Happy new year folks!
The FDA sent out a flurry of notices in the last 2 weeks of 2023. Some fulfill legislative requirements under the 2022 Food and Drug Omnibus Reform Act (FDORA) or PDUFA VII. Staying current and reading up on which ones are most important to your organization can be overwhelming. Although not an exhaustive list, we've captured some key points we think may be important to our clients and small / scaling sponsors engaging with the FDA this year .
Table of Contents:
- Master Protocols for Drug and Biological Product Development (Draft)
- Direct-to-Consumer Prescription Drug Advertisements (Final)
- Data Standards for Drug and Biological Product Submissions Containing Real World Data (Final)
- Digital Health Technologies for Remote Data Acquisition in Clinical Investigations (Final)
- Rare Diseases: Considerations for the Development of Drugs and Biological Products (Final)
- Update on In-Person and Virtual Meetings (effective 1/22/24)
- EMA & FDA Joint Q&A on Quality Development and SMP for PRIME and BT Applications
Master Protocols for Drug and Biological Product Development
What is it?
A master protocol is designed with multiple substudies.
- Substudies may have different objectives
- Substudies are coordinated within an overall study structure to evaluate:
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- One or more medical products
- One or more diseases or conditions
Who is it for?
Sponsors interested in taking advantage of the master protocol for multiple therapies or conditions outside of COVID-19.
Master protocols may be utilized:
- Umbrella trial: Evaluates multiple medical products at the same time for a single disease or condition
- Platform trial: Evaluates multiple medical products for a disease or condition and medical products can enter or leave the platform in an ongoing manner
- Basket trial: Evaluates a medical product for multiple diseases, conditions, or disease subtypes
Why is it important?
Trials conducted under master protocols can share control arms, protocol elements, infrastructure, and oversight, thereby maximizing the amount of information obtained from a research effort.
The Goal is to plan clinical investigation strategies from a platform or franchise perspective. Much more efficient and economical to 'matrix' your drug/biologic investigational trials to leverage safety data for related patient populations and clinical indications.
Quick History: Master protocols began in 2021 for COVID-19 trials and were intended as temporary under section 319 of the Public Health Services Act. FDA sees the expiring guidance has recommendations beyond COVID-19 and emergency health for other therapies.
Where to learn more:
Listen to the Podcast: https://www.fda.gov/media/174982/download?attachment
Podcast Transcript: https://www.fda.gov/drugs/guidances-drugs/guidance-recap-podcast-master-protocols-drug-and-biological-product-development
Complimentary Reading: FDA's complementary clinical trial design for Oncology guide from 2022: https://www.fda.gov/media/120721/download?attachment
Direct-to-Consumer Prescription Drug Advertisements:
Presentation of the Major Statement in a Clear, Conspicuous, and Neutral Manner in Advertisements in Television and Radio Format Final Rule Questions and Answers. Document is in Q&A format.
What is it?
A Q&A document establishing standards to help ensure major statements in advertisements are presented in the manner required by the CCN Final Rule modifying 1 CFR 202.1(e)(1).
Who is this for?
Small entities to understand and comply with the standards for Direct-to-Consumer Prescription Drug Advertisements in TV and Radio.
Why is it important?
Required by law. Sponsors inclusive of small entities must comply with the CCN Final Rule which modifies (21 CFR 202.1(e)(1) to reflect the requirement in section 502(n) of the FD&C Act (21 U.S.C. 352(n)) that human prescription drug advertisements presented directly to consumers (DTC) in television or radio format and stating the name of the drug and its conditions of use (DTC TV/radio ads) present the major statement relating to side effects and contraindications in a clear, conspicuous, and neutral manner.
Where to read more:
Download the guidance document: https://www.fda.gov/media/175074/download
Data Standards for Drug and Biological Product Submissions Containing Real-World Data
What is it?
Updated guidance provides recommendations to sponsors to help support compliance with the Federal Food, Drug, and Cosmetic Act (FD&C Act) when submitting study data derived from real-world data (RWD) sources in applicable regulatory submissions using standards specified in the Data Standards Catalog.
- Guidance addresses complexities of RWD collected globally from different data sources and domains.
- Document provides frameworks to apply RWD to define.xml, CDISC SDTM.
Who is it for?
Sponsors who run RWD and RWE postmarketing studies.
Why is it important?
Although not required, the updated guidance is a follow up to a draft document and provides the FDA’s current thinking and available resources.
Where to read more:
Download the guidance: https://www.fda.gov/media/153341/download
Digital Health Technologies for Remote Data Acquisition in Clinical Investigations
What is it?
Guidance that provides industry, investigators and others recommendations on the use of digital health technologies (DHTs) to acquire data remotely from participants in clinical investigations that evaluate medical products. Recommendations on the use of digital health technologies (DHTs) to acquire data remotely from participants in clinical investigations that evaluate medical products.
Who is it for?
Sponsors, investigators using DHT in clinical trials.
Why is it important?
Use of DHTs as recommended in this guidance may improve the efficiency of clinical trials for sponsors, investigators, and other stakeholders and may increase the opportunities for individuals to participate in research and make participation more convenient. This final guidance satisfies FDORA requirements.
Where to read more:
Download the document:https://www.fda.gov/media/155022/download
- Of note: This guidance uses the terms verification and validation to describe steps that help ensure that the DHT is fit-for-purpose for remote data collection in a clinical investigation.
- In submissions, the sponsor should explain how the DHT is fit-for-purpose: including information such as design and related technological characteristics of the DHT, data output provided to the sponsor and investigator, and information on how the DHT measures the clinical event or characteristic of interest (e.g., use of accelerometry to measure steps or use of photoplethysmography to count heartbeats).
- Other Major sections: Evaluating Endpoints, Statistical Analysis and Trial Design Considerations, Risk considerations (including privacy and informed consent), record keeping and retention strategies, roles and responsibilities.
Rare Diseases: Considerations for the Development of Drugs and Biological Products
What is it?
This guidance finalizes the draft guidance. Intended to assist sponsors of drugs and biological products for treatment of rare diseases in conducting efficient and successful drug development programs through a discussion of selected issues commonly encountered in rare disease drug development.
Who is it for?
Sponsors developing drug and biologics to treat rare diseases. FDA defines rare diseases as those that affect less than 200,000 patients.
Why is it important?
It addresses important aspects of drug and biological product development to support the proposed clinical investigation(s), including nonclinical pharmacology/toxicology; trial design and endpoint considerations to ensure quality and interpretability of data; standard of evidence to establish safety and effectiveness; and drug manufacturing considerations during drug development.
- Major changes from the draft document include:
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- Removal of the natural history section (because this is addressed in a separate guidance).
- Additional considerations regarding nonclinical studies.
- Information on the use of external controls and early randomization.
- A section discussing safety considerations.
- Information on changes to drug substance or manufacturing process.
- Sections discussing participation of patients/patient groups in drug development programs.
- Pediatric considerations in rare disease drug development.
Where to read more:
Download the document:https://www.fda.gov/media/119757/download
Update on In-Person and Virtual Meetings
What is it?
Notice on in-person and virtual meetings to satisfy PDUFA VII and BsUFA III commitments.
Beginning January 22, 2024, CDER and CBER will expand in-person FTF industry meetings (with a hybrid component) to include all PDUFA, BsUFA, and OMUFA meeting types.
Who is it for?
Sponsors developing drugs, biosimilars or OTC medications.
Why is it important?
Guidance expands the former guideline to include ALL meeting types.
Where to read more:
FDA website: https://www.fda.gov/industry/prescription-drug-user-fee-amendments/update-person-face-face-formal-meetings-fda
Joint FDA and EMA Question and Answer on Quality and GCP for PRIME and Breakthrough Therapies
What is it?
EMA and the FDA have just published a joint Q&A document on quality development and good manufacturing practice for Priority Medicines (PRIME) and Breakthrough therapy (BT) designation applications.
Who is it for?
Sponsors developing PRIME and BT therapies.
Why is it important?
PRIME and BT Programmes offer early and enhanced support to developers and accelerated assessment timelines for medicines that target an unmet medical need. This way these much-needed treatments can reach patients as quickly as possible in the EU and the US.
Q&A provides medicine developers with guidance on how to address challenges associated with expedited product development, so that robust quality and manufacturing data packages will be available to support their application.
Based on the experience with PRIME and BT programs, regulators and industry selected the following areas for discussion:
- process validation
- control strategy
- compliance with Current Good Manufacturing Practice (GMP) requirements
- comparability
- stability
- regulatory tools
The discussions and main conclusions from the workshop, including scientific elements and regulatory tools which already exist, or which would benefit from exploration, to help address development challenges, were captured in a meeting report.
Where to read more?
EMA website for the Q&A report: https://www.ema.europa.eu/en/documents/report/report-workshop-stakeholders-support-quality-development-early-access-approaches-ie-prime-breakthrough-therapies_en.pdf
EMA PRIME therapies: https://www.ema.europa.eu/en/human-regulatory-overview/research-and-development/prime-priority-medicines
FDA Breakthrough therapies: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy
Follow FDA and EMA on LinkedIn to stay up to date.
