Clinical trial phases

I am often asked what the main stages of pharmaceutical Clinical Trials are. In this post I will try and explain. I should point out that I am not a Clinical Trials expert, but this is my understanding.

Discovery stage

A new chemical undergoes chemical and biological studies.

Preclinical stage

Testing on isolated organs, tissues and animal.

Phase I

Testing on a small number of healthy human subjects. The aim is to assess chemical safety and how the body deals with the product.

Phase II

Drug is given to patients to see how effective the product is, usually over several weeks. Usually given to people with the condition that the medicine is trying to treat.

Phase III

Large scale study (and very expensive) to gain further evidence of drug safety and efficacy. This usually takes about a year and will include double-blind and multi-centre controlled trials. This will include comparison with similar products if they exist. Various dosages will also be tested to see which dose is the most effective. If successful this may lead to the drug being approved and marketed.

Phase IV

Post market monitoring on the overall effectiveness (including negative effects) of the drug.

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.

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.

More details