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CONTAINMENT
Author: Karen Rossington, Contec
How the GMP Draft Annex 1 will impact cleaning and disinfection.
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leaning and microbial contamination control are critical focus areas in the pharmaceutical industry. Robust cleaning and disinfection programmes are needed to meet the required cleanroom microbial grades, to prevent cross contamination and microbial contamination of products. Indeed incidents of contaminated products entering the supply chain with devastating consequences have happened in the last eight years. The manufacture of medicines in the EU is governed by EudraLex Vol 4 Good Manufacturing Practice and each country in Europe takes the legislation into their own guidance.
rewritten and now features new and expanded topics, with the concept of risk management embedded throughout. Thousands of comments were returned from industry and industry groups in response to the draft. CONTAMINATION CONTROL STRATEGY One of the main documentary requirements of the new draft is the requirement for a holistic contamination control strategy (CCS).
ANNEX 1 MANUFACTURE OF STERILE MEDICINAL PRODUCTS EU Annex 1 specifies guidance for the manufacture of sterile medicinal products and was first issued in 1989. With no complete review of the annex having been carried out for over 10 years, a complete rewrite was needed. The annex needed to catch up with both changes in sterile manufacturing technology and significant updates in regulatory expectation.
This document, either in one master document or separate related documents will reflect a site-wide strategy for minimising contamination. Whichever way is chosen, it must be a “living” document, which is kept up to date throughout the life cycle of the facility. For established facilities it probably already exists even if across separate documents and the manufacturer should try to include links and references in order not to rewrite all qualification documents. New facilities should start the CCS as early in the process as possible. Ideally it would form part of the design process and be included in URS and DQ documents.
Therefore, in December 2017 the European Commission via a GMP/GDP working group produced a draft of Annex 1. The document was completely
The draft states that “a contamination control strategy should be implemented across the facility in order to assess the effectiveness of all the
control and monitoring measures employed.” The main elements will include amongst others, design of plant and process, equipment and facilities, process risk management and cleaning and disinfection. CLEANING AND DISINFECTION The references to cleaning and disinfection have been expanded. The terminology of “cleaning” has been replaced with “cleaning and disinfection”. The text notes that “for disinfection to be effective, cleaning to remove surface contamination must be performed first”. This clarifies current best practice that cleaning and disinfection are two distinct activities trying to achieve different things. Cleaning is the removal of non-viable contamination and disinfection is “the process by which surface bioburden is reduced to a safe level or eliminated.” Many common and well used disinfectants leave significant residue on a surface, which can subsequently have a detrimental effect on the effectiveness of the disinfectant used. This is acknowledged in the new draft - “cleaning programs should be effective in the removal of disinfectant residues.” There are disinfectants available which do leave minimal to no residue, or which have residues which are free rinsing or easily removable.