DRUG DISCOVERY AND DEVELOPMENT IN USA US Food and Drug Administration (USFDA): FDAisan agency;within the US department of health and human services (HHS), the FDA is responsible for protecting the public health by make sure that human and veterinary drugs, vaccines, and biological products, medical devices, cosmetics, and dietary supplements are sae, effective and secure. Types of applications (FDA): 4. IND (investigational New Drug Application): IND application isthe application submitted to FDA before starting a clinical trial. This applications a proposal to study unapproved drug in humans. 2. NDA (New Drug Application): 22 Months ‘NDAs the application submitted to FDA after Phase 3 by a company, i they believe that the drug have enough evidence on the drug safety and efficacy for approval 3. ANDA (Abbreviated New Drug application): 12 Months ‘This ANDA contains data which is submitted to FDA forthe review and potential approval of a genetic drug product. ‘These generics, o not require clinica rials, they just ned to prove with a bioequivalence study to show that it acts similar Te the innovator drug ‘What are generics : Generics are copies of synthetic drugs (small molecules) 4, BLA (Biological License application}: 12 Months This is the application submitted to FDA for biological products. BLA is a submission that contains specific information on the manufacturing processes, chemistry, Pharmacology, and the medical effects of the biological product What are Bio-similars: Bio-similars are generics for biologics, they are not actualy similar to otiginator drug but are bioequivalent. FDA Advisory Committee (adcom committee): FDA sometimes takes advice from the FDA advisory committee to make decisions on approval of drugs in difficult situations. Based on this committee voting, FDA will decide whether to approve the drug or not. CCDER (Center for Drug Evaluation and Research): ‘CDER reviews and act on NDA submissions for 10months (standard timeline), and once review completed COER issues one of three types of letters to the drug sponsors ————eerrr 1. Approved letter: tis states that the drug is approved ‘After approval company will launch the approved drug in the market. it depends on the company ility/ and on company infrastructure to launch the products. For big pharma companies like AstraZeneca, Pfizer etc, willlaunch immediately within two months. Small companies som idsues Ta Taunching due to financial issues and need some other company collaboré Scanned with CamScannerCRL{Complete Response Letter): This states the drug can be approved later, once the drug ‘sponsors fulfil the additional requirements suggested by FDA CDER Ia company gets CRL (Complete Response Lette) from the FDA during the NDA review process, then the approval of the drug will be extended to 6 months or more depending on the FDA requirements FDA decides whether to approve a drug of nat even after the submission of CRL responses by the companies 4 InCRLFDA will ask for additional efficacy datg or 4 Additional clinical trial is required or Data related to manufacturing issues or process is needed 3. Non-approvable letter: this states that the drug cannot be approved or rejected Scanned with CamScanner‘DRUG DEVELOPMENT PROCESS AND FDA APPROVAL 1. Pre-clinical studies: {isa study to test a drug, or procedure or medical treatment in animals. These studies evaluate the safety of the drug Once the drug shows positive results (efficacy in Pre-tnical then the company (sponsor) submits IND to FDA to initiate clinical trials 2. Clinical trials Clinical trials are research investiga n which human volunteers are used to test new \reatments to prévent, detect, treat or manage various diseases pr medical condition Phase : +. 2010 100 healthy volunteers are considered. For some cases such as oncology, instead of healthy volunteers, patients are considered + Lenath ofthe study is from few months to.one year > + Purpose of the study: PK and PD studies + Approximately 70% of drugs move to next Phase Phase 2: ‘+ Upto several hundred,people with disease condition are considered ‘+ Length of the study i from several months to 2 years ++ Purpose of the study: Dosage evaluation, drug efficacy in larger population than Phase 4, evaluate adverse events + Approximately 33% of drugs move to next Phase > Phase 3: +. 300 t0 3,000 disease population are considered + Length of the study is from 1 year to. years 5 +. Purpose ofthe study: Monitoring efficacy ofthe drug and its adverse events in large population ~~ st Approximately 25-30% of drugs move to next Phase > Phase & s+ These studies are called as post-market surveillance studies. + These studies gather addtional information about the safety of dr, efficacy and ‘optimal care Scanned with CamScanneree] —_t pune t qenondde 340) t WiBs/VONS/VIA/VON ] easeud zee | Taseyd t t J ot got oe [eu <— [eaqwp-a4d <—serpmis oxr-u «—sajnoajow Burzyeuls «— sPea1 ont Scanned with CamScannerFile TIMELINES FOR APPROVAL OF NEW DRUG Case-4 (NDA filing date is available then drug approval will be 12 months) Hf regulatory filing information is available [NDA (New Drug Application) submitted to FOA’s Center for Drug Evaluat bo ‘After submission of NDA to CDER. it will takes 60 days (2 months) for ‘Accepting or rejecting the submitted NDA application + It eDA’s CDER accepts the NDA application then i takes 10 months for drug approval, sometimes FDA will give PDFUA (Prescription Drug User Fee Act) action date for the NDA application jon and Research For US: (2+10) 12 months fr the approval of the drug from the date of NDA submission to FDA For EU: 15 months forthe approval ofthe drug from the date of MAA (Marketing Authorization Application) ‘submitted to EMA (European Medicines Agency) —— European Medicines Age PDUFA date: (Prescription Drug User Fee Act) “& PDUFA dates are deadlines for the FDA to review new drugs L pOFUA date isthe day when FDA takes its final decision on approval ofthe new drug final decision on approval of the P GDUFA date: (Generic Drug User Fee Act) “k. GDFUA date isthe day when FDA takes its final decision on approval ofthe generic deve he generic dv ase-ll (No NDA filing date, pivotal trial data release date avallable, drug approval will be 6#12=18months) IENDA fling date is not available, then considered available pivotal trial data release date data it takes 6 months and NDA submitted to FDA FDA standard approval 12 months For the compilation of pivotal Note: final, if pivotal trial data release date information is available, then the timeline ine for FDA approval of anew drug is 18 months (6+12) Scanned with CamScannerCase-ill (No NDA filing date and no pivotal trial data release date, PCD date is available, drug approval will be 346+12=21months) VENDA filing date and pivotal trial data release date are not available, then consid date) of the clinical trial (pivotal trial) | Pivotal trial data analysis will ake 3 months from the PCD fet PCD (primary completion For the compiation of pivotal trial data it takes 6 months and NDA submitted to FDA | FDA standard approval 12 months information is available, then the timeline line for FDA approval Note: So finally, if pivotal trial data release dat fof a new drug is 21 months (3+6+12) Scanned with CamScanner