Capsules are an important solid dosage form, especially during the early stages of pharmaceutical development. The prevalence of solid dosage in the pharmaceutical industry is clear — it remains the most popular dosage form — but what role do capsules play, and what role do capsule manufacturing service providers fill for pharmaceutical manufacturers?

To find out more about the current state of outsourcing capsule manufacturing within the pharmaceutical industry, Pharmaceutical Processing spoke with Almac Pharma Services — a company that offers immediate and modified capsule and solid oral dose manufacturing services — in order to get an inside look at the latest developments.

Capsule’s Role

Capsules are a common solution during the early stages of pharmaceutical development, since companies attempt to dose patients as early as possible, to reduce active pharmaceutical ingredient (API) usage and formulation costs. “Putting API in capsules is significantly easier and cheaper than formulating a tablet, particularly if you are assessing multiple dosages,” says John McQuaid, vice president, technical operations.

“Often these early-stage capsules are superseded by the development of a tablet formulation during mid- and later-stage trials,” but, in some cases, companies prefer to stick with capsules during later stages as well. “We do still see significant numbers of products in capsule presentation, with an ‘if it is not broken, don’t try and fix it’ approach,” McQuaid adds. “This is particularly true for multi-particulate formulations.”

Weighing Your Options

If a pharmaceutical company needs capsules — either for trials or for patient populations — but is unsure whether outsourcing is the right option for its needs, the next step is to make a list of pros and cons. Important criteria include:

• In-house vs. outsource costs (fully loaded cost burden).

• Mitigation of risk strategy.

• Contract development and manufacturing (CDMO) technical expertise and track record.

• Regulatory performance of CDMO.

• Scalability of equipment train within CDMO.

  Analytical capabilities of CDMO.

  Overall flexibility.

Outsourcing capsule manufacturing (and solid dosage manufacturing in general) can sometimes help pharmaceutical manufacturers cut costs.

“Why buy and build capital expenditures (capex) and headcount when a CDMO has those assets on hand?” says McQuaid. “Even with capital and headcount available, it is rare that a CDMO cannot do the same for less, when looking at fully loaded costs.”

CDMOs can also often deliver a high level of experience. “The CDMO should have executed multiple similar projects that can add a layer of expertise often lacking when building knowledge and experience from the ground up,” McQuaid adds.  

When creating a list of cons, a few considerations are crucial. McQuaid says overall, asset addition should only be considered when the pharmaceutical manufacturer has a blockbuster drug in its pipeline, but a few other possible negatives must be considered.

“When proprietary technologies are involved and significant intellectual property (IP) has been developed by the pharmaceutical manufacturer, then outsourcing this know-how can be questionable,” McQuaid warns. “Also when a company has ‘all its eggs in one basket,’ i.e. it’s a single-product company, then the attraction of having one’s own assets — and control of these assets — can be attractive.”

The Current Market

Depending on the chosen CDMO, the client, the client’s needs, and the CDMO’s capabilities, the outcome of an outsourcing relationship can vary. Additionally, as the market changes, CDMOs must adapt to new technologies and processes.

Within the last two years, Almac has witnessed four big trends that effect the capsule and solid-dosage outsourcing market: (1) Clients are moving to API in-capsule during early stage development, since drug-in-capsule uses less APIs; (2) multi particulate formulations are increasing, such as beads and pellets with controlled release coatings for dissolution profiling; (3) fixed-dose combinations have emerged; and (4) highly potent compound development and outsourcing has increased.

“From a commercial perspective, clients are seeking to free up internal capacities by outsourcing large-volume solid oral-dose products, particularly those that have controlled handling requirements, often due to elevated potency,” explains David Downey, vice president of business development.

In turn, some of these new trends foster the development of innovative advances. One such advance is new containment technologies, which are emerging to meet the needs of an industry that increasingly handles low-volume, high-potency products.

“Addressing the continuing pharmaceutical market trend of manufacturing medication at smaller but more potent doses, new containment technologies have emerged,” says McQuaid. In response, Almac has implemented containment solutions, which were designed in-house, within its development facilities.

In general API’s swelling prevalence is a big technology driver within the capsule and solid dosage outsourcing market. “Other key technologies have emerged to address the problem of API insolubility — for example, hot-melt extrusion, spray drying, etc.,” McQuaid adds. “Reduction in API usage is also a technology driver, whether at the small scale (Xcelodose [API in capsule]), or the larger commercial scale (continuous processing rigs).”

What to Expect

As the API trend demonstrates, processes within capsule outsourcing operations are diversifying. But, when it comes to service providers themselves, are they becoming more specialized or more diversified, and how will they evolve in the future?

“The marketplace for capsule and solid dose manufacturing has a range of players, from very small niche companies specializing in one specific service to larger CDMOs such as Almac that offer a wide range of services from API manufacture, pharmaceutical development, and clinical drug manufacture to large-scale commercial manufacture and packaging,” notes Downey.

This diversification may increase as capsule outsourcing grows. “Large pharma is recognizing the value of one-stop shopping and integrated service providers, as budgets are squeezed and outsource management time is at a premium,” Downey explains. “Going forward, we would expect consolidation of services or partnerships rather than niche offerings.”

The solid-dosage CDMO market as a whole seems poised to expand, mainly as a result of clients’ budget cuts. “We continue to see an increase in solid oral dose development and commercial outsourcing as pharmaceutical companies rationalize their internal and external supply chains in an effort to reduce budgets,” Downey confirms.

“We would foresee the use of capsules increasing,” adds McQuaid “Essentially, it is a more flexible dosage form than tablets, both within the development and commercial space.”