Looking back on the history of the pharmaceutical industry, it’s very much an evolving practice, with new knowledge bringing continuous improvements. Copious trial and error has brought us an industry very different from that of 150 years ago. And yet, one methodology has survived the decades essentially intact. The basic oral solid dose manufacturing methodology used today is very similar to the OSD manufacturing of the past — and that’s not necessarily a bad thing.
In 1843, British painter/author/inventor William Brockedon patented an invention that compressed sodium carbonate and potassium carbonate in a tube, to form solid tablets. Eliminating the need for moisture to bind ingredients in the pill making process, Brockedon’s invention ushered in a completely different type of “pill” — one that could be mass produced in different dosage forms.
And while the dosage form has not seen what OSD subject matter expert Dave DiProspero calls a “silver bullet change,” the sector has continued to stay relevant.
Recent FDA numbers lend support to this relevancy. If you look at the 2015 new drug approvals, 51 percent of the new molecular entities (NMEs) approved by the U.S. Food and Drug Administration were solid dosage products — a slight increase from the previous year. In 2014, 19 of the 41 NMEs were solid dosage products (46 percent); while in 2015, 23 of the 45 NMEs were solid dose products. Over the past three years, 37 new tablets and 22 capsules have been approved by the FDA.
In terms of oral-solid-dose facility construction, DiProspero, a senior consultant for CRB Consulting Engineers and also a leading committee advisor for ISPE’s Oral Solid Dose Community of Practice, notes that changes to the OSD sector have been “more along the lines of moderate upgrades and improvements to the process/facility. Not a lot of significant changes.”
“Over the past few years there has been a slowdown in ‘new’ OSD facilities. We are not seeing a lot of greenfield, let’s-build-a-100,000-square-foot-OSD-facility type projects (though there are a couple). However, renovating and upgrading of processes and technologies in OSD remains relatively strong. Companies are still investing in projects and working to upgrade existing facilities,” says DiProspero.
Despite the solid dose slowdown, and the noticeable attention being given to newer, flashier biologics initiatives, pharma is still investing in solid dose capabilities. Capsugel, for example, recently completed construction on a $25 million spray-dried dispersion (SDD) commercial facility in Bend, Oregon (discussed in detail here). Capsugel, now with the largest SDD facility in North America, is solving a number of different formulations and stability challenges faced with capsule and tablet dosage forms. In another example, prescription opioid pioneer Purdue Pharma invested big in the construction of a new 190,000-square-foot, oral-solid-dosage manufacturing plant in Durham, N.C., in 2014. The company is currently expecting to file for full manufacturing approval from the FDA in the second half of this year.
With the large number of oral solid dose drugs plunging off the inevitable patent cliff, generic solid dose products have stepped in, poised to compensate for any future decline in OSD NMEs. As the role of generics in the OSD sector continues to grow, so does the regulatory scrutiny of generic solid dosage products. With 86 percent of all prescriptions in the United States now filled by a generic drug products, the Office of Generic Drugs began to notice that many ANDAs were being submitted to the FDA with tablets and capsules that were much larger in size than the reference product. While the generic formulations of these drug products are required to be both pharmaceutically and therapeutically equivalent to a reference listed drug (RLD), the agency was concerned that differences in physical characteristics of solid dose generics (size, shape, weight) would affect patient compliance and cause medication confusion.