8 Characteristics of a State-of-the-Art Highly Potent API Facility

Alcami’s Germantown high-potency facility was built using physical and engineering segregation processes as the dominant contamination-control strategy. An entire section of the facility was dedicated to high-potency manufacturing. It builds multiple levels of containment into the facility itself rather than relying on human-based administrative procedures. Facility-based containment characteristics include air-pressure control to assure no particles go in or come out; process-level equipment with hard-wall containment and/or isolator technology; sensor technology to monitor and alert in the event of a problem, and PPE usage as a backup in the highly rare event of multiple system failures.

2. Holistic facility design
Equipment should be selected not only based on its ability to run needed chemical processes, but also for its ability to provide the required containment. The advantage of building from scratch, as Alcami’s Germantown facility was, is the ability to assess the entire system all the way back through the support systems , and create dedicated utilities such as vacuum, HVAC and waste lines. This also allows the facility designers to consider how maintenance will be performed on that equipment to ensure the potential for migration of materials into utility systems is eliminated. For the Germantown facility, the equipment was specifically designed or selected to ensure easy cleaning within a closed state.

3. Focus on material transfer considerations
Weighing and dispensing of materials is one of the riskiest aspects of any high potency operation. Solid/powder materials are especially risky if the transfer ports are not parked perfectly. If material is being transferred out of a drum, there is the risk materials will go airborne. Therefore, the deployment of isolator systems or containment enclosures to keep that process contained is an integral part of a state-of-the-art high potency facilities.

4. Design for purpose
The advantage of designing and building a facility specifically for high-potency manufacturing is that the space can be made to fit the equipment and processes rather than forcing the equipment and processes to fit the space. A strong understanding of the processes is necessary for this to work. A look across Alcami’s diverse chemistry portfolio ensured the development of a user requirement that covered a wide range of chemical processes, such as hydrogenation and cryogenic reactions.

5. Design for future need
The needs of today should be considered, of course, but what about the needs of tomorrow? Given the growth in the high-potency drug segment, there is limited capacity to meet the demand, both in overall capacity and in future capabilities. A flexible design allows for future technologies within the existing footprint. For example, the Alcami facility in Germantown was designed specifically to accommodate the potential future manufacturing of antibody drug conjugates.  While the facility is not currently performing this kind of manufacturing, we keep an eye on the future during the design process.

6. Usage of modern technology & automation tools
Usage of programmable logic controller (PLC) system automation to efficiently and effectively manage all processes remotely is critical. Additionally, audio and visual sensors and alarm systems should be in place to assure that necessary containment levels are maintained. Utilizing technology to manage containment and monitor process performance is an expectation within a state-of-the-art HPAPI manufacturing facility.

7. Industrial hygiene validation
While some highly potent API facilities do not perform industrial hygiene surrogate studies and monitor ongoing process performance, this measure was important to Alcami to assure operations that meet and maintain the desired levels of containment.

Surrogate studies verify all of the containment is in place and functioning as it should, and generate data to show established containment standards are being met. These surrogate studies help ensure the facility is capable of handling compounds of given OEL levels. It is also used as a qualification method for operators working in that space. Ongoing monitoring and product specific studies ensure the controls are maintained in normal operation.

8. Reduce supply chain risks by doing things right
The most pressing demand on a top-tier CDMO is that processes are developed in a way that substantially reduce risks at every point in the supply chain. Alcami’s integrated approach to process design and control strategy ensures that sound chemical and process development practices use a right-first-time approach to manufacturing. The manufacturing of HPAPI drug products adds another layer of risk that must be managed with high levels of expertise and commitment. It is this expertise and commitment that assures clinical milestones are met, with high-quality products, regulatory compliance and no disruptions in supply.

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