Proposed Regulations and Draft Guidances
3/15/2019: A Risk-Based Approach To Monitoring of Clinical Investigations: Questions and Answers
This document provides guidance to industry on a risk-based approach to monitoring of investigational studies of human drug and biological products, medical devices, and combinations thereof. This guidance expands on FDA’s guidance for industry "Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring" (RBM guidance) by providing clarifications and additional guidance to facilitate and encourage sponsors’ implementation of risk-based monitoring.
FDA’s experiences since the RBM guidance was finalized in 2013 suggest that additional guidance would be beneficial regarding FDA’s recommendations for planning a monitoring approach, developing the content of monitoring plans, and addressing and communicating monitoring results. The questions and answers in this guidance are intended to provide more detailed guidance to assist sponsors in planning and conducting risk-based monitoring.
Comments are due by May 14, 2019
The Food and Drug Administration (FDA) is reopening the comment period for the proposed rule entitled “Institutional Review Board Waiver or Alteration of Informed Consent for Minimal Risk Clinical Investigations” that appeared in the Federal Register of November 15, 2018. FDA is taking this action due to technical difficulties at the Federal eRulemaking portal. The proposed rule can be accessed at https://www.gpo.gov/fdsys/pkg/FR-2018-11-15/pdf/2018-24822.pdf. Comments on the proposed rule may be submitted at https://www.regulations.gov (Docket No. FDA-2018-N-2727).
Comments are due by March 7, 2019.
The Food and Drug Administration (FDA) is extending the comment period for the proposed rule entitled “Institutional Review Board Waiver or Alteration of Informed Consent for Minimal Risk Clinical Investigations” that appeared in the Federal Register of November 15, 2018. FDA is taking this action in response to a request for an extension to allow interested persons additional time to submit comments. The proposed rule can be accessed at https://www.gpo.gov/fdsys/pkg/FR-2018-11-15/pdf/2018-24822.pdf. Comments on the proposed rule may be submitted at https://www.regulations.gov (Docket No. FDA-2018-N-2727).
Comments are due by February 13, 2019.
FDA is proposing to amend its regulations to implement section 3024 of the 21st Century Cures Act. This proposed rule, if finalized, would allow an exception from the requirement to obtain informed consent when a clinical investigation poses no more than minimal risk to human subjects and includes appropriate safeguards to protect the rights, safety, and welfare of human subjects. The proposed rule, if finalized, would permit an IRB to waive or alter certain informed consent elements or to waive the requirement to obtain informed consent, under limited conditions, for certain FDA-regulated minimal risk clinical investigations.
Comments are due by January 14, 2019.
04/09/2018: Draft Guidance - Pregnant Women: Scientific and Ethical Considerations for Inclusion in Clinical Trials
This draft guidance discusses the ethical and scientific issues when considering the inclusion of pregnant women in clinical trials of drugs and biological products. This draft guidance is intended to advance scientific research in pregnant women, and discusses issues that should be considered within the framework of human subject protection regulations.
Comments are due by June 8, 2018.
This draft guidance provides recommendations to sponsors, clinical investigators, IRBs, CROs, and other interested parties on the use of electronic records and electronic signatures under part 11 in clinical investigations of medical products. The draft guidance clarifies, updates, and expands upon recommendations in the 2003 part 11 guidance for recommendations that pertain to FDA-regulated clinical investigations conducted under parts 312 and 812. Thus, the guidance is limited to the scope and application of part 11 requirements to such clinical investigations.
The goals of the draft guidance are to clarify and update recommendations for applying and implementing part 11 requirements in the current environment of electronic systems used in clinical investigations and to encourage and facilitates the use of electronic records and systems to improve the quality and efficiency of clinical investigations.
The guidance discusses the procedures that may be followed to help ensure that electronic records and electronic signatures meet FDA requirements and are considered to be trustworthy, reliable, and generally equivalent to paper records and handwritten signatures executed on paper. The guidance also discusses the use of a risk-based approach when deciding to validate electronic systems, implement audit trails for electronic records, and archive records that are pertinent to clinical investigations conducted under parts 312 and 812.
Comments due by August 21, 2017.
07/15/2014: Informed Consent Information Sheet Guidance for IRBs, Clinical Investigators, and Sponsors (Draft)
This draft guidance is intended to assist IRBs, clinical investigators, and sponsors involved in clinical investigations of FDA-regulated products in carrying out their responsibilities related to informed consent. The guidance provides the Agency’s recommendations and requirements for informed consent to assure the protection of the rights and welfare of human subjects in clinical investigations. This guidance describes the basic and additional elements of informed consent and includes topics such as review of patient records, children as subjects, and subject participation in more than one study.
The comment period for the draft guidance published July 25, 2014 is extended. Comments will be received through October 27, 2014.
5/9/2013: Draft Guidance: Charging for Investigational Drugs Under an IND - Q&As
This draft guidance is intended to provide information for industry, researchers, and physicians about the implementation of FDA’s regulation on charging for investigational drugs under an Investigational New Drug Application (IND) (21 CFR 312.8), which went into effect on October 13, 2009. It includes information concerning charging for investigational drugs made available under expanded access programs.
Comments are due by July 8, 2013
5/9/13: Draft Guidance: Expanded Access to Investigational Drugs for Treatment Use - Q&As
This draft guidance is intended to provide information for industry, researchers, physicians, and patients about the implementation of FDA’s regulations on expanded access to investigational drugs for treatment use under an investigational new drug application (IND) (21 CFR part 312, subpart I), which went into effect on October 13, 2009.
Comments are due by July 8, 2013
The Food and Drug Administration (FDA) is proposing to amend its regulations on acceptance of data from clinical studies for medical devices. We are proposing to require that clinical studies conducted outside the United States as support for an investigational device exemption (IDE) application, a premarket notification (510(k)) submission, a premarket approval (PMA) application, a product development protocol (PDP) application, or a humanitarian device exemption (HDE) application be conducted in accordance with good clinical practice (GCP), which includes obtaining and documenting the review and approval of the study by an independent ethics committee (IEC) and obtaining and documenting freely given informed consent of study subjects. The proposed rule is intended to update the standards for FDA acceptance of data from clinical studies conducted outside the United States and to help ensure the protection of human subjects and the quality and integrity of data obtained from these studies. As part of this proposed rule, we are also proposing to amend the IDE and 510(k) regulations to address the requirements for FDA acceptance of data from clinical studies conducted inside the United States. The proposed amendments are intended to provide consistency in FDA requirements for acceptance of clinical data, whatever the application or submission type.
Comments are due by May 28, 2013.
This document provides guidance to industry on enrichment strategies that can be used in clinical trials intended to support effectiveness and safety claims in new drug applications (NDAs) and biologics license applications (BLAs). Similar strategies may also be useful in studies conducted in earlier stages of development.
Comments are due by February 15, 2013
11/20/2012: Guidance for Industry Electronic Source Data in Clinical Investigations
This draft guidance document provides recommendations to sponsors, Contract Research Organizations (CROs), data management centers, clinical investigators, and others involved in capturing, reviewing, and archiving electronic source data in FDA-regulated clinical investigations. This draft guidance document promotes capturing source data in electronic form, and it is intended to assist in ensuring the reliability, quality, integrity, and traceability of electronic source data.
Comments are due by January 22, 2013
9/7/2011: Guidance on Exculpatory Language in Informed Consent
This draft guidance has been prepared jointly by the Office for Human Research Protections (OHRP) and the Food and Drug Administration (FDA). This document applies to non-exempt human subject research conducted or supported by the Department of Health and Human Services (HHS) and is intended for clinical investigators, institutional review boards, and funding agencies that may be responsible for review or oversight of human subject research conducted or supported by HHS. This document also applies to human subject research regulated by FDA and is intended for clinical investigators, sponsors, and institutional review boards conducting or reviewing such research.
This document provides guidance on the regulatory prohibition on the inclusion of exculpatory language in informed consent. The document includes examples of language that OHRP and FDA consider acceptable as well as examples of language that the agencies would consider exculpatory. When finalized, this document will supersede OHRP’s November 15, 1996, guidance entitled, “‘Exculpatory Language’ in Informed Consent” and question number 52 in FDA’s January 1998 guidance entitled, “Institutional Review Boards Frequently Asked Questions – Information Sheet Guidance for Institutional Review Boards and Clinical Investigators.”
Comments are due by November 7, 2011.
The Office of the Secretary of the Department of Health and Human Services (HHS) in coordination with the Office of Science and Technology Policy (OSTP) is issuing this advance notice of proposed rulemaking (ANPRM) to request comment on how current regulations for protecting human subjects who participate in research might be modernized and revised to be more effective. This ANPRM seeks comment on how to better protect human subjects who are involved in research, while facilitating valuable research and reducing burden, delay, and ambiguity for investigators.
The comment period for the proposed rule published July 26, 2011, at 76 FR 44512 is extended. Comments will be received through October 26, 2011.
This draft guidance document is intended to clarify the types of in vitro diagnostic (IVD) products that are properly labeled “for research use only” ("RUO") or “for investigational use only” ("IUO"), and provide the responses of the Center for Devices and Radiological Health (CDRH) and the Center for Biologics Evaluation and Research (CBER) to some frequently asked questions about how such products should and should not be marketed. This document is intended for manufacturers and distributors of RUO and IUO IVD products and any other entities who label IVD products.
Comments are due by August 30, 2011
This guidance is intended to assist clinical investigators, sponsors, and sponsor-investigators in determining whether human research studies must be conducted under an investigational new drug application (IND), as described in Title 21 of the Code of Federal Regulations, part 312 (21 CFR part 312) (the IND regulations). This guidance describes when an IND is required, specific situations in which an IND is not required, and a range of issues that, in FDA’s experience, have been the source of confusion or misperceptions about the application of the IND regulations.
Comments are due January 12, 2011
2/19/2010: Proposed rule - Reporting Information Regarding Falsification of Data
The proposed rule will require sponsors to report information indicating that any person has, or may have, engaged in the falsification of data involving studies including, but not limited to, clinical investigations, nonclinical laboratory studies, and clinical studies in animals.
Comments are due May 20, 2010.
1/17/06: Withdrawal of the Advance Notice of Proposed Rulemaking entitled "Institutional Review Boards: Requiring Sponsors and Investigators to Inform Institutional Review Boards of Any Prior Institutional Review Boards Reviews"
After reviewing public comments on this ANPRM, FDA concluded that rulemaking on this matter was not warranted at this time. A notice withdrawing this ANPRM published in the Federal Register on Jan. 16, 2006. This notice can be found on regulations.gov, Docket FDA-2001-N-0203-0002.
The effective date for this withdrawal is February 16, 2006.