Experts predict PAT/QbD and CM adoption may take ten years, with smaller generic players to drop out of the market if unable to innovate in time
CPhI Worldwide – held in Frankfurt, October 24-26 and organised by UBM – announces the findings of part ii of the 5th edition of the CPhI Annual Report, which focuses on the immediate and long-term trends in pharmaceutical manufacturing and ingredients.
The second part of the report is being launched ahead of CPhI Worldwide, taking place next week (October 24-26, 2017), with the full report unveiled to more than 42,000 executives during the event. Three manufacturing and ingredients experts have given their perspectives on both the near- and long- term trends – Emil Ciurczak, President at Doramaxx Consulting; Brian Carlin, the excipients iconoclast, and Girish Malhotra, President at EPCOT International.
The overall findings reveal that the trend towards the increased use of modern manufacturing processes and quality systems is occurring very slowly – with the current small molecule drugs pipeline not yet possessing the economic models and incentives to stimulate faster adoption (e.g. changing to continuous processing is expensive and may not deliver advantages over batch for certain drug classes). A lack of excipient innovation and multivariate analysis are also identified as a potential growing risk. Collaboration to develop new excipients will be needed, however, biologics are the most likely to support the development of new excipients, given the high product value and susceptibility to excipient impact on quality.
Girish Malhotra, President of EPCOT International, feels that the global pharma industry is now at a critical point in its history and needs to adopt new business models for the next century. “The current approach of developing new drugs for rare and orphan diseases, and for only the most affluent patient cohorts, is actively discouraging manufacturing innovation” he warns. Adding, “these newer drug are produced in smaller qualities and often feature high margins and profits – meaning the incentive to improve manufacturing processes is not there.” Malhotra presents a number of methods whereby big pharma can sustain long-term profits, open up access to emerging markets by improving manufacturing efficiencies, and therefore reduce their total costs. Most importantly, this will increase the number of patients that can benefit.
“Making drugs affordable is the best long-term way to improve the total sales in the developing countries. Because of the income differences between developed and developing countries, the differences in drug processes will remain for the foreseeable future. Economies of scale and better manufacturing technologies can make drugs more affordable and increase sales. However, to achieve all of this will require a business model review and substantial change. This is not an easy task for an industry that has not aggressively embraced change and innovation. Their focus has always been on new drug development and marketing – drug affordability is an unknown area”, commented Malhotra.
Emil Ciurczak, President at Doramaxx Consulting forecasts that it might take as long as a decade for the industry to see the full potential of its impact – but resistance is futile and, ultimately, only those that adopt QbD/PAT and continuous manufacturing (CM) will survive. However, should the regulators (EMA and FDA) harden their positions and force the industry to work towards a QbD and PAT deadline, we will see rapid purchasing of new equipment, with a race to compete like has happened with serialisation in the last few years.
“Large companies will naturally be the first movers, followed in parallel by their strategic outsourcing partners, and this will become an established practice over the next three-years. For generic companies, and particularly smaller ones, there is an existential debate pending. Do they A, close; B, merge with or acquire other small companies to have the critical mass to invest; or C, as is happening now, partner with the larger Pharma companies to produce their off-patent, older (but still in-demand) brands. In ten years, the market will be made of fewer, but larger companies, and the profit generators will be the ones that understand and properly implement QbD”, commented Ciurczak.
Brian Carlin, Excipient Iconoclast, echoed Emil’s thoughts and warned that the industry needs to move to smarter control of its processes, and increased use of PAT, if excipients (amongst other factors) are not to introduce critical and often unforeseen risks into products. He argues that the industry as a whole must now embrace multivariate control over the next couple of years, as current practices are not predictive and will yield passing results until sudden failure. “Investment in PAT and data mining will involve additional costs, but this must be balanced against the increasing Cost of Poor Quality (COPQ) associated with regulatory initiatives on quality metrics and quality culture” added Carlin.
Biologics, he argues, may be the exception to the rule and is the area most likely to support the development of new excipients. Overall, Carlin believes regulators need to provide approval mechanisms for excipients, as the current indirect route of approval via incorporation in a finished product is inimical to innovation. Instead, collaboration between users and the excipient developers must be sought to reduce the commercial risk of new excipient development.
Orhan Caglayan, Brand Director Europe, UBM EMEA: “As the industry’s annual meeting point, the discussions next week at our eponymous global event will be vital in furthering development throughout the industry. From the experts’ point of view, long-term success is dependent on companies adopting modern manufacturing processes, including QbD and PAT, to reduce inefficiencies and excipient risks. We produce this report each year to help our exhibitors and the wider industry to stay ahead of trends and prepare for change, opportunities, and threats. It also helps our attendees to be better informed during discussions with partners at CPhl Worldwide.”