.1 and 3.8 percent of the global economy will be
lost by 2050 if we fail to act. Yet few new antibiotics are in development. Most large drug companies
have fled the field. The reason is simple: To conserve their effectiveness, new antibiotics are put on the
shelf to be used only when older antibiotics stop working. That makes perfect sense for public health,
but companies cant make a profit on what they cant sell. This mismatch between the huge social value
of new antibiotics and the relative indifference of drug manufacturers could spell disaster.

Aware of the problem, Congress has taken some initial steps to address it. In particular, the 2012
Generating Antibiotic Incentives Now Act grants to manufacturers an extended, exclusive period to sell
newly approved antibiotics. By keeping generics off the market for longer, Congress hoped to sweeten
the pot for manufacturers and encourage needed research.

But the law probably wont stimulate much innovation. A couple more years of poor sales are a small
incentive and may actually promote overuse of antibiotics. The law is also poorly targeted. Some new
antibiotics are similar to existing compounds so similar that bacteria are already resistant to them. We
dont need to reward manufacturers for tweaking antibiotics that we already have. We need them to
develop entirely new antibiotics.

A few federal agencies have shown more initiative. Medicare, for example, has moved to require
hospitals and nursing homes to adopt plans to prevent the spread of drug-resistant infections and to
assure the proper use of antibiotics. The Centers for Disease Control and Prevention is taking steps to
limit the spread of resistant infections and to reduce unnecessary use of antibiotics. The Food and Drug
Administration has simplified approval standards and has worked with industry to limit the use of
antibiotics in livestock, which today accounts for three-quarters of antibiotic sales in the United States.
And the Biomedical Advanced Research and Development Authority has been working creatively to
build public-private partnerships to support the most promising research.

But Congress needs to think bigger if it wants to fix the broken antibiotic business model. Although the
patent system is good at producing new blood-pressure medications and cardiovascular drugs, its not
the right fit for antibiotics. Because new antibiotics may be held in reserve for years, manu-facturers
cant sell enough during the patent term to justify large research investments. Congress should instead
reward manufacturers that bring a targeted, highly innovative antibiotic to market with a substantial
financial prize; in exchange, manufacturers would surrender their patent.

This kind of market-entry reward would enable public health officials and physicians to deploy new
drugs precisely where theyre needed. Manufacturers would no longer have an incentive to milk their
patent, marketing the drug for inappropriate uses. The antibiotic could also be sold at a reasonable price
in developing countries, which might otherwise be unable to afford a patented antibiotic.

31
Financing market-entry rewards would be expensive, perhaps $4 billion per year in total, or about 10
percent of the annual global bill for antibiotics. But you cant defeat bacteria on the cheap. Theyve
survived for billions of years because theyre so good at adapting to new threats. Staying one step ahead
will require ingenuity, money and radical change. Tinkering around the margins isnt going to cut it.

The Fight Trump Faces Over Drug Prices

By KATIE THOMASJAN. 23, 2017
https://www.nytimes.com/2017/01/23/health/the-fight-trump-faces-over-drug-prices.html?_r=0

President Trump has made it clear that he thinks drug prices are too high and that the pharmaceutical
industry, as he put it at a news conference this month, is getting away with murder. He joins a host of
lawmakers and others who have excoriated drug makers in recent years for high-priced drugs that are
out of the reach of many Americans. On Monday, Sean Spicer, Mr. Trumps press secretary, reaffirmed
that the issue would be a priority. One of Mr. Trumps proposals to force drug makers to bid for the
right to sell their products to Medicare beneficiaries has repeatedly failed to attract enough support in
Congress, especially among his fellow Republicans. Pharma has a lot of lobbyists and a lot of power,
and there is very little bidding, Mr. Trump said at the news conference this month, in comments that
briefly sent pharmaceutical stocks tumbling. Were the largest buyer of drugs in the world, and yet we
dont bid properly, and were going to save billions of dollars.

Polls show that the public is in favor of doing away with a legislative provision that prohibits the federal
government from negotiating directly with pharmaceutical companies for drugs that are paid for by
Medicare, the government health care program for people who are over 65 or have disabilities.
Removing that prohibition is a favorite cause of liberal politicians like Senator Bernie Sanders of
Vermont, but it has been opposed by the pharmaceutical industry and Republicans, including
Representative Tom Price of Georgia, the nominee for secretary of health and human services. Mr. Price
declined to say at a confirmation hearing last Wednesday whether he supported Mr. Trumps position,
and Democratic senators are likely to question him again on the issue when he appears before the Senate
Finance Committee for another hearing on Tuesday. Whether freeing the government to negotiate on
drug prices would lower costs, however, is any-thing but clear. And its chances of passing a Republican-
led Congress are even less so.

32
Why cant the government haggle with drug companies?

Medicare did not cover prescription drugs until 2006, after Congress expanded the program to add a
drug benefit, known as Part D. But the measure included something called the noninterference clause,
which was backed by the pharmaceutical industry and prevented the federal government from
negotiating directly with drug makers.

This prohibition does not mean that pharmaceutical companies can set any price they want. Pri-vately
run prescription drug programs, which control the benefits for large groups of Medicare beneficiaries,
negotiate on the governments behalf. These programs are run by the same companies including
Express Scripts, CVS and UnitedHealth that manage the drug plans for large employers and insurers.

What is the argument for removing this clause?

Those who favor letting the federal government negotiate directly on drug prices argue that other
countries, including Canada and Britain, already have that leverage with many multinational drug
corporations. Their government-run health programs are the only game in town and hold significant
power in setting drug prices. Supporters say that if the United States government were allowed to
negotiate drug prices for all 41 million Medicare beneficiaries enrolled in drug coverage, it would lead
to lower prices across the health care market.

The pharmaceutical industry and Republicans have long opposed such a change, however, saying that
significantly cutting payments to drug makers would stifle innovation and prevent them from investing
in new lifesaving drugs.

Would negotiating Medicares drug prices actually lower costs?

Many health care experts are skeptical that a repeal of the negotiating ban would have much im-pact,
and certainly not the billions of dollars in reductions that Mr. Trump recently promised. The
nonpartisan Congressional Budget Office has concluded more than once that a repeal would result in
only modest savings, in part because private drug plans are already negotiating on the governments
behalf, albeit for smaller pools of beneficiaries.

And even if the ban were repealed, another provision would stand in the way. Under Medicare, the
government must cover all drugs in six protected classes: broad and often expensive treatment areas
for patients with conditions such as cancer, depression, epilepsy and H.I.V.

The Veterans Health Administration and the Defense Department are able to negotiate lower prices in
part by covering fewer drugs and pitting drug companies against one another.

Well

Get the best of Well, with the latest on health, fitness and nutrition, plus exclusive commentary by Tara
Parker-Pope, delivered to your inbox every week. Receive occasional updates and special offers for The
New York Times's products and services. You get your largest negotiating power from your ability to

33
walk away, said Dr. Aaron S. Kessel-heim, an associate professor at Harvard Medical School who has
written frequently on drug prices.

Even if Medicare were to remove those protections and agree to cover fewer drugs a politically
unpopular move that has failed in the past drug companies might find ways to make up the financial
losses, said Dan Mendelson, president of Avalere Health, a consulting firm that works for drug
companies, hospitals, insurers and others. Todays most expensive drugs typically treat rare conditions,
like cystic fibrosis and certain types of cancer, for which there are few options. In those cases, drug
companies hold the bargaining power, no matter who is on the other side of the table.

I worry that if you force one price across the market, you may well end up with a higher price in
noncompetitive categories than you would otherwise, Mr. Mendelson said.

And even if the negotiating ban were lifted, the United States would still not have the same clout as, say,
Britain, whose universal health care coverage makes the government the countrys only buyer of drugs.

Some worry that if the United States government were to significantly lower drug prices for Medi-care
beneficiaries, pharmaceutical companies would respond by raising prices for the millions of people
insured through large employers or private insurers. Others contend that if the prices negotiated by
Medicare were public, the transparency could level the playing field and lower prices across the board.

What has Mr. Trumps position been on drug prices?

During the campaign, Mr. Trump joined his Democratic opponents, Mr. Sanders and Hillary Clinton, in
calling for the federal government to be allowed to negotiate the price of drugs.

After his election, the drug industry exhaled when the health care section of his transition website
included more traditional Republican (and industry-friendly) priorities and did not mention the
negotiation provision.

In December, Mr. Trump pledged in an interview with Time magazine to bring down drug prices, and
this month, he promised to create new bidding procedures but did not offer specific details.

Will such a proposal ever clear Congress?

It seems unlikely, given that Republicans control both the House of Representatives and the Senate.Its
been a nonstarter with Republicans, and its the traditionally Democratic talking point, said Alana
Dovner, a research analyst at Beacon Policy Advisors, which advises investors on develop-ments in
Washington. Something as dramatic as allowing Medicare to negotiate drug prices that would be
such a radical change, and so opposite the traditional Republican health care policies, that it just seems
unfathomable at this point.

Mr. Price opposed a Democratic-led measure in 2007, calling it a solution in search of a problem.

Ms. Dovner and others said that even Democrats were unlikely to support a measure that would allow
Medicare to stop covering drugs in protected areas like cancer. A limited effort to do that in 2014 failed

34
amid bipartisan criticism. You are by definition saying yes to some drugs and no to others, Mr.
Mendelson said. He called that position politically dangerous, saying it would be denounced as
government practice of medi-cine.

FDA Approves Xyrem (sodium oxybate) Oral Solution Generic with a REMS Program
January 18, 2017
https://www.fda.gov/Drugs/DrugSafety/ucm537281.htm

The FDA has approved the first generic version of Xyrem (sodium oxybate) Oral Solution, to treat
cataplexy and excessive daytime sleepiness in patients with narcolepsy, which is a potentially
debilitating disease. Cataplexy is a primary symptom of narcolepsy where patients suddenly lose muscle
tone, including voluntary muscle control, while awake. Muscle weakness or paralysis associated with
cataplexy may cause a person to collapse. Approximately 70 percent of people with narcolepsy have
cataplexy. Sodium oxybate is the only medication approved to treat cataplexy in patients with
narcolepsy.

The use of Xyrem has been associated with serious side effects including seizures, trouble breathing,
changes in alertness, coma, and death. Additionally, the active ingredient in Xyrem (and in the newly
approved generic) is sodium oxybate. Sodium oxybate is the sodium salt of gamma hydroxybutyrate
(GHB). GHB has not been approved for any medical use and has the potential for abuse, such as in cases
of sexual assault. Because of the potential risks associated with Xyrem, it is subject to strict safety
controls on prescribing and dispensing under a program called a Risk Evaluation and Mitigation
Strategy (REMS). FDAs approval of generic sodium oxybate is subject to a REMS with strict safety
controls that are comparable to those currently required for Xyrem.

Specifically, under both the Xyrem REMS and the generic sodium oxybate REMS, sodium oxybate can
be prescribed only by a certified prescriber, and dispensed only to an enrolled patient by a certified
pharmacy. Only a certified pharmacy that ships directly to patients can dispense sodium oxybate.
Sodium oxybate will not be available in retail pharmacies. In approving this generic version of Xyrem,
the FDA is maintaining strict safety requirements for sodium oxybate, while providing patients with
access to a generic medication option for narcolepsy.

FDA Approves Trulance (plecanatide) for Chronic Idiopathic Constipation

https://www.drugs.com/newdrugs/fda-approves-trulance-plecanatide-chronic-idiopathic-constipation-
4474.html

January 19, 2017 -- The U.S. Food and Drug Administration today approved Trulance (plecanatide) for
the treatment of Chronic Idiopathic Constipation (CIC) in adult patients. No one medication works for
all patients suffering from chronic gastrointestinal disorders, said Julie Beitz, M.D., direc-tor of the
Office of Drug Evaluation III in the FDAs Center for Drug Evaluation and Research. With the
availability of new therapies, patients and their doctors can select the most appropriate treat-ment for
their condition. According to the National Institutes of Health, an estimated 42 million people are

35
affected by constipation. Chronic idiopathic constipation is a diagnosis given to those who experience
persistent constipation and for whom there is no structural or biochemical explanation. Trulance, taken
orally once daily, works locally in the upper GI tract to stimulate secretion of intesti-nal fluid and
support regular bowel function.

The safety and efficacy of Trulance were established in two 12-week, placebo-controlled trials in-
cluding 1,775 adult participants. Participants were randomly assigned to receive a placebo or Tru-lance,
once daily. Participants in the trials were required to have been diagnosed with constipation at least six
months prior to the study onset and to have less than three defecations per week in the previous three
months, as well as other symptoms associated with constipation. Participants receiving Trulance were
more likely to experience improvement in the frequency of complete spontaneous bowel movements
than those receiving placebo, and also had improvements in stool frequency and consistency and
straining. Trulance should not be used in children less than six years of age due to the risk of serious
dehydration. Trulance should be avoided in patients six years of age to 18 years of age. The safety and
effectiveness of Trulance have not been established in patients less than 18 years of age. Trulance should
not be used in patients with known or suspected mechanical gastrointestinal obstruction.

The most common and serious side effects of Trulance was diarrhea. Patients may experience severe
diarrhea. If severe diarrhea occurs, patients should stop taking Trulance and contact their health care
provider. Trulance is manufactured by New York, New York-based Synergy Pharmaceuticals Inc.

Pharmaceutical sector: 4-5 per cent drugs substandard, need concerted effort and stern action
Deepak Patel
http://indianexpress.com/article/business/business-others/pharmaceutical-sector-4-5-per-cent-drugs-
substandard-need-concerted-effort-and-stern-action-4456296/

Three to five per cent of the drugs in the Indian market are still substandard and the central drug
regulator and state regulators would require to put in concerted effort and take stern actions to deal
with it, stated G N Singh, Drug Controller General of India (DCGI), in his letter to all state drug
regulators on December 30. Although the menace of spurious drugs has reduced over the years, the
percentage of Not of Standard Quality drugs reported in the country are still hovering around 4-5 per
centTherefore, I solicit your sincere cooperation for making a concerted effort to reduce to a great
extent the occurrence of substandard and spurious drugs even if it requires stern actions G N Singh
noted.
India has 36 drug regulators. Each of them keep testing the drugs on various quality parameters.

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Issues related to quality/safety of drugs and pharmaceuticals manufactured, distributed and con-sumed
require to be resolved as a whole. Drugs comprise of a major portion of health budget and we cannot
compromise on the quality of our health service owing to the questionable standards of quality and
safety of drugs which may otherwise lead to failure in our health programmes, wasteful expenses and
loss of income and productivity, Singh mentioned in his letter.

According to a November 28 report of The Indian Express, in a major crackdown since March this year,
the drug regulators of seven states found that 27 medicines sold by 18 major drug compa-nies in
India were of substandard quality, citing grounds such as false labelling, wrong quantity of
ingredients, discolouration, moisture formation, failing dissolution test and failing disintegration test. Of
the 18 companies, only two said they had stopped sale of the affected drug batches and just one said the
affected batch had been recalled. The tests on the 27 medicines were done by regulators of Maharashtra,
Karnataka, West Bengal, Goa, Gujarat, Kerala and Andhra. Wishing the state regulators a happy new
year, Singh stated in his letter: As we have the prime objective to ensure the safety, quality and efficacy
of drugs, we cannot lag behind in such issues and cannot hurt the expectations of our society and global
community. Understanding the seriousness of the situation, the government is currently planning to
amend the Drug and Cosmetics Rules, 1945, in order to create an effective recall system for the drugs
that are found to be substandard by any drug regulator in the country. At present, neither there is a
nation-wide drug recall system in the country nor are there any rules mandating the companies to
withdraw substandard drug batches from the market.

Save Health Sector From Collapse, Experts Urge FG

http://www.pharmanewsonline.com/save-health-sector-from-collapse-experts-urge-fg/

In line with the World Health Organisation (WHO)s recommendation that every country allocates at
least 15 per cent of its annual budget to healthcare, as well as making health insurance compulsory for
all its citizens, some experts in the health sector have described the 3.6 per cent allocation to healthcare
in the last national budget as not just ridiculously low but totally unacceptable. The disclosure was one
of the submissions made at the 12th Annual General Meeting and Scientific Conference of the
Healthcare Providers Association of Nigeria (HCPAN) held recently at NECA House, Ikeja, Lagos.
Speaking at the event, Dr (Chief) Adeyeye Jimi Arigbabuwo, former national vice president of HCPAN,
decried the way federal governments handling of health sector in 2016, stressing that if care is not
taken, the presently ailing sector may eventually collapse. Our health sector is struggling. What we are

37
trying to do is to make sure we call for rescue, and in calling for rescue, all of us must form the rescue
team and we must learn to tell each other the truth, he said. He further emphasised the need for
immediate implementation of the National Health Act, which according to him, had been left
unimplemented since 2014.

In his words: I want to tell you that by not implementing that law, every health facility you see around
today is illegal because the law states that after two years (and that was since 2014), if cer-tain things are
not met, it is as good as if we are operating an illegal healthcare delivery system. So the number one
thing to do now is to implement the Act.

He added that government needs to urgently address the issue of scarcity of healthcare workers and
maldistribution of the few available ones. According to him, out of the estimated 40,000 doctors that the
country currently has, more than 70 per cent of them are serving in urban areas, leaving the remaining
30 per cent to serve the rural population which he said constitute the bulk of the population. So, apart
from scarcity, we have to look at human resource in the health sector and ensure that there is proper
distribution, Arigbabuwo said.

Speaking in the same vein, Dr Umar Oluwole Sanda, HCPAN president, stated that the healthcare sector
did poorly in 2016, as the budget allocated to it was clearly inadequate, adding that the fed-eral
government must increase its budgetary allocation to the sector so that it doesnt end worse in 2017.
There is need for government to show more interest in health insurance, as many Nigerians cannot
afford the bills of hospitals, Sanda said. In most healthcare facilities in the country, it is quite difficult
to access healthcare services because of the cost; so it is important that the government invest in the
future of health insurance, especially in a recession period like this. Speaking further, Dr Sanda noted
that one of the challenges facing the association is the issue of capitation being paid to health workers by
the National Health Insurance Scheme (NHIS), stressing that the money is too meagre to meet the needs
of the workers. He also stated that the best way to ensure quality health care delivery for Nigerians at all
times is to encourage them to invest in health insurance as they wouldnt need to pay out-of-pocket.

Since many citizens find it difficult to even purchase simple malaria drugs and pay their hospital bills
especially with the increased price of majority of health products due to the ongoing recession, HCPAN,
a private elementary association of various health professionals including medical doctors, nurses,
pharmacists and laboratory scientists, has decided to partner with the government and the public sector
to relieve Nigerians of financial burden while receiving quality health treatment, Sanda said. In their
own submissions, the duo of Dr (Mrs) Adenike Olaniba, a public health consultant and im-mediate past
president, HCPAN; and Dr Kalada Richard, registrar and chief executive officer of Institute for
Healthcare Financial Management, disclosed that health insurance in Nigeria has had very little impact
since its debut in 2005, as it has only been able to capture about five percent of the population.

According to Olaniba, until the NHIS is able to capture the remaining 95 per cent of the population who
are yet to be covered by the scheme, the impact of the scheme will continue to remain limited. Other
dignitaries at the event were Pharm. Olumide Akintayo, immediate past president, Pharma-ceutical
Society of Nigeria (PSN), who was the chairman of the event; Dr Kalada Richard, keynote speaker;
Pharm. Madehin Gafar, chairman, Organising Committee and national secretary, HCPAN; Pharm.

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Anthony Oyawole, vice-president, pharmacy, HCPAN; Dr Priscilia Imade; and Mr Igwe Aku-jobi,
among others.

Two new drug therapies might cure every form of tuberculosis

Andy Coghlan
Daily News, 15 February 2017
https://www.newscientist.com/article/2121354-two-new-drug-therapies-might-cure-every-form-of-
tuberculosis/
Tuberculosis, the worlds leading infectious killer, may have finally met its match. Two new drug
therapies may be able to cure all forms of tuberculosis even the ones most difficult to treat. We will
have something to offer every single patient, says Mel Spigelman, president of the TB Alliance, the
organisation coordinating trials of the two treatments. We are on the brink of turning TB around. It
presently takes six months of drug treatment to cure ordinary TB, and two years to cure people whose
infections are resistant to drugs. People may need to take up to 20 tablets a day, plus injections.
Together, the new treatments, called BPaMZ and BPaL, could make treating TB much simpler and more
effective. BPaMZ involves taking four drugs once a day. Trials carried out in 240 people across 10
countries in Africa suggest that it cures almost all cases of ordinary TB in four months, and most people
with drug-resistant TB in about six months. In the majority of cases, the TB bacterium had disappeared
from sputum within two months. The alliance has never before seen such rapid action against TB
bacteria, says Spigelman.

Meanwhile, BPaL, a therapy that involves taking three drugs once a day, has so far cured 40 of 69
patients with extremely-drug-resistant TB the most difficult form to treat. Whats more, it achieved
this within six months. The 29 remaining participants in this trial are still to be assessed. The TB
Alliance says that BPaMZ has the potential to treat 99 per cent of people who catch TB each year, while
BPaL could treat the remainder. Researchers presented results from both sets of trials at the Conference
on Retroviruses and Opportunistic Infections in Seattle this week.

Caution needed

The arrival of new drugs is long-awaited, says Spigelman, because the existing treatment for TB is now
50 years old. According to the latest figures from the World Health Organization, there were 10.4
million new cases of TB in 2015, but only 20 per cent of those with resistant TB were treated, and of
those only half were cured. Once mass produced, BPaMZ could cost just a tenth of the $3000 it now
costs to treat drug-resistant TB. Spigelman cautions, however, that larger trials are needed to confirm the
effectiveness of both therapies and for them to be approved for global use. At best, this would take at
least three years for BPaMZ, he says, although the therapy for extremely-drug-resistant TB may be
available sooner. The results are exciting and encouraging, but we must be cautious saying we can treat
everyone with these regimes, says David Moore at the London School of Hygiene and Tropical
Medicine. These are only preliminary data, so theres a danger of jumping the gun.

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