New requirements in the manufacture of sterile drugs

The sterility test of a drug product has a very limited effectiveness, as it is destructive and performed on a reduced sample. For this reason, special attention is paid to the prescribed sterile medicinal products by both manufacturers and regulatory authorities.

The recent publication of the new document dedicated to the Manufacture of Sterile Medicinal Products (the revision of Annex 1 of the European Commission’s GMP) obliges us to update and familiarize ourselves with the requirements that, as of August 2023, will be required for the production of this type of medicinal products. For the point dedicated to lyophilizers, the implementation period is extended to two years.

Thus, the new version of Annex 1, deepens the mechanisms available to ensure the sterility of drugs.

Basis of the new revision

In this revision published almost five years after the 2017 draft, it states that manufacturers must prepare a basic document known as a “Contamination Control Strategy” (CCS). The strategy is based on analyzing processes in detail, identifying the hazards involved and proposing control mechanisms to ensure that the final risk level is acceptable. Clearly, the CCS will rely on the elements that make up a pharmaceutical quality system, as defined in the ICH Q10 guide, and will involve an improved understanding of the risk management process (ICH Q9). The designed strategy will allow the implementation of a performance monitoring system, detecting deviations and trends, reviewing the results and applying continuous improvement.

Classification vs. process monitoring

It is necessary to identify the critical points, with their action and alert limits, in order to monitor them. For this reason, Annex 1 details in depth which aspects must be taken into account and monitored. It is important to emphasize his insistence on clearly differentiating between classification and monitoring of clean areas and air systems.

Although already known practices, the new Annex 1 insists on the need to record all events, to qualify facilities, services and equipment and to validate production processes, whenever they are considered to affect product quality.

Final considerations

In summary, Annex 1 states that in order to achieve an acceptable level of safety (or, in other words, a low level of risk) for a sterile parenteral product to be of suitable quality, it is necessary to implement adequate monitoring mechanisms for the control of microorganisms, endotoxins/pyrogens and particulates.

As a complementary element to this monitoring of production processes, Aseptic Process Simulation (APS), the well-known “media fills”, and also the performance of a sterility test of the final product are required. It should be noted that none of these elements, taken in isolation, provides sterility assurance. It is the combination of all of them that makes it possible to certify and release a batch and, for this reason, Annex 1 requires that the final review of the documentation of the manufacturing batches covers all of them.

In short, the new version of Annex 1 significantly increases the level of control and monitoring requirements for sterile drug manufacturing processes.

Training of personnel and equipment

En STE Engipharm nos mueve la pasión por nuestra profesión y queremos contribuir al futuro del sector a través de diversos programas de capacitación farmacéutica.

Given the extent and level of detail of this new Annex 1, we offer various types of in-company training to adapt to the needs of our customers.

We invite you to contact us to learn about the various formats for training your team in this area. You can do so through this form or by writing directly to formaciones@stegroup.com.