This final article looks at the new requirements in section 10 on Quality Control. It is also a useful point at which to reflect on the 2022 version of annex and what might it mean, i.e., what might the ramification be as we move through the implementation phase which began in August 2023.
Let begin with section on Quality Control. By compassion with the other sections, it is short, and much is unchanged from the outgoing version. That said, there are notable additions.
Annex 1 now adds to the requirements around training and competence but now specifically QC staff, who should be appropriately trained and experienced in microbiology, sterility assurance and process knowledge. This is to be able to support process design, environmental monitoring, and investigations assessing microbiological impact of events that can impact on patient safety.
While implied in Chapter 4 on documentation, annex 1 requires specifications to explicitly cover microbial, particulates, endotoxin limits where the CCS and or monitoring requires them.
Bioburden monitoring prior sterilization requirements have been relocated from the “Processing” section of the 2008 Annex 1 plus the results should be considered as part of the final batch review. Bioburden samples should be taken to represent the worst-case scenario (e.g., at the end of hold time). There are new requirements where parametric release is authorised beyond requirements for each batch testing. Any organisms found during bioburden testing should be identified and their impact on the effectiveness of the sterilising process determined.
Additional requirements are also added to those for the sterility test. For example, the sterility test should not be used to assure sterility where the product does not meet its design, procedural or validation parameters. Sterility tests for each sub-batch produced, should be undertaken. For short shelf-life products, the implications of releasing prior to completion of sterility test should be risk assessed and documented. Risk being mitigated by additional process design considerations and or additional EM and alternative methods.
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:
Sampling requirements for the sterility test have also been enhanced by adding the consideration of sampling after critical interventions based on risk and including samples from different lyophilised loads. Also, where the process results in sub-batches, sterility samples should come from each sub batch and a sterility test performed per sub batch. Processes to disinfect external sample surfaces should be assessed to ensure there is no negative impact on microorganism recovery should there be any present in the product itself.To minimise risk of failure the sterility test should be performed under aseptic conditions and these conditions should be monitored. The data and trends should be reviewed for batch release. There should be an SOP for dealing with out of trend environmental monitoring results.
For products with short shelf life, a mitigation for no sterility test result in the data, but in the case where it is not yet available the compliance should include a review of the most recent available data. For this reason, manufacturers are being recommended to consider the use of rapid or alternative monitoring methods.
The final subject covered in the new Annex 1 is about the growth media used which should be QC tested. Sterility test media should be tested as per Pharmacopoeial expectations. Environmental monitoring and Aseptic Process Simulation media QC testing should incorporate the use of standard and environmental strains as appropriate. QC testing should be by end user or use of supplier information suitably justified.
So, what are all these changes likely to mean. Well in many cases, not a lot, as much of Annex 1 simply documents what has been long standing expectation or in common practice any way.
For environmental monitoring (EM) and Aseptic Process Simulation (APS) there is more onus on the manufacturer to set the requirements based on risk and scientific rationales. Tightening of limits is subtly likely to drive organizations to move to Isolation technology and automation. Also keeping current with new technologies helps organisations to move forward from the “old ways” such as with the greater use of Isolators, RABS etc. as well as single use systems. Finally, there is the introduction of real time monitoring as well as rapid sterility test methods and rapid ID systems which can bring real advantages to short shelf-life product assurance.
However, the increased alignment with ICH Q10 and ICH Q9 means that knowledge management is essential going to be increasingly important. Annex 1 talks of developing people with the right knowledge (and attitude), and the need to retain and apply knowledge. People need to be able to think critically. This can help improve the risk assessment process and avoid the Sat Nav approach, “I know where I need to get to so lets get our risk assessment to map out the route” rather than “what are all our options, issues etc. and by understanding them, where does it take us?” Likewise, the Contamination Control Strategy (CCS) should lead to greater organizational understanding of sterility and sterility assurance, but it needs that knowledge and understanding and awareness.
As final thought, in some but hopefully many organisations the CCS, knowledge management etc will become part of the culture, “it’s the way we do things around here”.
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.
