The ever present need for efficiency, combined with capacity constraints and interest in continuous manufacturing are changing what the pharmaceutical industry demands of its technology suppliers. This, in turn, is fostering innovation in the production technology sector according to industry experts.
Pharmaceutical manufacturing has changed significantly in the past decade. Historically, the main goal for firms making small molecule drugs has been higher production volumes while maintain quality. And, while this remains the focus, the greater diversity of dosage forms and delivery systems combined with regulators’ ever stricter quality requirements has significantly increased the challenge.
In the large molecule sector the challenge is quite different.
Producing biopharmaceutical products in living systems is a highly complex and, rather than being on volume, the focus is on achieving a manufacturing line that is consistent for the full lifecycle of the product. Likewise, for emerging areas like cell and gene therapy, the aim is to make high quality product in smaller batch sizes.
The impact of these trends on the technology sector has been dramatic. Both small and large molecule drug producers want platforms that meet their aims, while minimizing manufacturing costs. And the drive for even greater efficiency and speed is ever present.
Batch to continuous
One of the major trends impacting the small molecule drug sector is increasing regulatory support for continuous manufacturing. In recent years the US Food and Drug Administration (FDA) and the European Medicines Agency [EMA] have been encouraging drug firms to switch processes from batch to continuous production [1, 2].
The argument is that continuous manufacturing – if applied to everything from active pharmaceutical ingredient production, through formulation and packaging – has advantages in terms of efficiency, automated quality monitoring and traceability.
In 2015, the US agency wrote “advances in manufacturing technology have prompted the pharmaceutical industry to consider moving away from batch manufacturing to a faster, more efficient process known as continuous manufacturing.”
The agency began taking steps to help manufacturers implement continuous manufacturing technologies- notably through its emerging technology program . In 2016, it approved a change in production from batch to continuous manufacturing for Janssen Products’ medication to treat HIV-1 infection, Prezista (darunavir) .
Regulatory support for continuous manufacturing is feeding back in to production technology development with increased investment in flow chemistry and in-process monitoring technologies .
Dosage form diversity
Demand for dosage forms that allow multiple APIs to be delivered at the same time or those that release ingredients at specific organ targets is increase as pharmaceutical companies seek to improve the efficacy of their products and minimize side effects. Likewise, forms that enhance patient compliance are becoming a major focus.
Manufacturing a greater range of more complex dosage forms has driven innovation. In recent years technologies that enable better powder flow and those that support enhanced granulation or processes like hot-melt extrusion have become available . Similarly, in areas like capsule manufacturing, new more accurate filling technologies have been developed to help improve quality and minimize wastage .
Going forward techniques like additive manufacturing, otherwise known as 3D printing , are likely to become more widely used as companies follow the path set by Aprecia with its epilepsy drug Spritam (levetiracetam) in 2015 .
While technical challenges of making large molecule drugs therapies differ from traditional products differ, the factors driving production technology development are the same says Eric Langer, CEO of Bioplan Associates.
“The biopharmaceutical industry is continuously growing, evolving and demanding new and improved bioprocessing technologies to reduce costs, increase efficiencies, and improve weak development pipelines, especially in developing economies.”
He added, “Facilitating this trend of growth, are the incremental innovations in improved manufacturing productivity. These are a driver for many biopharmaceutical advances. Innovation also speeds discovery, increases manufacturing strategy options, and can drive down costs and improve overall productivity.”
Langer cited BioPlan Associates’ 15th Annual report to support his comments about productivity, explaining that, “The average titer for reported new commercial-scale monoclonal antibody (mAb) upstream bioprocessing was 3.20 g/L, up from 2.80 g/L last year.
“Nearly all the other yearly data back to 2008 show consistent incremental increases to the present. In related trade periodical articles, BioPlan has reported incremental increases in titer over the past 3+ decades, starting from at best a few 10ths of a gram/L back in the 1980s.”
Higher upstream productivity is still not being matched downstream according to Langer, who said, “Downstream processing, particularly purification, and within this, chromatography, continues to be the areas cited as responsible for most constraints (bottlenecks) in production.
“This year, 72.0% of U.S. and 70.9% of Western Europeans survey respondents reported that their facility was experiencing at least some degree of capacity bottleneck.” Clearly, any advances in downstream separation and purification technology will be of considerable interest to the sector.
Growing drug industry and contract manufacturer interest in biosimilars and biobetters is also impacting the bioprocessing technology sector according to Langer. He told us “nearly all biosimilar developers using single-use systems as much as possible for manufacturing, including adopting single-use for commercial manufacturing.”
Langer also believes that growth of the biosimilars sector is shaping technology development in another way. He told us “Marketing will be fiercely competitive, including product costs, and this is forcing developers to adopt optimally efficient bioprocessing technologies.
“Biosimilar manufacturers, many starting with no biopharmaceutical expertise or infrastructure, are often more receptive to adopting new technologies compared to innovative products developers.”