Dr. Robert Lee, President
June 2019, Drug Development and Delivery Magazine
No matter the area of specialty, CDMOs find they must shift toward providing value-added services by establishing themselves as a one-stop-shop for pharma clients. “When you work with multiple contract services organizations during the drug development and manufacturing process, it takes more time, increases costs, and involves greater risk,” says Robert Lee, PhD, President, Particle Sciences. “If there are five or six organizations working on different elements of the same project, it’s more difficult to manage and you need to ensure that someone is keeping track of all the players and arranging the logistics. For example, we’ve found that when another company does the analytical work for a client, we can wait weeks for the analytical data we need to help support our formulation efforts. When we do the analytical work ourselves, then those delays don’t happen and we are in control of the information flow.”
Working with a one-stop-shop means that everything is done in one place, removing time and risk mitigation concerns. This is a particularly critical issue when transferring between late-phase clinical to commercial. Dr. Lee says some CDMOs can get a pharma to Phase 1/2, but transferring a complex formulation to another CDMO can involve cost and time.
A number of factors in the market are reshaping the approach to dosage forms, resulting in a rise in non-traditional dosage forms such as nasal sprays and drug-eluting implants. One reason for taking these new approaches is the number of drugs that contain poorly water-soluble APIs.
“When poorly water-soluble drugs are delivered through traditional dosage forms such as oral solid dose, they fail to dissolve, have severely limited bioavailability, and therefore have limited therapeutic effect,” says Robert Lee, PhD, President, Particle Sciences. “There are multiple techniques available to increase the solubility or dissolution rate of drugs and improve their delivery, particularly the use of amorphous solid dispersions and nanoparticle formulations.”
Alongside the issue of poor solubility is the increase in 505(b)(2) approvals – an FDA regulatory pathway that involves taking existing, marketed APIs into a different route of administration. These approvals grew 50% last year and this regulatory path has become increasingly popular over the last decade, usually involving innovative dosage forms or drug delivery methods that are considered complex, explains Dr. Lee.
“Navigating the regulatory pathway and ensuring a molecule reaches the clinical trial phase is relatively straightforward for simple dosage forms such as an oral solid dose or a sterile injectable solution, but with more complex formulations involving nanoparticles, there are a lot of layers,” he says. “It’s hard enough to develop a complex formulation that tackles poor solubility without the added obstacle of inadequate regulatory knowledge that could see a product fall at the first hurdle.”
Preventing failures related to complex formulation challenges is something Dr. Lee takes seriously. “Clients sometimes come to us with formulations that have been developed on benchtop only or by organizations that just don’t have experience in complex dosage forms,” he explains. “We take on these sub-optimal formulations and use a more scalable process in conjunction with optimizing the formulation to make a much better product that is acceptable for GMP production and commercial production.”
When the API is a particularly challenging molecule, it is important to come up with better formulation methods. For example, one molecule Particle Sciences worked on recently was poorly water soluble. Dr. Lee says a novel formulation was identified that was comprised of GRAS liquids that had strong solubilization characteristics, and Particle Sciences filed a provisional application. “This approach enabled us to produce a solution with the required pharmacokinetic profile to match the commercial product given by a different route of administration,” he says. “By doing so, we were able to provide our client with additional intellectual property protection for their asset.”