From Two Divergent Sites to Biologics Approvals in the US and EU
Nnamdi Nwachukwu — Protection + Compliance
The Moment
A client had just acquired a biologic asset and was heading into a pivotal Phase 3 trial, with a Biologics License Application (BLA) planned in the US and a Marketing Authorisation Application (MAA) in the EU. Underneath the deal sat an uncomfortable question. Nobody was sure the existing data could support the BLA.
The product depended on laboratory and manufacturing operations in the US and the UK. If those sites weren't aligned, regulators could refuse the application outright, and there wouldn't be enough product to run a multinational trial. Other companies had competing products in development, so on a multi-million dollar program, coming in second meant losing.
The in-house team had already tried to sort this out on a compressed timeline. It didn't get them where they needed to be.
The Diagnosis
The original plan was to manage the assessment and the alignment remotely. That fell apart fast. Within the time available, the only way to move quickly enough was to be in the room, so Nnamdi went to both labs.
Once there, the root cause was easy to see. Each site had developed its own culture and its own way of getting things done, and nobody had appreciated how far apart they had drifted. In places, what the dossier described and what the plant was doing were two different things. When management saw the gap laid out, they backed the fix completely.
The Work
There was no written definition of success at the start, only the sponsor's assumptions about what needed doing. So the first step was a gap assessment to replace those assumptions with facts, from both a regulatory and a quality standpoint.
- Assessed the regulatory history
Reviewed the asset's regulatory record and all correspondence with the agencies.
- Audited every site in person
Visited each laboratory and each manufacturing facility and audited the operations directly.
- Mapped the divergence
Built a process map comparing what the dossier said with what was happening on the manufacturing floor, and walked management through the risks.
- Wrote the remediation plan
Laid out the studies that had to be run and the SOPs and change controls to implement in the global quality system.
- Rewrote Module 3
Pulled the new lab and manufacturing picture together and updated Module 3, the quality section, of the FDA and EMA submissions.
- Tracked execution to the finish
Followed the plan through with weekly updates to the executive team. Unexpected hurdles came up, as they do in any drug development program, and each call was weighed against the end goal.
The Outcomes
Both regulators needed to see one consistent product, backed by data that matched what the plants were doing. By the end, they did.
- Both dossiers were accepted, and licenses were issued in the US and the EU
- Lab and manufacturing operations in the US and UK were brought into line under the global quality system
- The original goal was met with minimal slippage in the timeline
Without this engagement, another sponsor would likely have gotten there first and the program would have been written off. Nnamdibrought experience in consent decree environments, biologics manufacturing, process engineering, and multi-jurisdiction work on small molecules, vaccines and orphan drugs. That background is why the problems were found on the plant floor instead of in a letter from a regulator.