Structuring your contamination control strategy

BY DR TIM SANDLE  |  6 JANUARY 2023

 

 

A contamination control strategy (CCS) is a system that considers all the integral elements of pharmaceutical product manufacturing. A CCS should cover:

 

  • Microbial contamination
  • Cleaning and disinfection
  • Sterility assurance
  • Facility design
  • Chemical and particle contamination
  • Other forms of contamination that can arise from mix-ups, damaging primary or secondary packaging, distribution problems, and environmental fluctuations

 

The need for a CCS forms a core part of the revision to EU GMP Annex 1 however its easy to feel cautious when creating a CSS for the first time. In this blog we look at how developing the strategy might be approached, with due care taken in regards to how it is pieced together by the right personnel in possession of the relevant education, experience and technical knowledge.

 

Confirmation of compliance and gap analysis

 

Gap analysis is a useful first step as the process assesses the differences in performance between current operations and the requirements of the regulation. This method can be used to confirm compliance and identify where the evidence of compliance is located.

 

Below is an example of gap analysis using Annex 1’s requirement for the frequency of isolator glove integrity testing and any changes to be determined and scientifically justified.

 

  • If no such frequency exists, this is a gap to address
  • If the frequency exists, then it needs to be checked as to how this has been risk assessed
  • If the assessment is satisfactory, there is no gap, but a connection is required into the overarching strategy

 

When looking at carrying out gap analysis, there are different ways to structure the model. Figure 1 demonstrates one example:

 

Fig 1 - Gap analysis model structure

 

 

Each gap should be risk assessed using the multitude of different risk tools available. With contamination control it is beneficial to keep the process simple, by grouping outcomes into high, medium and low risk, based on likelihood and severity, such as:

 

Fig 2 - Risk assessment table

 

 

Fig 3 - Contamination control strategy

 

 

 

 

 

When carrying out risk assessments, it is important that the process is not used to justify poor design and bad practices.

 

Control should foremost be achieved through good design, followed by appropriate procedures. Monitoring is a means to assess the effectiveness of control, rather than a control in its own right.

 

Design

 

Design should be approached using appropriate, current technologies. with facilities based on suitable people, product and waste flows such as:

  • Sterilisation of equipment
  • Control of people and gowning
  • Materials controls
  • The appropriate classification of support and filling rooms
  • The use of barrier technology

 

Areas need to be appropriately designed and of sufficient space. Any activities should be supported with equipment of appropriate design, including the implementation of single use, sterile disposable technologies. Procedures need to be well-written as they play an important part of risk mitigation, especially in relation to critical steps such as running the process, line assembly, interventions and cleaning and disinfection. Monitoring needs to be based on a sound, scientifically based strategy. In the context of Annex 1, it is useful to break each clause down in order to assess each point. Figure 4 is an example using Section 8 of the Annex:

 

Fig 4 - Example display format for breaking down individual clauses

 

Once any gaps have been identified they need to be prioritised, depending upon the mitigations in place, how long they need to apply for, and for when any necessary works can be programmed in. Not everything can be done at once and objective criteria is required to sort the gaps into a priority order. This involves risk ranking and risk filtering, estimating likelihoods and consequences.

 

 

 

 

 

Putting the analysis together

 

The analysis forms a core part of the finished document, structured both horizontally and vertically.

With the vertical aspect, each of the main sections within the Annex should be covered. These can be thought of as pillars (detailed in Figure 5)

 

Fig 5 - Vertical pillars of the CSS

 

 

With the horizontal aspect, each primary form of contamination should be addressed not only within the pillar, but between pillars, and with consideration of how contamination could be transferred through different activities and across cleanroom grades. For example, this could be represented as:

 

 

Review

 

The contamination control strategy should be subject to regular review, ensuring the inclusion of the following reviewed assessment areas:

 

  • Information from the system’s feedback
  • Change controls, deviations and other feedback
  • Changes in technologies

 

In order to keep the strategy current, the CCS needs to be considered as a ‘life cycle’:

 

Conclusion

 

Whether the final strategy should be one document, or a series of documents will depend on the size of the facility and the scope of operations. With the level of detail required, the information can either be captured in the strategy directly or cross-referred with other documents, such as position papers, rationales, policies and procedures. The most important thing is that the elements described are risk based and scientifically justified.

 

In summary, the contamination control strategy should be implemented across the facility and successfully function to assess the effectiveness of all the control and monitoring measures employed. The strategy needs to consider all aspects of contamination control and its life cycle with ongoing and periodic review and update of the strategy as appropriate.

 

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