Pharma expert discusses effort to standardize CMC quality information

BETHESDA, MD – The pharmaceutical industry and the US Food and Drug Administration (FDA) are collaborating on a structured data platform for submitting chemistry, manufacturing, and controls (CMC) information in new drug applications. This initiative is part of Project PRISM, which is the FDA’s regulatory cloud submissions platform.

Ciby Abraham, senior director of project and product leadership at AstraZeneca reported on these efforts on Wednesday at DIA’s Regulatory Submissions, Information and Document Management Forum.

“Despite unprecedented advancements in medicines, regulatory filings remain predominantly paper-based, leading to inefficiencies and potential delays in the review, evaluation, and collaboration for drug applications,” Abraham said. This issue is worsened by the large number of new drug applications and requests for post-approval changes, along with the varying requirements specific to each country.

Abraham explained that Project PRISM (PrecisionFDA Regulatory Information Service Module) aims to transform the submission process by developing a structured, cloud-based template for submitting quality information in Modules 2 and 3 of the Common Technical Document (CTD).

This initiative seeks to convert unstructured PDF dossiers into a structured CMC submission format within a cloud environment. The platform features shared interactive review spaces that allow sponsors and the FDA to collaborate on the same documents simultaneously.

The pilot was launched in 2023 to fulfill a commitment outlined in the Prescription Drug User Fee Act (PDUFA VII) commitments letter and is expected to continue this year. Seven companies are currently signed up for the program: Bayer, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, EMD Serono, Gilead, and Takeda.

The pilot study includes a mock case study of a fictional company called “Sakura Bloom.” In this pilot, the sponsors are seeking approval for a second manufacturing site for their immediate-release 20 mg film-coated tablet. This tablet is produced using a wet granulation process, followed by compression and film coating.

Abraham explained how the information to support the post approval change is moved into a cloud environment. This involves “deconstructing” the data from a static PDF file to structured data. AI tools are then used to evaluate the post-approval change. For example, an AI prompt asks the sponsor to provide a graphical analysis comparing the impurity profile of the product from the original Sakura Bloom manufacturing site and the second manufacturing site.

The structured dataset is organized into a Fast Healthcare Interoperability Resources (FHIR) bundle, which is then submitted to PrecisionFDA for review by the FDA.

There are plans to incorporate this case study in a future revision of the ICH M4Q(R2) guideline. Abraham said that the current draft guideline is a “significant change” from the existing guideline and represents a highly anticipated modernization of the CTD Quality modules 2.3 and 3. This transition shifts from static documents to a structured, data-driven, and risk-based format.

The draft M4Q(R2) guideline was released in May 2025. (RELATED: ICH releases guidelines on developing medicines for pregnant population and quality information in CTD, Regulatory Focus 28 May 2025)

Abraham observed that in the CMC area, there is a significant divergence and differing interpretations of quality among regulators. He cited a 2022 study from the International Society for Pharmaceutical Engineering (ISPE), which found that there is only an 8.7% likelihood that the quality information presented in the electronic Common Technical Document will be accepted by regulators in the US, Europe, and Japan, based on an analysis of 112 marketing applications submitted by 11 companies.

Pharma expert discusses effort to standardize CMC quality information

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