Richard Steiner reports on the changing face of drug development and production
The opportunity to obtain more data from less product during development and eliminate the cost and risk of batch-based scale- up has inspired the introduction of small-scale, continuous equipment that can process small quantities of material during R&D while also being able to operate for variable lengths of time to match market demand during commercial production.
GEA believes that the ongoing growth of small-scale, continuous manufacturing (CM) systems will represent one of the most important paradigm shifts in pharmaceutical drug production. Flexible development options will facilitate the commercial manufacturing process and enable greater process understanding to be achieved with smaller quantities of material.
For more than 20 years, the batch-based production of blockbuster solid dosage forms dominated the industry. Profitability was such that companies were not incentivised to innovate or risk developing new manufacturing technology. In the post-blockbuster era, however, it is increasingly recognised that material costs during drug development are considerable, new drug products are likely to be manufactured in much smaller quantities and that, for novel treatments, the development of a commercial manufacturing process is not guaranteed.
Such pressures have put the costs, risks and timelines associated with traditional batch-based development and manufacturing under scrutiny. In most industries, CM is seen as the low-cost solution to producing low value, high volume products in which there is little need to focus on the cost of materials used in process development and, often, little need for product changeover.
Regulators are increasingly supportive of CM and manufacturers are recognising that current quality assurance costs are disproportionately large compared with other industries, wherein the production, detection and removal of out-of-specification product is vanishingly small. Earlier in 2016, for example, the US Food and Drug Administration approved a CM process at Janssen’s facility in Gurabo, Puerto Rico, for the production of its HIV drug, Prezista.
“Although it’s not easy for drug manufacturers to transition from batch to continuous manufacturing, there are significant rewards,” commented Lawrence Yu, FDA’s deputy director for the Office of Pharmaceutical Quality, adding: “FDA encourages others in the pharmaceutical industry to consider similar efforts.”
CM is generally considered to be more efficient as it consistently delivers a higher quality product. And, as Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, noted: “A number of companies are on the verge of adopting advanced manufacturing techniques such as CM, which are not susceptible to many of the problems of traditional production models. CM can transpire in a single small room, starting with raw materials at one end and finishing with tablets on the other.”
When she advised the pharmaceutical industry to get ready for the concept of continuous drug production, GEA was already there. The company has long been working on flexible development options that facilitate the commercial manufacturing process and enable greater process understanding to be achieved with smaller quantities of material.
Potential API savings of more than 60% and time-to-market reduced by more than a year have been identified by companies using small-scale CM systems. And, it’s predicted that in 10 years, the vast majority of tablets will be produced on CM lines that are installed in modular facilities that are a fraction of the size of current plants.
FDA has said for several years that if drug-makers paid more attention to high quality manufacturing, it would prevent the regulatory problems that lead to plant closures and costly fixes. “CM also allows manufacturers to respond much quicker to changes in demand, potentially contributing to the prevention of drug shortages,” Yu added.
In fact, the agency recently designated an oral solid dosage form that has been developed and produced using GEA’s ConsiGma CM platform, as a breakthrough therapy. The approval allows expedited development and review, effectively giving the company – a GEA customer – the green light to manufacture the drug using CM technology.
The ConsiGma continuous tableting line is a multipurpose platform that has been designed to transfer powder into coated tablets in development, pilot, clinical and production facilities in a single compact unit.
Furthermore, the ConsiGma 25 unit forms the basis of an innovative collaboration between Pfizer, GSK and G-Con to develop the next generation of portable, continuous, miniature and modular (PCMM) solutions for pharma production. These on-demand mini-factories can be set up to manufacture medicines at any production scale, anywhere in the world where basic facilities are available.
GEA believes that CM is fundamental to the future of the pharmaceutical industry and represents an exciting step forward in drug production.
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Richard Steiner is with GEA.