Good Manufacturing Practice (GMP )
Time taken for each step is typically:
- 1 year for process development,
- 6 months for tech transfer (if process is transferring to different sites/scales of production)
- 4 months for GMP manufacture,
- 4 months for QC tests.
Every vaccine is slightly different, and it depends whether it's a completely novel process or is slotting into existing technology, in which case the overall process could be 1 year shorter.
- Deciding on the expression system
- Isolating a suitable clone (which is a high producer and genetically stable)
- Designing the upstream process (in particular scale of manufacture, and whether to use shake flasks, wave bags, fermenters etc)
- Designing the downstream process eg use of affinity purification tag, use of chromatography
- Deciding on QC assays and specifications needed for the Master Cell Bank and Final Product eg what purity is required, how potency will be measured – and developing these assays ahead of time.
- Validating GMP master seed bank
- Considering throughout whether the process will be GMP compliant eg use of purification tags, and consulting the regulators where necessary
- Deciding on formulation buffer and storage conditions
- Tech transfer of the final process to the manufacturer (see text on ‘Process Development’ map, behind ‘Tech Transfer’ icon
- GMP manufacture
- QC and stability testing
There are many bottlenecks. It is essential to consider all of the above in good time in order to coordinate all of the necessary activities. Good communication with the CMO is essential to ensure smooth/timely tech transfer.
Some specific bottlenecks:
- Getting a high producing clone
- Process development
- Tech transfer
- Identifying a suitable CMO and obtaining quotes
- Securing slots at the CMO and all of the testing companies
- Employing a project manager with industrial/GMP experience for each vaccine project
- Ways of facilitating communication between industry and academia
- List of suitable CMOs and testing houses – this would be very helpful at the Jenner (we have experience with GMP but recently have needed to expand capacity)
- Developing a generalised production process which can be used for different vaccines, removing the need for optimisation of each new vaccine – we have already done this at the Jenner for viral vectored vaccines, it may be possible with other technologies eg VLPs
For academic groups who want to manufacture a vaccine, there is typically
- Lack of necessary expertise/understanding of the whole process, and the need to think about GMP compliance as early as possible so that time isn't wasted e.g. remaking a clone with animal free media.
- Lack of money – GMP is expensive