Written by: Gerald L. Klein, MD: Burak Pakkal, MD; Roger E. Morgan, MD; Renu Jain, PhD; Shabnam Vaezzadeh, MD; Pavle Vukojevic, MD; Larry Florin, MBA; Victoria Manax, MD
Drug Development
In 2023, the U.S. Food and Drug Administration (FDA) published numerous significant guidance documents. Below is a selection of these key publications.
Numerous types of real-world data can be analyzed in non-clinical trials such as registries, electronic health records, medical claims, and data on products used in clinical practice as part of a package for FDA regulatory product approval.[1]
The FDA suggests the following:
Early engagement will allow for timely identification of challenges in the design and planning of a non-interventional study and for discussion of how such challenges might be addressed.
When submitting a meeting request, sponsors should include adequate information - as outlined in FDA guidance for formal meetings - for FDA to both assess the potential utility of a meeting and to identify relevant FDA subject matter experts who should address the proposed agenda items.
Optimizing the dosage for oncology products now requires a strong rationale for choice of dosage which should be provided before initiating registration trial(s):
To support a subsequent indication and usage:
Especially for oncologic diseases not adequately represented in completed dose-finding trials or for new combination regimens.
If sufficient rationale for choice of dosage cannot be provided, additional dose-finding should be conducted.[2]
The FDA further states that different dosages may be needed in different disease settings or oncologic diseases based on potential differences in tumor biology patient population, treatment setting, and concurrent therapies (for combination regimens), among other factors.
Applicable nonclinical and clinical data should be considered to support the proposed.
Different dosages may be needed in different disease settings or oncologic diseases based on potential differences in tumor biology, patient population, treatment settings, and concurrent therapies (for combination regimens), among other factors.
Applicable nonclinical and clinical data should be considered to support the proposed.
For additional information, please see FDA’s Project Optimus:
When developing drugs for rare indications, the FDA frequently allows the use of innovative trial designs. These should be discussed with the appropriate division very early on. This may include Bayesian methods, n-of-1 clinical studies, randomized delayed-start designs, crossover designs, and master protocol.[3] These studies require a detailed statistical analysis plan including key features of the clinical investigation design and preplanned analysis discussed with the review team before the study initiatives.
Canadian Regulatory Pointers
On December 4, 2023, Health Canada’s Regulatory Operations and Enforcement Branch revised the medical device establishment licence (MDEL) application form. The form is used to:
Apply for an MDEL
Apply for an MDEL after a cancellation
Submit changes to your existing MDEL
Cancel your MDEL
Apply for a reinstatement of your MDEL after a suspension
For specific details, visit the following website: https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/establishment-licences/medical-devices-compliance-bulletin/updates-frm0292-instructions.html
Medical Affairs
Direct-to-Consumer Prescription Drug Advertisements in television and radio in new guidance document:[4]
First Standard: The major statement is presented in consumer-friendly language and terminology is readily understandable.
Second Standard: The major statement’s audio information, in terms of the volume, articulation, and pacing used, is at least as understandable as the audio information presented in the rest of the advertisement.
Third Standard: In advertisements in television format, the major statement is presented concurrently using both audio and text.
Fourth Standard: In advertisements in television format, for the text portion of the major statement, the size and style of font, the contrast with the background, and the placement on the screen allow the information to be read easily.
Fifth Standard: During the presentation of the major statement, the advertisement does not include audio or visual elements, alone or in combination, which are likely to interfere with comprehension of the major statement.
1. Considerations for the use of real-world data and real-world evidence to support regulatory decision-making for drug and biological products. Guidance for Industry. August 2023.
2. Optimizing the dosage of human prescription drugs and biological products for the treatment of oncologic diseases. Guidance for Industry January 2023.
3. Rare Diseases: Considerations for the development of drugs and biological products. Guidance for industry. December 2023.
4. 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 Q&A. Guidance for Industry December 2023.