In this article we expand upon the equipment section but looking at Utilities as described in section 6. The level of control of Utilities such as water, steam, compressed gases and so on depends on risk which should be documented in the contamination control strategy.
The highest risk utilities are those that interact with the product such as water for equipment rinsing, gases and steam for sterilisation. Utilities should be designed and installed to ensure that they function correctly. As with other equipment there should be relevant qualification documentation in place which is updated as needed. Documentation should include schematic diagrams including pipe and installation diagrams (P and IDs) as well as construction material lists and system specifications. These are intended to show flow direction, slopes, tank, and vessel details as well as valves, filters, drains, sampling, and user points etc.
The relevant equipment should be maintained and monitored against critical parameters which can be trended to ensure that system capabilities remain appropriate by introducing remedial CAPAs, for example.
Chapter 4 requires that all exposed surfaces should be smooth, impervious, and unbroken there should be no recesses that are difficult to clean effectively. It is no surprise therefore that in this section pipes, ducts and other utilities should not be present in cleanrooms. However, if unavoidable, then they should not create recesses, unsealed openings and surfaces which are difficult to clean.
The subsection on control of water significantly enhances the guidance on water in the 2008 Annex 1. This has been driven by the adoption of reverse Osmosis to produce WFI which is a riskier process than distillation. So, new requirements are added concerning design to reduce biofilm risk e.g., dead legs removal or reduction and ensuring systems are fully drainable. Water systems should also be validated to account for seasonal variation in feed water quality. There should be rregular sanitisation and monitoring of user points including a representative sample on each day a batch is made. Results should be monitored for trends. Limits should be set, and excursions Investigated. There should be continuous TOC measurement and turbulent flow to minimise biofilm development. Storage tanks should include a hydrophobic venting filter.
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
To see all of the articles on Annex 1 2022 select the button below:
New additions to Annex 1 are steam, gases, hydraulic and vacuum systems. Water supplying clean steam generators should be suitably purified. Steam generation systems used for sterilization should be designed, installed, operated, and monitored as well as suitably qualified to ensure that there are no unacceptable levels of additives that could impact the product. Condensate should meet WFI Pharmacopoeial specifications although microbiological limits are excluded. Steam quality should be assessed periodically including steam non condensable gas levels, dryness fraction and superheat potential.
For Gas and vacuum systems these should be of appropriate chemical, particulate and microbiological quality for contact with product. Compressed gases sterilized via 0.22mm filters at point of use and integrity tested for venting and overlay purposes. When used with the product there should be periodical micro monitoring of the gases. These filters should be integrity tested and the results reviewed as part of the batch certification/release process. In the case of vacuum backflow can cause a contamination risk to the product so there should be mechanisms to prevent backflow when the vacuum is shut off.
The final utility in annex 1 is that of heating, cooling, and hydraulic systems. The fluids used can themselves be significant contamination risks ands should therefore be outside a filling room where possible, with appropriate spillage control and system leak testing in place.
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.
