FDA Releases Draft Guidance on Registering Pharmaceuticals for Human Use

FDA has released a draft of the guidance document “M4Q(R2) The Common Technical Document for the Registration of Pharmaceuticals for Human Use: Quality (1). The guidance is being distributed for public comments through March 23, 2026. Information on how to ensure FDA considers a comment on the draft priorto beginning work on the final version can be found here.

The M4Q(R2) draft guidance is a globally harmonized framework developed by the International Council for Harmonisation (ICH) that establishes the location, structure, and granularity of quality information for medicinal product registration applications (2). Endorsed in May 2025, it applies to all medicinal products for human use, supporting initial marketing authorizations, post-approval changes, and master file submissions. Its primary goal is to ensure that safe, effective, and high-quality medicines are developed and maintained efficiently by standardizing regulatory expectations across global regions.

How is quality information structured under the M4Q(R2) framework?

The guidance organizes quality information into two complementary sections: Module 2.3 (Quality Overview) and Module 3 (Body of Data) (2). Module 2.3 provides a comprehensive, science- and risk-based evaluation of the medicinal product and serves as the primary basis for regulatory assessment. It includes general information, overall development strategies, and core quality information, which covers the essential data necessary for marketing authorization and lifecycle management. Module 3 acts as a repository for the detailed technical descriptions, methods, and supportive data that validate the summaries provided in Module 2.3.

A central feature of this update is the DMCS (Description, Manufacture, Control, and Storage) model. This standardized structure is applied to all materials within the medicinal product, including:

• Drug substances and substance intermediates.

• Excipients, starting materials, and raw materials.

• Drug products and product intermediates.

• Medical devices and packaged medicinal products.

By utilizing this four-pillar structure, the guidance ensures information is presented with enough granularity to facilitate digitalization, easy knowledge management, and efficient regulatory analysis.

How does the guidance address development strategies and product lifecycle management?

The guidance emphasizes a holistic overall control strategy that addresses the manufacturing process from initial starting materials to the final packaged drug product. Applicants must provide a quality target product profile and identify critical quality attributes to demonstrate how their development strategy ensures intended quality. This is supported by Section 2.3.4 (Development Summary and Justification), which provides science-based rationales for key development choices, such as the selection of manufacturing processes, container closure systems, and analytical procedures.

Furthermore, M4Q(R2) is designed to be highly flexible, accommodating emerging technologies and novel processes that impact product quality. This includes the use of:

• AI and machine learning.

• Advanced manufacturing and continuous manufacturing processes.

• Bioinformatics and advanced analytical tools.

For ongoing product maintenance, the guidance integrates lifecycle management concepts from ICH Q12, such as the identification of established conditions and the maintenance of a product lifecycle management document. These tools allow for more efficient post-approval changes by defining specific reporting categories and change management protocols. For complex regulatory pathways, an optional section for product quality benefit–risk considerations is included to help mitigate uncertainties related to evolving product knowledge.

References

1. FDA. Guidance Document: M4Q(R2) The Common Technical Document for the Registration of Pharmaceuticals for Human Use: Quality. Accessed Jan 21, 2026.
2. FDA. M4Q(R2) The Common Technical Document for the Registration of Pharmaceuticals for Human Use: Quality. Accessed Jan 21, 2026.