Global Submission of IND& NDA pptx
- 1. GLOBAL SUBMISSION OF IND & NDA NON CLINICAL DRUG DEVELOPMENT REGULATORY AFFAIRS Presented by Chitrang R Patil (M23027) F.Y.M.Pharmacy Guided by Miss. Ashwini Bhoir Mam Pharmaceutics Konkan gyanpeeth rahul dharkar college of pharmacy, karjat
- 2. PRECLINICAL INVESTIGATION The testing of new drugs in humans cannot begin until there is solid evidence that the drug product can be used with reasonable safety in humans. This phase is called "preclinical investigation." Goal of preclinical investigation is to assess potential therapeutic effects of the substance on living organisms and to gather sufficient data to determine reasonable safety of the substance in humans through laboratory experimentation and animal investigation A preclinical investigation usually takes one to three years to complete.
- 3. INTRODUCTION The INVESTIGATIONAL NEW DRUG APLICATION (IND) is the formal process by which a sponsor requests approval for testing of a drug in humans. It includes information developed during preclinical testing regarding safety and effectiveness. A pre- IND meeting can be arranged with the FDA to discuss a number of issues The design of animal research, which is required to lend support to the clinical studies. The intended protocol for conducting the clinical Trial. The chemistry, manufacturing, and control of the investigational drug.
- 4. Includes an investigational brochure that ensures that clinicians conducting the trial and their institutional review board(IRB) are adequately informed about possible effect of the drug. If the FDA accepts the IND request within 30 days of submission, clinical testing of new molecule on human may begin by the investigator. If at any time during clinical testing, the data furnished to FDA indicate the IP to be toxic under the criterion of FDA's Benefit/Risk ratio, FDA can terminate clinical trial and its actions are not subject to any judicial review. INTRODUCTION
- 5. TYPES OF IND Investigator IND- submitted by a physician who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. Emergency Use IND-allows the FDA to authorize use of an experimental drug in an emergency situation that does not allow time for submission of an IND in accordance with 21CFR, Sec. 312.23 or Sec. 312.20. Treatment IND-is submitted for experimental drugs showing promise in clinical testing for serious or immediately life- threatening conditions while the final clinical work is conducted and the FDA review takes place.
- 6. THE IND APPLICATION MUST CONTAIN INFORMATION IN THREE BROAD AREAS Clinical protocols and investigator information Animal pharmacology and toxicology Manufacturin g information
- 7. REGULATORY AND ADMINISTRATIVE COMPONENTS The content 21CFR part 312. and format of IND application is laid out in Cover sheet -312.23(a)(1)(FORM FDA 1571) Table of contents-313.23(a)(2) Introductory statement and a general investigational plan -312.23(a)(3) Investigators brochure-312.23(a)(5) Clinical Protocols-312.23(a)(6)
- 8. REGULATORY AND ADMINISTRATIVE COMPONENTS Chemistry, manufacturing and control information- 312.23(a)(7) Pharmacology and Toxicology information-312.23(a)(18) Previous human experience with the investigational drug- 312.23(a)(9) Other relevant information like no of IND submissions- 312.23(a)(10) Number of copies to be submitted (1+2) Protocol amendments, any changes in the protocol.- 312.(a)(11)
- 9. IND APPLICATION PROCESS Compile the components of the IND Application. Items with original signatures should be scanned as PDF files. Refer to FDA website for submission addresses.
- 10. IND APPLICATION SUBMISSION FDA will send an acknowledgement via email and in a letter with the following information: Date of IND receipt IND number Contact name Phone at FDA for questions Address and instructions for future submissions of the IND FDA has up to 30 days in which to respond to the sponsor- investigator regarding the IND if there are clinical, regulatory, or other concerns
- 11. IND SUBMISSION: THE FIRST 30 DAYS • IND arrives to the Central Document Room If electronic: loaded in the Electronic Document Room (EDR) If paper: Sent to the White Oak Document Room Data entered into DARRTS (Document Archiving, Reporting, and Regulatory Tracking System • IND forwarded to CPMS (Chief, Project Management Staff) • PM (Project Manager) assigned • Review Team assigned
- 12. IND SUBMISSION: THE FIRST 30 DAYS The Review team will determine within 30 days of receipt of your IND whether your study is "safe to proceed" or will be placed in clinical hold
- 13. FDAADMINISTRATIVE ACTIONS • Comments Or Requests For Modifications FDA communications to the sponsor-investigator within the 30-day window following FDA receipt of the IND must be answered promptly Updated materials submitted to the FDA in response to a request for changes/information should be submitted in the same manner as the original IND. • Approval of IND Research may commence 30 days following of receipt of the IND if the FDA has not made any request for additional information or changes to the IND Application as submitted. FDA Approval of the IND will be sent electronically and in a letter to the sponsor investigator.
- 14. IND PROCESS IN INDIA No clinical trial for new drug for any purpose be conducted without permission, in writing, of the Licensing Authority(DCGI). Application for conducting clinical trials in India require submission by the sponsor on Form 44 along with fee(Rs 50K) and documents as provided under Schedule Y to Drugs and Cosmetic Act 1940.
- 15. Data to be submitted along with the application on Form44 to conduct clinical trails (2 hard copies and 2 soft copies) 1.Application on Form44 2. Introduction of the drug 3.Fee Rs 50K through challan form 4.Chemical and pharmaceutical information as per Appendix I of Schedule Y. 5.Animal pharmacology as per Appendix IV 6.Animal toxicology as per Appendix III. 7.Human/clinical pharmacology data as per Appendix I. 8. Regulatory status in other countries as per Appendix i.
- 16. After receiving the application, the Central Drug Standard Control Organisation (CDSCO) Headquarter in New Delhi refer it to The New Drug division where it is reviewed by IND committee. The committee submits its report to DCGI along with its recommendations. If the report by committee is favorable, DCGI approves the INDA.
- 18. New Drug Aplication The New Drug Application 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 IIIA Pivot trials. The official definition of New Drug is in Sec 20 l(p) of Federal Drug, Food and Cosmetics Act as; Any new drug , the composition of which is such that it is not recognized among expels qualified by scientific training as safe and effective tor use under prescribed, recommended or suggested conditions.
- 19. Any drug the Composition of which is such that it as a result of investigations to determine safety and efficacy for use has become recognized, but which has not, otherwise in such investigations been used to a material extent . The following letter codes describe the review priority of the drug; S-STANDARD REVIEW: For drugs similar to currently available drugs P-PRIORITY REVIEW : For drug that represent significant advances over existing treatments
- 20. Classification of drugs in NDA Center of drug evaluation and Research(CDER) classifies new drug applications according to the type of drug being submitted and its intended use: A. New molecular entity B. New salt of previously approved drug C. New formulation of previously approved drug D. New combination of two or more drugs E. Already marketed drug product- Duplication (i.e., new manufacturer) F. New indication (claim) for already marketed drug (includes switching marketing status from prescription to OTC) G. Already marketed drug product ( no previous approved NDA)
- 21. In US following 4 types of applications are submitted for approval of drug for marketing depending upon the type and nature of the drug: A. New Drug Application (NDA) B. Biological License Application (BLA) C. Application u/s 505(b)(2)-Paper NDA D. Supplemental New Drug Application (SNDA)
- 22. FORMAT AND CONTENT OF NDA The application is required to be submitted in common technical document format with the following different sections: FDA Form 356h User Fee Cover Sheet (FDA Form 3397) Cover letter (Comprehensive table of contents for Modules l to 5) Summary Chemistry, Manufacturing and Control Samples, Method Validation, Package and Labeling The application is required to be submitted in common technical document format with the following different sections:
- 23. Nonclinical Pharmacology and Toxicology Human Pharmacokinetics and Bioavailability Microbiology (For anti-microbial drugs only) Statistical methods and analysis of Clinical Data Safety Update Repos (typically submitted 120 days after NDA submission) Statement regarding compliance to IRB and Informed Consent requirements Case Report Tabulations Case Report Forms Patent information and certification Other information.
- 24. General requirements for filing NDA • The new NDA regulations require the application tobe submitted in 2 copies: A. An Archival Copy- lt is a complete copy of application submission that serves as its permanent record. B. A Review Copy- It is divided into 6 technical sections: i. Chemistry, Manufacturing and Controls (CMC) ii. Non clinical Pharmacology and Toxicology iii. Human Pharmacokinetics and Bioavailability iv. Microbiology (if required) v. Clinical data vi. Statistical
- 25. • On receipt of NDA, the CDER stamps with a receipt date to enable FDA to forward action within 180 days called ‘Review Clock’ under Review Time Frames (21 CFR 314.1OO). The FDA assigns the application for review. • The FDA has to intimate the applicant if it is incomplete within 60 days according to Filing Time Frames (21 CFR 314.101). • FDA notifies the sponsor of its completion/ incompletion and if complete sends it for secondary review process. FDA inspects the manufacturing facilities for the drug, It may also inspect sample of clinical trial locations to verify the accuracy of data submitted
- 27. • Throughout the process FDA and sponsor communicates through in person meetings, telephone conferences, fax etc. to seek clarification if necessary. Once all reviews are complete; the Divisional Director evaluates the reviews and makes FDA’s decision. The FDA may: • Approve the drug for marketing. • Approve the drug with condition when problem exist with the application that needs to be addressed before approval. • Refuse to approve the drug, when it may require additional research or reformulation of the drug product.
- 28. NDA PROCESS IN INDIA • In India, New Drug is defined under Rule 122-E of Drugs and Cosmetics Act as: A. A drug which has not been used in the country to any significant extent under various conditions B. A drug already approved by DCGI for certain claims which is now proposed to be marketed with new claims like indications, dosage, dosage form etc. C. A fixed dose combination of two individually approved drug being combined for the first time in a fixed ratio or new already marketed combination.
- 29. D. All vaccines are considered as new drugs. E. A new drug continues to be considered as new drug for a period of 4 years from its approval or its inclusion in Indian Pharmacopoeia. F. After successful finishing of clinical trials, the applicant seeking for approval to manufacture a new drug requires to submit application on Form44 along with data as given in Appendix I to Schedule Y Of Rules 1945 to DCGI who grants its approval in Form 46 or 46-A. G. In his name while applying to manufacture a new drug to State Licensing Authority. Thus the applicant is required to obtain necessary approval from DCGI as well as SLA for manufacturing a new drug for sale purposes in India. H. The approval issued is ‘manufacture for sale’ rather than ‘marketing approval’ as per the practice world over.
- 30. PERMISSION TO MANUFACTURE A NEW DRUG: Brief introduction of the new drug Chemical and pharmacological information Animal pharmacology and Toxicology Human/ Clinical Pharmacology (Phase I) Exploratory Clinical Trials (Phase II) Confirmatory Clinical Trial s(Phase III) Bio-availability, dissolution and stability study data Regulatory status in other countries Application for test license Marketing information
- 32. References 1. Chakraborty R, Yadav K (2018) Drug approval process in US, Europe and India and its regulatory requirements: A Review 6: 31-39. 2. Mahapatra AK, Sameeraja NH, Murthy PN (2014) Drug Approval Process In United States of America, European Union and India : A Review. AcrcTra 1: 13-22. 3. https://www.jpsr.pharmainfo.in/Documents/Volumes/vol9Issue10/ jpsr09101759.pdf 4. Gupta NV, Reddy CM, Reddy KP, Kulkarni RA, Shivakumar, et al. (2012) Process of Approval of New Drug in India with Emphasis on Clinical trials 13: 17-23.
- 33. 5. https://www.gao.gov/products/HEHS-96-71 6. http://www.cdsco.nic.in/writereaddata/Guidance%20documents.pdf 7. http://www.cdsco.nic.in/writereaddata/Guidance_for_New_Drug_ Approval-23.07.2011.pdf 8. http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.375.519&rep=rep1& type=pdf 9. Norman GA Van (2016) Drugs and Devices. JACC Basic to Transl Sci 1: 399-412. 10. http://www.cdsco.nic.in/ 11. https://www.fda.gov/ 12. http://www.edqm.eu/
- 34. PREVIOUS YEAR QUESTIONS Write a note on global submission of IND, NDA, ANDA. Write in brief about non clinical drug development process
- 35. THANK YOU !!