With more than a century of safe, effective usage, oral solid dose products are a proven pharmaceutical market mainstay. Despite the increasing number of biologics and even parenteral small molecule drugs, OSD remains dominant in the market.
This is not to say the dosage form is without challenges. With many traditional blockbuster oral solid dose products now off-patent, next-generation OSD products, such as high potency drugs and personalized medicines, necessitate smaller volumes of production, with shorter lead times. A trend toward more regionalized manufacturing also means smaller production volumes. These factors, combined with a more intense pressure to control costs, and improve operational efficiencies and quality standards, boils down to this: OSD manufacturers need a more modular, flexible process.
On the innovation front, 2016 saw the percentage of solid dose new molecular entities approved by the FDA slip from 53 to 32 percent. The sector may already be mounting a comeback though, as 5 of the 7 already approved NMEs in 2017 are tablets.
This novel drug approval number does not include generic approvals - a category where OSD is still the dosage form of choice. With the large number of OSD drugs losing patent protection, generic solid dose products have stepped in, poised to compensate for future decline in OSD NMEs. There were 630 ANDA approvals and 183 tentative approvals in 2016 (the highest number in history), with 73 of them being first-time generic drug approvals. About 70 percent of these first-time generic approvals were solid dosage products.
With all areas of pharma firmly invested in oral solid dose products, the dosage form surely isn’t fading away any time soon - and yet it continues to be challenged to stay competitive in a changing pharma market. What follows is a discussion of how the industry’s most stable drug form is innovating and evolving to stay relevant.
OSD OVER INJECTABLES
Consultants at NNE pharma engineering point to an emerging trend in biopharmaceuticals whereby manufacturers are choosing to formulate biopharma products in oral solid dosage forms, rather than as injectables. The familiar, accessible OSD format promotes increased patient compliance.
One example is in oncology. The global market for cancer drugs has recently reached an annual sales value of $100 billion. OSD oncology drugs are much more common now than even five years ago, and oral drugs are increasingly making up a larger proportion of the oncology drug costs.
The three oncology approvals in 2017 - Kisqali, Xermelo and Revlimid - are all oral dosage products.
Already familiar with the containment issues surrounding highly potent, toxic products, OSD manufacturers are well-positioned to handle oncology drugs. Equipment manufacturers are offering assistance with solutions that prioritize containment for manufacturing oncology drugs. Advances in solubility enhancement technologies, such as spray-dried dispersions, are enabling faster dissolution and enhanced bioavailability in OSD products, allowing them to compete in a space previously dominated by injectables.
Although definitely not a new concept, a decade ago, continuous manufacturing was somewhat of a theoretical discussion in the pharmaceutical industry. Batch production had a long history of success under its belt, and many in the industry questioned such a huge paradigm shift.
During a recent panel discussion at Interphex 2017, Fernando Muzzio, distinguished professor of chemical and biochemical engineering at Rutgers University, made the following analogy: “People in the early 1900s asked ‘why do we need cars when we have so many horses?’”
Today, as OSD manufacturers are realizing the critical need for a more flexible, efficient process, the continuous process - which itself is also evolving - is shaping up to be an important tool.
“Continuous manufacturing has gained and continues to gain traction. It is the biggest ‘hot button’ for OSD right now,” says OSD subject matter expert, Dave DiProspero.
While both biopharma and OSD are playing in the continuous manufacturing space, OSD has the power of concrete examples and FDA approvals in its corner. Vertex has been using a continuous manufacturing process for cystic fibrosis drug, Orkambi, since its approval in July 2015. Janssen made history last year by getting the first FDA approval for a manufacturer’s production method change from “batch” to continuous manufacturing for its HIV tablet, Prezista. Most recently, Eli Lilly took home two 2017 ISPE Facility of the Year awards for the drugmaker’s three replicate operational continuous Oral Solid Dosage production facilities.
Initially viewed as a solution best suited for high volume, new products, continuous manufacturing is proving to have broader applicational benefits.
Janssen proved that continuous manufacturing is not just for new products. “Continuous manufacturing opens the door for increased efficiency and quality, which can decrease the manufacturing costs for new and existing products. The solution really has the potential to work both ways,” confirms DiProspero, who is a senior consultant for CRB Consulting Engineers.