Aseptic Process Sampling Risk Mitigation – A Regulatory Perspective

By Janmeet Anant, Regulatory Advocate, Marc-Antoine Kaag, Global Product Manager, Sampling

There are significant consequences associated with microbial contamination during biopharmaceutical manufacturing. Contamination increases risks for the operator, the company, and potentially the patient, all of which can result in significant negative impact. The contamination of a biologic can result in a lengthy shut down of a facility to conduct the investigations necessary to identify the root cause and prevent reoccurrence and worse, delay production and delivery of critical, life-saving medicines.

Sampling of biopharmaceutical process intermediates and the final product is essential for manufacturing workflows where the final product cannot be terminally sterilized. In addition to ensuring patient safety through bioburden monitoring, sampling is needed to support several key imperatives as driven by global regulatory trends including process analytical technologies (PAT) and quality by design (QbD).

Among the drivers for improved, more robust sample processing is the need to assess the state of the process in terms of verifying, detecting, and adjusting the parameters required to produce the drug product. A second driver is the need to extract materials for later assessment. The materials extracted must be representative and in a quantity that is adequate for regulatory requirements in terms of sample storage for later assessment. Finally, sampling is needed for the transfer of materials, including adjustment by addition of different raw materials or seeding by inoculation.

Unfortunately, “traditional” sampling methods are not closed systems and therefore do not maintain a barrier to contamination entering the process during sampling. As a result, the sampling process itself, which is critical to the success and safety of the manufacturing workflow, can lead to contamination of a unit operation and possibly an entire batch. In contrast, aseptic sampling systems are disposable, closed units that always maintain aseptic conditions and ensure the security of the process, operator, and the sample.

This whitepaper provides a summary of regulatory guidelines for sampling, describes the traditional methods available for sampling and their limitations, and explores the advantages of aseptic, single-use sampling and how this approach more effectively aligns with regulatory guidelines.