FDA Refreshes M12 Drug Interaction And Oct Labeling Index

Regulatory affairs teams preparing NDA and BLA submissions now have two updated reference points to reconcile: FDA's M12 Drug Interaction Studies guidance (August 2024) and the draft Drug Interaction Information in Human Prescription Drug and Biological Product Labeling (October 2024), both listed on the agency's refreshed drug interaction guidance index. Submissions that were benchmarked against earlier frameworks may require a gap assessment before filing.

The index consolidates drug-drug interaction guidances, clinical pharmacology references, and labeling documents into a single navigable resource. Beyond M12, the collection includes the June 2023 guidance on drug-drug interaction assessment for therapeutic proteins, the March 2023 evaluation of gastric pH-dependent interactions with acid-reducing agents, and the June 2023 guidance on clinical studies with combined oral contraceptives. Each carries distinct study design and data analysis expectations that feed directly into submission packages.

For teams working on complex modalities, two additional documents carry near-term relevance: Clinical Pharmacology Considerations for Antibody-Drug Conjugates (March 2024) and Clinical Pharmacology Considerations for the Development of Oligonucleotide Therapeutics (June 2024). Both sit under the related clinical pharmacology and biopharmaceutics section of the index and address characterisation requirements that intersect with interaction study design.

Several documents in the labeling section remain in draft status, including the October 2024 drug interaction labeling guidance and the January 2023 guidance on dosage and administration content and format. FDA notes that when finalised, these will represent the agency's current thinking; until then, sponsors should track the FDA guidance page for version updates, as the index itself is updated periodically and earlier cached versions may not reflect the most recent revisions.

The index also references MAPP 4000.4 Rev 1, which documents CDER's internal good review practices for clinical pharmacology review of NME NDAs and original BLAs, providing regulatory affairs leads with visibility into the review lens applied to their submissions.

Sponsors with submissions in active review cycles should confirm that their drug interaction study packages and labeling sections align with the August 2024 M12 guidance and account for the expectations outlined in the October 2024 draft labeling document before those positions are finalised.

Source: FDA CDER via What's New: Drugs RSS Feed, 1 October 2026.