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PharmTech.com Trends in Manufacturing eBook May 2023 Pharmaceutical Technology ® 11 Biologics ventilation (f low), and detect external microbes. Im- plementation of environmental controls is essential to produce a safe final product and is also necessary for adherence to CGMP requirements. I nteg rat i ng mu lt iple env i ron ment a l cont rol s greatly reduces the risk of contamination. One exam- ple of environmental control is the implementation of a restricted access barrier system (RABS), which pro- tects process materials from potential contaminants in the environment through a barrier and positive airf low. Monitoring air quality within the RABS fill- ing unit allows for real-time monitoring and reduces the need for aseptic interventions. Both viable (e.g., bacteria and fungi) and non-viable (e.g., dust parti- cles) particulate counters can be used for air quality surveillance. Utilizing viable and non-viable count- ers enables real-time monitoring and confirms a state of aseptic processing control. Real-time monitoring also helps identify the potential cause of contamina- tion (9,10) in the event of a breach. A state of environmental control is confirmed with the use of contact plates and swabs within the RABS filling unit to detect the presence of microorganisms. Personnel working within the filling room should also be monitored by personal contact plates, which will detect microorganisms carried on the sterile per- sonal protective equipment to safeguard against mi- crobial contamination introduced or spread by staff. Industry movement to single-use systems Cross-contamination between staff members and equipment is a big r isk dur ing DP product ion. A common method of reducing the risk of cross-con- tamination is the use of single-use systems (SUS), which do not require cleaning from staff for steriliza- tion. The biopharma industry has started using SUS equipment to reduce labor and costs. The reduction in time for cleaning and decontaminating reusable equipment has led to a growing preference for the use of SUS in the industr y. As a result, many drug manufacturers are replacing components in aseptic processing, such as formulation containers and fill- ing tubing pathways, with SUS systems. However, SUS equipment is not always a viable op- tion for all manufacturing components. Scaling up to high manufacturing volumes and incompatibil- ity with certain therapeutics can pose practical chal- lenges for SUS usage as well as supply chains. When using non-SUS technologies such as stainless-steel equipment, it is important to guarantee effective cleaning as remnants of previous products on contact surfaces would contaminate future batches. Cleaning systems of product residuals require rou- tine validation as regulatory bodies necessitate prod- uct-contacting surfaces (stainless steel or equivalent) to be consistently cleaned. Expertise and experience needed T here i s a v it a l need for e x per ience a nd e x per- t i se to ef fec t ively i mplement a sept ic processes a nd systems w it h in a biologics pipeline. T he ap- proach to selecting sterilization methods will be project-specific and tailored to each molecule, and any adaptation will depend on the unique needs of processes or molecules. When par tnering with a contract development a nd ma nufact ur ing orga n izat ion (CDMO), devel- opers w i l l need to eva luate equ ipment a nd pro- cesses based on the critical process parameters and critica l qua lit y attributes of each product. Work- ing in par tnership wi l l a lso be impor tant to per- form a complete technica l ana lysis and a robust technology transfer process. Specialized CDMO partners can provide personnel and specialized facilities needed for aseptic processing. As a result, companies can reduce time spent for train- ing personnel in aseptic processing techniques and avoid costs related to expanding in-house capabilities. Final takeaways Contaminant breaches in biologics manufacturing can cause many types of damage. Potential outcomes include a negative impact on patient health and busi- ness-related consequences, such as damage to the company's reputation and financial losses. To prevent contamination, tight regulations and protocols are in place to govern biologics development. To reduce conta m i nat ion r isk associated w it h aseptic filling processes, an extensive end-to-end process review must be completed to effectively drive risk to low levels. Having a capability to conduct spotless aseptic pro- cessing is critical as it empowers a CDMO to stead- fastly manufacture safe and effective therapeutics for patients. However, the complexity tied to safeguard- ing sterility can lead to difficulties when aiming to implement a robust aseptic process. Biopharma de- velopers can ease the burden of these complex aseptic protocols by partnering with a CDMO that possesses Cross-contamination between staff members and equipment is a big risk during DP production.