Finalization
Internalize External Knowledge
CMC work done, final milestone closely ahead, valuable Exit within reach. And of course, a lot of CMC data on file. But data does not equal knowledge.
Biopharmas frequently hit that wall, trying to change a supplier, running analytical methods at different labs or entering a Due Diligence. The data on file is insufficient and the full knowledge remained with the former partner. Smart Biopharmas internalize 3rd party knowledge when approaching the CMC finish line.
Biopharmas frequently hit that wall, trying to change a supplier, running analytical methods at different labs or entering a Due Diligence. The data on file is insufficient and the full knowledge remained with the former partner. Smart Biopharmas internalize 3rd party knowledge when approaching the CMC finish line.
Your Data Under Your Control
Data and reports supplied by CROs do not contain all the knowledge generated during a CMC development process. Reports are rather a brief synopsis of all that happened, of all that was observed, of all that was decided and so on. In short - Biopharmas receives just a small subset of the entire knowledge. The majority remains with the CRO. Not a desirable situation because it limits the Biopharma in future decisions like changing a CRO. Not a desirable situation because the Biopharma payed for a valuable task like "Development of API Manufacturing" but receives far less, just the ability of a single vendor to supply API.
Internalizing external knowledge is an important step and should happen during finalization of CMC work at the latest. The challenge is to figure out the gap between supplied and retained knowledge. We support Biopharmas with knowledge internalization.
Knowledge Base
Successful Exit needs results, knowledge and capabilities. In CMC terms, the capability to upscale API manufacturing at any CDMO, not the constraint to synthesize all upcoming batches at the long-term manufacturing partner. Or the availability of transferrable analytical methods for release testing, not the constraint to always run release testing at the identical lab.
All knowledge generated on behalf of the Biopharma should be collected, internalized, organized and neatly stored in a Knowledge Base. That way Biopharmas will be prepared for the next steps - either further development or Due Diligence, partnering and Exit.Knowledge & Capability Base
- All knowledge collected
- All knowledge internalized
- All knowledge organized and stored readily available
- Well prepared for next steps – Due Diligence, Partnering, Exit
Knowledge Equals Value
The analytical method for API release testing had been reported by the API supplier some weeks ago. Quite a convincing report, lots of tables, all validation parameters compliant with ICH guidelines, nice executive summary, compliance statement and quadruple signature on the front page. Report´s PDF stored on the Biopharma´s internal server - one more CMC box ticked.Until the report was forwarded to the analytical team of another CRO and that team tried to reproduce the method. Two different column types stated to be used, column parameters not reported anyway, chromatographic plots in the wrong scale, dilution cascade not reproducible with reported information, confusing information on reference standards, unclear batch numbers of API batches used for validation and so on.
Hard to believe? Maybe, but an example taken from real life. The Biopharma was not to blame, since they had no internal analytical expertise and many mistakes were far too specific to be easily identified. Nevertheless, the damage would have been at the side of the Biopharma. Imagine a potential partner´s due diligence team claiming the API release method to be worthless, together with all API batch information of the last three years. Not an experience to look forward to during a Due Diligence.
The example above was the result of sloppy working, but sloppiness is not necessary to send Biopharmas to the uncharted waters of insufficient knowledge. Problems will appear during any development process. Deviations from established routine. Changes from the original plan. Trouble shooting in the middle of a running process. Each of those were probably assessed carefully by the CRO. Each corrective action was probably the best to take. However, the process leading to the action, the result of the assessment, the experts involved, the data which lead to problem identification normally remain exclusively at the side of the external CRO.
Looking back at the development process after some years reveals a plethora of seemingly random and pointless swaps, changes or deviations. A Biopharma trying to get anybody to reproduce the process will just receive a lot of "why" questions. "Why did you change to that critical solvent?", "Why did you introduce the change that reduced yield dramatically?", "Why did you change the release specification?" and so on. Good questions and the answers are probably available - they just never made it to the knowledge base of the Biopharma. The most likely outcome is a costly re-development of an already existing and well-developed process.
Knowledge equals value. Make sure to internalize all your knowledge.