Best Practices in Tech Transfer:
Success Hinges on Multifunctional Team Efforts
Successful technology transfer originates from a dedicated, multidisciplinary tech transfer team assembled as soon as the product enters development. This group, consisting of quality, engineering, supply chain, development, QA, QC, regulatory and operations personnel, is actually easier to put together at a small pharm/biotech company where professionals wear several hats.
"Larger firms tend to have a lot of specialty silos," says Chatterjee of Pharma Tech. For the duration of the project, team members report to the project leader rather than to their functional managers on tech transfer matters.
Chatterjee also warns about expectations gone awry during tech transfer. Unless they have manufactured the product themselves at full scale, even top companies may have difficulty understanding cost escalations as batch sizes increase. This disconnect with reality most likely will occur when transferring a process to a CMO. "The manufacturing line may not be the same for commercialization as for Phase III," he says.
According to VaxGen’s James Panek, a successful tech transfer project demands that scientific and technical personnel from the originator company be present at the technology transfer site, especially in the early stages and during initial full-scale runs.
"Those are the people you need to talk to when something goes wrong, or if there is a question about how to carry out an operation," he says." It’s very difficult to get those answers from QA/QC or project management." He describes projects where process questions are answered by an intermediary as like a game of telephone. “You may not get the answer to the question you’re asking, and even if you do, it is not in real time.”
Panek also suggests maintaining an updated project plan, so all the principals know exactly where the project stands within the timelines and whether milestones such as fill date, regulatory filing or clinical trial start will occur on time. A technology transfer project plan consists of a detailed list of operations broken down by task. "When things happen, you check them off and everyone is assured the timelines are met," he says.
The plan may be annotated or supplemented with appropriate documents (e.g., a drug development or substance characterization report). Each component should include metrics for assessing progress, quality, completeness and completion. When communicating the plan to a client, a CMO should construct a timeline that is as detailed as possible, listing every item and its expected duration.
"Communication" has become cliché in discussions of pharma collaborations, but it cannot be over-stressed when transferring technology to overseas manufacturers. "Tech transfer issues are multiplied as you enter the global CMO sphere," says Matthew Hudes of Deloitte. BMS’s Korean venture is perhaps an extreme example, but cultural and other issues arise as a function of geographic distance. Companies with the resources can overcome these issues by forming global technology transfer centers of excellence, where scientists and engineers can exchange process knowledge.
A common mistake during scale-up and technology transfer is an under-appreciation for the impact of batch volumes on mixing, and ultimately product quality, for sterile, pre-mixed drug products. Temperature, mixing time and the sequence and rate of addition can greatly affect degradant formation, as Baxter’s Chilamkurti points out. On the other hand, compared with solids, solutions have more predictable physicochemical properties. Dissolved drug formulation processes are therefore easier to transfer from R&D to manufacturing or to a contract manufacturer, and simpler to scale.
Another impediment to smooth tech transfer is the reluctance on the part of innovators to provide full details on the drug, its physical properties, formulation, analytic information and manufacturing details. Many companies adhere to a "need to know" policy with respect to contract manufacturers. However, what the manufacturer needs to know is not always obvious.
Processes and unit operations benefit from easily-transferred “platform” deployments of process analytical technologies (PAT). For PAT to be effective, engineers must test the systems with many process variables to be sure it will behave during normal operation. It may not be possible to predict these variations during PAT tech transfer, due to slightly different reactor configurations, agitation, heat transfer and other variables.
"This is not plug and play," says BMS’s Grosso, who estimates that only 50-75% of the knowledge gained from one Raman PAT deployment is directly transferable to a second process.