All CGMP requirements, including supporting activities, are critical in aseptic sterile manufacturing to ensure product quality and patient safety, says Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates.
Question:
I work for a small contract manufacturing company that produces aseptically filled sterile injectable products for some clients. We are constantly being audited and told we are not in compliance with current good manufacturing practices (CGMPs) for sterile manufacturing. Some of the requirements can be costly to implement and maintain. Are there any requirements that we can eliminate, such as smoke studies, and still be considered to be in compliance?
Answer:
The short answer is no. The CGMP requirements for aseptic sterile manufacturing are in place to ensure product quality and patient safety. Each requirement plays a vital role in determining the suitability of the product and the conditions under which it was manufactured. Under section 501(a)(2)(B) of the Food, Drug, and Cosmetic (FD&C) Act, a drug is deemed to be adulterated if: “ the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this chapter as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess” (1).
EudraLex Volume 4, Annex 1, Manufacture of Sterile Medicinal Products gives similar advice by stating: “The manufacture of sterile products is subject to special requirements in order to minimize risks of microbiological contamination, and of particulate and pyrogen contamination. Much depends on the skill, training and attitudes of the personnel involved. Quality Assurance is particularly important, and this type of manufacture must strictly follow carefully established and validated methods of preparation and procedure. Sole reliance for sterility or other quality aspects must not be placed on any terminal process or finished product test” (2). Let’s look at just a few requirements to illustrate why they are important.
Media fills are a supporting activity for determining the suitability of the product. Media fills are important because they demonstrate that the process controls are performed appropriately, cleanliness is maintained throughout the fill, and contamination risks are not introduced by the personnel or the process. Another supporting activity are smoke studies. The primary objective of smoke studies is to demonstrate that the filling stations have sufficient design and control to reduce potential contamination and to identify areas that may be away from or adjacent to the filling area that may contribute to any potential contamination during operations. Particulate monitoring during operations is important for demonstrating that the air quality was controlled before, during, and after the operations were conducted.
Environmental monitoring is another supporting activity critical to ensuring product quality. The information from this activity will provide assurance that ongoing operations are kept in control. This is also a process control that shows that operations conducted in the qualified areas are able to maintain the appropriate cleanliness on an ongoing basis.
Another critical support activity is the cleaning/disinfectant/sanitization process. The object of cleaning and disinfecting is to achieve appropriate microbiological cleanliness levels for the class of cleanroom for an appropriate period of time. Cleaning and disinfection of cleanrooms are an important part of contamination control, especially for manufacturing lines that produce more than one product. These are just some of the requirements needed to support the manufacturing of sterile medicinal products.
Aseptically filled sterile products are the highest risk products to manufacture. The supporting requirements are fundamental in ensuring patient safety and product quality, and they must be an integral part of a company’s ability to comply with the regulations.
References
- CFR Title 21, 225.1 (Government Printing Office, Washington, DC). ecfr.gov/current/title-21/chapter-I/subchapter-C/part-225.
- Annex 1 Manufacture of Sterile Medicinal Products. EudraLex Volume 4. August 2022.
About the author
Susan J. Schniepp is distinguished fellow at Regulatory Compliance Associates.
Article Details
BioPharm International
Vol. 37, No. 10
November/December 2024
Page: 34
Citation
When referring to this article, please cite it as Schniepp, S. Complying with CGMPs for Sterile Manufacturing. BioPharm International 2024 37 (10).
