FDA Guidance Portal

To comply with the 21st Century Cures Act, the Food and Drug Administration (FDA or USFDA) has released a Notice of Proposed Rulemaking (NPRM). This NPRM describes changes to FDA regulations to harmonize with the Common Rule regarding informed consent requirements. It describes the requirements for a “key information” section to be placed at the start of the consent form. This section should provide a summary of the most important information that may lead someone to decide whether to participate in a trial. FDA is also proposing to include three additional elements of informed consent, which have already been included in the revised Common Rule. IRBs, institutions, and investigators involved in the review and conduct of federally-funded research have already adopted many of these provisions in 2018 in the Common Rule, but other commercial sponsors and investigators should update consent form templates and other documents to comply with this proposed rule.

On August 21, 2024, The International Council for Harmonization of Technical Requirements for Pharmaceutical Use for Human Use (ICH) finalized Guideline E11A on Pediatric Extrapolation. The purpose of the guideline is to provide recommendations and facilitate global harmonization for the use of pediatric extrapolation to support the development and approval of pediatric medicines. The Food and Drug Administration (FDA) adopted this guideline as FDA guidance in December 2024. The guidance contains additional information specific to pediatric extrapolation and builds on information in the ICH E11 (R1) guideline “Clinical Investigation of Medical Products in the Pediatric Population: Guideline and Addendum,” which was also adopted by the FDA as guidance. By exploring the ICH E11A guideline, this piece defines pediatric extrapolation and the regulatory expectations, describes ethical considerations, and shares study design adaptations for pediatric extrapolation.  

On August 15, 2023, FDA published a final guidance entitled, “Informed Consent, Guidance for IRBs (Institutional Review Boards), Clinical Investigators, and Sponsors.” This final guidance supersedes the September 1998 guidance entitled “A Guide to Informed Consent” and replaces the July 2014 draft guidance “Informed Consent Information Sheet.” The final guidance references where the differences exist between FDA regulations and the 2018 Common Rule, where there are plans to update the regulations and how IRBs, investigators and sponsors might navigate the differences between the two processes in the meantime. This whitepaper provides a summary of the final guidance and offers insights into its value as a resource for IRBs, Investigators and sponsors when considering the informed consent process.

The Food and Drug Administration (FDA) published final guidance, “Conducting Clinical Trials With Decentralized Elements” on Sept. 18, 2024. This final version does not differ substantially from the previously published draft guidance released in May 2023, but it does provide more specific guidance on how to designate decentralized research personnel as either investigators or other personnel based on their role in the research.

In July 2024, the Food and Drug Administration (FDA) released a draft guidance for industry entitled “Pediatric Inflammatory Bowel Disease: Developing Drugs for Treatment.” The draft guidance is intended to help sponsors developing drugs to treat pediatric patients with inflammatory bowel disease and includes recommendations about the necessary components of clinical studies for the treatment of pediatric ulcerative colitis or pediatric Crohn’s disease, including study population, study design, efficacy considerations, and safety assessments.

On April 29, 2024, The FDA announced a final rule aimed at helping to ensure the safety and effectiveness of laboratory developed tests (LDTs). The rule amends the FDA’s regulations to make explicit that in vitro diagnostic products (IVDs) are devices under the Federal Food, Drug, and Cosmetic Act (FD&C Act) including when the manufacturer of the IVD is a laboratory. This whitepaper discusses a brief history of diagnostic assay oversight (or lack thereof) and provides support for the FDA’s decision to establish clear regulatory pathways for LDTs.

In March 2024, the Food and Drug Administration (FDA) revised its draft guidance for industry entitled “Early Alzheimer’s Disease: Developing Drugs for Treatment”. This guidance applies specifically to trials targeting patients with early sporadic Alzheimer’s disease (AD), prior to the onset of overt dementia. The previous draft guidance published in 2018 required revisions due to the rapidly changing landscape of AD clinical trials, which are increasingly focusing on early disease stages. While cognitive and functional endpoints remain crucial, the 2024 guidance offers more flexibility in their application. Recognizing the challenges in capturing functional changes in early disease stages, the guidance supports the use of sensitive cognitive assessments and other innovative approaches to detect clinically meaningful changes, thus offering a more nuanced understanding of drug efficacy in this context.

This guidance is one in a series of guidances addressing eligibility for clinical trials of oncology drugs.  Specifically, this guidance includes recommendations regarding expanding eligibility criteria to include patients with a wider range of performance status (PS).

On April 4, 2024, the National Institutes of Health released a finalized amendment to the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines). As noted in the Federal Register notice, the amendment goes into effect September 30, 2024. As of that date, certain genetically engineered cellular therapies will be subject to the NIH Guidelines and biosafety requirements outlined therein. This blog post provides additional details from our experts and insights about what the changes could mean for your research.

This guidance provides recommendations to sponsors and investigators who are considering submitting a non-interventional study, also referred to as an observational study, to FDA to contribute to a demonstration of substantial evidence of effectiveness and/or evidence of safety of a drug. 

The FDA has provided a question and answer document on Dietary Supplements. This whitepaper will examine what sponsors/investigators need to consider when designing a study with dietary supplements to ensure compliance with the FDA requirements. When reviewing a proposed study, the IRB applies the regulations that govern dietary supplements, as well as the regulations that govern drugs. Under current regulations, if the objective(s) of a clinical investigation of products lawfully marketed as dietary supplements meet the FDA’s definition of a health claim, an IND is usually required. However, if the objective(s) of the study are to assess the effect of a dietary supplement on the body’s structure, function, or mechanism of action, then an IND may not be required.

The release of the FDA’s draft guidance on Data Monitoring Committees (DMCs) aims to modernize and clarify expectations for DMC involvement in safeguarding participant well-being and ensuring trial integrity. Several topics are highlighted including risk/benefit assessment, maintaining independence and reducing bias, sharing oversight responsibilities, defining analyses, and utilizing unbiased statistical support. Potential benefits to the clinical trial industry include enhanced participant safety, increased study rigor and integrity, and reduced time to market.

FDA’s Path toward Diversity in Clinical Trials: The DEPICT Act and Sponsor Responsibility” describes the DEPICT Act and its practical effect within the clinical trials space. The DEPICT Act requires the FDA to require clinical trial sponsors to submit Diversity Action Plans with their protocols for Phase III or other pivotal trials.  This white paper further discusses the DEPICT Act’s effect on Sponsor responsibility and accountability as it pertains to the diversity of populations enrolled in their clinical trials. Recommendations are provided for the facilitation of the requirements of the DEPICT Act as well as recognition of some of the challenges ahead.

In May 2023, The FDA issued a draft guidance on the topic of decentralized clinical trials for drugs, biological products, and Devices. This blog post seeks to assist sponsors/CROs in understanding the IRB’s requirements for submitting research locations for decentralized clinical trials.

On March 30, 2023, FDA and OHRP published a Draft Guidance that describes the process for referral of research involving children as subjects and not otherwise approvable by an IRB.  The Draft Guidance describes the required documents that must be provided to FDA and identifies IRBs and institutions as the organizations that are expected to make the 21 CFR 50.54, 45 CFR 46.407 referrals. This blog post describes current WCG policy, which is to encourage sponsors, rather than the IRB, to initiate communication with, and directly interact with, FDA, OHRP or both regarding research on investigational products under an IND or IDE.

To comply with the 21st Century Cures Act,1 the Food and Drug Administration (FDA or USFDA) has released two Notices of Proposed Rulemaking (NPRMs). One NPRM describes a potential requirement for multi-site research that is under FDA oversight to use a single IRB for the review of all study sites. Commercial sponsors and CROs should be prepared to address this new requirement if and when it is implemented, although the change should lead to less administrative burden on sponsors and CROs as only one IRB will review each study.

On January 7, 2025, the Food and Drug Administration (FDA) issued a draft guidance entitled “Considerations for the Use of Artificial Intelligence (AI) To Support Regulatory Decision-Making for Drug and Biological Products.” This long-awaited guidance provides recommendations to the industry and other interested parties on the use of artificial intelligence (AI) to generate information or data to support regulatory decision making. The draft guidance specifically focuses on the use of AI to support establishing the safety, effectiveness, and quality of drugs using a risk-based credibility assessment framework for a particular context of use (COU). The draft guidance does not address the use of AI in areas such as drug discovery or operational efficiencies in drug development since these generally do not impact participant safety, the reliability of results from clinical or non-clinical studies, or drug quality.

On October 2, 2024, the Food and Drug Administration (FDA) released the guidance, Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers. The guidance expands on the part 11 guidance from 2003, which is narrowly interpreted by the FDA. Since technology capability and uses have expanded, this guidance provides additional recommendations to the still applied 2003 guidance for current technology. Together, the purpose of the two guidances is to ensure the authenticity, integrity, and confidentiality of electronic data and records for clinical investigations when they are created, modified, maintained, archived, retrieved, or transmitted. This 2024 guidance question and answer format goes into greater detail, organized by section: electronic records, electronic systems, information technology service providers and services, digital health technologies, and electronic signatures.