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 NDA2 3. New Drug Application Since 1938, every new drug has been the subject of anapproved NDA before U.S. commercialization The NDA application is the vehicle through which drug sponsorsformally propose that the FDA approve a new pharmaceuticalfor sale and marketing in the U.S. The data gathered during the animal studies and human clinicaltrials of an Investigational New Drug (IND) become part of theNDA 3 4. Goals of NDA Safety and Effectiveness of a new drug in its proposed use(s) Whether the drugs proposed labeling (package insert) is appropriateMethods used in manufacturing the drug and the controls used tomaintain the drugs quality are adequate to preserve the drugs identity,strength, quality, and purity The benefits of the drug outweigh the risks4 5. NDAPre Clinical Clinical studies FillingstudiesI Phase-I Phase-IIPhase-IIIAnimalNtesting of aD New drug SafetyFi Effective Rlness EApprovallVi More Info. InE Short term gW DisapprovalLong term 5 6. NDA Forms & Electronic Submissions Form FDA- 356h. Application to market a New drug, biologic or an antibioticdrug for human use Form FDA- 3397. User fee cover sheet Form FDA- 3331. New drug application field report Guidance documents for electronic submissions6 7. Submit information regarding distributed Drug products an articles toFDA, Which contains(i) Any incident that causes the drug product or its labeling to be mistakenfor another article(ii) Any bacteriological content/ chem. and physical detritioration/ failure to meet the specification7 8. The NDA may have as many as 20 different sections in addition to the FormFDA-356h itself The specific contents of the NDA will depend on the Nature of the drug productand the information available at the time of submission the application Form FDA-356h serves as Checklist as well as Certification that, the sponsoragrees to comply with a range of legal and regulatory requirements 8 9. ContdNDA Section 1 IndexNDA Section 2 LabelingNDA Section 3 Application summaryNDA Section 4 Chemistry, Manufacturing, and Controls (CMC)NDA Section 5Nonclinical pharmacology and toxicology9 10. ContdNDA Section 6Human pharmacokinetics and bioavailabilityNDA Section 7Clinical microbiologyNDA Section 8Clinical dataNDA Section 9Safety update reportsNDA Section 10 Statistics10 11. ContdNDA Section 11 Case report tabulationsNDA Section 12 Case Report Forms (CRFs)NDA Section 13 Patent informationNDA Section 14 Patent certificationNDA Section 15 Establishment description11 12. ContdNDA Section 16 Debarment certificateNDA Section 17 Field copy certificationNDA Section 18 User fee coversheetNDA Section 19 Financial disclosureNDA Section 20 Other12 13. ContdNDA Section 3: Application Summary : This is an abbreviated version of the entire applicationIt should give reviewers a clear idea of the drug and its applicationThe summary usually comprises 50 to 200 pagesNDA Section 4: Chemistry, Manufacturing, andControls(CMC) : The first technical section of the NDA It includes information The three main elements areChemistry, manufacturing and controls informationSamples (Submit only upon FDAs request)Methods validation package 13 14. ContdCMC Drug Substance The description The physical and chemical characteristics Structural elucidation Drug substance manufacturing methods Drug substance analytical controls Drug substance stability14 15. ContdCMC Drug Product List of all components, quantities Drug product manufacturing methods Drug product packaging The drug product stability 15 16. ContdNDA Section 7: Clinical Microbiology: Required for anti infective drug products Biochemical basis of the drugs action on microbialphysiology The drugs antimicrobial spectrum Mechanisms of resistance to the drug Clinical microbiology laboratory methods 16 17. ContdNDA 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 studiesNDA Section 12: Case Report Forms (CRFs): CRF for each patient who died during a clinical study Patients who were dropped from the study17 18. Guidance Documents for NDAs These documents are prepared for FDA review staff and applicants/sponsorsto provide guidelines to the processing, content, and evaluation/approval ofapplicationsCDER gives guidance documents to help prepare NDAs CDER - Centre for Drug Evaluation and Research Drug Registraion & Licensing System ICSR-Individual Case Safety system Reporting18 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 anapplication 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 NDAsContd Submitting documentation for the Stability of human drugs and biologics Format and content of human pharmacokinetics and bioavailability section of anapplication Providing clinical evidence of effectiveness for human drug and biologicalproducts NDAs- Impurities in drug substanses Drug Master Files (DMF) Required specifications for FDAs IND, NDA and ANDA drug master file binders Refusal to file 20 21. Common Technical Document In 1997 the FDAs CDER, Published guidelines that allow sponsors tosubmit NDAs electronically instead of on paper21 22. Specifications for FDAs DMF bindersPolyethylene 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 FDAs DMF bindersPaper 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 binder23 24. Assembling Applications for SubmissionThe ReviewThe 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 forms25 26. The cover letter Form FDA- 356h The Administrative section Comprehensive NDA- index The labeling section The applicantion summary 26 27. ApplicaApplicant NDA-tionFilableNoYes Refuse to FileLetter is Issued Review by CDERMedicalStatisticalBiopharmaceuticalChemistryPharmacology Microbiology Dis approval Approval27 28. FDAFast Track ApprovalPriority ReviewAccelerated Approval 28 29. Fast Track ApprovalDrugs For Serious diseases Fill an unmet medical need Must be requested by the drug company. FDA- 60 Days-Review- Decision29 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, orphysical sign - that is used in clinical trials as an indirect or substitutemeasurement that represents a clinically meaningful outcome, suchas survival or symptom improvement 30 31. A Priority Review designation is given to drugs that offer major advancesin 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 minorimprovement over existing marketed therapies (Ten months for Approval)31 32. 32 33. 33 34. 34 35. 35