An appeal to the European health authority for leeway on the August 2023 compliance date has been rejected, putting the onus back on drug manufacturers to justify and provide new transparency around their contamination controls/risk management linked to sterile medicinal products.
Compliance with the updated EU GMP Annex 1 requirements, related to the Manufacture of Sterile Medicinal Products, is expected by the end of August this year for almost all relevant production scenarios.
For many facilities, the approaching deadline is now causing some trepidation, because these companies now need to be able to explain and justify the measures that are in place to control contamination and manage risk. This requires clear visibility (and good documentation), and also a confident sense of purpose around the way current manufacturing processes are designed and managed – and that nothing is being left to chance.
No extensions, no special lenience
Such has been the panic across the market, at the sudden realisation of the approaching Annex 1 compliance deadline, that there was a recent appeal to EMA to extend the timescales and give manufacturers a bit more leeway. But in the last couple of weeks EMA has responded with an unequivocal No. The August 2023 deadline still stands.
Yet there is really no need for panic. As it is, the draft for the updated requirements was issued some five years ago, so the demands have hardly been sprung on the market. In other words, the opportunity to align with the new expectations has been ample.
Some are confusing the new requirements with a need for certain new technology, when in actual fact this is more about companies showing they have strong controls and a robust risk management plan in place around potential contamination. Which in turn means that they need to able to clearly set out and demonstrate how they think about and manage this – and what additional controls might be needed (e.g. through the application of new technology).
Showing willing is half the battle
Although there is a deadline of this coming August for compliance with most updated Annex 1 parameters, the key to keeping the right side of EMA is manufacturers being able to show that they are ‘on the case’: specifically that the requirements have been fully evaluated; a gap analysis performed; and that measures to address any such gaps are now underway.
The expectation is that these gaps are tackled by August, especially for those considered critical. If a company falls short, the inspector will formalise these omissions with an observation. Renewal of the GMP certificate will depend on the impact (risk) of these observations in guaranteeing the quality and sterility of the product. As long as it’s evident that proactive work is ongoing to bring contamination control strategies and appropriate risk-based measures into line, where these are indisputably needed, inspectors are likely to be satisfied and simply make a note to closely monitor progress and final delivery of compliance.
Making plans & measures fit for purpose
The appropriate measures part of all of this is important. Previous approaches to risk management have been much more ‘checkbox’ in nature – manufacturers have simply followed a positive list of requirements without really thinking through why those measures might be needed, or what the risk ultimately could be to the manufacturing process and therefore the resultant sterile medicinal products.
The biggest change with the updated GMP Annex 1 expectations is that EMA is now looking for clear rationale to any measures being taken to ensure there is no risk to the quality and integrity of sterile products.
The real work for drug manufacturers over the remaining months, then, is about going back to basics and understanding the way they manage their relevant facilities and why. To fully contain risk, they must identify any gaps in their current facilities and processes, and work out a plan for amending these as needed – earmarking appropriate investment.
As long as a clear plan is in place for rolling out those improved measures (which might include new cleanroom technology, for instance), the actual implementation of these can take place as time permits – albeit under the watchful eye of the Regulator.
We can help with any or all of the above work, so would encourage any sterile drugs manufacturer to get in touch ASAP – whether that’s for support in performing a gap analysis or developing and rolling out a relevant technology implementation plan.
- A more detailed guide on the updated requirements is available on our web site at https://www.rephine.com/resources/ebook/compliance_with_eu_gmp_annex_1/