Case study

Biogen SwissMedic Regulatory Challenge – $25M and 12-month project delay saved

The context

In 2013, Biogen began construction of a new facility in Luterbach, near Solothurn, Switzerland, expected to launch 2019. The facility was designed to be built as per existing Biogen sites, i.e., to house the drug substance process in CNC environments as far as possible, utilizing closed system technology. This approach is accepted by most regulatory authorities. Indeed, a previous ‘Type C’ meeting, with the FDA was positive towards the approach.

Biogen

The story

In 2016, SwissMedic (the local regulatory authority) informed Biogen that Grade D minimum was required for the room classification, not the CNC as was designed, as no other facility in Switzerland uses CNC areas for manufacture. However, this was not communicated to the correct project team members until 2018, with the facility construction nearing completion. As such, either the regulators would need to change their stance, or the facility as built would have to be upgraded to Grade D.
The Biogen team held an informal meeting with SwissMedic to explain the rationale behind the CNC design. However, the design was still not accepted by SwissMedic.

A second, formal meeting was held with SwissMedic, attended by their senior inspector, when Biogen gave a clear presentation explaining the risk-based approach to the facility design leveraging CS in CNC. Published outputs from BioPhorum’s Closed Systems workstream were utilized to support this presentation.

The outcomes

Following the meeting, the design as built with CNC areas was accepted (albeit with additional gowning and environmental monitoring required). This was the first facility in Switzerland to not use Grade D as a minimum.

SwissMedic stated that the ‘industry collaboration’ evidenced in BioPhorum’s supporting materials gave strong credibility to the approach.

An upgrade of the facility from CNC to D would have cost an estimated $25M and resulted in a 12-month delay to the project, with an unquantifiable potential loss in revenue.

Lessons learned

• Understand local culture – in this instance all materials were hand delivered to SwissMedic regulators as pre-reads.
• Don’t have informal meetings with regulators – have strong formal presentations, practised intensively.
• Ensure effective formal project communications – in this case, the initial requirement that Grade D was necessary did not reach the right people due to staff turnover.
• Understand specific local regulatory requirements – just because the FDA accepts a design, does not mean that others will. Partner with authorities to develop data-driven solutions.

Drivers and Best Practices
Risk-based, data-driven approaches should be used to support design, specifically for implementation of closed systems in CNC environments.