Issue link: https://www.e-digitaleditions.com/i/1248960
40 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2020 P h a r mTe c h . c o m Operations aseptic processing in isolators, the surrounding cleanroom classification is Grade C or D. Aseptic critical transfers are the primary containers like vials, syringes, stoppers, settle plates for the viable environmental monitoring, etc. Furthermore, sterile transfers and connections are vulnerable to contamination. PharmTech: What are the most crtitical areas where contamination can occur: equipment, per- sonnel, and/or materials? Denk (SKAN): If we look at the critical areas for aseptic processing in biopharmaceutical manufac- turing, the personnel are considered as the high- est concern about contamination to sterile product. This is the reason why in the newest draft of the [European Commission's] Annex 1 from Feb. 20, 2020, the following is mentioned in the chapter pri- ciples, 'The use of appropriate technologies (e.g., Restricted Access Barriers Systems (RABS), isola- tors, robotic systems, rapid microbial testing, and monitoring systems) should be considered to in- crease the protection of the product from potential extraneous sources of particulate and microbial contamination such as personnel, materials and the surrounding environment' (1). This means the operators should not have direct access to critical aseptic operations. Developing a contamination control strategy PharmTech: What are the steps for developing a contamination control strategy for sterile product manufacturing? Denk (SKAN): The development of a CCS is part of the quality risk management. If we take this into consideration of an aseptic filling line in an isolator, the risk assessment should identify the critical sterile operations, interventions, tranfers from ourside the isolator to the inside, as well as the material transfer like for the transport of the primary container like vials, syringes, etc., or the pharmaceutical product transfer from the storage tank to the sterile filling head. The risk assess- ment is the tool to indentify the critical areas and define procedures and safety measures to reduce the contamination risk to a lowest possible level. Based on the risk assessment and the CCS, the en- vironmental montoring for viable and non-viable mornitoring is defined. PharmTech: In regard to preventing product con- tamination, is there a more effective system (e.g., open system, single use, fully closed)? Denk (SKAN): Closed systems are good tools of preventing product contamination from the sur- rounding. Another option for preventing product contamination is process automation. The more the process is automated without human interven- tions, the less the contamination risk. Fully auto- mated systems like robotic filling lines in combi- nation with rapid microbial monitoring, validated transfer systems (for example, ready-to-use com- ponents like nested vials or syringes in tubs with E-Beam surface sterilization technology or UV-C decontamination) are, beside closed systems, the highest protection [from] product contamination. PharmTech: What should a company evaluate when choosing equipment used in sterile manu- facturing, specifically for biologics? "The more the process is automated without human interventions, the less the contamination risk." —Richard Denk, SKAN