In the last article, I discussed the scope of the latest update to Annex 1. In this article I want to focus on section 2, “Principle”.
The fundamental basis upon which Annex 1 is now build is written into the principle and its associated clauses. It covers elements of contamination control such as design and qualification, personnel, monitoring systems and control of raw materials and packaging materials. It reemphasises the scope and the need for QRM. It also introduces the outline for a contamination control strategy. Let us explore these in a bit more detail starting with design and qualification. Design, qualification and indeed validation and on-going verification is applied to facility, equipment, and processes. Importantly we see the first of many references to the use of appropriate technologies such as Isolators, Restricted Access Barriers Systems (RABS) as well as automation and rapid or alternative methods specifically designed to protect the product from a range of contamination risks and to achieve fast identification of such risks. People involved in manufacture and testing of sterile products should be adequately trained, experienced, and should adopt suitable behaviours for the protection of sterile products. This includes personnel having appropriate process, engineering, and microbiological knowledge. Raw materials and packaging materials should be adequately controlled and evaluated to ensure that level of bioburden and endotoxins etc are suitable for use.
QRM principles should be used to allow for the proactive identification, scientific evaluation and control of potential quality risks. This includes where an alternative approach, not specified in Annex 1 is proposed for which there should be a rationale, risk assessment and mitigation. Applying fundamental GMPs such as good facility, equipment, and process design with well-designed documentation, as well as appropriate monitoring is always a good starting point for mitigating risk.
The main principle though is that of contamination control and a Contamination Control Strategy (CCS) should be implemented across the facility. This should be seen as more than cleaning and disinfection or selection appropriate garments. It is about identify all the critical control points and assess the effectiveness of controls and monitoring practices used to mitigate risk relating to product quality and safety. Essentially, the CCS should establish robust assurance of contamination prevention. The CCS should be regularly reviewed as part of continual improvement and be part of periodic management review. While a CCS implies a single document it does not have to be. It could be a collection of links to other policies, plans and strategies. Documenting the CCS is implied in Annex 1 but remember it is part of the Pharmaceutical Quality system (see the next article) which should be documented as specified in EU GMP chapter 1.
About the author
Andy Martin
Andy started working in the Pharmaceutical industry in 1985 as a lab technician for Smith & Nephew. Following this, he had a number of roles culminating when he took over as QA Microbiology Manager. In 2003 he moved into Pharmaceutical Training and then in 2007 he moved back into Microbiology when he took up the position of Microbiology Manager for Catalent Pharma Solutions. Since 2012 he has operated as a consultant specialising in Microbiology and Quality Systems.
Training courses on Annex 1
There are a number of half-day workshops organised to take you through the changes in more detail and to look at how they relate to your organisation.
Our 2-day course is updated for Annex 1 changes
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In depth technical and process knowledge is essential for developing a robust CCS. For this the organisation needs to have those knowledge people in a range of disciplines so that the potential sources of relevant types of contamination can be understood and managed.
The diagram below summarizes the key areas for consideration within a CCS.
Many of these may appear to be obvious while others may need clarification. For example, vendor approval should include those that sterilize components and that supply single use systems (SUS). Critical outsourced activities such as those that provide contract sterilisation services should also be included. Preventative maintenance should be to a standard that ensures no additional risk of contamination. Monitoring systems should include assessment for use of alternative methods for environmental contamination detection. Regarding prevention mechanisms, the CCS should utilize trend analysis and root cause analysis investigation tools with CAPA to drive improvement. Changes to any element of the CCS should be assessed for impact and the Strategy amended accordingly.
These areas should be assessed, controlled, and monitored individually but consideration should also be given to the holistic effectiveness.
Finally, the Principle section reminds the organisation that they should assure the sterility of the products manufactured within its facilities and that sole reliance for sterility or other quality aspects should not be placed on any terminal process or finished product test i.e., the sterility test.
About the author
Andy Martin
Andy started working in the Pharmaceutical industry in 1985 as a lab technician for Smith & Nephew. Following this he had a number of roles culminating when he took over as QA Microbiology Manager. In 2003 he moved into Pharmaceutical Training and then in 2007 he moved back into Microbiology when he took up the position of Microbiology Manager for Catalent Pharma Solutions. Since 2012 he has operated as a consultant specialising in Microbiology and Quality Systems.
Training courses on Annex 1
There are a number of half-day workshops organised to take you through the changes in more detail and to look at how they relate to your organisation.
