Cerbios highlights importance of QbD approach to ADC development

Lugano, Switzerland: – Pharmaceutical ingredient specialist CDMO Cerbios-Pharma SA (Cerbios) has highlighted the importance Quality by Design (QbD) disciplines in the development and manufacturing of complex molecule antibody drug conjugates (ADCs).

Current trends, emphasizing the importance of the key role of the linker in ADC safety and efficacy and with significant implications for drug development and manufacturing, are featured in a magazine article and will form the topic for a discussion at the World ADC conference in London later this month.

Lunchtime seminar on ADCs

The January/February 2022 edition of the online magazine Chimica Oggi (Chemistry Today) includes an OpEd article ‘Experiencing the evolution of ADC payloads towards extremely complex molecules from a development and manufacturing perspective – a CDMO opinion’ by Cerbios R&D Director Dr. Alberto Terraneo.

Dr. Terraneo will deliver a similarly titled presentation in person at a Proveo-hosted lunchtime seminar on Day One of the WADC event, March 30, as the starting point for an immersive discussion on optimized development of ADCs.

Focus on the linker

Dr. Terraneo points out that the linker, while devoid of pharmaceutical activity, is now recognized as playing crucial part in the safety and efficacy of the whole ADC system, demanding great efforts to improve the pharmacological and biological properties of this fundamental element of ADCs.

However, Dr. Terraneo emphasizes, this focus has come at the expense of molecular complexity of the linker-toxin, which are now very large molecules, with tens of defined stereocenters, very flexible structures and highly hydrophilic functional groups.

A more modern QbD approach

Researchers are pursuing new epitopes to enlarge the applicability of ADCs to new tumor classes, but apart from the search for new targets for mAb, for which development strategies and industrial production technologies are well established, significant research is now being devoted to the linker – payload part of the ADC.

Dr. Terraneo argues that these technical issues, and the demanding timeframes of innovators to reach a successful Biologics License Application (BLA) requires a more modern approach to chemical process development, that is fundamentally different to that used for small molecule substances.

Dr. Terraneo says its requires QbD methodology to prioritize the issues to address plus extensive use of preparative high-performance liquid chromatography (HPLC) as the principal control strategy, along with tangential flow filtration and lyophilization for recovery. These are the keys to the successful development and production of the most recent linker-payloads, he argues.

The Age of ADCs

Dr. Terraneo, who holds a PhD in organic chemistry from University of Milan, is responsible for the chemical and biotechnological research and development activities of Cerbios-Pharma. He says the pharma world has entered the Age of ADCs, with 2021 seeing the approval of an eleventh Antibody Drug Conjugate (ADC), Zynlonta, by the US Food and Drug Administration (FDA) following recent approvals and more than 150 other ADCs currently undergoing clinical trials.

He points out that  literature and clinical trials results clearly indicate that the success for an ADC is largely dependent on correct selection of its components: the monoclonal antibody, the cytotoxic drug and the linker with development of Mylotarg providing a powerful case study of a problematic development of an ADC: approved in 2000, withdrawn from market in 2010 and then re-approved in 2017 with a different dose regime.

Embracing complexity 

Dr. Terraneo says Cerbios-Pharma experience in ADC development shows that there is no “one-size-fits-all” solution available for the development and production of toxic and complex linker – payloads.

“Nevertheless, a development strategy based on QbD in addition to creative problem solving, is what we have found to be the most effective in terms of time saved and quality of the solutions obtained,” he declares.

“As final remark, the trend that one can observe examining patents and literature, clearly shows that complexity in the world of ADC linker – payloads is here to stay, so will special technologies be needed for their development and QbD,” he concludes.

About Cerbios-Pharma

Cerbios is a privately held company located in Lugano, Switzerland, specialized in manufacturing Pharma Products and in offering CDMO services.

Cerbios is a global leading supplier of a portfolio of Generic APIs primarily used in Oncology and for the treatment of Respiratory and Dermatological disorders. Cerbios has additionally a 40 years’ experience in the probiotics field: the portfolio includes a FDF based on proprietary strain SF68® for treatment of diarrhea and dysbiosis by antibiotics and two new Food Supplements for the management of ACNE & Seborrheic dermatitis and to boost immune response.

Cerbios is also the ideal CDMO partner from clinical to commercial supply of API, HPAPIs, Payloads, ADCs, live Biotherapeutics, Proteins and Antibodies. Services offered include Process & Analytical Development, Scale-up and Clinical Supply, Industrial Validation, Commercial Supply, Full CMC Regulatory Support. Proveo (TM) is a Cerbios division recently created to provide end-to-end development and manufacturing services for ADCs.

Learn more at: https://cerbios.swiss 

Resources

Click on Chimica Oggi online: Issue 1/22 to read full article (pp. 33-35).
Click on Cerbios-Pharma at World ADC Europe 2022 for more information.