As you know, GMP Annex 1 is a guideline developed by the European Medicines Agency (EMA) and the European Commission that provides guidance on manufacturing sterile medicinal products. It includes the manufacturing requirements for sterile drugs made in and imported into the EU.
In 2015, a revision was triggered to address technological advances and industry trends in the pharmaceutical manufacturing sector by applying the tools described in ICH Q9 and ICH Q10. The long-awaited revised Annex was published on August 25, 2022, and it will go into effect on August 25, 2023.
In this blog post, we will examine the requirements of the Annex 1 revision and discuss ways to guarantee its implementation.
What Is It About?
The Annex offers guidance for manufacturing sterile products covering the design and control of facilities, equipment, systems, and procedures.
One of the key aspects of the revision is the application of quality risk management (QRM) to the product and process lifecycle as described in its scope:
"This Annex provides general guidance that should be used in the design and control of facilities, equipment, systems and procedures used for the manufacture of all sterile products applying the principles of Quality Risk Management (QRM), to ensure that microbial, particulate and endotoxin/pyrogen contamination is prevented in the final product."(1)
For this purpose, the guidelines state that you should consider the following areas for risk minimization:
- Facility, equipment, and process should be appropriately designed, qualified, and validated.
- Personnel should have adequate qualifications and experience, training, and behavior.
- Processes and monitoring systems for sterile product manufacture should be designed,
commissioned, qualified, monitored, and regularly reviewed.
- Raw materials and packaging materials should be adequately controlled and tested.
In conclusion, processes, equipment, facilities, and manufacturing activities should be managed in accordance with QRM principles to proactively identify, scientifically evaluate, and control potential risks to quality.
Additionally, there is a requirement to implement a contamination control strategy (also known as a CCS). The CCS should define all the control points and evaluate the effectiveness of the controls and monitoring measures (i.e., their design, procedure, technical, and organizational aspects).
What Do You Need To Be Compliant?
The short answer is that you need an effective pharmaceutical quality system (PQS).
Effective means that, according to the requirements detailed in Chapter 1 of the GMP guidelines, it needs to:
- Have an effective risk management system integrated into all areas of the product lifecycle.
- Guarantee that the manufacturer has knowledge and expertise of the products, equipment, engineering, and manufacturing methods employed.
- Perform root-cause analysis of procedural, process, or equipment failure in a way that correctly identifies and understands said risks.
- Apply risk management to the development and maintenance of the CCS.
- Assure senior management effectively oversees the state of control throughout the facility and product lifecycle.
- Prevent the compromise of processes connected to the finishing, storage, and transport of sterile products.
- Provide the persons responsible for product certification or product release with access to manufacturing and quality information.
Last, but not least, all non-conformities should be adequately investigated before the certification or release of each batch.
Making Sure Your PQS Is Ready
To ensure your PQS is ready for what the Annex 1 revision requires, we propose implementing a digital risk management platform.
It’s essential that your risk management system can support the extensive risk management demands of the Annex 1 revision. To accomplish this, we recommend centralizing your risk management activities in a single platform with workflows that are consistent across your company.
These workflows will, in turn, allow you to identify, quantify, and prioritize the risks in an effective, cost-efficient way. Additionally, this platform should:
- Easily map out your quality attributes, process parameters, and operations for all product lifecycle stages.
- Evaluate, mitigate, and design robust control strategies aligned with QbD practices.
- Perform cross-area and cross-site assessments, including cross-contamination, systematically.
Whether you’re already halfway through implementing the Annex 1 revision or just getting started, ValGenesis can support you with the most complete digital risk management tool. Reach out to one of our experts to find a solution tailored to your needs.
- “The Rules Governing Medicinal Products in the European Union, Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use”, European Commission. Accessed on June 26, 2023.