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 What’s new in the latest version?

 The EU GMP Chapter 4 on Documentation came into force on 30th June 2011.  Many of the updates were in-line with existing good practices.  Some of the main changes are summarised below.  You should refer to the actual document,  Chapter 4 Documentation, for the full details.

 In general, there is increased coverage of the use of computer systems

 This reflects the increase in the use of computers, coverage in GMP has been poor historically and limited mainly to Annex 11.

 For the first time a Site Master File (SMF) is mentioned (see “Principle”)

 This document described what goes on at your site and is submitted to the Regulatory Authority as part of the site approval process.  It needs to be kept up-to-date.

 For the first time, a Standard Operating Procedure (SOP) is mentioned (see “Principle”)

 Most sites refer to their procedures as SOPs.  Whilst procedures have always been described in GMP the term Standard Operating Procedure or SOP has never been used in GMP before now.

 You now have to follow your documents! (see 4.1)

 A strange omission in GMP, but you could argue that if you didn’t follow your procedures then chaos would soon follow.  There was no mention before (in Chapter 4) of actually having to follow any of your procedures.  If you looked hard enough however you could find the requirement to follow your procedures in Chapter 1 “the finished product is correctly processed and checked, according to the defined procedures” (see 1.1 vi) and Chapter 5 “all handling of materials and products, such as receipt and quarantine, sampling, storage, labelling, dispensing, processing, packaging and distribution should be done in accordance with written procedures or instructions and, where necessary, recorded” (see 5.2).

 Documentation in “house” format (see 4.4)

 For the first time, there is the requirement for some form of standard format and layout for your procedures – “imperative mandatory style”.

 More clarity on how long you keep records for (see 4.11)

 Nothing new here for “normal” medicinal products, however, the previous version of Chapter 4 just stated records should be kept for “one year after the expiry of the batch”.  Elsewhere in GMP it also stated “or at least five years after certification of the batch by the Qualified Person, whichever is the longer”.  Here in the update they just bring the two sentences together.

 What is new is further clarity on records associated with the manufacture of clinical trial materials (“at least five years after the completion or formal discontinuation of the last clinical trial in which the batch was used”).

 Increased requirements for areas of policies, procedures and records (see 4.29)

 Now we have the first mention in GMP of a “policy”.  Most firms have lots of policies.  There is also an enhanced list of activities that should be subject to policies, procedures and records.  These include technology transfer, change control, investigations into deviations and non-conformances, internal audits, product quality review and supplier audits.

 Master list of documents required (see 4.32)

 Here for the first time, a formal list of documents is required – “an inventory of documents within the Quality Management System should be maintained”.

 As stated earlier, many of these new additions are a reflection of existing best practice and are unlikely to cause you any problems.  It will be a good idea to actually read the whole chapter however and do a check that you are actually meeting all of these new requirements.

 I hope you found this article useful.  Please feel free to make a comment if you like.

 Learn more about modern pharmaceutical quality management on one of our forthcoming training courses.

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 Martin

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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