The MHRA Papers - Part 5

Mind your own business

SUMMARY: there were problems with several pre-release batches of the Comirnaty vaccine, but the minutes are written in impenetrable language, and anyway, the manufacturers reassured the EWG that they thought all was well, so mind your own business - It’s all secret, anyway.

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We continue our review of the minutes of the meetings of the MHRA’s ​​Commission On Human Medicines (CHM) COVID-19 Vaccines Benefit Risk Expert Working Group,  

On 28 November 2020, the EWG considered the Quality Assessment Report of what we presume is Comirnaty (although this is not specified in the text, the attendees whose names are redacted were all from Pfizer/BioNTech). Dr June Raine, CEO of MHRA, attended as an “observer”. We report below the text of some of the salient parts of the meeting. 

The prose is written in the usual dense, jargon-laden way, either because everyone in the meeting understood the jargon or possibly because they did not give too much away in the minutes, which might sooner or later be subject to FOI requests. Mind your own business anyway.

As usual, the emphasis is ours on what we think or sense is important:

‘The EWG quality sub-group heard that there had been a last-minute change to the batches relevant for the UK for a potential Regulation 174 opinion as of the evening of Friday 27th November. The immediate concerns of comparability as associated with the original two batches under review were no longer a priority whereas a discussion of the particulate ‘defect’ became more urgent as this impacted on the batch being considered as of this date. The EWG quality sub-group also heard that two further batches are also identified as being the next two batches intended for UK supply. One of these batches was associated with an investigation of a late migrating RNA species by capillary electrophoresis which was also characterised as a priority concern.’ 

‘The company joined the meeting to address questions on the concerned batches, which prioritised the following issues: i) particulate matter found in EJ0553; ii) “late migrating species” in Batch EJ1688); iii) RNA integrity in early Process 2 batches; iv) stability data available for the proposed deployment model (e.g. -90 °C vs -60 °C).’ 

‘The EWG quality sub-group considered the late migrating RNA species (LMS) found in a drug product batch and not found in drug substance. The comparability of the drug substance source used for the proposed batch (EJ0553) and the tested clinical batches was discussed at length, particularly considering the critical parameters such as particle size, RNA integrity, and 5’ capped RNA.’

The company do not intend to submit any further stability data that would qualify additional transportation nodes in the deployment of vaccine.” 

Some readers might be able to translate the text into English. We think this means some of the batches were unstable, and the lipid nanoparticle envelopes came apart, spewing out mmRNA, which then did weird stuff. Despite this, we won’t bother you with this issue again. 

We think that is the correct interpretation given the following text:

‘The EWG quality sub-group discussed the particulate matter found in the batch of immediate interest (EJ0553). It was highlighted that vials containing particulates were removed from the batch based on 100% visual inspection. With regards to the visual inspection, it was highlighted that this particular batch failed to meet its own AQL for major defects on inspection. Discussions considered the nature of these particles, and when they are formed in the process, and that < 1.5% of the total batch was removed due to the appearance of white-coloured particulate matter. On examination the company explained that these “lipidassociated particles” are around 500-600 µm in length and not spherical. Initially, the company commented that these particles only consisted of lipids, but later indicated that these particles also contain RNA.’

The EWG reported it was reassured, as the manufacturers did not think all this affected the stability of the product:

‘The particles were described as “flaky” in appearance. The company said that the particles were process-filling line-associated (after sterile filtration) and not a stability-indicating phenomenon.

The company further explained that these particles did not alter the concentration of the drug product and they did not think this would have an impact on safety and efficacy of the product. 

The reflections of the EWG quality sub-group were that the particulate matter for this batch was an OOS (out of specification) observation; the particles were described as intrinsic in nature; whilst not typically expected were not understood to be associated with a change in concentration of RNA containing LNPs, all of which provided some reassurance that efficacy is not adversely impacted.’

So there you are: All’s well, take the manufacturer's word for it. Oh, and it’s all secret.

This post was written by two old geezers who think it is everyone’s business to understand the properties of an intervention rolled out under duress to millions.