Continuous manufacturing: pharma adoption challenges remain according to CMAC

Economics, regulatory inexperience and a lack of technical skills are holding back drug industry adoption of continuous manufacturing says CMAC industrial director, Craig Johnston.

Johnston made the comments at an industry conference in Barcelona, Spain this week explaining that although some larger organisations have implemented continuous processes, most producers have not embraced the approach.

Continuous is becoming the norm for some in the innovative sector” he said, adding that “GEA alone has sold 70 of its continuous platforms and the first two commercial products [made using such technologies] have been approved, Janssen in Puerto Rico and Vertex in the US.”

Regulators want the drug industry to make greater use of continuous processes according to Johnston.

This time last week we co-organised a conference with MIT in Boston, Janet Woodcock from the US FDA spoke there and certainly from a high level regulator perspective there is support.”

Regulatory experience

CMAC is a UK-based organisation that aims to help develop the tech, processes and know-how needed for continuous production in the drug industry and other sectors. The organisation is focused on active pharmaceutical ingredient (API) crystallisation.

The idea is to create a critical mass that encourages industry to embrace continuous manufacturing according to Johnston, who said while the potential benefits of the approach are recognized, more training is needed for both regulators and chemists.

We’ve done some training for regulators…and I have to say that their level of technical ability was very low” Johnston said, adding that “we are working with the FDA and the MHRA in the UK, but it is quite a fragmented landscape.”

He cited issues like fouling and variation as areas in which regulators need more continuous manufacturing-specific experience.

The reality is that in continuous processing you are using less volume so the issue of fouling is actually easier to address, however, there is perception among regulators that this is more complicated than in batch production.”

Technical skills and economics

There is also a limited of experience in the drug industry according to Johnston, who said: “Many development chemists and engineers lack the skills needed for continuous manufacturing.”

He suggested that few innovative drug companies have invested in training their staff in continuous techniques and contrasted this with the contract services sector, where having a broader skill set is a competitive advantage.

Continuous synthesis has been largely driven by CMOs,” he said, adding that “Lonza, DSM and others are prime movers particularly in areas such as hazardous chemistry.”

Johnston did predict drug companies will invest in training and technology, but only when the economics of doing so make sense.

Continuous manufacturing only really works for a drug company from an economic standpoint if value is derived.

A crystallisation process that takes 10 hours which can be reduced to 10 minutes [using continuous manufacturing] is of no real benefit if the batch is then waiting at the next stage.”