In the last article, I described the premises requirements for sterile product manufacture. In this article we look at the general requirements for the equipment used in the manufacturing of sterile products.
Depending on the complexity of the equipment Annex 1 requires a written, detailed description of the equipment design including for example process and instrumentation diagrams. It reminds us of Annex 15 although doesn’t directly refer to it because it suggests that the documentation should form part of the initial qualification package, particularly we would be considering the URS, Design Qualification, and Installation qualification stages as a minimum. Complex equipment is subject to change over time through maintenance, adaption and so on therefore this information should be kept up to date.
The monitoring requirements for the equipment should be defined in the URS, during early stages of development, and confirmed during qualification. This is a bit of a vague statement. We should consider both what the equipment is designed to monitor (if anything) and how the equipment will be monitored for example, to ensure it continues to perform adequately. This may be as simple as defining maintenance and calibration frequencies. Certainly, where the equipment utilizes alarms, process and equipment alarm events should be acknowledged and evaluated for trends. The frequency at which alarms are assessed should be based on their criticality but it is expected that critical alarms are reviewed immediately.
Further supporting the desire to keep unnecessary people out of critical areas, Annex 1 requires that equipment, fittings, and services should be designed and installed so that operations, maintenance, and repairs can be performed outside the cleanroom. Where this is not practical, maintenance can be undertaken in the cleanroom provided that the required standards of cleanliness are maintained for example maintenance of grade and wearing of the appropriate clothing. If these standards cannot be maintained, then precautions such as restricting access to the work area to specified personnel should be employed. There should be clearly defined work protocols and maintenance procedures. On completion, there should be additional cleaning, disinfection, and environmental monitoring. Where unplanned maintenance of equipment critical to the sterility of the product is required, it should be risk assessed and recorded.
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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Equipment cleaning processes need to be validated. This is to ensure removal of residues that could adversely affect the effectiveness of the disinfecting agent used. If sterilisation of equipment is required, it should be carried out, wherever possible, after complete reassembly.
Where equipment is to be used for aseptic processing, it should be sterilized. This included both contact and in-direct contact parts. Direct contact is defined as where the product passes through or is in contact with the equipment e.g., filling needles or pumps. Indirect contact is defined as where the equipment encounters other sterilized parts that are critical to the sterility of the product. e.g., sterilised stopper bowls and sterilised components.
Validation and planned maintenance e.g., for sterilizers, HVAC systems and water systems is required, and the subsequent return to use should be approved.
Section 5 finishes with a more focused discussion around the control of particle counters. It requires control on sample tube diameter and bend radius pointing to the manufacturer’s recommended specifications. It also suggests that the sample tube length not be longer than 1m unless justified and the number of bends should be kept to a minimum.
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.
