FDA Releases Draft Guidance on Sampling and Testing of In-Process Materials and Drug Products

FDA published a draft guidance document on Jan. 2, 2025 that provides considerations for complying with 21 Code of Federal Regulations (CFR) 211.110 (1). This specific section of the CFR focuses on production and process controls for sampling and testing of in-process materials and drug products. The guidance, Considerations for Complying With 21 CFR 211.110, Guidance for Industry, Draft Guidance, applies to human drug products and biologics, but not to the manufacture of APIs. The guidance document also discusses how process models can be incorporated into commercial manufacturing control strategies.

Batch uniformity and drug product integrity current good manufacturing practice requirements state that manufacturing processes must be designed and controlled to ensure that in-process materials meet predetermined quality requirements. In the document, FDA states robust product and process development are crucial for establishing and maintaining control strategies throughout the product’s lifecycle so that quality attributes are obtained.

“To ensure conformance to drug product quality requirements, the manufacturer should identify which critical quality attributes and in-process material attributes to monitor and control,” FDA states in the document (1). “Section 211.110 allows flexibility in the in-process controls, and testing, or examinations that are employed to ensure that processes deliver in-process materials and drug products with the appropriate quality attributes. To ensure that drug products have the properties that they are represented to possess, the in-process materials used throughout the manufacturing process should be of consistent quality.”

In addition, the guidance details quality considerations for drugs manufactured using advanced manufacturing technologies (AMTs). “All manufacturers, regardless of whether they are using advanced manufacturing, should apply a scientific- and risk-based approach to controlling processes and ensuring drug product quality,” FDA states in the guidance document (1). “This approach should be based on robust product and process understanding. Manufacturers must maintain the process in a state of control over the life of the process to ensure drug product quality, even as materials, equipment, production environment, personnel, and manufacturing procedures change. Planning and executing a system that monitors process performance and drug product quality helps ensure that a state of control is maintained. An effective monitoring system helps maintain a state of control in multiple ways, which include helping manufacturers: ensure that processes and controls are continuously capable of producing a drug product of desired quality; and identify areas for continual improvement.”

Additional guidance on advanced manufacturing was also published by FDA in January, explaining requirements for those in industry that wish to participate in the agency’s Advanced Manufacturing Technologies Designation Program (2). The Advanced Manufacturing Technologies Designation Program was required under section 506L of the Federal Food, Drug, and Cosmetic Act to provide a framework for those requesting designation of a drug manufacturing method as an AMT. The program provides early interaction opportunities before application submission as a way to encourage adoption of AMTs (3).

References

1. FDA. Considerations for Complying With 21 CFR 211.110, Guidance for Industry, Draft Guidance (CDER, CBER, January 2025).
https://www.fda.gov/media/184825/download
2. FDA. Advanced Manufacturing Technologies Designation Program, Guidance for Industry (CDER, CBER, December 2024).
3. Haigney, S. FDA Publishes Final Guidance on Advanced Manufacturing Technologies. PharmTech.com. Jan. 2, 2025.