2023 US FDA Drug Quality Guidance Expected To Include 20-Year CTD Update, Much More

A revision of the ICH Common Technical Document expected this year will set the global stage for eventual “structured” quality submissions. Meanwhile, the FDA plans to complete work on ICH impurities guidance and advanced manufacturing technology guidance.

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The FDA points the way to expected guidance.

A major update of the format for quality submissions headlines the US Food and Drug Administration’s Center for Drug Evaluation and Research agenda for new and revised drug quality guidance in 2023.

The list includes an FDA-proposed revision of the September 2002 International Council on Harmonisation guidance on the quality aspects of the Common Technical Document for drug applications. The changes will account for two decades of evolution in science- and risk-based regulatory approaches, lifecycle and knowledge management, and product and process innovation.

The ICH M4Q(R2) revision also enables the use of digital tools for submission and assessment, setting the stage for planned ICH guidance on “structured” product quality submissions that can transmit data elements, not just electronic text files.

A Stepwise Structuring of Quality Submissions

ICH chose to modernize M4Q in a stepwise approach, Henrik Kim Nielsen, Novo Nordisk A/S VP, global regulatory sciences, said 24 January at the CASSS WCBP conference in Washington DC.

The plan was to define the new structure of modules 2.3 and 3 of the CTD with the M4Q(R2) revision. As ICH parties reach consensus on the structure in Step 2 of the ICH process for that revision, Nielsen said a concept paper would be submitted to launch the next stage, called structured product quality submissions.

Nielsen described some areas of focus for the revision. For example, the update should show where to put lifecycle management elements and how to better capture pharmaceutical development and control strategy elements like the quality target product profile, or QTPP, while the format should facilitate knowledge management and support emerging concepts.

Some of industry’s key objectives for the revision include fostering global harmonization of quality submissions, while keeping GMP documents out of the dossier, and enabling full use of the Q8-Q14 ICH guidance documents that followed the last M4Q revision.

Industry also wants the revision to support new modalities and technologies, while enabling firms to tell the stories of their products and link them to patients.

Nielsen said the current thinking of the M4Q(R2) expert working group is that the guideline will establish Module 2 as the basis for regulatory assessment, and will be supported by Module 3, where the detailed information will be kept in a more accessible format that lays the foundation for structured product quality submissions.

More CMC Guidance In The Works

Another ICH guidance to expect this year adds to the series of ICH Q3 impurities guidance documents, the Q3E guidance on assessment and control of extractables and leachables. (Also see "Revised US Approach For Parenteral Drug Leachables Could Prevent Regulatory Missteps" - Pink Sheet, 11 Apr, 2021.)

There also will be congressionally mandated guidance on a program to designate advanced manufacturing technologies for expedited review. (Also see "US Funding Law Could Speed Approval Of Drugs And Biologics Manufactured In Advanced Ways" - Pink Sheet, 9 Jan, 2023.)

Additional regulatory CMC guidance expected this year will address:

• stability issues related to drug substances

• potency assays for monoclonal antibodies and other therapeutic proteins that target viral pathogens

• reformulating products with certain excipients – thickening agents called carbomers – that may contain benzene, a known human carcinogen

• quality considerations for topical ophthalmics

• container closure systems

• post-approval changes for biosimilars

Expectations For GMP-Related Guidance

Here’s what’s in store for the GMP arena:

• guidance on the FDA’s use of alternative tools in assessing manufacturing facilities named in pending applications

• administrative/procedural guidance on responding to FDA Form 483 GMP observations

• guidance on refuse to receive actions for abbreviated new drug applications (ANDAs) with drug master files that reference deficient facilities

• revised draft guidance on GMPs for positron emission tomography drugs