21 CFR Part 312 and 21 CFR 314 presentation.pptx

21 CFR 312 and 314 are two separate, but related, US Food and Drug Administration (FDA) regulations for the drug approval process. 21 CFR 312 covers the regulations for an Investigational New Drug (IND) application, which must be submitted before clinical trials can begin. 21 CFR 314 deals with the application for FDA approval to market a new drug, which includes both NDA and ANDA.

1. 21 CFR Part 312: Investigational New Drug Application Made by, Aaditi Kamble. Assistant Professor DRA Department

2. Subpart B- Investigational New Drug Application (IND)   312.20   - Requirement for an IND : IND to be submitted to FDA to conduct the clinical trials. FDA provides written documentation within 30 days after receiving IND application. 312.22   - General principles of the IND submission : Submission of the data of phases Submission of annual reports of status Central focus on investigational plan and protocols of human studies   2

3. 312.23  - IND content and format Coversheet Table of contents Introductory statement and general investigational plan Investigator’s Brochure Protocols CMC Pharmacology and toxicology information Additional information Relevant information 312.30   - Protocol amendments: New study: new protocol Changes in protocol: significantly affecting safety of subjects New investigator Content and format: new protocol(significant differences), change in protocol(brief description, date and number), new investigator(name, qualification) 3

4. 312.31  - Information amendments: New toxicology, chemistry, or other technical information A report regarding the discontinuance of a clinical investigation. 312.32  - IND safety reporting: Definitions: life threatening events, serious adverse events Review of safety information by sponsor Follow-ups 4

5. 312.38  - Withdrawal of an IND: If the IND has been withdrawn, FDA is notified and all the clinical investigations are stopped and the drug is returned to the sponsor. If the withdrawal is due to safety, the sponsor should inform the FDA, investigators and the IRB’s with the reason for withdrawal. Subpart D--Responsibilities of Sponsors and Investigators 312.50  - General responsibilities of sponsors : Selecting qualified investigators Ensuring proper monitoring Investigation is conducted in accordance with investigational plan and protocols  Reporting of new adverse effects or risks of drug to FDA and participating investigators 5

6. 312.59  - Disposition of unused supply of investigational drug: If the investigation of the drug is discontinued or terminated, sponsor shall return the unused investigational drug and shall maintain record about the same. 312.60  - General responsibilities of investigators: Investigator shall ensure that the investigation is carried out in accordance with plan and applicable regulations in order to protect the rights of safety and welfare of the subjects. 6

7. 312.64  - Investigator reports: Progress report: annually submitted Safety report 312.68 – Inspection of investigator's records and reports: authorized officer or employee of FDA can have access to, and copy and verify any records or reports made by the investigator. 312.70 – Disqualification of a clinical investigator: Clinical investigator is disqualified, if FDA has information indicating that an has failed to comply with the requirements of this part, or has submitted to FDA or to the sponsor false information in any required report 7

8. 21 CFR Part 314: Applications for FDA approval to market to a new drug 8

9. Subpart B—Applications 314.50  - Content and format of an NDA: Application form Table of contents Basis for ANDA submission Conditions of use API ROA, dosage form, strength Bioequivalence Labeling CMC 9

10. 314.60  - Amendments to an unapproved NDA, supplement, or resubmission: Submission of major amendment Field copy. 314.65  - Withdrawal by the applicant of an unapproved application: An applicant may withdraw an application that is not yet approved by notifying the FDA in writing. But till then if the FDA has reviewed the application, they send the deficiencies in the application. 10

11. 314.70  - Supplements and other changes to an approved NDA: Changes to an approved NDA Changes requiring supplement submission and approval prior to distribution of the product: drug product, production process, quality controls, equipment, or facilities. 314.71  - Procedures for submission of a supplement to an approved application: Only the applicant may submit a supplement to an application. archival copy and a review copy that include an application form and appropriate technical sections, samples, and labeling. 11

12. 12 314.72 - Change in ownership of an application: New owner shall submit an application form signed commitment to agreements, promises, and conditions made by the former owner. 314.80 – Post-marketing reporting of adverse drug experiences: Information on the patient, date of adverse drug reaction, route of administration used, description of adverse drug experience etc.

13. Subpart H--Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses 314.600 – Scope: Studies for the safety, effectiveness and therapeutic benefit to patients over existing treatments 314.520  - Approval with restrictions to assure safe use: If the drug is approved by FDA for marketing, it restricted only to certain facilities or physicians. 13

14. Subpart I--Approval of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible 314.600 – Scope: applies only to those new drug products for which human efficacy studies cannot be conducted because it would be unethical. 314.610 - Approval based on evidence of effectiveness from studies in animals: results of animal studies establish that the drug product is reasonably likely to produce clinical benefit in humans 14

15. Reference : https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRsearch.cfm?CFRPart=312 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?cfrpart=314 15