CGMP Manufacturing Facility Design and Evolution

Mike Alston, Jr.,director, project engineering, Avid Bioservices

Presented by: Mike Alston, Jr.,director, project engineering; and William Leonardi, PhD, senior project manager, Avid Bioservices

These two speakers shared lessons learned in the design and buildout of current good manufacturing practice (CGMP) manufacturing facilities at Avid. Leonardi began with a history of the company’s 28+ years of biologics development and manufacturing and its track record as a successful contract and development manufacturing organization (CDMO).

Avid’s main campus comprises a cluster of buildings in Tustin, CA. GMP, process-development, and quality-control laboratories are housed in the Franklin facility, which has served as the company’s legacy facility, with both single-use and stainless-steel capabilities. In 2016, Avid commissioned the Myford North facility for late-stage clinical and the commercialization of Bavi (bavituximab). As upstream throughput increased, that building was retrofitted in 2017 with additional production bioreactors — but that began to shift the bottleneck downstream. So an additional downstream suite is being added to allow for increased drug-substance production.

Further expansion of single-use capacity is being planned through the design of a Myford South plant. That will allow Avid to increase overall capacity from 12,400-L production bioreactors to about 26,400 L, reflecting more than a two-fold increase of production capacity.

William Leonardi, PhD, senior project manager, Avid Bioservices

Leonardi handed the presentation to his colleague, Mike Alston, who provided more information and described lessons learned through Avid’s facility-design process. Alston detailed elements of the Myford facility expansions. Once Avid became a full-scale CDMO, the Myford North design needed to offer greater manufacturing flexibility through an expanded footprint for harvest and final purification suites. The initial design also no longer could accommodate the increased buffer capacity needed — which was complicating storage and product transfer activities. Along with the addition of three 2,000-L bioreactors, a second, larger purification suite is being added that also allows for more efficient material flow and fluid transfer. Attention to mechanical design is critical to monitoring air flow and personnel movement to ensure that no contamination will be introduced.

The design of the Myford South facility will accommodate six 2,000-L, four 500-L, and two 25-L single-use bioreactors, occupying 42,000 ft2 and an estimated 14,000-L capacity. The bioreactor room will provide the flexibility to run multiple downstream purification suites. Design was begun in February 2021, with GMP manufacturing expected to begin 18–24 months later.

In summarizing the lessons learned from Avid’s expansion designs, Alston noted the importance of the overall multiproduct design approach with a focus on closed-processing automation for efficiency. Moving away from a unidirectional to a bidirectional flow also created a cost-effective operating model and improved movement throughout the facility. By projecting “worst-case” capacity needs, the designers were able to build in the flexibility needed to ensure debottlenecking of future operations.

A secondary media/buffer suite will be integrated into the Myford South design to ensure efficient and effective buffer operations, with proper adjacencies to the manufacturing suite. Because warehousing space is at a premium, the Myford South design will place air handlers on the roof to enable the company to take full advantage of its expanded manufacturing capacity.

The Myford North facility houses equipment from multiple suppliers to offer a full capability range in the industry. By contrast, the Myford South design will incorporate more standardized platforms based on surveys of client needs. That also will help ensure shorter lead times for consumables and deliveries.