Dedicated facilities with dedicated filling lines are increasingly being replaced by multiproduct facilities as more and more specialized therapeutics, developed for targeted patient populations within a specific therapy area, are reaching the market. In this article, Tobias Struller, Manager, Process Performance & Qualification at Baxter BioPharma Solution’s Halle/Westfalen, Germany, facility, provides insight into the challenges of manufacturing cytotoxic and noncytotoxic drugs together in a multiproduct facility.
Why are multiproduct facilities becoming more common?
The required quantities of niche products are very small, and the companies developing them tend to be small biotech companies and start-ups with very limited manufacturing footprints. This results in their production often being outsourced to a contract manufacturing organization (CMO) that operates from a shared facility.
When different drug products are produced in shared facilities, the potential for cross-contamination is a concern and needs to be proactively addressed. Drug products provide a benefit to the intended patient; however, as a cross-contaminant, they can also pose a risk. This is especially true when manufacturing oncology drugs, as many of them are highly potent substances with cytotoxic, genotoxic or reprotoxic effects.
How can CMOs be a good resource for pharma clients?
Established CMOs can be a great resource for their pharma and biotech clients, both large and small, as they can provide unique expertise in the complex landscape of cytotoxic manufacturing, including safety issues, compliance topics and regulatory matters. As an established CMO, Baxter BioPharma Solutions has deep experience in handling a multitude of molecule types with various toxicology profiles.
How is the risk of cross-contamination mitigated?
At every step of the manufacturing process, there is a risk of cross-contamination. Even in the warehouse, there is a potential for a mix-up if the proper protocols and procedures are not in place. Cytotoxic manufacturing involves handling an extremely toxic product, so it is vital that the safety of the operator be a top priority. Risk mitigation and robust procedures need to be defined throughout the entire manufacturing process.
What are some of the steps that need to be taken during the evaluation process?
Completing a risk assessment is an essential starting point. You need to characterize your product and the processes relevant for the manufacturing of the product. This is where having extensive experience and state-of-the-art equipment for handling products that require specialized containment become important. Along with this, you need to ensure that all the necessary maintenance activities are continuously performed on the isolators and that control elements and functionality for critical equipment are in place (e.g., maintenance, integrity tests, etc.). In this way, you secure both the operator and the product. Good engineering practice for the design of the equipment and good manufacturing practice in the design of the processes are the keys to minimizing cross-contamination risk.
Not only are effective processes essential, but there is a real need for well-trained operators, because these processes cannot be fully automated. Operators must know exactly what they are doing, and that comes down to having experience with sophisticated types of projects. At Baxter’s Halle/Westfalen, Germany, facility, we train our operators to know exactly what they are handling.
With good standard operating procedures (SOPs), operators have robust and comprehensible instructions that are easy to follow. During risk assessment, manufacturers can define actions and illustrate how to mitigate any potential problems and bring risk down to an acceptable level. Any additional risk is simply not acceptable in cytotoxic manufacturing and when handling such toxic materials.
How does Baxter BioPharma Solutions’ Halle/Westfalen, Germany, facility help to ensure continuous safety compliance?
Baxter’s oncology contract manufacturing facility in Halle/Westfalen, Germany, carefully assesses each new product that is introduced, taking both toxicological and physical properties into consideration. Each new product is compared to the current “worst-case product,” and if it is a new worst-case product, then cleaning validation and/or verification for the equipment must demonstrate successful depletion of the product after manufacturing.
Baxter employs state-of-the-art organizational procedures and technical standards in accordance with current industry guidance to prevent any mode of potential cross-contamination, from airborne to mechanical transfer, residual carry-over or mix-up. This includes the utilization of dedicated, or single-use, equipment. The facility undergoes on average more than 35 audits per year by clients. In addition, it has been audited by 14 regulatory authorities since 2008. Baxter BioPharma Solutions continuously demonstrates that it operates and helps mitigate risk to the highest standards.