Challenges in Sterile Products Manufacture
The PHSS conference concerning sterile manufacturing took place at the Mere Golf Resort and Spa in Knutsford, Cheshire on 8th June. Sales Manager, Andrew Barrow and yours truly manned the Cherwell Laboratories stand, looking to impress potential new customers and engage with our old friends and acquaintances. This event was very much focussed to the core market Cherwell Laboratories sells to and is always interesting to attend the various talks and discussion sessions.
EU GMP Annex 1
The opening talk, which everyone listened to intently, was delivered by Andrew Hopkins, senior GMDP inspector of the MHRA. No surprises, the subject matter was about the new revision of EU GMP Annex 1. Everyone in steriles manufacturing has been waiting with baited breath for the latest revision to be published which many expected to be out by now. Andy Hopkins firstly explained at what stage the revision was at. There are a number of interested parties including PIC/S, the European Medicines Agency, WHO, even the US FDA and Japanese PMDA. Draft version 2.0 was circulated to PIC/S and the EMA inspection working group (IWG) in February 2017 for comment. After comments, version 3.0 was circulated to the IWG which has been approved. The next stage which happened the previous week was release for public consultation. Three months will be given for comment, and if required a second consultation will take place in the autumn. It is hoped that the new Annex 1 will be published toward the end of the year. The remainder of the talk was about the reasons behind the update and the new content, which I have covered before in earlier blogs.
Aseptic filling of rare disease medicine
Next up was Brian Cullinan of Alexion, talking about the aseptic filling of rare disease medicines. Brian gave a summary of who Alexion is and what it manufactures. Their focus is on developing medicines to combat ultra-rare diseases. An ultra-rare disease affects 1 in 50,000 people. He then went onto describe in detail the work that took place in installing the new filling line in an existing facility, along with the lessons learned during that process.
Clarity in GMP
Tim Eaton from AstraZeneca led the first of three discussion groups. His discussion session was titled “clarity in GMP”. The aim of this session was to discuss possibly contentious issues from Annex 1. Of the topics covered, the first was about the term “Grade A air supply”. This term is used in the environment where vials are being capped. This term should no longer be used, as far as Andrew Hopkins was concerned, vials should be capped in a grade A environment such as an isolator. Another delegate made the point that the term grade A air supply should apply to the source of the air rather than the quality of the air at the point of capping.
Also covered was the use of rapid microbiological methods for environmental monitoring. Questions asked included whether the technology was mature enough to use with confidence, and the risk of false positives. There was a consensus that although it may not yet be suitable for grade A/B areas, they can definitely be of use in grade C/D areas, where a spike in counts could have an effect in the A/B areas. It will allow the operator to correlate the spike immediately with an event in that area and take appropriate actions. The other topics covered concerned cleaning and disinfection, and cross contamination.
Incubation regimes for environmental monitoring plates
The final discussion session I attended was chaired by Ian Symonds of GSK. The main topic concerned incubation regimes for environmental monitoring plates. There is currently no consensus in the industry as to what the best incubation regime is. Ian Symonds conducted a study which was published last year1 comparing the recovery of naturally occurring microorganisms under different temperature conditions. It is pretty much expected in pharma cleanrooms that plates undergo a dual incubation, 20-25°C for 3-5 days followed by 30-35°C for a further 2-3 days. Ian Symonds findings challenged the effectiveness of the dual incubation regime, claiming 20-25°C had increased recovery of Bacillus spores. It was accepted a move to a new incubation regime will give that facility a different perspective on their microflora as the recovery potential has changed. Comments made included 30-35°C was more practical in grade A/B areas as the target organisms are skin commensals. Andrew Hopkins commented that should you choose to change your incubation regime, it should be supported with significant scientific data to prove the improved recovery of microorganisms compared to previous regime. Other topics covered in Ian Symonds session included process monitoring and aseptic hold times.
This concluded my day at this event. There was one more discussion that we couldn’t stay for – I had a long journey home to go and vote as it was general election day – I just about got home in time!
As always it was a pleasure to meet our customers. Please don't hesitate to contact us if you need any further information on any of our products or services on display at the event. We're always happy to help.
1. Symonds ID, Martin DL and Davies MC, Facility based case study: A comparison of the recovery of naturally occurring species of bacteria and fungi on semi-solid media when incubated under standard and dual temperature conditions and its impact on microbial environmental monitoring approach. European Journal of Parenteral & Pharmaceutical Sciences 2016; 21(1): 7-15
Microbiology Product Specialist,