The rapid growth of cell and gene therapies (CGTs) means that many companies rely heavily on contract development and manufacturing organizations (CDMOs) for process development, clinical supply, process validation and the commercial supply of these lifesaving therapies.
Streamlining the technology transfer process for new products into a CDMO is critical. However, although technology transfer and process validation are performed routinely and are well-established for biotherapeutics, CGTs have several unique aspects that must be considered for a successful transfer.
If client sponsors, large or small, do not consider these unique aspects they could experience transfer failures, delays and complications. They may also face financial and quality impacts to their products and problems when they submit regulatory filings – ultimately delaying product launches. Simultaneously, these unique CGT issues could affect the CDMO for both the incoming products and those they make for their other customers.
This has led BioPhorum to publish Cell and gene therapy considerations when assigning responsibilities during a product transfer between a sponsor and a contract development manufacturing organization.
The paper outlines a shared understanding and proposed ownership of these unique aspects of CGT. Its recommendations are divided into five sections, each containing several tables, describing the activities that are relevant to CGT technology transfer and process validation:
- Process design
- Analytical methods
- Supply chain
- Facility and equipment
- Regulatory and quality.
In each section, key topics are identified in a responsibility matrix. The tables provide high-level guidance on how the weight of responsibility should be distributed between the sponsor and CDMO during the collaborative transfer process, with a specific emphasis on who should be ‘responsible’ and who should be ‘consulted’ – with reasons why these are different to biotherapeutics.
The table format can be easily used in expectation-setting documents and shared in meetings during the early stages of sponsor-CDMO interactions (such as a new product introduction kick-off meeting). It can be used as a checklist to help ensure all critical CGT considerations are covered to minimize unexpected situations. The recommendations could also be used to support master supply agreement and quality agreement discussions.
Crucially, this educational paper was developed through a unique collaboration between CGT sponsors and CDMOs to highlight the potential validation risks from both sides.
What we have tried to do in this paper is anticipate some of the specific challenges that we could encounter as we transfer new processes from a client into a CDMO,” said Senthil Ramaswamy, Director of Cell and Gene Technologies R&D at Lonza. “This allows us to make sure that we have talked through those specific aspects ahead of time and have a plan to address them before we encounter some of those challenges.”
Rapid, predictable and successful process transfers and validations are critical for the success of CGT products, but following a standard biotherapeutics transfer process is unlikely to work for CGTs because of their unique nature. If discussed early in the new product introduction process, these considerations could help align expectations and reduce the risk of unplanned disruptions during transfer.
With CGT being a fledgling industry, now is a great time to educate everyone involved in the art of CGT-specific transfers and validations.