As part of the work initiated in 2021 by the International Council Harmonization (ICH), the revision of Guideline M4Q(R1) (in force since 2002) is currently under public consultation. Regarding the quality section of the CTD, module 3 (and section 2.3 of module 2), the document provides information on the characteristics, manufacturing, and control of the medicinal product, popular known as CMC (Chemistry, Manufacturing, and Controls). This is the only complementary guideline within the ICH M4 framework that had not yet been reviewed.

The new proposal (R2) is available for review and comments and redefines the structure and technical content of the quality module. The objective of this revision is to improve the structure to include registration and post-registration, expand the scope to new and complex products available, and support digital transformation, considering technologies such as continuous manufacturing, artificial intelligence, statistical modeling, platforms, and structured data to make regulatory assessment more efficient and accelerate the availability of new drugs to patients.

The main and most impactful change in Module 3 is that it will become a “repository” for documents that support the information in Module 2. As a result, the quality of Module 2 will be improved, so that it is no longer a simple summary of the information provided in Module 3, but will be standardized to increase efficiency and effectiveness by including benefit-risk discussions, a detailed summary of product development, and general quality information considering the product and the manufacturing process, including a subsection focused on post-registration.

The new proposal for section 2.3 of module 2 has the following structure:

▫️ 2.3.1 – General information (e.g., common name, pharmaceutical form, route of administration);

▫️ 2.3.2 – Overall Development and Overall Control Strategy (QTPP, CQAs, and OCS);

▫️ 2.3.3 – Core Quality Information (CQI): includes essential data for regulatory assessment and life cycle management;

▫️ 2.3.4 – Development Summary and Justification (e.g., formulation studies, impurity control, validation, E&L, adventitious agents);

▫️ 2.3.5 – Product Lifecycle Management (PLCM);

▫️ 2.3.6 – Product Quality Benefit Risk (optional).

Within section 2.3.3 and module 3, there is also a subdivision following the DMCS model (Description, Manufacture, Control, Storage), for each type of material covered. These materials include drug substance (DS), substance intermediates (SI), starting/source materials (SM), excipients (EX), impurities (IM), reference material (RS), drug products (DP), product intermediates (PI), medical devices (MD), among others.

Therefore, this revision is an alignment with other guidelines, such as ICH Q8 to Q14, M7, M9, M13, and allows the connection between concepts of QbD, Design Space, Real-Time Release Testing (RTRT), multivariate models, impurity control, and life cycle. Based on this review, a decrease redundancy is expected, along with changes in structure that will bring flexibility to incorporate all types of drugs and post-registration changes, greater compatibility with the e-CTD digital format, and greater similarity in terms of structure with the safety guideline, M4S (R2), and efficacy guideline, M4E (R2).

Public participation is available and open to all interested parties. Contributions from Brazil should preferably be written in English using the electronic form (link: electronic form). The deadline for submitting contributions is September 5, 2025.

The current stage involves regional collection of contributions. According to the information available on the ICH website, the deadlines are:

ANVISA, Brazil – Deadline for comments by 5 September 2025

EC, Europe – Deadline for comments by 24 October 2025

EDA, Egypt – Deadline for comments by 1 December 2025

Health Canada, Canada – Deadline for comments by 25 September 2025

SFDA, Saudi Arabia – Deadline for comments by 15 October 2025

Swissmedic, Switzerland – Deadline for comments by 24 October 2025

TFDA, Chinese Taipei – Deadline for comments by 29 August 2025

TITCK, Türkiye – Deadline for comments by 24 October 2025

Further information available at https://www.ich.org/page/public-consultations

At Vita Pharma Consulting, we closely monitor international regulatory trends and are ready to support your company in adapting to these new requirements.

Count on us to assist your company in developing drug products registration and post-registration projects in Latin America and Europe.