Solid Dose Realities: Reaching for More

Real-time characterization of Oral Solid Dose formulation in process and nearly prescient control are doing great things for both batch and continuous drug manufacturing

By Steven E. Kuehn, Editor in Chief

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While biopharma’s parenterals may be the belle of the ball lately, Oral Solid Dose’s (OSD) dance card remains booked — the form of choice for thousands of medicines and billions of patients. Far from the dowdy, aging wall flower one might expect from such a mature segment, in reality some of the most exciting technological advancements in Pharma processing are occurring right now as Branded, Generic and CMO players reach out for more speed, more capacity and quality in solid dose cGMP operations.

It’s always worth a moment to take a quick look at the category as a whole, just to calibrate on how important the OSD form is to the Pharma universe. With the exception of one product (Lantus), OSDs represent most prescribed medications. According to IMS Health, Synthroid (levothyroxine), with 22.6 million prescriptions, remains the nation’s most-prescribed drug; the antipsychotic Abilify (aripiprazole) at $7.2 billion, has the highest sales (see Table 1). Of the top 10 highest-sales drugs, OSDs lead, garnering $28.5 billion in sales versus $23 billion for liquid injectables. 

There’s no doubt that contract manufacturing organizations (CMOs) are capitalizing on the continued expansion of the OSD market. In 2014, says Kate Hammeke, director of marketing intelligence at That’s Nice, the contract manufacturing market for solid dosage forms is projected to be $19.6 billion, representing 58 percent of the total CMO market, valued at $33.7 billion.

“While the market value percentage for solid dose has been drifting downward,” says Hammeke, “and likely related to the shift towards biologics — which are more expensive to develop and manufacture — the propensity to outsource oral solid dosage forms continues to grow modestly.” Nice Insight’s annual survey results indicated that solid dose manufacturing will be outsourced with the greatest frequency (55 percent) followed by injectables (50 percent), semi-solids (44 percent), then specialty dosage forms (42 percent).

Who’s outsourcing solid dosage forms? According to Nice Insights, Big Pharma is (60 percent) followed by Biologics (50 percent), Emerging Biotech (70 percent), Emerging Pharma (49 percent) and lastly Specialty Pharma (51 percent). Who’s getting the business? Some of the biggest names head the list (See Table 2), many offering margin-enhancing efficiency and expertise to those Big Pharma players looking to get the most bang for their buck out of patent-expired formulations.

Hammeke says those responding reported they would outsource finished dosage forms with a greater frequency than API manufacturing (for both large and small molecule APIs). “When it comes to outsourcing behaviors,” explains Hammeke, “respondents who will contract solid dose manufacturing in 2014 showed a greater likelihood for considering emerging market providers than the general population, with nearly nine out of 10 stating they include CMOs in emerging markets on their shortlists.”

She noted that, among cautions expressed by respondents to the Nice Insight study, intellectual property (IP) concerns were a top reason for not considering emerging market providers because this issue corresponds much more strongly to primary manufacturing/API production than secondary manufacturing of dosage forms.

Among the product types, controlled release tablets were of most interest to Nice Insight survey respondents (62 percent), followed by oral disintegrating tablets (56 percent), immediate release filled capsules (55 percent), and immediate release tablets (54 percent). Other types like controlled release capsules, powder-filled capsules and resin or bead-filled capsules followed at 49, 44 and 33 percent, respectively. Study respondents indicated that timed-release technologies, either rapid or delayed were of significant interest, but of most interest were technologies that protected formulations from stomach acids.
“Both outsourcing and offshoring have shown their efficacy in cutting costs for pharma companies when it comes to solid dose manufacturing,” says Hammeke. Another potential development to emerge from reducing capital outlay on in-house manufacturing equipment and technologies, says Hammeke, is the shift from tactical relationships for OSD projects toward more strategic, long-term agreements with manufacturers.

REACHING FOR MORE
Everyday, the economics of drug manufacture are growing more complex to manage effectively. If there is one thing for certain, the future health of the industry is resting squarely on the shoulders of its manufacturing operations, and clearly drug makers are striving to get the most out of their production capacity. Drug safety, supply, access, compliance and shareholder return all hinge on getting manufacturing and process operations right for both drug maker and drug owner. Industry behavior reflects how important manufacturing excellence is to business success and is reflected in recent merger and acquisition activity, the development of strategic and long-term manufacturing related partnerships, and strategic investment in new-era manufacturing technologies.

Without being too remedial, the traditional manufacturing oral solid dosage forms is a primarily a physical (not chemical) multi-stage process. This well-established process involves dispensing, milling or sizing particles and blending the formulation’s primary ingredients (APIs, excipients). Granulation is another primary step, and both wet granulation and dry granulation are used by manufacturers to prepare the formulation for direct compression into tablets or to fill capsules. Because a variety of processes can be applied to manufacture OSDs, including drying, compaction and coating, there are a number of factors associated with these fundamentals processes that can significantly impact the chosen form’s uniformity, stability and bioavailability.

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