In this fourth article I shall explore Section 3, the Pharmaceutical Quality System. This is a short section aimed at highlighting the additional requirements beyond those also required from EU GMP chapter 1.
It is important to remind ourselves that Annexes are designed to support the basic requirements in the nine chapters but adding a section on the PQS implies that a dedicated PQS might be required for sterile products, which is not the case. Indeed clause 3.1 clearly states,
“In addition to the PQS requirements detailed in Chapter 1 of the GMP guidelines (Part I – Basic Requirements for Medicinal Products.”
So, this section has been created to emphasize the additional controls that are needed for the manufacture of a sterile product which is recognised as being complex in nature. The manufacturer therefore needs ensure that their PQS addresses these specific requirements. Areas of most concern are described below.
The role of a contamination control strategy, outlined in section 2, in the management of risk of microbial, particulate and endotoxin/pyrogen contamination requires an integration throughout the business and is expected to cover the product lifecycle. Annex 1 suggests that essential for this is that the manufacturer has sufficient knowledge and expertise in relation to the products manufactured and the equipment, engineering and manufacturing methods employed. This being through its staff and includes those releasing finished product. This adds to what is already in chapter 2 which requires at 2.1,
“The manufacturer should have an adequate number of personnel with the necessary qualifications and practical experience. Senior management should determine and provide adequate and appropriate resources (human, financial, materials, facilities, and equipment) to implement and maintain the quality management system and continually improve its effectiveness”
As we mentioned with section 2, risk and the contamination control strategy are inextricably linked and this is further indicated in section 3 by reminding us that risk management is applied in the development and maintenance of the CCS, to identify, assess, reduce, or eliminate and control contamination risks. Therefore, risk management should be documented and should include the rationale for decisions taken in relation to risk reduction and acceptance of residual risk. The role of ICH Q9 will be important here. It should also be note that risk assessments should be reviewed regularly be it part of routine quality management, during change implementation or triggered at management review. Much concern was raised in the early years of updating Annex 1 concerning whether sterile products manufacturing should be risk based. Much of this concern was voiced by inspectors making statements like “professional and responsible risk assessment” and “avoiding risk assessment to justify current controls”.
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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To ensure the quality of sterile products, problems need to be resolved so Annex 1 further emphasizes the value of root cause analysis of procedural, process or equipment failure to implement suitable corrective and preventive actions (CAPA). Furthermore, Annex 1 specifies that nonconformities such as sterility test failures, environmental monitoring excursions or deviations from established procedures should be adequately investigated before certification and release of a batch is undertaken. Consideration should be given to assessing the potential impact upon the process and product quality as well as other processes and batches. The reason for including or excluding a product or batch from the scope of the investigation should be clearly justified and recorded.
From the introduction of ICH Q10, the role of senior management has been clarified and top management commitment is expected. According to Annex 1 they should effectively oversee the state of control throughout the facility and product lifecycle.
Finally, finishing, storage and transport of sterile products should not compromise the sterile product. Therefore, container integrity, risks of contamination and avoidance of degradation should be ensured through compliance with registered requirements.
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.
