Pharmaceutical manufacturing sites in the UK will be more than familiar with the “Orange Guide”. This British publication has for decades contained the requirements of Good Manufacturing Practice. This article provides a brief overview of the history of this book and also covers why it is certainly no longer a guide.
First published in 1971 the original Orange Guide contained British Good Manufacturing Practice and was entitled “Guide to Good Pharmaceutical Manufacturing Practice”. Not much more than 30 pages in length this voluntary guide was an aid to manufacturers to understand the needs of the regulatory authority’s requirements for the manufacture of pharmaceutical products.
Later editions followed in 1977 and 1983, these been more expansive with more detailed requirements for manufacturing sites. You could argue that the 1983 version was the last true Orange Guide as the next (1993) version was entitled “Rules and Guidance for Pharmaceutical Manufactures”. In other words containing some “rules” in addition to “guidelines”. Others argue that the 1983 version was the last true Orange Guide, as this was the last publication containing British GMP.
In the late 1980’s and early 1990’s the European Union’s (EU) role in regulating pharmaceutical manufacturing sites was increasing and becoming more harmonised. In the early 1990’s EU Directive 91/356/EEC was signed. This removed different national GMPs from Europe into a single GMP for the whole of the European Union, and from this point onwards EU GMP was born. EU GMP was created using the leading two written GMPs of Europe at that time, namely those of the British and the French.
From the mid-1990 the UK’s Regulatory Authority continued to publish the “Orange Guide”, but it now contained EU GMP rather than British GMP. This is still the case today even after the UK’s exit from the European Union. In addition Good Distribution Practice (GDP) has also made its way into the book. The book was published again in 1997, 2002, 2007 and then 2022. As it is still published in a book with an orange cover the nick-name of the Orange Guide remains today. It now contains more than just GMP, with sections covering both UK and EU legislation on pharmaceuticals (so it is not just a guide) as well as Good Distribution Practice and Active Pharmaceutical Ingredients GMP, plus a lot more.
I hope that this is of interest. Feel free to add comments below.
THIS ARTICLE WAS FIRST PUBLISHED IN 2012 AND REVISED AND UPDATED IN DECEMBER 2022.
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 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.
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I still have a copy of the original one in the attic somewhere. It certainly bears very little similarity with the current one!
Sue Batten