Issue link: https://www.e-digitaleditions.com/i/1248960
Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2020 41 Denk (SKAN): Aseptic fill/finish is very often seen in sterile manufacturing. To fulfill the current and future GMP [good manufacturing practice] requirements like the new draft [EU] Annex 1, isolators are highly recommended as they pose the lowest risk to the sterile product. Intervention through the isolator gloves should be reduced as much as possible with appropriate technologies like a high degree of automation. Beside this, the filling line should be hygienically designed without any disturbance of the first air and easy to clean. All transfer systems from a lower cleanroom grade area in the isolator should be carefully investigated about the risk of contamination. The complete process should be evaluated in a risk assessment and result in a contamination control strategy. PharmTech: How important is personnel training in preventing contamination during biopharma manufacturing? Denk (SKAN): The more manual operations are performed, the more important the personnel training becomes. As mentioned before, the new draft of the Annex 1 requires more barrier systems like isolators to avoid [having] peronnel close to critical operations. The following information is about CCS from the newest draft of the Annex 1, Pharmaceutical Technology spoke with John Harmer, vice president, marketing at Vanr x Pharmas ys tems about considerations in choosing the best system and equipment for contamination control in pharmaceutical manufacturing. Process vulnerabilities PharmTech: Where in the manufacturing process is product most vulnerable to contamination? Harmer (Vanrx): Contamination can occur at any stage in the biopharmaceutical manufacturing process, due to unsuitable materials, equipment, or the method itself. However, the most common type of contamination is caused by humans. Personnel supervising or directly involved in the manufacturing process are the number one cause of microbiological contamination of drug products—often due to lack of training, inadequate use of PPE [personal protection equipment], or simple human error. The product is particularly vulnerable to contamination in this way anywhere in the process where there is an open container. The solution is to isolate the product from the personnel as much as possible. PharmTech: In regard to preventing product contamination, is there a more effective system (e.g., open system, single use, fully closed)? Harmer (Vanr x): Given that human operators are the single largest potential source of product contamination, the most effective system will be one that reduces their contact to a minimum. A fully closed system that makes full use of pre-sterilized single-use and ready-to-use materials is the best solution. Note that this approach requires a redesign of the aseptic production processes; it is not enough to simply enclose existing processes in a closed isolator. Choosing equipment PharmTech: What should a company evaluate when choosing equipment used in sterile manufacturing, specifically for biologics? Harmer (Vanr x): As an example, Vanrx has a customer manufac turing gene therapies. They evaluated dif ferent aseptic filling technologies in terms of drug product quality risks and presented the data at the AAPS PharmaSci 360 conference (1). The evaluation concluded that the redesigned aseptic process of a gloveless robotic isolator presented the lowest risks to patient safety. A closed robotic isolator eliminates human inter vention in the aseptic process. Because gene therapies are sensitive, limiting drug product contact to the single-use flow path and the inside of the vial was crucial. Data [showed] that using press-fit vial closures with integrated stoppers eliminated the quality risks presented by stopper bowls and aluminum crimp capping. Looking at the data, it strongly showed that the closed robotic system provided better control over risk than other technologies. Reference 1. T. Page, "Biologic Manufacturing from Concept to Fill-finish Opera- tions," presentation at the Academy of Applied Pharmaceutical Sciences (AAPS) PharmaSci 360 Conference on November 4, 2019. —Susan Haigney Best systems and equipment for contamination control