Chapter 8 of European Union Good Manufacturing Practice (EU GMP) has been updated and came into operation on 1st March 2015. This post summarises the main changes. The EU GMP Chapter 8 OLD and EU GMP Chapter 8 NEW versions of the chapter can be found by clicking on these links so you can compare the two for yourself.
The first change to be pointed out is the change in title of the chapter itself, from “Complaints and Product Recall” to “Complaints, Quality Defects and Product Recalls”. This mirrors the greater scope of the newly updated chapter, with much more coverage of dealing with problems (Quality Defects) rather than just complaint and recall related issues.
This is also a substantial rewrite of the whole chapter, with double the number of clauses (from 16 to 31). These new requirements essentially cover the use of risk management principles, more detailed requirements to get to the root-cause of problems and taking appropriate corrective actions to prevent recurrence. In this respect this chapter follows a similar approach to dealing with problems first suggested in the new Chapter 1 on the “Pharmaceutical Quality System”.
The main changes to the sections of the new Chapter 8 are covered below.
This is now a much larger section and covers the requirement to inform the relevant competent authority (the Regulatory Authority) in a timely manner in the case of confirmed quality defects, such as faulty manufacturing, product deterioration, falsified product, non-compliance with the marketing authorisation and any serious quality problem.
There is also new guidance on clarifying the roles and responsibilities for dealing with the above should any activities be outsourced.
Personnel and Organisation
This is a wholly new section covering the training and experience of those involved in making decisions related to complaints, quality defects and product recalls. It also adds that these people should be independent of Sales and Marketing, so they have less commercial influence when it comes to making key decisions.
In addition there is guidance on there being a sufficient number of trained personnel and the necessary resources to deal with such issues. Should this be performed by a central functional group (typically with multi-national companies) then this should not bring about any delay in any decision making at the manufacturing site. There is also a clause covering the requirement to use multi-disciplined teams when it comes to dealing with problems, confirming the general requirement of problem-solving that different people add an alternative view-point when investigating issues.
Procedure for handling and investigating complaints including possible quality defects
This new section has similarities with the previous corresponding section on “Complaints”, but you will see from the title of the section then there is greater scope here. One of the main new aspects of this section is at clause 8.9, with much more detail on what to do when a quality defect is investigated. These include:
- The description of the reported quality defect
- The determination of the extent of the quality defect
- The need to request a sample, or the return, of the defective product from the complainant and the need for an evaluation to be carried out
- The assessment of the risks posed by the quality defect, based on its severity and extent
- The decision-making process that is to be used – such as batch or product recalls
- The assessment of the impact that any recall action may have on the availability of the medicinal product and the need to notify the relevant authorities of such impact [NOTE how the bigger picture needs to be considered here – will this issue cause a reduction in supply of the product on the marketplace?]
- The internal and external communications in relation to a quality defect and its investigation
- The identification of the potential root cause(s) of the quality defect
- The need for appropriate Corrective and Preventative Actions to be identified and implemented
Most of the above is new in this chapter.
Investigation and Decision-making
This new section gives guidance for the first time on investigating and corresponding decision making. It includes the requirement to gather all of the information initially, assess the risks and scale of the problem and the degree of investigations and actions needed. There is the requirement to consider other batches affected by the issue and if these are recurring problems. The latter would suggest that problems are not being dealt with correctly in the first place!
There is also the fact included that you may not have all of the information available at the start of the investigation, and that appropriate risk-reducing actions should be taken as appropriate.
Importantly (clause 8.14) is the need to document all decisions and measures taken. I have dealt with many manufacturing sites in the past 2 years who have failed to do this correctly and have got into serious trouble for being unable to explain (often 12 – 18 months later) what actions were taken, why, by who and when. Do take care here to thoroughly document any investigations and corresponding decision-making that you take.
Root Cause Analysis and Corrective and Preventive Actions
This new sections takes further terms introduced really for the first time in the new Chapter 1 of EU GMP, updated just over 2 years ago, namely Root Cause Analysis and Corrective and Preventive Actions. The first two clauses (8.16 and 8.17) covering “an appropriate level of root-cause analysis” and “where human error is suspected … this should be formally justified and care should be exercised so as to ensure that process, procedural or system-based errors or problems are not overlooked” are almost the same as the similarly new requirements in Chapter 1. Here again we see GMP now tells us to not just to do “Correction” but take “Corrective Action” following a detailed investigation into the cause of a problem. At the same time, don’t just blame the operator (“human error”) when something goes wrong – look for what caused the person to make the error in the first place.
Product Recalls and other potential risk-reducing actions
This new section has similarities with the previous corresponding section on “Recalls”, but you will see from the title of the section that there is greater scope here too. In the first instance one of the main differences is including recalls of clinical trial materials (not mentioned before). There is also the requirement to consider the impact of any recall on the ongoing supply of medicines and the need to inform the relevant authorities of this.
There is also the requirement to justify and document what is done with regard to re-working and re-use of recalled materials.
Finally there is a requirement to perform a mock recall. This was a requirement in the previous chapter, but less explicit as it used to state “the effectiveness for arrangements for recalls should be evaluated regularly”. As you can see it is much clearer now.
I hope that you have found this post useful. If you would like further information on our practical and interactive Problem Solving training course, then please visit our website and/ or get in touch with us. You won’t be disappointed!
Annex 1 has finally arrived, 25th Aug 2022 saw the publication of Annex 1. Normally, updates to GMP chapters and Annexes have a 6-month lead time for implementation. In the case of the new Annex 1, the lead time is 12 months, except for clause 8.123 relating to lyophilization which has 24 months lead time.
Annex 1 was first issued in 1971 as the only annex in the first ever UK guide to Good Manufacturing Practice. Since then, there have been several updates but not full revisions. In 2012 there was a proposal to revise Annex 1 with a re-proposal in 2014 by the UK’s MHRA. At the time, a full rewrite was considered unlikely and instead the intention was to provide a document that would confirm regulatory expectation and as such, not place any new requirements or costs on the pharmaceutical industry.
While this principle, is still upheld, it was clear from the first draft for public comment of December 2017, that a rewrite was being undertaken. The first draft created around 6200 comments coming from regulatory organizations, such as the pharmaceutical cooperation scheme, regulatory bodies outside of the EU, support organizations such as the Parenteral Drug Association, the Parenteral and Healthcare Sciences Society, the Pharmaceutical Microbiology Interest group as well as representatives from the manufacturers within the pharmaceutical industry to name just a few. Rarely do updates require a second public consultation but in the case of the annex 1 update a second draft was issued in March 2020 although this was a more targeted review in terms of the sections and clauses that comment was being sought for.
About the author
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
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