M4Q(R2); The Common Technical Document for the Registration of Pharmaceuticals for Human Use: Quality; Draft Guidance

The commenter, a pharmaceutical quality-control and analytical-development professional, supports the adoption of the ICH M4Q(R2) guideline as a step toward digitalization and clearer lifecycle management. They propose specific modifications to the dossier structure to explicitly define "critical sample-preparation parameters" and to provide a designated location for documenting AI-assisted or algorithmic decision-support tools.

Module 3 Solutions, LLC, a vendor and standards contributor, supports the M4Q(R2) draft guidance as an important step toward digital harmonization. They request specific U.S.-specific implementation guidance and technical clarifications regarding eCTD v4.0 compatibility, lifecycle traceability, and cross-center governance to ensure a smooth transition for sponsors.

Veeva Systems, a cloud-based software company for the life sciences industry, supports the FDA's proposal to require the ICH M4Q(R2) format for CMC information. They offer specific recommendations regarding lifecycle management of structured data, alignment with existing standards, and the development of global transition plans.

Otsuka Pharmaceutical Development & Commercialization, Inc. expresses support for the draft guidance regarding the Common Technical Document for the registration of pharmaceuticals. They suggest specific improvements, such as clarifying the inclusion of raw materials like processing aids and requesting a transition period for industry compliance.

Insmed Incorporated expresses support for the draft guidance on the Common Technical Document for the Registration of Pharmaceuticals for Human Use: Quality. The company proposes several specific refinements and additions to the guidance to improve consistency, clarity, and reduce redundant post-approval filing burdens.

The Association for Accessible Medicines (AAM) supports the modernization of the M4Q(R2) draft guidance but requests a long transition period of at least five years to manage the operational impact on generic and biosimilar manufacturers. They also advocate for the guidance to be applied prospectively rather than retroactively and request further clarification to avoid information duplication within the new framework.

The commenter is seeking clarification on specific technical requirements within the draft guidance, particularly regarding drug substance information in DMFs and the handling of reference standards. They propose specific language to ensure that specifications for in-house reference materials are only provided where relevant to product quality.

A regulatory CMC professional opposes the draft guidance, arguing that it is poorly organized, illogical, and overly complex. The commenter suggests that the document's structure is nonfunctional and proposes creating separate guidelines for biologics and combination products instead.

Sartorius, a manufacturer of tools and materials for drug and biological product manufacturing, provides specific technical feedback on the draft M4Q (R2) guidance. They request clarifications on implementation timelines, the handling of legacy products, and how the new structure supports cross-referencing independent master files for raw materials and intermediates.

The Pharmaceutical Research and Manufacturers of America (PhRMA) supports the FDA and ICH's efforts to revise the M4Q(R2) guidance to enhance clarity, reduce duplication, and support global harmonization of pharmaceutical submissions. They provide specific recommendations to improve the structure of the Common Technical Document (CTD), particularly regarding Core Quality Information (CQI), lifecycle management, and the integration of medical device information.