Head of Chemical Development and Commercial Manufacturing.

Stefan Abele, the senior vice president and head of chemical development and commercial manufacturing, has been associated with Idorsia, Switzerland, since 2017. He has been working in the pharmaceutical industrysince 1999 and has also played an important role in the success of his former employers, Carbogen-Amcis and Actelion. With more than two decades of experience, Stefan is one of the prominent leaders in the Swiss pharmaceutical industry.

What are your roles and responsibilities in Idorsia?

Idorsia Pharmaceuticals Ltd started operations after de-merging from Actelion following its acquisition by Johnson & Johnson in 2017. Idorsia has a 20-year heritage of drug discovery, a broad portfolio of innovative drugs in the pipeline, over 1’300 skilled employees from all disciplines from bench to bedside.. Its operations are dispersed across Europe, Japan, and the United States. As a member of the Idorsia Leadership Team, I am in charge of chemical development and commercial manufacturing at Idorsia. I lead  teams in charge of Chemistry Process R&D, kilo lab production, and all activities related to the Development and Manufacturing of aActive Pharmaceutical Ingredient (API) for the clinical phases, involving validation, registration with National Health Authorities, launch, and uninterrupted commercial supply. For the GMP supplies, my teams have built up and manage a diversified network of global CDMOs (Contract Development and Manufacturing Organizations).

What are the challenges and latest trends you are witnessing in the industry? How are these affecting the pharmaceutical industry?

From the overall pharmaceutical perspective, new modalities, personalized medicines, and enhanced genetic engineering and biologics are becoming more prevalent among all big pharmaceutical companies.

Looking through Idorsia’s viewpoint, we concentrate more on catering to the vital need for innovative small molecules. This strong demand stems from various benefits that small molecules have over biologics. Small molecules meet the affordability criterion, enable ease of administration, and allow for clear patent protection

From a manufacturing perspective, after the clarion call of the pandemics, supply chains especially from Asia have been troubled. This has sparked initiatives, both governmental and corporate, to render supply of API more resilient, like onshoring of more elements of the complex manufacturing of APIs and Drug Products, governmental programs to stimulate local R&D and manufacturing. In addition, the well-proven concept of stockpiling and multiple sourcing (“just in case”) is receiving more attention than the more aggressive “just-in-time”. However, there is no panacea against supply bottlenecks. Building up new reliable suppliers takes time in a highly regulated environment and hinges on available talent, equipment, and plants.  We at Idorsia apply the principle “vide cui fidas” (meet and see whom you trust), have full control of the end-to-end supply from raw material to the final drug, and leverage multiple sourcing to maintain high resilience

“Sound and innovative process chemistry will always be in strong demand and even more so because this art is important to tame the growing complexity of small molecule APIs.”

From a pharma company–CDMO perspective, we are experiencing a strong seller’s market, despite massive CAPEX investments across the globe. Many large pharma have reduced their in-house manufacturing capabilities and the pandemics led to a surge of urgent requests for the manufacture of covid drugs

Last but not least, from a perspective of talented young chemists, engineers, or CMC experts, times have rarely been better to find interesting jobs..

The strength of a country’s supply chain can best be guaranteed by a free exchange of goods, money, and talent across several countries. Idorsia’s location close to Basel is an asset, being embedded in a global hotspot for biotech and pharma. Also, for the supply chain to be resilient, it is essential to consider the high volatility of the cost of commodities.

How is technology accommodating to the aforementioned trends? Are there any technological advancements to look out for from your perspective?

Organic chemistry know-how reduced to practice will always be in strong demand to tame the complexities of small molecule API. At Idorsia we have a strong chemistry process R&D unit to design innovative ways to produce APIs and scale them up. Regarding technological advancements, green chemistry is one of the key drivers. Resource-intensive pharmaceutical production is in full effect now, implementing elements like solvent recycling, green solvents or only aqueous systems, intensified processes, and continuous manufacturing. Again, all those improvements require sound and innovative process chemistry, help our planet and allow to spend the saved costs for new R&D. Fluorine is so abundant in current API’s.  I see a need for practical and environmentally benign methods for the introduction of fluorine or fluoroalkyl groups which use less resources. The use of enzymes or bio-catalysis is a prime example of environment-friendly and economically efficient technology being used at Idorsia. The new enzymatic process is not only significantly less expensive with compressed cycle times, it is also much greener in terms of the used materials and waste per kg API. Another example is the use of photochemistry in flow for the production of an intermediate on kg-scale

What advice would you want to give our readers regarding the processes that they should look towards to implement for a streamlined workflow?

At Idorsia, we have a strong Chemistry Process R&D unit whose mission is to devise and develop new routes, including 2nd generation routes and to produce non-GMP API on a kilolab scale.  The CMC leaders in my teams manage further development through validation and manufacturing of APIs for our clinical studies and our commercial drugs with a broad and diversified global portfolio of CDMOs. Commercial operability needs capacity, and those CDMOs who have the capacity to be flexible on the volume, size, or spare volume of their plants have a significant upper hand over the ones that do not. Another asset is having experienced chemists and analytically trained and talented staff. Regarding special technology, it is always beneficial to have at least three capable suppliers in the portfolio, enabling the company to jumpstart any project at any given time. We at Idorsia connect to new suppliers by contacting them from our end or meeting them at trade shows like CPHI in Frankfurt.

Idorsia has a large portfolio of suppliers constantly maintained and challenged against our key performance indicators. It is crucial for us to to partner with promising CDMOs and build a long-termrelationship with them built both on a successful track record and trust.