Considerations for the revised EU GMP Annex 1 requirements – Now Live!

Contamination control strategy, Quality risk management & clean room tech: adherence with the revised EU GMP Annex 1 – now live


In August, the revised EU GMP Annex 1 requirements, related to the Manufacture of Sterile Medicinal Products, were issued, starting the clock for compliance. All but one of the new provisions must be fulfilled within a year.

The updated requirements, designed to protect and increase confidence in the sterility of these products, are significant and wide-ranging, spanning the Quality system and the manufacturing process itself. Now that the full expectations are known, there is no time to lose in preparing for adherence.

The revised expectations span three key areas:

  • A comprehensive and continuously evolving contamination control strategy (CCS), covering everything from facilities, equipment, utilities, raw materials, cleaning and more;
  • Manufacturing facilities and the use of new technology/robotics to minimise human intervention and the associated risk of contamination; and
  • Quality systems, with an emphasis on continuous Quality risk management.

While the vast majority of pharma manufacturers will be well aware of the detailed revisions to EU GMP Annex 1, which have been five years in the making, it’s likely that many will not have initiated improvements in earnest until now. Although some work was already underway on Annex 1 updates a couple of years ago, delays to the publication of the final requirements eroded companies’ sense of urgency, so that resources were not prioritised to update plants and Quality systems.

Contamination control: a strategy
Developing and refining the CCS, which must ensure that consistent standards are upheld end to end across manufacturing operations, will require substantial resources. Certainly, this is not intended to be a one-off undertaking, in which provisions are agreed and definitively documented at the start. Rather, there will need to be periodical reviews of its efficacy – evidenced by data, triggering adjustments as needed. All of this will require an ongoing commitment of time and resources.

Next-generation clean rooms
Facilities-wise, the revisions to EU GMP Annex 1 require more proactive measures to remove direct human involvement in critical areas such as clean rooms, through the use of restricted access barrier systems (RABS), isolators and robotic systems. Investments here will help reduce the burden of CCS and Quality risk management, too, building confidence through the minimised scope for contamination.

Continuous Quality improvements
While Quality risk management in itself is not a new expectation for drug companies, there is heightened emphasis now on consistency across all plants and processes, and the importance of periodical reviews to ensure ongoing vigilance and enable continuous improvement.

Moving forward
While there is an additional year’s leeway around Annex 1 Point 8.123, which refers to the frequency of sterilisation of lyophilisers (pharma laboratory freeze dryers) and the transfer of the product and its loading/unloading to and from these facilities, for everything else provisions need to be in place – and tested – by August 2023.

With time ticking on, it’s important that manufacturers have clarity over the scale of the task ahead of them, and a plan for the improvements they now need to make. While a large pharma organisation with extensive resources might be able to pull off an effective transition within 6-8 months, the transformation is likely to take at least the full year for smaller manufacturers, depending on how modern their existing facilities and monitoring capabilities are.

We can help with all of this, from performing a gap analysis for compliance with the updated requirements (something that should be underway right now); to advising on and implementing the contamination control strategy; and helping to design and test new facilities and technologies.

For guidance and active support, you can reach our experienced team at Rephine group 

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