Minimizing risk in viral vector projects

There are multiple risks that can affect the prospects of success for a viral vector project. The obvious one at the outset, of course, is the absence of a proven manufacturing process for the vector. There will be little data to suggest the quality and yield that might be expected, either. And while the same holds true for any novel drug, the added complexity of vector manufacture exacerbates the risk. 

But looking more broadly, there is the risk inherent in tech transfer. If a process has to be transferred from one site to another, or from one team to another, this will always be a significant point of risk, regardless of the nature of the project. If the development and scale-up are carried out by the same company and in the same location, the integrated teams go a long way to reducing those risks.  

Planning for successful scale-up 

The scale-up itself also poses risks. If the early lab development has been carried out without an eye to how it will work on scale-up, the delays can be significant. Will all the necessary raw materials be available, and in sufficient quantities? Are they GMP compliant? 

However, perhaps the most unpredictable risk comes on the regulatory side. We follow the regulatory landscape very closely, and it is evolving, and can be unpredictable. The vast majority of gene therapies are being developed to treat rare diseases, which is a rapidly changing field itself. It creates a ‘double whammy’ of regulatory risk. As an example, FDA has issued a draft guidance on individualized therapies for ultra-rare diseases, and this has important consequences for the CMC strategy of therapeutic developers. 

The recent introduction of Annex 1 to the EU GMP requirements added to the compliance demands. But we have the significant advantage that, as part of Siegfried, we have the backing of their 30-strong group of regulatory affairs experts. Across the group, we are proactively looking out for any regulatory changes that may apply to us and to our technologies. It is such a new and evolving field that the regulatory environment for viral vectors is moving quickly. Keeping on top of the regulators’ requirements is critical if unnecessary hurdles are to be avoided. We even offer our customers support in writing their IND documents and other regulatory files.  

Avoiding costly process changes 

 It’s fair to say that customer expectations may not align with regulatory expectations. Moving fast to get to a Phase 1 tool more quickly may mean they have used a process that is not designed with a larger scale in mind. While it may meet GMP requirements, the process is neither sufficiently robust nor scalable. Process changes will be inevitable as it moves on to Phase 2 and 3. But making process changes later on introduce additional risks. The regulators may even require comparability studies, adding to the challenge. This will, inevitably, push the timeline back while an alternative process is developed and validated.  

Thinking beyond early clinical development 

In the US in particular, this failure to plan ahead can cause broader concerns. It is rare for Phase 1 or even Phase 2 manufacturing facilities to be inspected by FDA, meaning their first regulatory inspection is likely to be as it moves into commercial manufacture, upping the potential cost of inspection failure.  

Continuity of manufacture between early and late stages, and using a CDMO that is well versed in the evolving regulatory situation, should remove some of the layers of regulatory risk in GMP manufacture.