CPhI Worldwide has announced the findings of part II of its 2015 annual report (entitled: ‘Quality, metrics and continuous processing’) ahead of CPhI Worldwide 2015 in Madrid. Three World-renowned experts – Bikash Chatterjee, President and CSO, Pharmatech Associates; Emil Ciurczak, President at Doramaxx; and Brian Carlin, Director Open Innovation at FMC – look at the implications of QbD, continuous processing, excipient criticality, and process validation on pharma manufacturing.
The overall findings reveal there is clearly now a global commitment to move forward with the principles of QbD, however, the rate of adoption remains highly uneven. At the advanced end of the spectrum there are a limited number of Western manufacturers that are moving towards continuous processing. However, 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 real time release.
Emil Ciurczak believes that within 10-years all manufacturing globally will be continuous and it is only inertia and the fact that big pharma can still largely charge what they want in the USA that is preventing faster implementation – he warns that those manufacturers that fail to implement change early enough wont see out the decade. The rate of adoption is now accelerating and he states we will see the industry’s leaders producing one or two products per year pace for the next several years, before only submitting NDA’s that include Continuous Manufacturing.
He argues it will be at this point that we will see the biggest game changer however, as the largest generics companies (Teva and Sandoz perhaps) start purchasing equipment. Following in their lead, the remainder of the market will quickly start investing. Overall, this could bring the cost of drug manufacturing down by as much as 50 per cent if started at the development stage. He concludes that generic and orphan drug companies will see the greatest benefits.
Bikash Chatterjee outlined that, in particular, the gradual integration of QbD principles is going to be transformational over the next few years as companies strive to implement guidelines from the EMA and FDA. In Europe and the US, Contract Development and Manufacturing Organizations (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 USA and Europe. For the remainder, we will see an uneven implementation similar to that of GMP in China over the last decade.
Both Emil and Brian Carlin feel the situation with regards to excipients is more complicated, Emil states that continuous processing will not be a factor here and Brian warns of the residual risk from excipient complexity even when using QbD principles. For finished product quality it is the multivariate balance of properties, not just each property separately, that must be controlled. Excipient variability must be addressed. 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 impact products.
The experts agreed that global harmonisation, greater raw material understanding, QbD and continuous processing trends will continue. Emil argues 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.
Says Chris Kilbee, Group Director Pharma at CPhI: “Regulation, metrics and quality controls across the pharma industry are evolving, and over the next few years, our experts show that we will be working towards harmonization, improved standards, and in continuous processing, some fairly revolutionary manufacturing techniques. At CPhI Worldwide, we want to make sure we are central to the debate around how pharma is changing and we encourage our experts to use this forum to drive the industry forward. The annual meeting is now a place to not only do business, but also debate how we can partner and improve. By implementing the recommendations from our panel, the pharma industry will advance more quickly, develop better and safer drugs and usher in a new age of lower cost and modernised manufacturing.”