By Ziva Abraham, Jim Polarine, and Morgan Polen

If you are responsible for the contamination control during the manufacturing of medicinal products, then you need to know about significant changes to Annex 1 of the EU-GMP guide.

The 2020 revised guidance draft aims to further protect against product contamination and patient harm by requiring companies to formally document a contamination control strategy. Sterile and non-sterile medicinal product manufacturers must meet new requirements and specifications. This impacts the work of cleanroom facility design, construction qualification, and operations.

While the draft is not yet final, it indicates the contamination control that medicinal product manufacturers must demonstrate through risk management and effective documentation.

Why is the EU-GMP Annex 1 update important?

The 2020 draft revision of EU-GMP Annex 1 is an example of the most recent regulatory thinking for the manufacturing of medicinal products. It is designed to remove ambiguities, eliminate loopholes and misunderstandings, and encourage the use of new technologies in sterile manufacturing, the increased use of isolators and RABS designs as well as the changes in ISO Cleanroom Standards (ISO 14644-1&2:2015). The main message of this revision is that science is no longer isolated; it is living across the lifecycle of the product/process within a quality risk management system.

Based upon inspectors’ observations of inadequate root cause analysis, ineffective use or application of CAPA, and incorrect implementation of ICH Q9 quality risk management, this comprehensive document provides an outline for risk assessment when developing a documented Contamination Control Strategy (CCS).

A new structure was developed by the European Commission in close collaboration with the World Health Organization and PIC/S to link their standards and recommendations and reach globally agreed-upon standards. It attempts to give the Annex a clear structure with a sensible sequence of its sections.

Key highlights include:

• Emphasis on the requirement for a formal broad-reaching, organization-wide, risk-based strategy for minimizing contamination and cross-contamination of medicinal products. This strategy is the CCS.
• Importance of implementing the CCS across all departments and functions to define all critical control points and assess the effectiveness and monitoring of all the contamination control risks (design, procedural, technical, and organizational). A CCS should not be treated as simply a document or a paper exercise created as a check box for compliance. It should be viewed as a living, breathing contamination control strategy of which all employees are aware and participate in.
• Outlines new elements to include and assess in the CCS.

The 2020 draft has a few shortcomings. While it clearly defines requirements, it does not provide enough detail on the execution. The CCS cannot be developed using only the Annex 1 document. Knowledge of other regulations, standards, and guidance is required to produce a comprehensive CCS. It also requires thorough technical and process knowledge about potential sources of contamination. Then, managers must plan to routinely update the CCS to drive continuous improvement of the manufacturing and control methods.

How can I learn more?

This week IEST kicks off its webinar training course series, “Practical Considerations for Implementing a GMP Annex 1 Contamination Control Strategy.” This series will help you identify real-world risk scenarios, identify gaps, develop a mitigation strategy, optimize contamination control, and prepare a CCS that complies with current regulatory thinking about contamination control.

We recommend completing the two introduction modules before moving on to the other modules (which you can take in any order) in the in-depth series.

The instructors all have extensive, real-world experience in developing science-based and risk-based contamination control strategies for all types of medical products. They will share their experience on subjects and provide practical instructions related to their field. They will also provide references to additional materials useful for performing a comprehensive risk assessment as well as identifying and mitigating gaps.

This ongoing training will allow the attendees to gain knowledge from vetted, subject-matter experts on:

• Scope and Principal of the CCS (Feb. 8 training)
• Premise and equipment (Feb. 9 training)
• Cleaning and Disinfection (Feb. 15 training)
• Personnel (March 2 training)
• Sterilization technologies (Date TBA)
• Non-Viable Monitoring (Date TBA)
• Viable Monitoring (Date TBA)
• Quality Control (Date TBA)
• And more

Registration closes Feb. 7 for the introduction training courses, so be sure to sign up quickly!

Ziva Abraham is CEO of Microrite, Inc., providing consulting and training services to pharmaceuticals, biotechnology, medical devices and in-vitro diagnostics in the areas of quality assurance, quality control, microbiology, and validation.

Jim Polarine is senior technical service manager at STERIS Corporation, where he has worked for 22 years. His current technical focus is cleaning and disinfection and microbial control in cleanrooms and other critical environments.

Morgan Polen is a cleanroom contamination control expert for Microrite, Inc., providing science-based solutions to companies in a variety of industries including pharmaceutical, medical device, semiconductor, data storage, aerospace, defense, automotive, optical, food and beverage.