Edition 4 / November 2019
In manufacturing highly potent drugs, it is extremely important to be able to ensure the safety of the personnel, integrity of the product and the surrounding environment. Under CordenPharma’s Highly Potent & Oncology Platform, we have over 30 years of experience in developing and manufacturing highly potent APIs, with the engineering controls, containment culture and an occupational health program to safely handle small molecule products of all potencies for both APIs and finished Drug Products. Our facilities use a containment methodology of isolation technology, pressure cascade, airlock and access controls, supported by a robust industrial hygiene program. In addition to engineering controls, there are other aspects to consider for the safe & effective manufacture of highly potent compounds. These include, but are not limited to:
Managing the risk associated with highly potent compounds requires a knowledgeable team, an effective safety program and a well-designed facility.
There are 4 facilities within the CordenPharma network that are able to handle highly potent products. Two API facilities in Boulder, Colorado (CordenPharma Boulder and CordenPharma Colorado) and two Drug Products sites, CordenPharma Plankstadt in Germany, specializing in oral solid doses, and CordenPharma Latina in Italy, specializing in injectables.
The case study that follows took place at CordenPharma Colorado.
Recently, a customer requested CordenPharma Colorado to develop and manufacture an API with an OEL of picograms per cubic meters to support clinical trials. Although we have extensive experience with highly potent APIs, this was the first time we were presented with a sub-nanogram OEL.
Before starting any work, we had to demonstrate our ability to contain and clean to a safe & operable level. We first collected toxicity information (human & animals) from our client, performed literature searches on similar compounds, and engaged a third-party occupational toxicology company to assist our team in developing a monitoring & cleaning procedure, including a deactivation solution. This was followed by a study with a surrogate product to test the equipment and demonstrate containment. Picogram per cubic meter containment levels were confirmed by an integrated industrial hygiene sampling. Of the 28 personal and area samples analyzed, one hundred percent of them demonstrated effective picogram containment.
A thorough review of the manufacturing process was performed, and changes were proposed to improve containment during the unit operations. In addition, analytical methods were developed & validated with sufficient sensitivity for API detection. Ultimately, modifications to the analytical lab were also necessary to be able to handle samples and required analysis.
In the end, our customer was satisfied with the safe & successful manufacture of their valuable API.
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