Build it Right: A Quality Perspective on the Design and Build of a Viral Vector CDMO Manufacturing Facility

Chris Berger, executive director of quality, viral vectors at Avid Bioservices.

Avid Bioservices is a contract development and manufacturing organization (CDMO) offering process development (PD) and good manufacturing practice (GMP) manufacturing for mammalian proteins and viral vectors. Berger addressed how important it is for builders of advanced-therapy manufacturing facilities to define a project’s scope, stakeholders, and requirements along with programming the space, managing risk, and ensuring performance. Such preparation determines whether a facility will manufacture only drug substance or also drug products and whether it will use suspension or adherent cultures. Other questions Berger advised asking include

• Will we manufacture a single virus family?
• Are we using multiple virus families?
• Are we working at one or multiple scales?
• Are we culturing with adherent or suspension-adapted cells?
• Are we producing drug substance or drug products — or everything [all of the above?]?
• Are we building a facility that can handle multiple aspects of viral-vector manufacturing, or are we focusing on a single viral vector and a single platform for our facility?

Typical stakeholders in a project are facilities and engineering teams, along with external contractors that will design and build the facility. A manufacturing science and technology (MSAT) analysis is needed, as is a plan for technology transfer from a PD to a manufacturing group. Teams must determine whether there is enough room for process buffers. Avid’s approach is that both quality assurance (QA) and quality control groups examine all aspects of a facility. Including business development early into a build helps ensure that the facility is competitive within the marketplace. Once stakeholders and the project scope are in place, a project team is formed based on both scope and user requirements.

General requirements that are universal to biologic and viral-vector facilities include lighting, temperature, humidity, ventilation, and room classification. Additional considerations for viral-vector production include HVAC design needs and overall air-handling specifications. Multiproduct manufacturing plans require viral segregation strategies. He noted that Avid separates viral-positive, dedicating each zone to one product, one campaign. Viral-negative zones are separated in place once the virus is added.

He stressed the importance of determining biosafety levels throughout manufacturing and explained how to implement cleaning needs into product changeover and other procedures. A final consideration is to define how personnel flow through the facility, how materials will enter and leave, and how waste will be neutralized and disposed of. Berger stressed the importance of taking a dry run of your facility: Avid teams “walk through” an initial design repeatedly on paper before beginning a build, tracing out personnel and material flows to ensure that the design will support the planned campaigns.

A CDMO facility needs to accommodate visiting clients. Key considerations include what level of facility access clients will need, what level of training they will require, whether they need to gown during a facility tour (or whether viewing corridors suffice), and ultimately, how to minimize work disruptions during client tours. Berger detailed Avid’s design solutions to such concerns.

A CDMO needs platforms that appeal to different clients. Biomanufacturers increasingly are moving toward enterprise systems that can be validated once and implemented across multiple sites. Avid’s entire facility is based on disposable technology. Berger described how Avid uses upstream trains that feed into a central downstream process, then to a dedicated drug-product fill–finish line in a SKAN isolator with semiautomated filling equipment.

Berger outlined other steps including designs to meet regulatory expectations, managing contractors, establishing robust change-control procedures, and identifying hazards and risks. Once a facility is built, its equipment, systems, and processes all need to be validated and associated equipment qualified. HVAC, water, building and enterprise management systems (BMSs, EMSs), and controls need to be validated to the appropriate standards, after which the entire facility is qualified.

He concluded by summarizing features of Avid’s custom-designed viral -vector manufacturing facility: 5,000 f² of PD space, 5,000 f² of QC space, and 15,000 f² of GMP viral-vector, cleanroom suites. The facility is aligned with US and EU regulations and capable of viral-vector drug-substance and drug-product manufacturing regardless of virus family. It accommodates multiple product trains, houses fully segregated viral-positive suites, and provides on-site QC/QA with complete lot-release capabilities.

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