Breaking barriers: Can continuous manufacturing prevail despite hurdles?

Regulations, recruitment and facility refits are holding continuous manufacturing back, but a Rutgers’ associate behind J&J’s recent success believes industry can overcome these hurdles.

It may be argued that we are on the brink of a paradigm shift in the pharma industry as after years of uncertainty, continuous manufacturing – rather than batch production – is becoming a possibility in the production of solid dose drugs.

Last year, the US Food and Drug Administration (FDA) approved Vertex’s breakthrough therapy Orambi (lumacaftor/ivacaftor) which uses a continuous manufacturing process, while earlier this month, J&J offshoot Janssen received regulatory approval to change the production method of its HIV drug Prezista from batch to continuous at its plant in Puerto Rico.

Janssen has been working with researchers at Rutgers University over the past five years to instigate this shift, and continues to do so. In-Pharmatechnologist.com therefore spoke with associate director of Rutgers’ Center for structured Organic Particulate Systems (C-SOPS) Doug Hausner to find out what challenges continue to hinder industry’s shift.

in-Pharmatechnologist (IPT): FDA director Janet Woodcock last year described continuous manufacture as ‘the future,’ and over the past twelve months the Agency has begun investing in projects and developing guidelines to support continuous manufacturing (CM). But what regulatory hurdles still exist?

DH: The issue here is not so much in the US, but globally. The FDA has been pretty clear on CM and that will continue.   Many pharma companies are worried about other markets and multiple manufacturing processes if approvals don't happen there.   The issue is mostly a lack of familiarity in other markets.  Eventually that will change, but this will take time.

Still, there are many other potential channels for guidance type information.  A perfect example are things like USP guidelines.   We recently started working with the USP and will be holding a workshop with them this summer with the goal of beginning the guideline process. 

IPT: A major problem is the fact many drugmakers have invested heavily in their current plants and systems, which are equipped for batch production. How big a barrier is the need to refit a facility?

This is the most difficult and least difficult at the same time. Right now there is a huge issue with existing capital. That coupled with the fact that most business models for CM still have a lot of batch "baggage" and even miss out on key advantages. Once a few companies become proficient at CM development, the speed to market advantage alone, will force other companies to reconsider how existing capital is factored. 

IPT: What about the processing equipment itself? Surely the cost and availability of CM systems are major issues?

This is about to change too. In 2015 companies other than GEA started to talk seriously about CM.  The issue is more of a business one than a technical one. Systems exist including the one at Rutgers using components from multiple manufactures to create an integrated system. This is not popular though as companies don't want to integrate themselves and prefer to have that done by equipment vendors. This has forced pharma vendors to work together in new ways. 

IPT: While guidelines and access to new equipment will help encourage a shift, the lack of CM talent and expertise has previously been cited as restricting adoption. Is this still the case?

DH: This is one we are looking to address in academia. It is still hard though because the interest outweighs the rate at which good people are being generated. Training programs - even hands on -and courses only go so far. We hope that in the short term we are able to leverage government and industry support to create a shared facility where we can increase the ability to involve others collaboratively.

IPT: Thank you very much