When the market landscape for a pharmaceutical drug changes, there is a need to respond swiftly and decisively. This was the case when a second-generation isotretinoin formulation entered the market.
The Challenge
Isotretinoin is a treatment for severe acne, and while Douglas had already developed and launched a first-generation product, it had to be taken with food. The launch of a second-generation product from a competing innovator changed the market landscape, allowing for patients to take the drug in a fasted state (on an empty stomach) and expanding consumer choice.
When presented with an opportunity to partner with a mid-sized US based pharmaceutical company to develop a generic isotretinoin drug, Douglas rose to the challenge. With a strong track record in softgel technology and experience with existing isotretinoin products, Douglas had the expertise to modify its first-generation isotretinoin formulation into a generic that could be taken in a fasted state.
To expedite approval ahead of patent expiry, Douglas and its partner filed a paragraph IV abbreviated new drug application (ANDA) with the US Food and Drug Administration (FDA).
Chris Cuthbertson, Programme Manager of New Product Development at Douglas, played a central role in the project. He explains, “With the paragraph IV ANDA submission approach, we developed a formulation that did not infringe the formulation patent that existed. You formulate around the patent, but your product must still demonstrate bioequivalence to the reference listed drug, have a stable shelf-life, and validated processes must be demonstrated.”
These factors made for a technically challenging development process, particularly under time pressure. Chris explains the advantage of Douglas’ experience,
“At Douglas, we have deep experience with softgel capsules, and we know how to develop and manufacture a quality product from decades of experience.
For companies new to this technology, there can be a learning curve that adds complexity. Building on our previous isotretinoin launches, we were able to confidently take on this project.”
The Approach
The innovator product required the development of four distinct dosage strengths: 10, 20, 30, and 40 mg. The initial hurdle for the Douglas team was that each strength demonstrated non-linear pharmacokinetic properties. Consequently, formulations had to be individually developed for each dosage strength capsule as their release mechanisms varied.
Bioequivalence (BE) studies are a critical component of an ANDA submission, demonstrating that the generic product matches the reference drug in performance.
Partway through development, the FDA updated its guidelines regarding its criteria for BE studies. Previously, only two BE studies were required for the maximum dose – in this case, studies in a fed and fasted state for the 40 mg dose.
The updated guidelines required fed and fasted studies for each strength. Despite this, the team maintained momentum through close collaboration.
“Developing the formulation and demonstrating bioequivalence was complex, but we delivered at speed. Regular communication, transparent reporting, and solution-focused problem-solving helped us maintain progress without delaying timelines.”
To maximise speed to market before patent expiry, Douglas’ partner submitted two ANDAs, with the lower dose strengths filed ahead of the 40 mg product.
“The submission process required a huge amount of time and perseverance from both teams to ensure the product launched on time,” Chris adds.
Strong project management was critical. The team implemented a proactive risk register, identifying likely FDA questions early and beginning work on high-priority responses in advance.
The Result
Douglas and its partner successfully launched the generic isotretinoin drug in 2021, achieving rapid sales growth. With support of a third partner for sales and marketing, the product captured a larger-than-expected market share, doubling initial forecasts.
To keep pace with demand, Douglas held dedicated resource planning sessions across commercial and technical teams to scale production efficiently.
The strong relationship developed between Douglas and the partnering company, built on trust, collaboration and mutual success, as well as the commercial success of the project, resulted in further collaborations.
“We’ve since launched four additional projects with this partner, which is an extraordinary achievement.”
Chris concludes that a client-centric, transparent, and solution-driven approach enabled Douglas to respond quickly to challenges and deliver a successful outcome.