It challenges the facility design, procedural controls, and operators to document sterile production through the manufacturing process. It is the basic requirement for the production of sterile products. Federal regulators have established guidelines that contract manufacturers of parenteral products must adhere to ensure the safety of products delivered to patients. They highlight the importance of this activity in a manufacturing organization and the criteria used in the evaluation of the aseptic manufacturing process.
There are five major components to an APS
Media – It is important to use media that effectively grows the microbes likely encountered in a manufacturing environment. Microbial growth and the presence of turbidity in a finished dosage form are essential to show failure to maintain sterile filling activities.
Interventions – The manufacturing process is performed by operators, and their actions directly impact the process. All manufacturing operators and quality control personnel review airflow visualization studies to ensure a thorough understanding of the impact of each intervention in the sterile environment. How an operator moves (slow versus fast), where they move tools, placement of their arms and hands, do they impact first air, what air disturbances they can influence, etc., all play a role in the potential for microbial egress in a sterile manufacturing environment. The likely actions an operator will perform during routine manufacturing must be performed. In addition, challenging or non-routine operations simulate worse-case scenarios during the manufacturing process. It is essential that all operators must be qualified individually for non-routine operations and those interventions are captured during the APS. Any failure indicates an operator that is not qualified for any aseptic operations during GMP manufacturing operations. A full requalification of the operator would be required. All operators must be periodically requalified to perform aseptic operations.
Process Challenges – It is essential that the APS challenges the boundaries of the manufacturing process. Careful consideration should be considered for a variety of parameters, including filling speeds, vial opening sizes, filling duration, inert gassing, facility or process changes, clean or sterile hold times, new components or configurations, and post-shutdown activities. The parameters evaluated during APS establish the boundaries for sterile manufacturing at the facility.
Incubation – All filled integral vials from the APS should be incubated under controlled conditions that promote microbial growth and are required to ensure the success of the APS. Two controlled temperatures are utilized (20-25°C and 30-35°C), as well as incubation for not less than 14 days, to ensure microbial growth of difficult-to-culture organisms.
Inspection – Vials are inspected by qualified microbiological quality control or sterility personnel and at defined intervals, typically 7 and 14 days. All incubated vials are inspected for signs of contamination. Turbidity is a sure sign of a failed APS.
The entire APS process is a challenge of your internal engineering and procedural controls put in place to prevent microbial contamination. Engineering controls, including airflow control, room air exchange rate, temperature and humidity controls, and facility layout and design are important aspects required to control contamination. Procedural controls include facility cleaning frequency and disinfectants utilized and personnel gowning and training implemented. In addition, how materials are passed through the facility with step improvements for cleaning as they move to manufacturing areas minimizes contamination.
Evaluation of defined interventions as well as monitoring the area should all be documented in well-defined risk assessments. It would be impossible to monitor all aspects of a manufacturing process, and the risk assessment provides the guidelines for high likelihood areas that should be challenged during an APS.
At Selkirk, each of these components is addressed in a comprehensive plan to ensure a robust and controlled manufacturing process. The facility is purpose-built for pharmaceutical manufacturing, utilizing unidirectional flow to minimize microbial egress into the manufacturing areas and equipment suited for the new Annex 1 and FDA regulations. Isolator technology eliminates direct human contact during the filling process and ensures a sterile environment using a vaporized hydrogen peroxide (VHP) decontamination cycle to prevent microbial contamination. Operators are fully qualified and ensure any performed interventions will meet GMP standards. Together, these controls ensure Selkirk has a robust and well-defined sterile manufacturing process.
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About Selkirk Pharma
Selkirk Pharma (www.selkirkpharma.com) is a world-class sterile fill/finish CMO in Spokane, Washington, USA. We are a key partner for companies that need a partner with a reliable, high-yield, US-based contract manufacturing organization (CMO). Selkirk Pharma was purpose-built by fill/finish industry veterans for on-time, in-full, sterile fill/finish GMP manufacturing of injectable drug products. You can count on our industry-leading processes, technologies, and support that reduce production bottlenecks, address product shortages, and onshore pharmaceutical manufacturing. Selkirk’s promise is the reliable delivery of your high-quality products. We offer best-in-class liquid vial filling in our Bausch + Ströbel VarioSys® fill line. We offer full Analytical and microbial services.
Want to learn more, visit our website at www.selkirkpharma.com, Virtually tour our facility, or reach out to our BD team at bd@selkirkpharma.com
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