The transition from discovery and research to full manufacturing marks a critical time in a drug candidate’s lifecycle. Whether a company completes the scale-up process entirely in-house, with a single CRO/CMO or with multiple CROs and a CMO, the principles remain the same: ensure the smooth transition of data and expertise across various scales and stages to bring the project stage to a satisfactory conclusion.
Sometimes, however, things get lost in translation. What if the CRO didn’t share appropriate genotoxic impurities (LINK to EVENT RECORDING) findings and strategies with the CMO? What if aspects of biopharmaceutical processing that required serious modifications at larger scales were poorly addressed? Or what if a route change was not properly documented?
Some reasons these issues typically arise are:
- Lack of regulatory expertise earlier in the research & development cycle
- Poor documentation
- Poor communication during hand-off to later stages
Bear in mind, these (and other) issues are not the exclusive domain of life sciences companies who contract with multiple CROs/CMOs at different stages of the product lifecycle. They occur in-house, as well – especially when aspects of the project fall outside a firm’s core competency.
One CRO/CMO – Fewer Challenges
It’s always advisable for a company to stick with the same CMO during the clinical through commercial phases, and I’m not saying this because Neuland offers most start-to-finish services. (We do.) I say this because bringing the same skill-sets and expertise to bear across the various stages of a project leads to fewer communication problems and regulatory hurdles.
In practice, using a single source contract firm can sometimes still be challenging. Priorities of development programs typically change as the project proceeds from IND to Phase 3/NDA filing. During the initial periods, companies generally seek out someone who is quick, flexible – and preferably local to speed communication and interaction. Early on in the process pharma companies seek out CROs that are good at process research, with cGMP compliance lower in this list of priorities. And since the volume of APIs consumed for IND studies or even Phase 1 studies are relatively small, engaging a US- or EU-based CMO (or CRO) is generally not cost prohibitive.
As the molecule moves forward in development, the emphasis changes from ‘quick and flexible’ to process optimization, the establishment of strong analytical controls, a strong cGMP culture, and economical manufacture.
3 Hints for Managing Your Drug Candidate’s Scale-Up
- Is your drug candidate in a niche therapeutic segment? If so, volumes may be lower in Phase III or full commercial production. While the numbers specific to your project would need to be crunched, it might still be viable to continue using the same small scale CMO that brought you through the earlier stages.
- If your candidate is geared towards mainstream indications (e.g., metabolic disorders, CNS, cardiovascular disease) it’s important to use a CMO who properly understands lifecycle management – and has the capacity as well as the expertise to properly manage the larger quantities of APIs your drug candidate will require.
- Getting a large-scale CMO involved at an early stage can sometimes be overkill. By implementing later-stage standards earlier in the development process, it is easy to quickly go over budget and exceed timelines. Experts warn that it can also set the bar too high with regulatory agencies for future development. Full service contract firms services that work across multiple scales must be flexible enough to maneuver the regulatory landscape at all stages of development.
Has your company overcome scale-up issues between phases? Tell us how you handled it below.
