EU GMP Annex 1 - Manufacture of Sterile Medicinal Products and Contamination Control Strategy

The revised draft of the EU GMP Guide Annex 1 "Manufacture of Sterile Medicinal Products" is available and the second consultation phase has been completed. Certainly, these comments will lead to further revision, but it is already foreseeable: the Contamination Control Strategy will remain.

Manufacturers of sterile dosage forms are following developments closely: the revision of Annex 1 is pending. Since 2015, with the publication of the concept paper, it has also been clear why: New technologies have made their way into the production of sterile and aseptically manufactured medicinal products. And the principles of risk management (ICH Q9) and new considerations for the design of the pharmaceutical quality system (ICH Q10) have also been formulated and await to be implemented.

A fundamental revision was published in the first draft at the end of 2017. The second round of comments on the revision of Annex 1 has been completed. The result is open; publication of the revision is expected in the course of this year.

The current document introduces a number of changes. The most important of these is the new holistic and integrated Contamination Control Strategy. This includes the entire manufacturing process and all associated areas. 

How can this general requirement be implemented? What will probably be the expectations of the authorities? A planned, targeted alignment and the expansion of the QM system are advised. 

For companies in the now also extended scope - all sterile products are now affected, i.e. also sterile excipients, primary packaging materials and active ingredients - this initially means a conceptual effort. A structured, proactive approach is required. The implementation of the new guideline requires some preparation time. A gap analysis reveals starting points for initial measures. Adjustments can then be planned and implemented on a selective basis.

gempex recommends customers who will be affected by the new version of Annex 1 to establish an SOP for the Contamination Control Strategy, which continuously accompanies the manufacture of sterile products as a life cycle document. Furthermore, performance reports on contamination control should be anchored. 

Practice already shows that a proactive approach, making the quality management system ready for the final new Annex 1, makes perfect sense and helps companies to prepare well for the customer and authority requirements to be expected in the future.

A link to the current consultation process of the European Medicines Agency (EMA) is provided at 

For questions on the topic or a first exchange of ideas, the gempex team will be happy to provide competent assistance.
Please contact Frank Studt, Managing Director of gempex, via