Pharmaceutical outsourcing is a mature industry but remains huge. A study by Cepton Strategies (Münich, Germany) estimates the value of outsourced R&D in 2008 at $18 billion, and of contract manufacturing at $39 billion. Technology transfer — the handover of knowledge between organizations — is the seminal event in all outsourcing arrangements, particularly for manufacturing.
Tech transfers may occur internally, within a company, or involve two or more corporate entities. Lateral transfers involve the same development or manufacturing stage; more commonly transfers involve successive lifecycle stages, such as development and scaleup.
Tech transfer issues arise from inconsistencies and miscommunication between donor and receiving organization, says Wei Chen, Ph.D., chief scientist at Phage Pharmaceuticals (San Diego). “These encompass the entire development environment comprising materials, equipment, disciplines, people and culture — all the physical, biological and interpersonal factors, both macro and micro.”
External tech transfers are the most prominent and prompt the most discussion. Contractors and sponsors have developed their own unique tech transfer subcultures. The key to success is not allowing those cultures to clash.
AMRI (Albany), a CMO that also offers scale-up development services, takes a two-pronged approach to external technology transfer that includes accompanying strategies for internal transfers. The first component, explains Christian W. Phillips, senior director, operations, involves the transfer of drug product knowledge from the innovator company to the CMO. “At this stage, a process engineer assimilates that knowledge and designs a development transfer plan, and ultimately a GMP process.”
This is the step where the CMO comes to understand the product’s critical quality attributes and known process control parameters within the scope of the customer’s business objectives. Once this occurs, a CMO should have a good idea of process design options.
What follows is a second, internal, technology transfer process whereby the CMO’s process engineer(s) transfer product/process knowledge to the manufacturing group. “These two successive tiers of technology transfer ensure that product knowledge is not only captured, but maintained within all organizational levels and throughout the project’s lifecycle,” Phillips says. After selecting engineering and quality controls, engineering presents QA a development plan to ensure consensus.
Because CMOs often work with many different products and platform technologies, manufacturing teams must possess deep understanding of GMP, and recognize potentially adverse process issues early enough to implement preventive actions proactively, rather than reactively. “It’s this depth of floor-level, product-specific manufacturing knowledge that provides the best chances of overall success,” Phillips adds.
Rick Soltero, president of PharmaDirections (Raleigh-Durham, N.C.), says that many sponsors overestimate a contractor’s capabilities, which leads to a misalignment of expectations. “CMOs are simply educated hands,” he says.
A common misalignment involves deliverables. Sponsors unfamiliar with formal requests for proposal fail to communicate their needs; contractors misinterpret poorly conceived RFPs. A sponsor reading three widely varying quotes will face an “apples-to-oranges” comparison. CMOs tend to respond to RFPs according to their skill sets: When your only tool is a hammer, every problem looks like a nail. Sponsors must detail everything they need in an RFP, and set clear expectations on deliverables and milestones, Soltero advises.
PharmaDirections, which serves as an intermediary between CMOs and sponsors, recommends including a demo or engineering batch into CMO contracts. “Hardly anything works right the first time,” Soltero says, “but it takes a lot of persuading for sponsors to understand that.” He views demo batches as insurance: It adds about one month to the project, but can help avoid much longer delays associated with a failed clinical batch.
According to Alex Kanarek, Ph.D., senior consultant at Bioprocess Technology Consultants (Woburn, Mass.), hurdles when moving a process to a CMO typically involve inadequate specification of the transferred processes, and failure to create a satisfactory quality agreement. “The agreement must be sufficiently detailed so there are no equivocal requirements in the process or product specifications that CMOs may misinterpret. There is a slight tendency for CMOs to assume that they ‘know it all’ and apply some familiar technology that is unsuitable for the product, or make incorrect assumptions.”
Ready for Kickoff
Patheon (Monza, Italy) initiates tech transfer with a tightly structured and documented kickoff meeting with the customer. Andrea Como, site technical business senior manager, calls this step “information transfer.” During this consultation, the business partners assemble a detailed technology transfer list that includes everything required to initiate and understand the project. After the CMO has reviewed the sponsor’s documentation package comes a “technical kickoff” meeting where the parties cover specific, anticipated chemical/engineering issues.
Bottlenecks arise when the sponsor does not or cannot provide a robust data package. Reports of sponsors holding back for reasons related to intellectual property emerge occasionally, but most are probably apocryphal. More often, sponsors may not fully understand tech transfer and the CMO’s expectations. Many small sponsors lack GMP, regulatory or analytical experience, and may underestimate their significance. As long as both parties appreciate the potential for adverse issues, appropriate precautions can be built into the project.