News & Press
Chemical & Engineering News, June 25, 2018, Volume 96, Issue 26
Although several contract manufacturers looked at the Acasti job and said, “No thank you,” CordenPharma welcomed the challenge. Formed in 2006, CordenPharma is a pharmaceutical services firm composed of facilities cast off by large drug companies. Its strategy is to buy the unwanted plants at a discount and continue manufacturing some products for their former owners while gradually bringing in outside customers.
One of CordenPharma’s first acquisitions was a facility in Chenôve, France, that had several past owners, including Merck & Co. and Solvay Pharmaceuticals. Dr. Stephen Houldsworth, CordenPharma’s Global Director for Small Molecules & Antibiotics Platforms, says the plant was a good candidate for the Acasti job. It had experience with natural products and was already producing an extract from tree bark.
But in evaluating the potential contract, the CordenPharma team saw a problem: Daily doses of the omega-3s are measured in grams, not milligrams like many small-molecule drugs. Extracting the required amount of EPA and DHA a batch at a time would involve large vessels and large amounts of solvent. “Phase III supply would be a challenge,” Houldsworth says, “and commercial was never going to be able to be done at Chenôve.”
That’s when engineers at the plant, led by site director Yves Michon, realized the solution might be to move from a traditional batch-manufacturing process to a smaller and safer continuous one. “They did a quick proof-of-concept experiment with very crude equipment and presented it to Acasti,” Houldsworth says.
CordenPharma had previously tried to convince customers to adopt continuous manufacturing, Houldsworth recounts. But as is often the case in the drug industry, conservatism prevailed. It was an easier sell for Acasti, according to Lemieux, because some people on his team, aware of the Neptune accident, were thinking along the same lines.
After the contract was signed, the partners worked with a process equipment firm to design a continuous decantation system. The equipment firm then built it, shipped it to Chenôve, and installed it on skids. “The footprint is a fraction of what the batch process would require,” Houldsworth says. The amount of solvent in the system at any given time is similarly reduced.
The partners’ adoption of a continuous-flow process comes at a time when FDA is advocating for more continuous production in the drug industry. It released several bulletins last year championing the approach. Not surprisingly, Lemieux says the agency responded supportively when informed of the plan to go continuous.
In addition to cost and safety improvements, a continuous process can offer better analytical control. In a batch process, Houldsworth notes, the analytical testing required for product release happens after making a batch. “In continuous processing, you push a lot of analytical testing into the process,” he says. “You get continuous data feedback and know almost instantly what the process is doing and how it’s performing.”
Continuous processes do involve batches, but they are defined by time or volume. To date, CordenPharma has made a number of such batches for Acasti’s Phase III trials. Houldsworth says the plant is now gearing up to start the process validation that is required before the company files a New Drug Application with FDA.
Lemieux and his team are already starting to think about what comes next. The current facility can produce about 20 metric tons of the CaPre® active ingredient per year—enough, he figures, for the drug’s first few years on the market. But if CaPre is as successful as Acasti hopes it will be, the firm will need a second, 200-metric-ton facility. Houldsworth would love to see it get built in Chenôve.
Today, Acasti ships the purified omega-3s from France to Canada for encapsulation, sealing, and packaging by other manufacturing partners. “It would be nice to have all the steps under one roof,” Lemieux says. A one-shop process would further extend the Acasti-CordenPharma partnership and mean even more business for the once-unwanted plant in Chenôve.