Andrew Badrot, CEO of C2 PHARMA, shares how the company assures security of supply for phyto-APISs
Phytochemical active pharmaceutical ingredients (APIs) provide significant therapeutic effects that help patients with many different diseases. Isolation of these complex molecules from plants continues to be the only means for accessing these important drug substances because no practical, cost-effective chemical synthetic routes have yet been developed. This can lead to significant security of supply challenges.
Environmental factors can impact both the harvest and the quality of the plant material, while extraction and purification of these complex and often sensitive and/or toxic compounds is also typically quite difficult. Phytochemical concentrations in plants are generally quite low and highly influenced by growing conditions including soil nutrients, temperature, and moisture/humidity.
Plants grown in different geographic locations on plantations that use diverse fertilisation practices will have variable phytochemical compositions. Excessive drought or rain and the timing of the harvest can also have large impacts on the levels of phytochemicals in plants.
For these reasons, it is necessary to combine many different batches comprising large quantities of dried plant material to produce commercial quantities of the purified API. Extraction and purification are not simple, either. Typically, many different often structurally similar phytochemicals are extracted together. The desired compound must then be separated from these compounds, which can require multiple steps.
To address these challenges, it is best to site plantations in locations with ideal growing conditions, implement good agricultural and collection practices (GAcPs) and leverage any synergistic effects presented by structural analogs that lead to more potent extracts and simplify the extraction and purification process.
It is interesting to consider that the weaknesses in the pharmaceutical supply chain uncovered by the COVID-19 pandemic already existed for phytochemical API supply, as I previously highlighted in articles on securing the supply chain for these important drug substances (see addendum below).
The history of supply of the phytochemical heart disease treatment digoxin, a WHO essential medicine, provides a good example of the importance of partnering for redundancy and reliability of supply. Shortages of digoxin occurred regularly in the past before C 2 PHARMA acquired the business due to a lack of investment by the incumbent manufacturer in manufacturing technology and supply-chain security measures.
Not only is digoxin a phyto-API, but it is also highly toxic and requires specialised expertise and equipment for its separation and purification via a series of extraction (from the Digitalis lanata plant), concentration and recrystallisation steps. The API must also be produced with the correct particle size distribution to ensure that each micro-dosed tablet of digoxin will dissolve evenly in the stomach.
After acquiring the business, C2 PHARMA invested in a new, redundant supply chain for Digitalis lanata and state-of-the-art manufacturing capabilities to avoid future shortages. The plant is grown across various fields and locations in Europe adhering to stringent GAcP regulations and a dedicated state-of-the-art drying facility was built to enable optimal drying of the leaves. In parallel, a program has been pursued with one of Germany’s leading universities to continue breeding more productive varieties of Digitalis lanata.
Furthermore, a modern production facility was established in Vizag, India that is operated by contract manufacturing partner Laurus Labs and an alternative digoxin product portfolio manufactured at a production facility in Poland was acquired from Nobilus Ent, which remains a manufacturing partner and releasing entity for the API. Both production sites have been audited by regulatory authorities in the US, Europe, and Asia.
Access to two sources of digoxin API with separate supply chains for the D lanata leaves enables C2 PHARMA to ensure a unique and redundant supply for digoxin API. The storage and shipment of digoxin products are handled by C 2 PHARMA’s affiliate Logistics4Pharma, which has comprehensive cold chain solutions and can support API and pharmaceutical product logistics requirements globally.
The level of commitment made by C2 PHARMA to ensuring security of supply for digoxin is applied to all phytochemical products offered by the company. We emphasise security of supply combined with quality, fair pricing and strong competency. Our focus is on ethically and sustainably supplying quality products to the market and we will continue to make necessary investments to deliver long-terms solutions that benefit both the customers and patients.