How to Run a Successful Clinical Study the First Time - Part One

Manufacturing_800-1.jpgWhen an innovative New England-based biotech company needed a fresh batch of Active Pharmaceutical Ingredients (API) for a quickly approaching clinical trial, they turned to Alcami. The neuroscience pioneer company previously partnered with Alcami and the proposed work would help secure their next round of financing. The biotech company utilized other vendors for formulation, solid-state and analytical services, believing they had their process under control. They later realized a fragmented supply chain and non-integrated control strategy led to a six month delay, requiring a repeat of their clinical study. The company relied on Alcami next for rapid and robust API manufacturing support.

Adam Kujath, Site Director at Alcami’s API manufacturing and development facility in Germantown, Wisconsin, recently spoke about the business challenges clients face, and the circumstances that led to the successful resolution of this customer’s issues.

Q. What are the common obstacles I may face with advancing my program through the clinic?

A. When moving through the clinic, drug developers encounter a variety of issues, potentially originating from the drug substance or drug product. Most often there’s a misalignment between critical attribute requirements of the drug substance for performance in a targeted formulation and their prescriptive control in the API manufacturing process. A disconnect can result in scalability or repeatability issues – things that may ultimately result in clinical delays. If that variability results in a change to formulation or even in vivo performance, you may have to go through further comparability studies or potentially clinical repeats. This costs money, but more importantly, time. Our approach ensures things are done right the first time, from drug substance all the way through drug product. We create reliable and repeatable processes through all of the clinical phases.

Q. How did this client’s challenge present itself?

A. Alcami had supplied initial API that successfully met the client’s formulation needs in the early clinical phases of their project. As with many early clinical phase drug substance projects, most of the focus was on getting powder in the bottle. The critical quality attributes (CQAs) impacting the formulation were not necessarily well-understood or defined.

For that first batch, we did the development and devised a sound API process that delivered good quality material of high purity, meeting typical ICH expectations, but no solid-state critical quality attributes were identified. Per the customer, this material was sent for analytical testing and release to a third party vendor, and for solid state characterization and formulation development and tableting to two other vendors. The batch worked well for first-in-human studies, and the client later asked us to supply a second batch. We repeated the same process at the same scale, meeting all of the same specifications, and then provided the material into the same supply chain, now totaling 4 different CDMO’s, for further testing and formulation.

When our client received the second batch, the formulation did not perform as expected. The tablets were of a high API concentration, and upon pressing, suffered from high friability. The formulation organization launched an investigation after also seeing varied dissolution rates from what was observed in the first batch. Eventually, it pointed back to something in the API.

Stayed tuned for the second half of this series which will delve into supply chain management and strategies involving the API process.

To learn more about our client’s story and how Alcami’s unique ProForm Select™ offering can help reduce timelines and prevent the repeat of a clinical study, be sure to download our on-demand webinar, “Critical Drug Substance Considerations for Formulation Success in Drug Product Development.”

On-Demand Webinar: Critical Drug Substance Considerations for Formulation Success in Drug Product Development

Topics: Thought Leadership