Since August 25, 2023, the revised version of EU GMP Annex 1 has applied with one exception, including the obligation to develop a contamination control strategy (CCS for short) and the obligation to wear plant socks when entering changing rooms in front of GMP B and C cleanroom areas.

The EU GMP Annex 1 is an important annex to the guidelines for the “Good Manufacturing Practice (GMP)“ of the European Union, which was revised in 2022. It is a specific guideline that focuses on the requirements and recommendations for the manufacture of sterile medicinal products.

More in-depth information on the new contamination control strategy (CCS) and the new plant sock requirement regarding GMP B and GMP C areas in cleanrooms can be found in this article.

What the contamination control strategy (CCS) should include

Since August 25, 2023, the new EU GMP Annex 1 has required a comprehensive and overarching Contamination Control Strategy( CCS), which is to be used as a control instrument for the rational management of risks in the manufacture of medicinal products. However, Annex 1 does not provide any specific requirements for the structure of the CCS document. A holistic risk-based approach to possible contamination hazards is expected. The CCS is a formalization and summary of existing requirements.

The following points should be taken into account in the contamination control strategy (CCS):

  1. Design of the system and the process
  2. Premises and equipment
  3. Personnel
  4. Operating resources
  5. Raw material control – IPC
  6. Product containers and closures
  7. Supplier approvals
  8. Evidence for outsourced services
  9. Process risk assessment
  10. Process validation
  11. Validation of the sterilization processes
  12. Preventive maintenance
  13. Cleaning and disinfection
  14. Monitoring systems
  15. Prevention
  16. Continuous improvement

Assistance with the development of a contamination control strategy (CCS)

Help in developing a contamination control strategy (CCS) is provided by the ECA Foundation, a non-profit organization that supports the pharmaceutical industry and regulatory authorities in promoting the transition to a harmonized set of GMP and regulatory guidelines by providing information and interpretation of new or updated guidelines.

In January 2022, the working group “ECA Task Force on Contamination Control Strategy” published a document to support those responsible in drawing up a contamination control strategy: “How to Develop and Document a Contamination Control Strategy“

Procedure for creating a CCS

When creating the CCS, it is important to consider whether it is being created for a new or an existing plant and how far the company’s understanding of the process has already been developed.

For a new plant with little know-how in sterile production:

  1. Acquire an understanding of the process
  2. Mapping of the manufacturing process to identify possible sources of contamination
  3. Risk assessment of all possible contamination hazards
  4. Establish preventive measures and controls including responsibilities
  5. Documenting evidence of the measures
  6. Assessment and control of the residual risk of contamination

For an existing system or with good to very well-developed know-how:

  1. Evaluation of existing contamination control measures
  2. Analysis and overview of possible gaps
  3. If necessary, supplement further measures
  4. Assessment and control of the residual risk of contamination

Data evaluation

One of the challenges for pharmaceutical manufacturers is to obtain a holistic view of the large amount of data that they have collected with the CCS control systems. In this respect, Annex 1 explicitly requires that a system supports the manufacturer in the evaluation.

Source: https://www.fostec.com/de/kompetenzen/big-data/

Monitoring

A continuous target/actual comparison is important so that deviations in quality can be identified in good time and rectified with the necessary precautions. Monitoring is carried out in various areas, including general procedures, particles and microbiology, cleanroom classification and cleanroom personnel.

Cleanroom staff and new sock requirement

When it comes to employees in the cleanroom, it is important for staff to be properly trained in the following points:

  • Behavior in the cleanroom
  • GMP & Hygiene
  • Dressing procedure
  • Training on the job

Staff training also depends on various factors. The dressing procedure, for example, varies depending on the cleanroom class, because the cleaner a cleanroom has to be, the more cleanroom clothing is required and the more carefully it has to be put on.

With the revision of EU GMP Annex 1, a new socks requirement was also introducedin relation to GMP B and GMP C class cleanroom areas. Point 7.14 of this new requirement states that no outdoor clothing, with the exception of personal underwear, may be worn before entering changing rooms that lead to GMP class B and C cleanroom areas, and specifically no outdoor socks.

Whether cleanroom socks must be worn instead in accordance with the new requirement under point 7.14 EU GMP Annex 1 is not explicitly stated there, but it is required that so-called “facility socks” must be worn, which do not pose a contamination risk for the changing area and processes. In this respect, cleanroom socks should be used that meet the requirements of the respective cleanroom area upstream of the changing area, i.e. GMP class B or GMP class C cleanroom socks, depending on the area. The “CELOS disposable socks“, for example, which are recommended for cleanroom classes GMP A/B, C and D, are suitable here.

You can buy CELOS disposable socks in the online store of cleanroom wholesaler abovo, for example.

More information and advice

You can find more information on the subject of cleanroom garments in ourinteresting facts section , including tips on how to wear cleanroom garments correctly and information on cleanroom garments by cleanroom class.

Of course, our experts will be happy to advise you personally on these topics. Contact abovo without obligation by e-mail or telephone.