The following is an excerpt from an article originally published in the October issue of BioProcess International, written by:
Robert Preti, PhD, President, PCT, and Senior Vice President, Development and Technical Operations and Chief Technology Officer, Caladrius Biosciences
Ann M. Daus, PhD, Vice President, Quality Assurance, Quality Control & Validation, PCT
Brian Hampson, VP, Global Manufacturing Sciences and Technology (MSAT), & Head of the Center for Innovation and Engineering
Cenk Sumen, PhD, Manager, Technology & Business Development, PCT
“One of the most important—and most complex—requirements to scale up for commercialization for any cell therapy developer is meeting the quality standards, including compliance with applicable regulations such as current Good Manufacturing Practices (cGMPs). Implementing a Quality Plan is desirable for achieving FDA-approvable commercial manufacturing readiness, whether a developer chooses to work in a dedicated facility designed solely for its own therapies or with a manufacturing partner. A Quality Plan should incorporate an inspectional systems approach that takes into account the following systems: quality, facilities and equipment, materials, production, packaging and labeling, and laboratory control.
A manufacturing partner that is truly prepared for commercialization, particularly in a shared manufacturing facility, will exhibit a foundational state of compliance underpinning the ‘right to operate’ in a compliant cGMP manufacturing environment. This means having a consistent adherence to one’s own quality systems that are consistent with applicable regulatory requirements such as cGMPs, both within the manufacturing site itself and across interactions with all cell therapy developers that partner with that site. While flexibility to meet developers’ needs may seem advantageous, a manufacturer that changes basic quality systems and processes for every developer opens itself up to potential risks related to product comparability and non-adherence to applicable quality regulations. A unified, consistent foundational state of compliance that is harmonized with best industry practices is the best way to mitigate potential regulatory risk.
Specifically, a cell therapy developer should establish at their manufacturing facility—or look for a manufacturing partner that offers—a foundational state of compliance in people, facilities, systems, and processes, as outlined below:
- People: Establish a facility-wide, multi-disciplinary Quality Task Force to lead parallel work streams that address the quality requirements for commercial manufacturing.
- Facilities: Implement facility design and renovations that ensure a strong foundational state of cGMP compliance that will support drug development strategies, incorporate on-site commercial manufacturing capacity, fulfill critical commitments to the cell therapy developers, and close any identified compliance gaps.
- Systems: Unify, align, and integrate harmonized quality systems across the shared facility that will withstand regulatory scrutiny, including the implementation of electronic quality systems where possible.
- Processes: Establish a seamless technology transfer process (the transfer of technology information from the cell therapy developer to the shared facility) that allows for commercial manufacturing of products.
Once this unified quality voice is established, a manufacturer must look at what quality elements contribute to the successful transition from clinical to commercial readiness. Those elements include process comparability and all the quality metrics used to demonstrate that comparability; control, including appropriate process and quality controls to ensure patient safety; compliance with all applicable regulatory standards such as cGMPs; and consistency of all quality metrics used to assess quality systems and processes (such as timelines, system checkpoints, and documentation procedures).
Finally, a best practice for any manufacturing partner to achieve commercial-readiness from a quality perspective is the establishment of a Quality Task Force (QTF). This group should include representatives from manufacturing, operations, and quality, with different areas of industry experience. The purpose of the QTF is to proactively lead the manufacturing facility and mobilize multi-disciplinary resources toward the establishment of proven commercial quality systems that will withstand regulatory scrutiny and will meet all applicable quality standards and regulatory requirements.
To understand the value of the QTF, consider the fact that many cell therapy developers who operate dedicated manufacturing facilities will bring in outside expertise when looking to optimize or overcome challenges related to quality. This expertise is often not sought out until the developer is in the troubleshooting—or worse, rescue-mission—stage, after quality oversights or hurdles have resulted in product development delays, regulatory actions, or standstills. Learning from one’s experience is internalized into the QTF and applied across all developers as a best practice moving forward.
Ultimately, the primary concern of a Quality division is patient safety; without adherence to quality standards, a cell therapy product cannot meet regulatory scrutiny and produce a commercial product.”
To view a PDF of the complete article in BioProcess International, click here.
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