The FDA is divided into many centers; each center comprising a division with specific regulatory responsibilitiesThe main centers are as follows: CDER—Center for Drug Evaluation and Research CBER—Center for Biologics Evaluation Research CDRH—Center for Devices and Radiologic Health CFSAN—Center of Food Safety and Applied Nutrition CVM—Center for Veterinary Medicine NCTR—National Center for Toxicological Research
Requirements forRegistration of aNew Drug Presented by – Nadim Dinani MSc-I Bioanalytical Sciences Ramnarain Ruia College Seat no: - XYZABC
What is a New Drug ? New substance meant for medical use in humans except during local clinical trials has not been used & recognized in the country to any significant extent composition is not generally recognized, as safe and effective under the conditions recommended in its labeling by qualified experts
fixed dose combination of 2 or more drugs , individually approved earlier for certain claims which are now proposed to be combined for the first time in fixed ratio marketed with modified or new claims but is already approved by the licensing authority for certain claims.
ApplicantApplication to Ethical IND application filing Committee to CDSCO Headquarters Report of ethical committee
IND application filing to CDSCO Headquarters Examination by New Drug Division Detailed Review by IND Committee Recommendation to DCGI IND Application ApprovedPositive response from Clinical Trials Ethical committee Starts
Completion of Clinical Trial Phase 3Application for New Drug Registration to CDSCO Reviewed by DCGI License is granted Refused to Grant License
Preclinical Studies Investigational New Drug Phase I Phase II Phase III New Drug Application FDA approval Phase IV
IND Investigational New Drug• synthesized and prepared for human administration?• identity and purity controlled?• protocol to be followed in proposed trial?• drug ?• qualifications (trial conductors and result evaluators)?• information sponsor provides clinicians?• convinced about safety of drug (enough to be tested on humans)?
Requirements for IND1. Cover Sheet (FDA Form-1571) [21 CFR 312.23(a)(1)]2. Table of Contents [21 CFR 312.23(a)(2)]3. Introductory Statement and General Investigational Plan [21 CFR 312.23(a)(3)]4. Investigators Brochure [21 CFR 312.23(a)(5)]5. Protocols [21 CFR 312.23(a)(6)]
6. Chemistry, Manufacturing, and Control Information [21 CFR 312.23(a)(7)] a) Chemistry and Manufacturing Introduction b) Drug Substance [21 CFR 312.23 (a)(7)(iv)(a)] c) Drug Product [21 CFR 312.23 (a)(7)(iv)(b)] d) A brief general description of the composition, manufacture, and control of any placebo to be used in the proposed clinical trial(s) [21 CFR 312.23(a)(7)(iv)(c)] e) A copy of all labels and labeling to be provided to each investigator [21 CFR 312.23(a)(7)(iv)(d)] f) A claim for categorical exclusion from or submission of an environmental assessment [21 CFR 312.23(a)(7)(iv)(e)]
7. Pharmacology and Toxicology Information [21 CFR 312.23(a)(8)] a) Pharmacology and Drug Distribution [21 CFR 312.23(a)(8)(i)] b) Toxicology: Integrated Summary [21 CFR 312.23(a)(8)(ii)(a)] i. A brief description of the design of the trials ii. A systematic presentation of the findings from the animal toxicology and toxico-kinetic studies. iii. Identification and qualifications of the individual(s) who evaluated the animal safety data and concluded iv. A statement of where the animal studies were conducted and where the records of the studies are available for inspection v. A declaration that each study subject to good laboratory practices (GLP) regulations was performed in full compliance
c) Toxicology - Full Data Tabulation [21 CFR312.23(a)(8)(ii)(b)] d) Toxicology - GLP Certification [21 CFR 312.23(a)(8)(iii)] e) Monitoring of Effects of these Clarifications8. Previous Human Experience with the Investigational Drug [21 CFR 312.23(a)(9)]9. 21 CFR 312.23(a)(10), (11) and (b), (c), (d), and (e)
NDA New Drug Application• drug safe and effective?• Do benefits outweigh risks?• labeling (package insert) appropriate?• manufacturing and drug quality control methods adequate?
Requirements for NDA NDA Scientific DocumentationRequirements
Scientific Requirements Manufacturing Methodology Authentication Testing of Drug for - safety - Efficacy
Scientific Requirements Bioavailability and Bioequivalence Studies Data Container Closure Systems for Packaging Human Drugs and Biologics Microbiological analysis Data Clinical Research Data Statistical Data Human Pharmacokinetics and Bioavailability test Data Non-clinical pharmacology and toxicology studies Data Clinical evidence of effectiveness Summary of New Drug Samples and Analytical Data – for Method Validation Manufacture process of Drug Impurities in the Drug
Documentation for NDAFIRST: Documents• Organization & administrative information• Certificates, information & administrative documents about the product• Technical file documents• Clinical studies documentsSECOND: Attachments to the registration file• 15 copies of internal information• 15 copies of “The approved information form of the drug” duly completed• 2 samples of finished productTHIRD : separate copy of technical file for analysis purpose to Drug Control Laboratory
Bibliography GUIDANCE FOR INDUSTRY ON PREPARATION OF COMMON TECHNICALDOCUMENT FOR IMPORT / MANUFACTURE AND MARKETING APPROVAL OF NEWDRUGS FOR HUMAN USE (NEW DRUG APPLICATION – NDA), CENTRAL DRUGS STANDARDCONTROL ORGANIZATION DIRECTORATE GENERAL OF HEALTH SERVICES MINISTRY OF HEALTH &FAMILY WELFARE GOVT. OF INDIA, NOVEMBER 2010 Richard A. Guarino ,M.D., New drug approval process, 5th edition, vol 190, 93-155 Dr. Harish Dureja, New Drug Approval Process: RegulatoryView, Pharmainfo.net online article – (link) http://www.fda.gov/RegulatoryInformation/Guidances/ucm129703.htm http://www.fda.gov/aboutfda/reportsmanualsforms/forms/default.htm http://cdsco.nic.in/ http://cdsco.nic.in/new_drugs_division.htm