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U.S. Department of Health and Human Services

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Selected FDA GCP/Clinical Trial Guidance Documents

Guidance documents accessible from this page represent the Agency's current thinking on good clinical practice (GCP) and the conduct of clinical trials. As with all guidance documents, they do not create or confer any rights for or on any person and do not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute and regulations. However, in many places throughout these documents, specific regulations are cited and the requirements of the regulations are reiterated. The regulations are enforceable.

Guidance Documents Grouped by Topic:

General

21 CFR 50.54, Process for Handling Referrals to FDA under, Guidance for Clinical Investigators, Institutional Review Boards and Sponsors)

This guidance is intended to assist clinical investigators, Institutional Review Boards (IRBs), sponsors, and other interested parties in understanding the FDA's process for handling clinical investigations that include children as subjects and that have been referred to FDA for review under 21 CFR 50.54.

Data Monitoring Committees, Establishment and Operation of Clinical Trial, Guidance for Clinical Trial Sponsors

This guidance is intended to assist sponsors of clinical trials in determining when a data monitoring committee (DMC) is needed for study monitoring, and how such committees should operate.

Data Retention When Subjects Withdraw from FDA-Regulated Clinical Trials, Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors (PDF - 71KB)

This guidance describes FDA’s longstanding policy that already-accrued data, relating to individual who cease participating in a study, are to be maintained as part of the study data.  This pertains to data from individuals who decide to discontinue participation in a study, who are withdrawn by their legally authorized representative, as applicable, or who are discontinued from participation by the clinical investigator.

Exception from Informed Consent Requirements for Emergency Research, Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors

This guidance is intended to assist Institutional Review Boards (IRBs), clinical investigators and sponsors in the development, conduct, and oversight of investigations to determine the safety and effectiveness of FDA regulated products (e.g., drugs, including biological drug products, devices) in emergency settings when an exception from the informed consent requirements is requested under Title 21, Code of Federal Regulations, Section 50.24 (21 CFR 50.24).

Financial Disclosure by Clinical Investigators, Guidance for Clinical Investigators, Industry and FDA Staff (PDF- 165KB)

This guidance is intended to assist clinical investigators, industry, and FDA staff in interpreting and complying with the regulations governing financial disclosure by clinical investigators, 21 CFR part 54. 

Financial Relationships and Interests in Research Involving Human Subjects: Guidance for Human Subject Protection (PDF – 35 KB)

This guidance document, developed at the department (DHHS) level, applies to all human subject research conducted or supported by HHS agencies or regulated by the Food and Drug Administration.

Investigational New Drug Applications (INDs)  — Determining Whether Human Research Studies Can Be Conducted Without an IND,  Guidance for Clinical Investigators, Sponsors, and IRBs (PDF - 288KB) 

This guidance is intended to assist clinical investigators, sponsors, sponsor-investigators, and institutional review boards (IRBs) in determining whether research studies involving human subjects 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. This guidance addresses only whether an IND is needed. If your study also involves the use of a device, you should determine whether such use is subject to 21 CFR part 812 (the IDE regulations).

Investigator Responsibilities — Protecting the Rights, Safety, and Welfare of Study Subjects, Guidance for Industry (PDF - 163KB)

This guidance provides an overview of the responsibilities of a person who conducts a clinical investigation of a drug, biological product, or medical device (an investigator as defined in 21 CFR 312.3(b) and 21 CFR 812.3(i)).  It is intended to clarify for investigators and sponsors FDA’s expectations concerning the investigator’s responsibility (1) to supervise a clinical study in which some study tasks are delegated to employees or colleagues of the investigator or other third parties and (2) to protect the rights, safety, and welfare of study subjects.

The Meaning of "Spouse" and "Family" in FDA’s Regulations after the Supreme Court’s Ruling in United States v. Windsor—Questions and Answers: Guidance for Industry, Consumers, and FDA Staff

On June 26, 2013, in United States v. Windsor, 133 S.Ct. 2675, the Supreme Court struck down as unconstitutional section 3 of the Defense of Marriage Act (DOMA). Using a question and answer format, this guidance document informs the public of FDA’s current thinking about the meaning of “spouse” or “family” in our regulations in light of this ruling.

Oversight of Clinical Investigations - A Risk-Based Approach to Monitoring, Guidance for Industry

This guidance assists sponsors of clinical investigations in developing risk-based monitoring strategies and plans for investigational studies of medical products, including human drug and biological products, medical devices, and combinations thereof. The overarching goal of this guidance is to enhance human subject protection and the quality of clinical trial data by focusing sponsor oversight on the most important aspects of study conduct and reporting.  The guidance describes strategies for monitoring activities that reflect a modern, risk-based approach that focuses on critical study parameters and relies on a combination of monitoring activities to oversee a study effectively. For example, the guidance specifically encourages greater use of centralized monitoring methods where appropriate.

Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims (PDF - 295KB)

This guidance describes how FDA reviews and evaluates existing, modified, or newly created patient-reported outcome (PRO) instruments used to support claims in approved medical product labeling.  A PRO instrument (i.e., a questionnaire plus the information and documentation that support its use) is a means to capture PRO data used to measure treatment benefit or risk in medical product clinical trials. This guidance does not address the use of PRO instruments for purposes beyond evaluation of claims made about a medical product in labeling nor disease-specific issues.

Pharmacogenomic Data Submissions, Guidance for Industry (PDF - 96 KB)

The guidance provides recommendations to sponsors holding investigational new drug applications (INDs), new drug applications (NDAs), and biologics license applications (BLAs) on what pharmacogenomic data to submit to the agency during the drug development process, the format of submissions, and how the data will be used in regulatory decision making. The guidance is intended to facilitate scientific progress in the area of pharmacogenomics.

Race and Ethnicity Data in Clinical Trials, Collection of, Guidance for Industry

This guidance recommends using a standardized approach for collecting and reporting race and ethnicity information in clinical trials conducted in the United States and abroad for certain FDA regulated products. The recommended standardized approach was developed by the Office of Management and Budget (OMB). The guidance lists the OMB categories for race and ethnicity and describes FDA's reasons for recommending the use of these categories. In addition, this guidance recommends a format for race and ethnicity data within study data that are submitted in standardized data sets such as the Study Data Tabulation Model or in the electronic Common Technical Document (eCTD).

Institutional Review Boards (IRBs) and Informed Consent

Adverse Event Reporting to IRBs- Improving Human Subject Protection, Guidance for Clinical Investigators, Sponsors, and IRBs

This guidance is intended to provide assistance to the research community in interpreting requirements for submitting reports of unanticipated problems, including certain adverse events reports, to the IRB.

Centralized IRB Process in Multi center Clinical Trials, Guidance for Industry on Using a 

This guidance is intended to assist sponsors, institutions, institutional review boards (IRBs), and clinical investigators involved in multicenter clinical research in meeting the requirements of 21 CFR part 56 by facilitating the use of a centralized IRB review process (use of a single central IRB), especially in situations where centralized review could improve efficiency of IRB review.

Considerations When Transferring Clinical Investigation Oversight to Another, Guidance for IRBs, Clinical Investigators, and Sponsors

This guidance discusses the regulatory responsibilities of institutional review boards (IRBs), clinical investigators, and sponsors when oversight of a previously approved, ongoing clinical investigation under FDA’s jurisdiction is transferred from one IRB to another IRB.  This guidance also addresses questions that have been previously raised concerning procedures and processes that are required and/or recommended by FDA when such oversight is transferred. 

HIPAA Authorizations Under FDA Regulations, IRB Review of Stand-Alone, Guidance for Industry (PDF - 614 KB)

This guidance provides clarification for IRBs of their responsibilities for reviewing and approving stand-alone authorizations under the HIPAA Privacy Rule.

Informed Consent Elements, 21 CFR 50.25(c), Questions and Answers on, Guidance for Sponsors, Investigators and Institutional Review Boards

This guidance is intended to help sponsors, investigators and Institutional Review Boards better understand the new informed consent requirement set forth in 21 CFR 50.25(c). The guidance will assist those involved in applicable FDA-regulated clinical trials better understand the new informed consent requirement, including small businesses.

IRB Continuing Review after Clinical Investigation Approval, Guidance for IRBs, Clinical Investigators, and Sponsors (PDF - 320 KB)
 
This guidance is intended to assist institutional review boards (IRBs) in carrying out their continuing review responsibility under 21 CFR 56.108(a) and 56.109(f) by providing recommendations regarding the criteria, process, and frequency of continuing review to assure the protection of the rights and welfare of human subjects enrolled in clinical investigations. This guidance should also help clinical investigators and sponsors better understand their responsibilities related to continuing review.
 

IRB Registration, Frequently Asked Questions, Guidance for Institutional Review Boards (IRBs) (PDF - 48 KB)

This guidance is intended to assist IRBs in complying with the requirement for IRB registration under amended 21 CFR 56.106, effective July 14, 2009.   Registration is accomplished through a modified version of the Internet-based registration system used by OHRP for registration of IRBs that are designated by institutions under FWAs.   This guidance document addresses basic information, such as why FDA issued a new rule requiring registration, which IRBs are subject to the regulation, the type of information to be provided when registering, and implications of non-compliance.

IRB Responsibilities for Reviewing the Qualifications of Investigators, Adequacy of Research Sites, and the Determination of Whether an IND/IDE is Needed, Guidance for IRBs, Clinical Investigators, and Sponsors   
 
All of the parties who conduct or have oversight responsibilities for biomedical research—sponsors, clinical investigators, and institutional review boards (IRBs)—have responsibility for ensuring that the research complies with applicable laws and regulations and that risks to subjects are minimized.  Although selection of clinical investigators and research sites, and determining if an investigational new drug application (IND) or investigational device exemption (IDE) is required are viewed primarily as sponsor responsibilities, FDA is issuing this guidance to clarify IRBs' responsibilities related to these activities and to encourage all parties to work together in order to protect the rights and welfare of study subjects. 

The Radioactive Drug Research Committee: Human Research Without An Investigational New Drug Application, Guidance for Industry and Researchers (PDF - 417KB)

This guidance is intended to provide information for those using radioactive drugs for certain research purposes to help determine whether research studies can be conducted under 21 CFR 361.1, Prescription Drugs for Human Use Generally Recognized as Safe and Effective and Not Misbranded: Drugs Used in Research, or whether research studies must be conducted under 21 CFR part 312, Investigational New Drug Application (IND).

The Radioactive Drug Research Committee: Human Research Without An Investigational New Drug Application - Guidance for Industry and Researchers (PDF - 276 KB)

This guidance is intended to provide information for those using radioactive drugs for certain research purposes to help determine whether research studies can be conducted under 21 CFR 361.1, Prescription Drugs for Human Use Generally Recognized as Safe and Effective and Not Misbranded: Drugs Used in Research, or whether research studies must be conducted under 21 CFR part 312, Investigational New Drug Application (IND).

Drugs and Biologics

Available Therapy, Guidance for Industry

This guidance is intended to provide guidance to industry on the meaning of the term "available therapy" as currently used by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) in the FDA in the specific circumstances described in the guidance.

Bioavailability and Bioequivalence Testing Samples, Handling and Retention of, Guidance for Industry (PDF - 166KB)

Inspection of clinical and analytical sites that perform bioavailability (BA) and bioequivalence (BE) studies frequently reveals the absence of reserve samples at the testing facilities where the studies are conducted. The guidance is intended to clarify how to distribute test articles and reference standards to testing facilities, how to randomly select reserve samples, and how to retain reserve samples.

Clinical Holds Following Clinical Investigator Misconduct, Guidance for Industry and Clinical Investigators on the Use of (PDF - 33KB)

This guidance for industry and clinical investigators provides information on one use by FDA of its authority to impose a clinical hold on a study or study site if FDA finds that human subjects are or would be exposed to unreasonable and significant risk of illness or injury.  Specifically, this guidance describes circumstances in which FDA may impose a clinical hold based on credible evidence that a clinical investigator conducting the study has committed serious violations of FDA regulations on clinical trials of human drugs and biologics.

Enforcement of Safety Reporting Requirements for INDs and BA/BE Studies, Guidance for Industry and Investigators (PDF - 41KB)
 
This document provides guidance to sponsors and investigators on enforcement of FDA’s final rule, "Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and Safety Reporting Requirements for Bioavailability and Bioequivalence Studies in Humans" (75 FR 59935, September 29, 2010). This guidance contains information regarding the Agency’s intent to exercise enforcement discretion regarding the reporting requirements in the final rule until September 28, 2011.

Exploratory IND Studies, Guidance for Industry (PDF - 220KB)

This guidance describes the preclinical and clinical issues as well as chemistry, manufacturing and controls information that should be considered when planning exploratory studies including studies of related drugs or biologics under an investigational new drug (IND) application.

FDA Acceptance of Foreign Clinical Studies Not Conducted Under an IND, Frequently Asked Questions, Guidance for Industry and FDA Staff (PDF - 108KB)
 
This guidance document is intended to clarify for sponsors and applicants how they can demonstrate compliance with the requirements of 21 CFR 312.120.  It provides recommendations for the submission of information, whether in an IND or application for marketing approval for a drug or biological drug product, to demonstrate that a non-IND foreign clinical study was conducted in accordance with GCP.

Food-Effect Bioavailability and Fed Bioequivalence Studies, Guidance for Industry (PDF - 166KB)

This guidance provides recommendations to sponsors and/or applicants planning to conduct food-effect bioavailability (BA) and fed bioequivalence (BE) studies for orally administered drug products as part of investigational new drug applications (INDs), new drug applications (NDAs) and abbreviated new drug applications (ANDAs), and supplemental applications.

Gender Differences in the Clinical Evaluation of Drugs, Guideline for the Study and Evaluation of, Guidance for Industry (PDF - 1.83MB)

This guideline presents guidance on FDA's expectations regarding inclusion of both genders in drug development.

Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment, Guidance for Industry (PDF - 220KB)

This guidance is intended to assist industry with risk management activities for drug products, including biological drug products, in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER).

IND Exemptions for Studies of Lawfully Marketed Drug or Biologicial Products for the Treatment of Cancer, Guidance for Industry (PDF - 188KB)

This guidance is intended to assist sponsors in deciding whether a study of marketed drugs or biological products for treating cancer falls within the exemption under § 312.2(b)(1) (21 CFR 312.2(b)(1)) from the general requirement to submit an investigational new drug application (IND).

Premarketing Risk Assessment, Guidance for Industry (PDF - 91KB)

This guidance is intended to assist industry with risk management activities for drug products, including biological drug products, in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER).

Providing Regulatory Submissions in Electronic Format – Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications, Guidance for Industry

This guidance discusses issues related to the electronic submission of new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), investigational new drug applications (INDs), master files, advertising material, and promotional labeling using the electronic common technical document (eCTD) specifications.

Safety Reporting Requirements for INDs and BA/BE Studies, Guidance for Industry and Investigators (PDF-228 KB)

This guidance is intended to help sponsors and investigators comply with the requirements for investigational new drug (IND) safety reporting and safety reporting for bioavailability (BA) and bioequivalence (BE) studies under 21 CFR 312.32, 312.64(b), and 320.31(d)(3). This document provides guidance to sponsors and investigators on expedited safety reporting requirements for human drug and biological products that are being investigated under an IND and for drugs that are the subjects of BA and BE studies that are exempt from the IND requirements. This guidance defines terms used for safety reporting, makes recommendations on when and how to submit a safety report, and provides advice on other safety reporting issues that have arisen from sponsors and investigators.

Safety Reporting Requirements for INDs and BA/BE Studies-Small Entity Compliance Guide, for Industry and Investigators (PDF-35KB)

This guidance is intended to help small businesses understand and comply with FDA’s safety reporting regulations for human drug and biological products that are being investigated under an investigational new drug application (IND) and for drugs that are the subjects of bioavailability (BA) and bioequivalence (BE) studies that are exempt from the IND requirements. The FDA has prepared this guidance in accordance with section 212 of the Small Business Regulatory Enforcement Fairness Act (Public Law 104-121).

Serious or Life-Threatening Diseases and Conditions, Information Program on Clinical Trials for, Guidance for Industry (PDF - 34KB)

This guidance is intended to assist sponsors who will be submitting information to the Clinical Trials Data Bank. It addresses statutory and procedural issues for submitting information to the data bank.

Medical Devices

Analyte Specific Reagents (ASRs): Frequently Asked Questions, Guidance for Industry and FDA Staff – Commercially Distributed (PDF - 139KB)

This guidance document is intended to clarify the regulations regarding commercially distributed analyte specific reagents (ASRs) (21 CFR 809.10(e), 809.30, and 864.4020), and the role and responsibilities of ASR manufacturers. This document is not intended to provide guidance on the role of clinical laboratories in the development of laboratory developed tests (LDTs). The guidance follows the substance, spirit, and meaning of the ASR regulations already in place.

Humanitarian Device Exemption (HDE) Regulation: Questions and Answers; Guidance for HDE Holders, Institutional Review Boards (IRBs), Clinical Investigators, and FDA Staff

This guidance document answers commonly asked questions about Humanitarian Use Devices (HUDs) and applications for Humanitarian Device Exemption (HDE) authorized by section 510(m)(2) of the Federal Food, Drug, and Cosmetic Act (the Act). It also reflects the additional requirements set forth in the Pediatric Medical Device Safety and Improvement Act of 2007.

Humanitarian Use Device (HUD) Designations, Guidance for Industry and Food and Drug Administration Staff (PDF - 92KB)

This guidance document is intended to assist applicants in the preparation and submission of Humanitarian Use Device (HUD) designation requests to the U.S. Food and Drug Administration’s (FDA or Agency) Office of Orphan Products Development (OOPD). It is also designed to assist FDA reviewers in their evaluation and analysis of HUD designation requests ("HUD requests" or "requests").

Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable, Guidance for Sponsors, Institutional Review Boards, Clinical Investigators and FDA Staff

This guidance informs sponsors, institutional review boards (IRBs), clinical investigators, and agency staff that the FDA intends to exercise enforcement discretion, under certain circumstances, with respect to its current regulations governing the requirement for informed consent when human specimens are used for FDA regulated in vitro diagnostic device investigations.

In Vitro Diagnostic (IVD) Device Studies -Frequently Asked Questions, Guidance for Industry and FDA Staff (PDF - 342KB)

This guidance document outlines FDA regulations applicable to studies for investigational IVD devices, including those regulations related to human subject protection. The guidance also explains data considerations that ultimately will affect the quality of the premarket submission. It includes a glossary, a reference list with related web addresses, and a quick-reference table.

Software Validation, General Principles of, Guidance for Industry and FDA Staff

The primary purpose of this guidance is to outline general validation principles that the FDA considers applicable to the validation of medical device software or the validation of software used to design, develop, or manufacture medical devices.  In addition, it contains useful validation principles applicable to software used in the conduct of clinical trials.

Manufacturing Requirements for Investigational Products

Current Good Manufacturing Practice for Phase 1 Investigational Drugs (PDF - 132KB)

This guidance is intended to assist in applying current good manufacturing practice (CGMP) required under section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) in the manufacture of most investigational new drugs (IND) used in phase 1 clinical trials. These drugs, which include biological drugs, are exempt from complying with 21 CFR part 211 under 21 CFR 210.2(c) (referred to as phase 1 investigational drugs).

Design Control Guidance for Medical Device Manufacturers

This guidance is intended to assist manufacturers in understanding quality system requirements concerning design controls. Assistance is provided by interpreting the language of the quality systems requirements and explaining the underlying concepts in practical terms.  As discussed under Device Advice, devices approved under an investigational device exemption (IDE) are exempt from the Quality System (QS) regulation, except for the design control requirements under §820.30. However, the sponsor may state an intention to comply with other parts of the QS regulation. The extent to which the Quality System regulation will be followed in manufacturing the device must be documented in the sponsor’s IDE records [§812.140(b)(4)(v)].

INDs for Phase 2 and Phase 3 Studies: Chemistry, Manufacturing, and Controls Information (PDF – 193KB)

This guidance provides recommendations to sponsors of investigational new drug applications (INDs) on the chemistry, manufacturing, and controls (CMC) information that would be submitted for phase 2 and phase 3 studies conducted under INDs. This document applies to human drugs (as defined in the Federal Food, Drug, and Cosmetic Act). It does not apply to botanical drug products, protein drug products derived from natural sources or produced by the use of biotechnology, or other biologics. The goals of this document are to (1) ensure that sufficient data will be submitted to the Agency to assess the safety, as well as the quality of the proposed clinical studies from the CMC perspective, (2) expedite the entry of new drug products into the marketplace by clarifying the type, extent, and reporting of CMC information for phase 2 and phase 3 studies, and (3) facilitate drug discovery and development.
 

Electronic Data

Computerized Systems Used in Clinical Investigations, Guidance for Industry  (PDF - 53KB)

This guidance provides recommendations to sponsors, contract research organizations, data management centers, clinical investigators and institutional review boards regarding the use of computerized systems in clinical investigations.

Part 11, Electronic Records; Electronic Signatures--Scope and Application, Guidance for Industry on (PDF - 215KB)

This guidance is intended to describe the FDA's current thinking regarding the scope and application of part 11 of Title 21 of the Code of Federal Regulations; Electronic Records; Electronic Signatures (21 CFR Part 11).