Regulations: Good Clinical Practice And Clinical Trials - FDA

FDA Regulations Relating to Good Clinical Practice and Clinical Trials

Here are links to FDA regulations governing human subject protection and the conduct of clinical trials.

• Electronic Records; Electronic Signatures (21 CFR Part 11)
• Regulatory Hearing Before the Food and Drug Administration (21 CFR Part 16)
• Protection of Human Subjects (Informed Consent) (21 CFR Part 50)
• Financial Disclosure by Clinical Investigators (21 CFR Part 54)
• Institutional Review Boards (21 CFR Part 56)
• Good Laboratory Practice for Nonclinical Laboratory Studies (21 CFR Part 58)
• Investigational New Drug Application (21 CFR Part 312)
• Applications for FDA Approval to Market a New Drug (21 CFR Part 314)
• Bioavailability and Bioequivalence Requirements (21 CFR Part 320)
• New Animal Drugs for Investigational Use (21 CFR Part 511)
• New Animal Drug Applications (21 CFR Part 514)
• Applications for FDA Approval of a Biologic License (21 CFR Part 601)
• Investigational Device Exemptions (21 CFR Part 812)
• Premarket Approval of Medical Devices (21 CFR Part 814)

Preambles to GCP Regulations

Each time Congress enacts a law affecting products regulated by the Food and Drug Administration, the FDA develops rules to implement the law. The FDA takes various steps to develop these rules, including publishing a variety of documents in the Federal Register announcing the FDA's interest in formulating, amending or repealing a rule, and offering the public the opportunity to comment on the agency's proposal. The Federal Register notice explains the legal issues and basis for the proposal, and provides information about how interested persons can submit written data, views, or arguments on the proposal. Any comments that are submitted are addressed in subsequent publications that are part of the agency's decision-making process.

The "preamble" to each of these publications includes all of the printed information immediately preceding the codified regulation. The preamble provides information about the regulation such as why the regulation is being proposed, the FDA's interpretation of the meaning and impact of the proposed regulation, and in those cases where the agency has solicited public comment, the agency's review and commentary on those comments . The preamble can also include an environmental impact assessment, an analysis of the cost impact, comments related to the Paperwork Reduction Act, and the effective date of the implementation or revocation (as the case may be) of the regulation.

The documents posted below include the various publications that contributed to the development of final rules related to FDA's regulations on good clinical practice and clinical trials.

Part 50- Informed Consent

• Protection of Human Subjects; Informed Consent; Final Rule (46 FR 8942, January 27, 1981)
• Protection of Human Subjects; Informed Consent; Standards for Institutional Review Boards for Clinical Investigations (53 FR 45678, November 10,1988)
• Protection of Human Subjects; Informed Consent; Proposed Rule [text] | [PDF] (60 FR 49086, September 21, 1995)
• Protection of Human Subjects; Informed Consent [text] | [PDF] (60 FR 66530, December 22, 1995)
• Protection of Human Subjects; Informed Consent, Informed Consent and Waiver of Informed Consent Requirements in Certain Emergency Research; Final Rule [text] | [PDF] (61 FR 51498, October 2, 1996)
• Protection of Human Subjects; Informed Consent Verification; Final Rule [text] | [PDF] (61 FR 57278, November 5, 1996)
• Human Drugs and Biologics; Determination That Informed Consent Is NOT Feasible or Is Contrary to the Best Interests of Recipients; Revocation of 1990 Interim Final Rule; Establishment of New Interim Final Rule [text] | [PDF] (64 FR 54180, October 5, 1999)
• Medical Devices; Exception from General Requirements for Informed Consent; Interim Final Rule [text] | [PDF] (71 FR 32827, June 7, 2006)
• Informed Consent Elements [text] | [PDF] (76 FR 256, January 4, 2011)
• Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing Burden, Delay, and Ambiguity for Investigators; Advance Notice of Proposed Rulemaking (ANPRM) [text] [PDF] (76 FR 44512, July 26, 2011)
• Institutional Review Board Waiver or Alteration of Informed Consent for Minimal Risk Clinical Investigations; Proposed Rule [text] | [PDF] (83 FR 57378, November 15, 2018)
  • Extension of Comment Period [text] | [PDF] (83 FR 65322, December 20, 2018)
  • Reopening of Comment Period [text] | [PDF] (84 FR 5968, February 25, 2019)

Additional Safeguards for Children in Clinical Investigations of FDA Regulated Products; 21 CFR 50, Subpart D

• Interim Final Rule[text] | [PDF] (66 FR 20589-600, April 24, 2001)
• Final Rule [text] | [PDF] (78 FR 12937, February 26, 2013

Part 56- Institutional Review Boards

• Protection of Human Subjects, Standards for Institutional Review Boards for Clinical Investigations Proposed Rule (43 FR 35186, August 8, 1978)
• Protection of Human Research Subjects; Standards for Institutional Review Boards for Clinical Investigations (46 FR 8958, January 27, 1981)
• Protection of Human Research Subjects; Clinical Investigations Which May Be Reviewed Through Expedited Review Procedure Set Forth in FDA Regulations; Notice (46 FR 8980, January 27, 1981)
• Protection of Human Subjects; Informed Consent; Standards for Institutional Review Boards for Clinical Investigations; Proposed Rule (53 FR 45678, November 10, 1988)
• Federal Policy for the Protection of Human Subjects; Final Rule (56 FR 28003, June 18, 1991)
• FDA Policy for the Protection of Human Subjects; Final Rule (56 FR 28025, June 18, 1991)
• Categories of Research That May Be Reviewed by the Institutional Review Board (IRB) Through an Expedited Review Procedure [text] | [PDF] (63 FR 60353, November 9, 1998)
• Human Drugs and Biologics: Determination That Informed IS NOT Feasible or Is Contrary to the Best Interests of Recipients; Revocation of 1990 Interim Final Rule; Establishment of New Interim Final Rule [text] | [PDF] ( 64 FR 54180, October 5, 1999)

IRB Registration Requirements 21 CFR 56.106

• Proposed Rule [text] | [PDF] (69 FR 40556, July 6, 2004)
• Final Rule [text] | [PDF] (74 FR 2358, January 15, 2009)

IRB Shopping: Requiring Sponsors and Investigators to Inform Institutional Review Boards of Any Prior Institutional Review Boards Reviews

• Advance Notice of Proposed Rulemaking [text] [PDF] (67 FR 10115, March 6, 2002)
• Advance Notice of Proposed Rulemaking; Withdrawal [text] [PDF] (71 FR 2493, January 17, 2006)

IRB Waiver or Alteration of Informed Consent for Minimal Risk Clinical Investigations

• Proposed Rule [text] | [PDF] (83 FR 57378, November 15, 2018)
• Extension of Comment Period [text] | [PDF] (83 FR 65322, December 20, 2018)
• Reopening on Comment Period [text] | [PDF] (84 FR 5968, February 25, 2019)

Part 54- Financial Disclosure by Clinical Investigators

• Financial Disclosure by Clinical Investigators; Public Hearing [text] | [PDF] (60 FR 29801, June 6, 1995)
• Financial Disclosure by Clinical Investigators; Proposed Rule [text] | [PDF](63 FR 5233, February 2, 1998)
• Financial Disclosure by a Clinical Investigator; Final Rule [text] | [PDF] (63 FR 72171-81, December 31, 1998)

Part 210- Current Good Manufacturing Practice in Manufacturing, Processing, Packing, or Holding of Drugs; General

• Current Good Manufacturing Practice Regulations and Investigational New Drugs [text] | [PDF] (January 17, 2006)

Part 312- Investigational New Drug Application

• Proposed New Drug, Antibiotic, and Biologic Drug Product Regulations (48 FR 26720, June 9, 1983)
• New Drug and Antibiotic Regulations (50 FR 7452, February 22, 1985)
• New Drug, Antibiotic, and Biologic Drug Product Regulations (52 FR 8850, March 19, 1987)
• Investigational New Drug Applications and New Drug Applications [text] | [PDF] (September 8, 1995)
• Investigational New Drug Applications and New Drug Applications [text] | [PDF] (February 11, 1998)
• Disqualification of a Clinical Investigator [text] | [PDF] (February 16, 1996)
• Disqualification of a Clinical Investigator [text] | [PDF] (September 5, 1997)
• Expedited Safety Reporting Requirements for Human Drug and Biological Products [text] | [PDF] (62 FR 52237, October 7, 1997)
• Clinical Hold for products intended for life threatening conditions [text] | [PDF] (65 FR 34963-71, June 1, 2000)
• Human Subject Protection; Foreign Clinical Studies Not Conducted Under an Investigational New Drug Application; Final Rule [text] | [PDF] (73 FR 22800, April 28, 2008)
• Reporting Information Regarding Falsification of Data
  • Proposed Rule [text] | [PDF] (75 FR 7412, February 19, 2010)
  • Withdrawal Notice [text] | [PDF] (83 FR 49023, September 28, 2018)
• Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and Safety Reporting Requirements for Bioavailability and Bioequivalence Studies in Humans; Final Rule [text] | [PDF] (75 FR 59935, September 29, 2010)
• Disqualification of a Clinical Investigator [text] | [PDF] (77 FR 25353, April 30, 2012)

Part 314 – Applications for FDA Approval to Market a New Drug Part 601 – Applications for FDA Approval of a Biologic License

• New Drug and Biological Drug Products; Evidence Needed to Demonstrate Effectiveness of New Drugs When Human Efficacy Studies Are Not Ethical or Feasible; Final Rule [text] | [PDF] (67 FR 37988, May 31, 2002)

Part 320- Bioavailability and Bioequivalence Requirements

• Retention of BE and BA Testing Samples; Final Rule [text] (58 FR 25918, April 28, 1993)
• Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and Safety Reporting Requirements for Bioavailability and Bioequivalence Studies in Humans;Final Rule [text] | [PDF] (75 FR 59935, September 29, 2010)

Part 812- Investigational Device Exemptions

• Medical Devices; Current Good Manufacturing Practice (CGMP)Quality System Regulations [text] | [PDF] (61 FR 52602, October 7, 1996)
• Treatment Use of Investigational Devices [text] | [PDF] (62 FR 48940, September 18, 1997)
• Withdrawal of Intraocular Lenses Regulation (Part 813) [text] | [PDF] (62 FR 4164, January 29, 1997)
• Disqualification of Clinical Investigators [text] | [PDF] (62 FR 12087, March 14, 1997)
• FDA Modernization Act of 1997: Modifications to the List of Recognized Standards [text] | [PDF] (64 FR 37546, July 12, 1999)
• Medical Devices; Investigational Device Exemptions (Modifications to the Medical Device and/or Study Protocol); Final Rule [text] | [PDF] (63 FR 64617, November 23, 1998)
• Disqualification of a Clinical Investigator [text] | [PDF] (77 FR 25353, April 30, 2012)

Human Subject Protection; Acceptance of Data From Clinical Studies for Medical Devices

• Proposed Rule [text] [PDF] (78 FR 12664, February 25, 2013)
• Final Rule [text] [PDF] (83 FR 7366, February 21, 2018)

Part 814- Premarket Approval of Medical Devices

• Medical Devices; Humanitarian Use Devices Part V ; Final Rule [text] | [PDF] (61 FR 33232, June 26, 1996)
• 30-Day Notices and 135-Day PMA Supplement Review; Final Rule [text] | [PDF] (63 FR 54042, October 8, 1998)
• Humanitarian Use of Devices; Final Rule [text] | [PDF] (63 FR 59217, November 3, 1998)
• Medical Devices; Exception from General Requirements for Informed Consent; Interim Final Rule [text] | [PDF] (71 FR 32827, June 7, 2006)

Miscellaneous

• Determination of Mode of Action in Combination Products (PDF - 13KB) (70 FR 49848, August 25, 2005) [text] This rule defines "mode of action" and "primary mode of action" and sets forth the algorithm FDA will use to assign combination products to an agency component for regulatory oversight.
• Good Guidance Practices. As required by the Food and Drug Administration Modernization Act of 1997 (FDAMA), FDA codified agency policies and procedures for the development, issuance, and use of guidance documents.
  • Administrative Practices and Procedures; Good Guidance Practices; Proposed Rule [text] [PDF] (65 FR 7321, February 14, 2000)
  • Administrative Practices and Procedures; Good Guidance Practices; Final Rule [text] [PDF] (65 FR 56468, September 19, 2000)
• Index and Copies of Presiding Officer Reports and Commissioner Decisions on the Eligibilty of a Clinical Investigator to Continue to Receive Investigational Products; Availabilty [text] | [PDF] (66 FR 45317-8, August 28, 2001)
• Part 11 Electronic Records; Electronic Signatures [text] | [PDF] (62 FR 13430, March 20, 1997)
• Privacy Act of 1974; Altered Sysytem of Records, Including Addition of Routine Use(s) to an Existing System of Records Notification of an altered system of records, including the addition of new routine use [text] | [PDF] (63 FR 55873-6, October 19, 1998)