New drug application
- 1. LAB PRESENTATION NEW DRUG APPLICATION Presented by Vineeth Kumar Ekbote M.Pharm. (Ist semester) Dept. Of Pharmaceutical Technology (Formulations) NIPER, S.A.S. Nagar, Punjab. 1
- 2. Flow of Presentation • What is NDA • Goals of NDA • When will we go for NDA • NDA Forms • Contents of NDA • Guidance document for submission of NDA • Submission of NDA • Review & Approval of NDA 2
- 3. New Drug Application Since 1938, every new drug has been the subject of an approved NDA before U.S. commercialization The NDA application is the vehicle through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing in the U.S. The data gathered during the animal studies and human clinical trials of an Investigational New Drug (IND) become part of the NDA 3
- 4. Goals of NDA • Safety and Effectiveness of a new drug in its proposed use(s) • Whether the drug's proposed labeling (package insert) is appropriate • Methods used in manufacturing the drug and the controls used to maintain the drug's quality are adequate to preserve the drug's identity, strength, quality, and purity • The benefits of the drug outweigh the risks 4
- 5. NDA Pre Clinical Clinical studies Filling studies I Phase-I Phase-II Phase-III Animal N testing of a D New drug Safety F i Effective R l ness E Approval l V i More Info. I n E Short term g W Disapproval Long term 5
- 6. NDA Forms & Electronic Submissions • Form FDA- 356h. Application to market a New drug, biologic or an antibiotic drug for human use • Form FDA- 3397. User fee cover sheet • Form FDA- 3331. New drug application field report • Guidance documents for electronic submissions 6
- 7. • Submit information regarding distributed Drug products an articles to FDA, Which contains (i) Any incident that causes the drug product or it’s labeling to be mistaken for another article (ii) Any bacteriological content/ chem. and physical detritioration/ failure to meet the specification 7
- 8. • The NDA may have as many as 20 different sections in addition to the Form FDA-356h itself • The specific contents of the NDA will depend on the Nature of the drug product and the information available at the time of submission the application • Form FDA-356h serves as Checklist as well as Certification that, the sponsor agrees to comply with a range of legal and regulatory requirements 8
- 9. Contd… NDA Section 1 Index NDA Section 2 Labeling NDA Section 3 Application summary NDA Section 4 Chemistry, Manufacturing, and Controls (CMC) NDA Section 5 Nonclinical pharmacology and toxicology 9
- 10. Contd… NDA Section 6 Human pharmacokinetics and bioavailability NDA Section 7 Clinical microbiology NDA Section 8 Clinical data NDA Section 9 Safety update reports NDA Section 10 Statistics 10
- 11. Contd… NDA Section 11 Case report tabulations NDA Section 12 Case Report Forms (CRFs) NDA Section 13 Patent information NDA Section 14 Patent certification NDA Section 15 Establishment description 11
- 12. Contd… NDA Section 16 Debarment certificate NDA Section 17 Field copy certification NDA Section 18 User fee coversheet NDA Section 19 Financial disclosure NDA Section 20 Other 12
- 13. Contd… NDA Section 3: Application Summary : • This is an abbreviated version of the entire application • It should give reviewers a clear idea of the drug and its application • The summary usually comprises 50 to 200 pages NDA Section 4: Chemistry, Manufacturing, andControls (CMC) : • The first technical section of the NDA It includes information • The three main elements are Chemistry, manufacturing and controls information Samples (Submit only upon FDA’s request) Methods validation package 13
- 14. Contd… CMC – Drug Substance • The description • The physical and chemical characteristics • Structural elucidation • Drug substance manufacturing methods • Drug substance analytical controls • Drug substance stability 14
- 15. Contd… CMC – Drug Product • List of all components, quantities • Drug product manufacturing methods • Drug product packaging • The drug product stability 15
- 16. Contd… NDA Section 7: Clinical Microbiology: • Required for anti infective drug products • Biochemical basis of the drug’s action on microbial physiology • The drug’s antimicrobial spectrum • Mechanisms of resistance to the drug • Clinical microbiology laboratory methods 16
- 17. Contd… NDA Section 11: Case Report Tabulations: • Complete tabulations for each patient from Phase II and Phase III efficacy study • Phase I clinical pharmacology study • Safety data from all clinical studies NDA Section 12: Case Report Forms (CRFs): • CRF for each patient who died during a clinical study • Patients who were dropped from the study 17
- 18. Guidance Documents for NDAs • These documents are prepared for FDA review staff and applicants/sponsors to provide guidelines to the processing, content, and evaluation/approval of applications • CDER gives guidance documents to help prepare NDAs • CDER - Centre for Drug Evaluation and Research Drug Registraion & Licensing System ICSR-Individual Case Safety system Reporting 18
- 19. Guidance Documents for NDAs Contd… • Bioavailability and bioequivalence studies for Orally administered drug products- General considerations • Formatting, assembling and sumitting new drug and antibiotic application • Format and content of Chemistry, Manufacturing and Control section of an application • Format and content of Microbiology section of an application • Format and content of Clinical and Statistical section of an application • Container closure system for packing human drugs and biologics 19
- 20. Guidance Documents for NDAs Contd… • Submitting documentation for the Stability of human drugs and biologics • Format and content of human pharmacokinetics and bioavailability section of an application • Providing clinical evidence of effectiveness for human drug and biological products • NDAs- Impurities in drug substanses • Drug Master Files (DMF) • Required specifications for FDA’s IND, NDA and ANDA drug master file binders • Refusal to file 20
- 21. Common Technical Document • In 1997 the FDA’s CDER, Published guidelines that allow sponsors to submit NDAs electronically instead of on paper 21
- 22. Specifications for FDA’s DMF binders Polyethylene binders : • Front- 248 X 292 mm • Back- 248 X 305 mm • Must be withstand at temp. of 150 degree C • Ink colour must be BLACK • FDA Form 2626 - Blue - NDA archival binder • FDA Form 2675 - Red - IND archival binder • FDA Form 3316 - Red - Drug master file binder • FDA Form 3316a - Blue - Drug master file archival binder 22
- 23. Specifications for FDA’s DMF binders Paper binder : • Front 267 X 292 mm • Back 267 X 305 mm • Ink colour must be BLCK, Maroon colour binder ink must be WHITE • FDA Form 2626a - Red - NDA Chemistry binder • FDA Form 2626b - Yellow - NDA Pharmacology binder • FDA Form 2626c - Orange - NDA Pharmacokinetic binder • FDA Form 2626d - White - NDA Microbiology binder • FDA Form 2626e - Tan - NDA Clinical data binder • FDA Form 2626f - Green - NDA Statistics binder • FDA Form 2626h - Maroon - NDA Field submission chemistry binder • FDA Form 2675a - Green - IND Chemistry binder • FDA Form 2675b - Orange - IND Microbiology binder 23
- 24. Assembling Applications for Submission The Review The Archival Copy Copy FDA 24
- 25. Archival Copy • The cover letter • Form FDA- 356h • The Administrative sections • Comprehensive NDA index • Four copies of labeling section • Three copies of CMC, Methods validation package • Case report tabulations & Case report forms 25
- 26. • The cover letter • Form FDA- 356h • The Administrative section • Comprehensive NDA- index • The labeling section • The applicantion summary 26
- 27. Applica Applicant NDA -tion Filable No Yes Refuse to File Letter is Issued Review by CDER Medical Statistical Biopharmaceutical Chemistry Pharmacology Microbiology Dis approval Approval 27
- 28. FDA Fast Track Approval Priority Review Accelerated Approval 28
- 29. Fast Track Approval Drugs For • Serious diseases • Fill an unmet medical need • Must be requested by the drug company . • FDA- 60 Days-Review- Decision 29
- 30. Accelerated Approval • In 1992 FDA instituted the Accelerated Approval regulation • Based on a Surrogate endpoint, not on clinical outcome • A surrogate endpoint is a marker- a laboratory measurement, or physical sign - that is used in clinical trials as an indirect or substitute measurement that represents a clinically meaningful outcome, such as survival or symptom improvement 30
- 31. • A Priority Review designation is given to drugs that offer major advances in treatment • The goal for completing a Priority Review is six months • It can given for Drugs use to Serious/ Nonserious diseases • Standard Review is applied to a drug that offers a most, only minor improvement over existing marketed therapies (Ten months for Approval) 31
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