One year GMP Annex 1: Expert Interviews Part 2

How does the guideline affect our customers' cleaning concepts in practice?
Is implementation equally feasible for everyone?

‘Implementation of the directive therefore involves the following five components in cleanroom cleaning:

1. Cleaning and disinfection are two separate steps.
2. Cleaning agents and disinfectants must be suitable. This means that they must be effective against microorganisms and at the same time residue-free or low-residue (risk assessment).
3. The cleaning activities must be monitored regularly.
4. This monitoring must be documented accordingly.
5. Cleaning staff must be trained to comply with the directive.

Mike Verkuijlen states for the Benelux region: ‘We carry out an assessment with our GMP customers every three months, identify possible deviations and optimise the processes if necessary.’ In general, changes to work instructions (SOPs) are very time-consuming and cost-intensive for companies that produce according to GMP guidelines.’

“Digitally structured companies have a clear advantage”, adds David Stolper. The fact that every organisation has to ensure and document the cleanliness and quality of its cleanroom cleaning itself can lead to more complex processes. If you have already set up this reporting digitally, it drastically minimises the administrative workload.  

Laura Giblin adds from a QM perspective: ‘Our customers in the pharmaceutical industry are aware of developing a contamination control strategy (CCS). Product selection and rotation of their cleaning and disinfection activities is key. Customers need to use more than one type of disinfectant to ensure the combined use is effective against the existing house germ spectrum. As described in Section 4, disinfectants and cleaning agents used in Class A and B areas should be sterile before use. Sterility may also be required for disinfectants used in Class C and D areas if specified in the CCS.’

Disinfectants may need to be proposed after review of contamination risks and Environmental Monitoring data (EM data) in the facility. Validation studies should demonstrate the suitability and efficacy of disinfectants for the specific nature of their use and for the type of surface material or, if justified, for representative material and demonstrate the shelf life of the prepared solutions.

Our customers in the medical sector endeavour to apply the general principles of the Annex where possible. If a manufacturer chooses to apply the guidance contained herein to non-sterile devices, they should clearly document which principles have been applied and confirm compliance.

Can you give examples of challenges that companies face when it comes to compliance?

From a quality manager's perspective, Laura Giblin says: ‘Customers from the pharmaceutical industry must ensure that the biocidal products used in their production facilities are also registered in the country in which they operate. The sale or use of an unauthorised biocide in accordance with the Biocidal Products Regulation (BPR) in Europe is otherwise illegal. The BPR provides a harmonised and more centralised authorisation and approval option for biocidal products at European level. All authorised biocidal active substance suppliers are listed in the Article 95 list. Since 1 September 2015, companies that manufacture or place biocidal products on the market must ensure that their active substance suppliers or they themselves are listed in the Article 95 list of the Biocidal Products Regulation.’

In day-to-day practice, the following challenges then arise, explains David Stolper: ‘For customers who have not implemented a monitoring strategy, a key question is often how they can check their cleaning success. Another challenge for many is the regular training of cleaning staff, simply because this takes time and resources. Another time-consuming issue is the documentation of cleaning and training.

In addition, we must regularly revise all SOPs as well as hygiene and cleaning plans together with our customers to guarantee cleaning in accordance with GMP Annex 1 in the long term. In some cases, this also involves changing processes with regard to the cleaning agents used, the cleaning frequencies, training materials, etc. All in all, it is always the amount of time needed that presents a challenge,’ says David Stolper.

Mike Verkuijlen adds: ' If a customer outsources cleaning to a specialist service provider and the disinfectants used leave behind residues, regular disinfectant residue removal in accordance with the risk analysis must be part of the contract.”

What strategies or approaches do you recommend to ensure continuous compliance with the guidelines for cleanroom cleaning concepts?

‘One aspect is the removal of residues just mentioned. Unfortunately, the wording in the guideline is not clear, as it merely states ‘is recommended’. As a rule, however, a third cleaning step or a complete change of the agents used must be provided for the removal. The frequency for this must be determined by the customer as part of a risk assessment. My recommendation here is to use disinfectants without a layer structure, if possible,’ says David Stolper.

Mike Verkuijlen adds: ‘I also recommend changing the disinfectant regularly to ensure that it remains effective against bacteria and fungi. But here, too, it is important to thoroughly remove any deposits and residues before using a new product!’

Another of David Stolper's recommendations relates to documentation. ‘Expand digital documentation and processes. This also applies to SOPs. The better an organisation digitises its administrative processes, the more efficiently and agilely it can handle such planning and reporting tasks.’

Laura Giblin adds the aspect of training. ‘Section 7 describes how staff must be appropriately qualified, trained and experienced to carry out cleaning tasks in a controlled environment. Customers should plan for regular training and an annual knowledge exchange, which is where our colleagues at the Cleanroom Academy are happy to help.’

In conclusion, David Stolper points out: ‘Companies should be proactive in the implementation of changes in line with GMP Annex 1. Plan your strategy well in advance and seek advice from professionals. Smart investments help to prevent production losses due to non-compliance.’

Thank you, David Stolper, Mike Verkuijlen & Laura Giblin for your opinions and for sharing your experiences!

Do you have challenges relating to cleanroom cleaning or would you like to entrust this responsible task to professionals? Don't hesitate – our cleaning experts will be happy to consult you.