Off-patent, highly potent pharmaceuticals represent a major opportunity. The companies that seize the opportunity will grow sales by delivering products that improve the lives of patients. However, the barrier to entry is high. Expensive, highly specialized technologies and dedicated facilities and extensive experience of global development, manufacturing, supply chains and regulations are needed. Recognizing the need for those capabilities, three companies have united to create a European hub for complex products. The three independent and certified European pharmaceutical companies – Bluepharma, Helm and Welding – joined forces after identifying a significant opportunity for a leading partnership that can develop and manufacture complex, differentiated and highly potent products for licensing to pharmaceutical companies operating in markets around the world. The opportunity is underpinned by upcoming changes in the intellectual property status of multiple, highly potent compounds.

From 2020 to 2024, more than 25 highly potent, anticancer molecules with annual sales of more than $26 billion could lose patent protection in at least one market.¹ Nine of the molecules are set to lose their intellectual property protection in more than one major market. More highly potent molecules, used to treat cancers and other diseases, will go off -patent in the second half of the decade.

The loss of patent protection on tens of therapeutically and commercially significant drugs is creating opportunities to improve health care. Off-patent medicines signifi cantly reduce health care spending, enabling more people to receive life-changing treatment. The price diff erential between branded and off -patent biologics suggests the expiration of intellectual property covering highly potent molecules could save health care systems billions of dollars – and drive signifi cant sales of generic therapies.²

Few companies are equipped to seize the opportunity, though. The development, production and distribution of complex, highly potent pharmaceuticals pose distinct challenges that cannot be met with infrastructure designed to handle conventional small molecules and biologics. Distinct expertise and capabilities are required.

Synthesizing highly potent molecules can be challenging, with some workfl ows entailing more than 10 steps and requiring the use of multiple advanced technologies. Manufacturers need to master the multistep synthesis workfl ows while managing the risks of working with highly potent molecules.

The potency of the molecules makes it critical to prevent cross-contamination during manufacturing. Similarly, the environment and people working at all steps in the supply chain must be protected from the molecules. Highly potent molecules have carcinogenic, mutagenic, teratogenic and cytotoxic eff ects and can have serious health consequences at very low airborne concentrations.^3,4

To mitigate the threats, companies need to establish containment and protection strategies that cover elements such as facility design, containment equipment and personal protective equipment. Few companies have those specialized capabilities or the means to establish them.

How ONConcept® Unlocks the Market

The barriers to entry, which if anything are rising as regulatory expectations increase, are deterring companies from capitalizing on the loss of patent protection on complex products and threatening to deprive health care systems of more aff ordable medicines.

Bluepharma, Helm and Welding, three European companies with a history of working together, have identified and addressed the problems by setting up ONConcept®, an integrated European specialist in complex products. Now, for the fi rst time, there is a European solution with a supply chain capable of delivering low-volume, hardto- manufacture products. Each of the experienced, trusted companies brings something unique to ONConcept®, resulting in a collaboration that benefi ts from the individual strengths of its founders.

Bluepharma, a Portuguese pharmaceutical company, operates as a contract development and manufacturing organization (CDMO) and has in-house all the capabilities needed to develop a medicine from scratch and, in the period before the formation of ONConcept®, began applying them to the development of complex products. Bluepharma has global regulatory approvals and experience fi ling submissions with authorities around the world.

“We built our reputation and industrial capability through partnerships with renowned pharmaceutical companies,” Sérgio Simões, a Bluepharma vice president, said. “Our ambition now is to create a hub that develops accessible products for global markets and, in doing so, supports the reindustrialization of Europe.”

Helm, a family-owned, 120-year-old German company, has a strong track record of collaborating with international partners to apply its scientific, regulatory and quality expertise to the development of generic pharmaceuticals. The work has turned Helm into an experienced coordinator of diff erent stakeholders and an expert in handling active pharmaceutical ingredients (APIs).

“We are specialists in identifying opportunities for diffi cult and complex molecules,” Bernd Stoiber, a member of the Helm executive board, said. “Through ONConcept® we are lowering market access barriers to create value and differentiated products.”

Welding, which, like Helm, is based in the German city of Hamburg, has built an excellent reputation for leading projects from start to fi nish. Since 1955, Welding has been involved in the supply of APIs, accruing experience in identifying and handling the ingredients and connecting their suppliers to the manufacturers of fi nished dosage forms.

“Our success is built on experts with a reputation for identifying opportunities and the promotion of new projects that create synergies with pharmaceutical companies active in markets including India, China and the US,” Lars Hallmayer, managing director at Welding, said.

Bluepharma, Helm and Welding are adding to their extensive existing capabilities by co-investing in a European manufacturing facility focused solely on complex, highly potent pharmaceutical products. The establishment of a European site for the production of highly potent pharmaceuticals will create a short, closely controlled supply chain that mitigates risks and equips the ONConcept® partners to provide small-volume, highvalue products at competitive prices. The facility is set to be operational in late 2021 to support launches in 2022.

The infrastructure will enable ONConcept® to be fl exible in terms of its business model and the product quantities it ships to customers. Notably, establishing a European hub for complex, highly potent products, rather than relying on facilities outside the EU, will equip ONConcept® to better accommodate the needs of its partners and customers. While ONConcept® is based in Europe, its founders have experience in exporting to markets around the world such as the US, South America and Asia-Pacific.

The manufacturing facility is just part of a broader service off ering that spans the entire value chain. Collectively, Bluepharma, Helm and Welding have expertise in areas key to the success of complex products. Experts with PhDs will handle development work, intellectual property specialists will determine the date of entry into diff erent markets, and a regulatory team with extensive global experience in fi ling dossiers will seek and secure the required authorizations. Again, while ONConcept® is based out of Europe its intellectual property and regulatory expertise span the globe.

ONConcept® also has easy access to a highly experienced, regulatory-compliant contract research organization (CRO). The close relationship with the CRO will enable ONConcept® to prioritize clinical projects to seize time-sensitive opportunities and have total confidence in the data generated by the service provider.

Building a Portfolio

Bluepharma, Helm and Welding plan to use those capabilities to develop a portfolio of more than 15 molecules and make them available for licensing and distribution by pharmaceutical companies around the world. The partners are set to make the dossiers for three to four products a year available through 2025, creating a steady stream of opportunities for the companies that partner with ONConcept® to enter the market for highly potent pharmaceuticals.

By creating a basket of products with different launch dates, ONConcept® is positioning itself to build long-term relationships and enable its customers to steadily expand their highly potent portfolios to leverage their commercial operations. In doing so, ONConcept®  stands to help its partners and customers alter health care by making life-changing yet aff ordable medicines available to many more patients.

The anticipated stream of patent expirations this decade means the opportunity is available to any company with the ability to develop, manufacture and distribute complex, highly potent molecules. Previously, the need for those capabilities represented an insurmountable barrier to entry for many companies. Through ONConcept®, Bluepharma, Welding and Helm have brought the barrier down.


REFERENCES
1. Boyd, B. Inside the market for high-potency APIs. https://www.dcatvci.org/6145-inside-the-market-for-high-potency-apis (2019).
2. ERIC releases groundbreaking research showing signifi cant savings from biosimilars: Large employers call for more competition. https://www.eric.org/press_release/eric-research-shows-savings-from-biosimilars/ (2020).
3. Heron, R. J. L. & Pickering, F. C. Health eff ects of exposure to active pharmaceutical ingredients (APIs). Occup. Med. 53, 357–362 (2003).
4. Tiwari, P. & Chowdhury, S. R. Sustainable production of highly active pharmaceutical ingredients (HAPIs). International Journal of Scientifi c and Research Publications 4, 1–5 (2014).