They believe the greatest benefits will be felt by generics firms and those investigating orphan drugs
There is clearly now a global commitment to move forward with the principles of QbD, however, the rate of adoption remains highly uneven, reveals the second part of CPhI Worldwide's 2015 annual report.
At the advanced end of the spectrum a limited number of Western manufacturers are moving towards continuous processing, but underestimating the complexity of both raw materials and finished products will continue to breed 'black swans', which could be particularly detrimental to continuous manufacture with realtime release.
In the report, Quality, metrics and continuous processing, three industry experts: Emil Ciurczak, President at Doramaxx; Bikash Chatterjee, President and CSO of Pharmatech Associates; and Brian Carlin, Director Open Innovation at FMC look at the implications of QbD, continuous processing, excipients, and process validation on pharma manufacturing.
Ciurczak believes that within a decade all manufacturing globally will be continuous and it is only inertia and the fact that Big Pharma can still largely charge what it wants in the US that is preventing faster implementation. He warns that those manufacturers that fail to implement change early enough will not see out the decade.
The rate of adoption of continuous processing is now accelerating
The rate of adoption of continuous processing is now accelerating and Ciurczak believes we will see the industry’s leaders producing one or two products each year for the next several years, before only submitting NDAs that include continuous manufacturing.
He argues that it will be at this point that we will see the biggest game changer when the largest generics companies (Teva and Sandox, perhaps) start purchasing equipment. Following their lead, the remainder of the market will quickly start investing, he says. Overall, this could bring the cost of drug manufacturing down by as much as 50% if started at the development stage. He concludes that generic and orphan drug companies will see the greatest benefits.
Chatterjee says the gradual integration of QbD principles is going to be transformational over the next few years as companies strive to implement guidelines from the European and US regulators. In these regions, contract development and manufacturing organisations (CDMOs), whose business model is geared toward partnering with virtual drug development companies, are likely to be the first to embrace the core tenets of QbD. However, contract manufacturers may lag a little in implementation, as they are not forced to embed these processes with new drugs.
Now that EMA and FDA guidelines are synergising, PIC/S rollout to 55 countries by 2023 will be transformational in terms of global adoption. In emerging markets, larger drug manufacturers with margin to build in these systems will be first to move across and will benefit from sales into the US and Europe. For the remainder, we will see an uneven implementation similar to that of GMP in China over the last decade.
Global harmonisation, greater raw material understanding, QbD and continuous processing trends will continue
Both Ciurczak and Carlin feel the situation regarding excipients is more complicated: the former states that continuous processing will not be a factor here, while the latter warns of the residual risk from excipient complexity even when using QbD principles. For finished product quality it is the variable balance of properties, not just each property separately, that must be controlled. Paradoxically, with fixed formulae and processes, the risk from raw material increases if there are no compensatory mechanisms to stop variability feeding forward. Without joint due diligence from users and suppliers pharmaceutical ‘black swans’ will continue to have an impact on products.
The experts agreed that global harmonisation, greater raw material understanding, QbD and continuous processing trends will continue. Ciurczak argues that in the longer term, this will lead to remarkable innovations such as variable dosage forms when combined with 3D printing. Additionally, the unique 'process signature' of a single production stream will also help identify counterfeits and tighten the supply chain further – lowering cost, individualising patient dosage forms and improving safety.
The full article will be featured within the CPhI annual report (parts 1-4), which is to be released at CPhI Worldwide 2015 in Madrid, 13–15 October.