Active pharmaceutical ingredients (APIs) derived from plant materials provide significant challenges when establishing a secure supply chain, especially regarding environmental factors that can impact both the harvest and the quality of the plant material.
If those APIs are complex, sensitive and/or toxic, the difficulties are amplified. Manufacturing issues and API shortages have significant ramifications for manufacturers. Producers of these pharmaceutical ingredients have a responsibility to ensure the reliable production of high-quality APIs.
Securing the digoxin supply
Digoxin is a well-known, life-saving, microdosed API for the treatment of various heart conditions. Patients that have been prescribed digoxin must take the medication continuously and without interruption.
There are only a few plant growers and API producers involved in the supply of this phyto-API as it is a highly toxic and sensitive compound that requires specialised expertise to achieve effective extraction from the leaves of the Digitalis lanata plant.
The concentration of the active ingredient is quite low … and large quantities of dried plant material are required to produce this API. In addition, because the drug product is microdosed, it is essential to achieve the proper particle size distribution (PSD) to ensure that each tablet contains the correct amount of digoxin.
The production process for the digoxin API is one of the most complicated in the industry. It requires continuous investment, focus and dedication ... all the way from management to the production facility. Lack thereof can quickly lead to issues, as recently demonstrated by repeated shortages in the marketplace.
Since then, C2 has invested in developing a new, redundant supply chain of Digitalis lanata and invested in a state-of-the-art manufacturing facility with modern analytics to ensure such shortages will never happen again.
More than US$10 million has been invested in this dedicated, cutting-edge production facility and supply chain for digoxin, operated by our contract manufacturing partner, Laurus Labs, in Vizag, India. We also recently acquired the digoxin API product portfolio of the Polish company, Nobilus Ent, which was self-developed and inherited from Roche/Galenus Mannheim. Nobilus will continue to be our manufacturing partner and releasing entity for this API.
By being able to offer two different sources of digoxin API, one manufactured at Laurus Labs in India and one manufactured at Nobilus in Poland, with each relying on a separate supply chain of leaves, C2 PHARMA is able to ensure a unique and redundant supply of digoxin API. Both the European and Indian sites have been audited by regulatory authorities in the US, Europe and Asia.
The logistics of shipping such highly potent APIs is handled by C2 PHARMA’s affiliate: Logistics4 Pharma (L4P). This association was created in 2017 when C2 PHARMA spun off its logistics department.
And, because early digoxin products required storage and transport under strict temperature-controlled conditions (2–8 °C), a comprehensive cold chain solution was developed through Logistics4 Pharma and is available to third-party companies looking to manage their API and pharmaceutical product logistic requirements globally.
A backward-integration approach
Digoxin is not the only phyto-API for which C2 PHARMA has implemented this type of backward-integrated supply chain.
As a key sponsor of the “Partnerships for a Better World” programme for the sustainable, traceable and fair-trade harvesting and sourcing of raw materials, the platform supports more than one thousand families involved in the production of pilocarpine, which is extracted from a native Brazilian plant to provide employment opportunities and contribute to the preservation of Brazilian biodiversity.
Our team is also in the process of establishing a portfolio of naturally derived cannabinoid products for the pharmaceutical market. Our raw materials will be sourced from our own proprietary supply chain in Europe, in full compliance with Good Agricultural Practices (GAPs). Our first product will be a naturally extracted GMP-compliant cannabidiol (CBD).
The development and/or chemical modification of CBD derivatives will be performed by our affiliate, ASM Research Chemicals, which C2 PHARMA acquired in 2017. This Germany based company specialises in R&D-scale contract synthesis services, analytical services, phytochemical profiling and impurities manufacturing.
The scale-up and manufacturing of CBD products would then be performed by a partner in Europe with extensive experience in manufacturing botanical extracts under cGMP conditions. GMP product testing will be managed through the contract research organisation, QUALIMETRIX (supplier), and logistics will be managed by L4P.
A portfolio of partners
Through our critical network of affiliated/owned and partner companies, C2 PHARMA is proud to be working toward a virtual manufacturing model that delivers real results.
Affiliated companies include ASM Research Chemicals (www.asm-research-chemicals.de) and Logistics4Pharma (www.logistics4pharma.com), and we are proud to partner with the following companies for research, manufacturing and the sourcing of materials:
- Laurus Labs (www.lauruslabs.com)
- QUALIMETRIX (www.qualimetrix.com)
- Centroflora Group/Partnerships for a Better World (centroflora.com.br/en/partnership).