NDA AND ANDA

NEW DRUG APPLICATION AND ABBREVIATED NEW DRUG APPLICATION

1. NDA AND ANDA PRESENTED BY , ANU TREESA THOMAS 1 ST MPHARM ST J0SEPH COLLEGE OF PHARMACY 1

2. CONTENTS Introduction NDA NDA classifications NDA contents Steps involved in NDA ANDA NDA vs ANDA review process ANDA steps Conclusion References 2

3. INTRODUCTION When the sponsor of a new drug believes that enough evidence on the drug’s safety and effectiveness has been obtained to meet FDA requirement ,then they submit a new drug application. Abbreviated new drug application contains data that when submitted to FDA ,provides for the review and ultimate approval of a generic drug product. 3

4. NDA(NEW DRUG APPLICATION ) It is the vehicle through which the drug sponsors formally propose FDA or DCGI to approve a new investigational drug for sale and marketing after phase 3 pivot trials. The official definition of New Drug is in Sec 201(p) of Federal Drug,Food and Cosmetics Act; Any new drug, the composition of which is such that it is not recognized among experts qualified by scientific training as safe and effective for use under prescribed,recommended or suggested conditions. 4

5. It is the critical component for drug approval process which is required to submit to USFDA before drug commercialization. The data gathered during the animal studies and human clinical trials of an Investigational New Drug (IND) become part of NDA. GOAL The NDA provide enough information to permit FDA reviewer to reach safety ,efficacy and quality for pharmaceutical production. 5

6. NDA CLASSIFICATIONS New molecular entity. New salt of previously approved drug. New formulation of previously approved drug.(not a new salt OR a new molecular entity) New combination of two or more drugs. Already marketed drug product – Duplication(i.e.,new manufacturer) New indication(claim) for already marketed drug(includes switch in marketing status from prescription to OTC) Already marketed drug product- No previously approved NDA. 6

7. NDA CONTENTS Section 1: Overall NDA index The NDA index is a comprehensive table of contents that enables the reviewers to find specific information in this massive document quickly. Section 2 : Labelling It must include all draft labelling that is intended for use on the product container ,cartons or packages ,including the proposed package inserts. 7

8. Section 3 : Application summary Proposed annotated package insert. Pharmacology class , scientific rational , intended use , and potential clinical benefits. Foreign marketing history. Chemistry , manufacturing and control summary. Nonclinical pharmacology and toxicology summary. Human pharmacokinetics and bioavailability summary. 8

9. Section 4 :Chemistry , manufacturing and controls Chemistry , manufacturing and control information Samples Methods validation package Section 5: Non clinical pharmacology and toxicology Provide individual study reports , including pharmacology , toxicology , ADME studies. Interactions with other drugs. Effects related to the therapeutic indication ,such as the pharmacodynamic ED50 in dose- ranging studies and the mechanism of action. 9

10. Section 6:Human pharmacokinetics and bioavailability Includes data from Phase 1 safety and tolerance studies in healthy volunteers. Summary of analytical method used in invivo biopharmaceutics study. Pilot or background studies. Bioavailability or bioequivalence studies. 10

11. Section 7 :Microbiology Requires the following technical information and data, A complete description of the biochemical basis of the drug action on microbial physiology. The drugs antimicrobial spectrum. Clinical microbiology laboratory methods. 11

12. Section 8:Clinical data Includes, List of investigators and list of IND and NDAs Background or overview of clinical investigations Clinical pharmacology Controlled clinical trials Integrated summary of effectiveness data Integrated summary of safety information 12

13. Section 9:Safety data Statements In draft labelling. Contraindications Warnings Precautions Adverse events Section 10: Statistical data All controlled clinical trial reports Integrated efficiency and safety reports Integrated summary of risks and benefits 13

14. Section 11 :Case report tabulations Section 12 :Case report forms Patent information Patent certification Other information 14

15. STEPS INVOLVED IN NDA Receipt of NDA application CDER stamps the application with a receipt date FDA assigns the application for review If the application is incomplete , then FDA has to inform to the applicant 15

16. If complete sends it for secondary review process FDA inspects manufacturing facilities of the drug Once all reviews are complete , the Divisional Director evaluates the reviews and make FDA’s decision. 16

17. ANDA An abbreviated new drug application contains data which is submitted to FDA for the review and the potential approval of drug product. Once approved , an applicant may manufacture and market the generic drug product to provide a safe , effective , lower cost alternative to the brand name drug it references. It termed abbreviated because they generally not required to include preclinical & clinical data to establish safety and effectiveness. 17

18. Generic applicants must scientifically demonstrate that their product performs in the same manner as the innovator drug by measuring the time it takes to reach in the bloodstream in healthy volunteers. This demonstration of “bioequivalence” gives the rate of absorption or bioavailability of the generic drug which can be then compared to the innovator drug. 18

19. Basic generic drug requirements are: Same active ingredients Same route of administration Same dosage form Same strength Same conditions of use Inactive ingredients already approved in a similar NDA. GOALS To reduce the price of drug. To reduce the development time. Increase the bioavailability of drug in comparison to reference list drug. 19

20. NDA vs. ANDA review process NDA requirement Labelling Pharmacology &Toxicology Chemistry Manufacturing Controls Microbiology Inspection Testing Animal studies Human studies Bioavailability ANDA requirement Labelling Pharmacology &Toxicology Chemistry Manufacturing Controls Microbiology Inspection Testing Bioequivalence 20

21. ANDA STEPS Filling review Co ordination of generic drug review process Bioequivalence review process Chemistry review process Labelling review process Putting it all together 21

22. Filling review The process begins when as applicant submits an ANDA to the OGD(Office of Generic Drugs) The staff assigns it an ANDA number and stamps a received date on the cover letter of ANDA. It is sent to a consumer safety technician who reviews the preliminary sections of ANDA checklist. 22

23. Within first 60 days of submission, filling review is completed. Regulatory Support Branch (RBS)is responsible for this process. RPM compares the contents of each section against a list of regulatory requirements. If the application contains all An applicant may not necessary regulatory receive letter when an inactive requirements ,an ingredient level exceeds the ‘acknowledgment’ letter is level previously used in an Issued to the applicant indicating approved drug product via the Its acceptance for filling. same route of administration. 23

24. Upon filling an ANDA , the RPM (Review Process Manager) forwads An Establishment Evaluation Request (EER) to the office of compliance. 24

25. Co ordination of the generic drug review process The application enters the review queue,means that the application is assigned to a bioequivalence reviewer , a chemist and a labelling reviewer. The chemistry project manager serves as the “Applicant “ project manager(APM). They plan , organize and co ordinate all review activities for the applicaions they manage. 25

26. Bioequivalence review Bioequivalence review process established that the proposed generic drug is bioequivalent to the reference listed drug, based upon a demonstration that both the rate & extent of absorption of the active ingredient of the generic drug fall within established parameters when compared to that of the reference listed drug. Chemistry/Microbiology review This process provides assurance that the generic drug will be manufactured in a reproducible manner. 26

27. Labelling review This process ensures that the proposed generic drug labelling is identical to that of the reference listed drug. Putting it all together After the final review and individual disciplines have resolved their deficiencies ,the application will either receive a full approval or a tentative letter. 27

28. DIFFERENCES NDA ANDA Applicable for new drug Applicable for generic drug Take longer time (12 – 15 years) Compare to NDA less time is taken(1- 2 years) More expenditure of money Comparatively less Cost of drugs are more Cost of drugs are less Nonclinical studies and clinical investigations are essential Nonclinical studies and clinical investigations are nonessential except bioavailability and bioequivalence 28

29. CONCLUSION NDA is applicable for a new drug whereas ANDA is for a generic drug This is a necessary procedure before the marketing of a drug product. Bioequivalence is measured in case of ANDA whereas clinical trials are necessary in NDA. 29

30. REFERENCES J.P.Douglas,S.M,David.FDA regulatory affairs,A guide for prescription drugs,medical devices and biologics.2 nd edition.Marcel Dekker,inc.p.69-108. V.A.Loyd,G.P.Nicholas,C .Howard.Ansel’s pharmaceutical dosage forms and delivery systems.8 th edition.Bpublication.p.25-65. 30

31. THANK YOU… 31