September 21, 2019
Sponsored by Avid Bioservices
Effective transfer of technology from a sponsor facility to a contract development and manufacturing organization (CDMO) is essential to rapid biomanufacturing, especially for early and late-stage clinical supply. But the process is not as simple as “plug and play.” In an Ask-the-Expert webinar on 25 June 2019, Roy Sevilla (senior manager of upstream process development at Avid Bioservices) explained how his company orchestrates transfer operations with cross-functional teams. Strong, frequent collaboration with process sponsors ultimately mitigates risks associated with scale-up, increasing the likelihood of project success and timeliness.
Sevilla’s Presentation
Successful technology transfer hinges on clear communication between sponsor and CDMO from the outset. Avid involves clients in all phases of the technology transfer process; this includes face-to-face meetings held at critical project milestones. A personalized, coordinated effort helps the CDMO gather crucial process data from the sending site and how the process can be modified to fit its manufacturing facility within a desired timeline.
Scale-up frequently requires process modifications. In a case study, Avid was contracted to develop a Chinese hamster ovary (CHO) cell culture inoculum expansion process to seed a fed-batch 200-L stirred-tank production bioreactor. The client used shake flasks and a rocking bioreactor during both seed-train expansion and n – 1 perfusion. To scale up and make the process fit the facility and equipment capabilities, Avid made modifications to the inoculum seed train and production bioreactor processes while keeping key performance indicators consistent with batches performed in the sending site.
Because scale-up frequently requires modifications, sending sites need to provide CDMOs with key information to allow for comprehensive gap and facility-fit assessments: process flow diagrams, bills of materials for cell culture media and buffer feed components, batch production records, and process data. The goal of this knowledge transfer is to identify scale-independent parameters (e.g., pH and temperature) and scale-dependent factors (e.g., seed volume). Learning those parameters early ensures that Avid can anticipate gap risks and alter a process quickly and appropriately to promote success on the first run.
But effective knowledge sharing is only part of the communication strategy. What most enables mitigation of project liabilities is a coordinated effort among Avid internal transfer teams that include members of process development (PD), manufacturing quality sciences (MQS), manufacturing technical operations (MTO), and manufacturing. PD focuses on the transfer itself while gathering data for scale-down and scale-independent parameters that can confirm project success. Using questionnaires, technology transfer spreadsheets, gap assessment reports, and other managerial tools, PD works with MQS to collect scale-dependent data and ensure that the process is scaled-up and operates as designed. The manufacturing unit verifies that operations comply with current good manufacturing practice (CGMP) and high quality standards. Technical operations proceduralize processes under scaled conditions and generate batch production records.
Getting the sending and receiving site stakeholders together up front is vital to success. Creating supportive conditions in which sponsors can share what they know and by asking technology transfer teams to work together across units can increase the likelihood of a successful process and site transfer substantially.
Questions and Answers
What improvements helped to increase inoculum expansion viability during the seed chain in your case study? A key consideration in process transfer is understanding as much about the equipment involved as possible. In most cases, tweaks to aeration and gassing strategies are required to optimize process performance. In this case, such modifications enabled us to improve process performance, viability, and growth in the second iteration of experiments.
What is the typical timeline for technology transfer? In favorable cases when little to no process modifications are needed, technology transfer duration can be as fast as four months from initiation of information transfer to GMP vial thaw. It is important to list raw materials and process and facility gaps. This is generally discussed in the beginning of the technology transfer program or earlier. That generally is discussed in the beginning of the technology transfer program so that Avid and the sponsor agree on a realistic timeline. All risk is identified and quantified up front so that we can get a project right the first time.
Is Avid strictly a clinical producer? We focus on development and CGMP manufacturing of biopharmaceuticals from mammalian cell culture, but we are both a clinical and commercial manufacturing organization. We have been producing commercial products for 14 years and have a successful regulatory track record with both US and European authorities.
More Online
The full presentation of this webcast can be found on the BioProcess International website at the link below.
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