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CPhI Report Evaluates Innovative Mfg. Processes


Experts predict PAT/QbD and CM adoption may take ten years

CPhI Worldwide has released 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 includes perspectives from manufacturing and ingredients experts on both the near- and long- term trends: Emil Ciurczak, president at Doramaxx Consulting; Brian Carlin, excipient expert, and Girish Malhotra, president at EPCOT International.
The overall findings reveal that the use of modern manufacturing processes and quality systems is occurring very slowly, with the current small molecule pipeline lacking 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, said, “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 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.”
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 serialization in the last few years.

“Large companies will naturally be the first movers, followed 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,” said Mr. Ciurczak.

Brian Carlin, an excipient expert, warned that the industry needs to move to smarter control of its processes, and increased use of PAT, if excipients 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 Mr. Carlin.
Biologics may be the exception to the rule and is the area most likely to support the development of new excipients. Overall, Mr. 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.