New EU GMP Annex 1 – Implications for QRM application

by Alessio Rosati
Sterility Assurance Executive Consultant – PQE Group

The issues exposed in this article were discussed in
“Risk Based approach to Qualification Activities” free Webinar by PQE
, on April 20th. Register now to watch it on-demand (coming soon).


After a long period of preparation and review, the new revision of EU GMP Annex 1 is about to be issued. An outstanding amount of new requirements, recommendations and detailed specifications are included in the Annex 1 draft 2020, altogether implying that sterile manufacturers will have to focus efforts, knowledge and time in getting full compliance for their products and processes.

The new target is to know ‘what’ to control with an active, scientific-based approach.

Some new requirements will ask for full revision of the current contamination control strategies, quality risk management, validation and qualification policies, as well the chance for the implementation of new technologies. But the core requirement beneath the new Annex 1 is to achieve an active, critical and science-based approach to the contamination risk management, to gain the awareness enabling manufacturers to know what to look at, analyse and manage to keep the process under control.

In this respect, the Quality Risk Management gains a paramount importance. It is no coincidence that the words “risk” and “risk assessment” are mentioned 99 times throughout the new Annex 1! Risk assessment and management tools are really effective at providing an objective and science-based way to identify, evaluate, and mitigate all the potential risks of products and processes contamination. And it is no coincidence that the new Annex 1 requires to use them so many times, to evaluate and manage a plethora of different aspects related to the sterility assurance of pharmaceutical products.

Annex 1 is driving a change in mind-set for Pharma manufacturers.

No need to go on talking about risk assessment tools and their modalities of application: there is a huge bunch of free articles and guidelines that can guide you through that. But I want to focus on what their use and the Annex 1 request implies: the need for a change of mind-set. Many pharmaceutical manufacturers have quality systems in place that are not based on a scientific and methodical approach anyway, even when rigid and severe. The result is often a time and effort consuming system of control and monitoring that can hardly be justified, supported and even verified for its effectiveness.

Even if at a first glance it can seem to be challenging, the application of quality risk management to evaluate and control almost every aspect of the sterility assurance of products and processes can provide an invaluable basis for the design of the contamination control strategies. But to achieve that, a change of mind-set is needed.

Quality Risk Management in manufacturing areas: Same ‘playground’, different approach to add value and control multiple risks.

Let’s consider just an example: the sampling plans for microbial and particle contamination of the manufacturing areas are usually defined (and now EU GMP Annex1 clearly states this requirement) based on a risk assessment study, that should take into account all the environmental and operational parameters resulting to be critical for the particle and microbial load of the production areas. Such a study can define a sampling plan in details, in terms of number and location of the sampling points, sampling methods to be used, sampling volumes, sampling frequencies and so on.

Now, what if the same approach was applied even to a monitoring activity that is usually (and wrongly) underestimated and considered as simple, the personnel monitoring? Cleanroom personnel monitoring is a critical activity aimed to assure not only a reliable control over the bioburden and microflora composition of the cleanrooms, but also for the qualification and overview of the personnel themselves. Indeed, microbial sampling on sterile operators’ suits is actually applied not only for routine monitoring but also for personnel qualification. From this perspective, the importance of defining an effective monitoring plans, even on a “simple” area like an operator suit, becomes evident. But applying a risk assessment tools at this purpose, can bring out one important –but not so evident- aspect: personnel routine monitoring is totally different from personnel qualification. In the former case, the most critical areas of the sterile suit to be monitored are the ones most likely to get in contact with surfaces (or be touched by the operators themselves) during working activities: usually, they may be gloves, forearms, chest, goggle, neck and so on. In the latter case, the monitoring plan is aimed to verify that the operator can wear the sterile suit in compliance with the operational procedures in place, and thus avoiding to contaminate the suit during gowning: the most critical areas will be inevitably different from the ones identified in the former case. The same “playground”, but two distinct monitoring plans with two distinct purposes and criticalities to focus on. And it becomes evident only once a risk assessment study is executed, evaluating the criticalities and the properties of the playground (the suit and the operators’ activities) with a methodic approach.

This is a very quick and simple example, but this is exactly the reason why quality risk management can provide an added value to the current contamination control strategies, and to the ones under design. And that’s why the new EU GMP strongly demands for that.

Want to know more?

Check out our on-demand  webinar (coming soon): “Risk Based approach to Qualification Activities” as part of ‘Annex 1 month’ initiative by PQE!

PQE Group staff comprises experienced and skilled experts that can support you in the goal for compliance with the new arriving Annex 1, in every aspect of your aseptic manufacturing: sterility assurance strategies, quality compliance, microbial monitoring, cleanroom design and revamping, equipment qualification, critical system validation, analytical methods selection and validation, and many others.
Check out Compliance Services, and contact our team to request a meeting with our experts.

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