Senior Cerbios scientist says new generation ADCs demand manufacturing revolution

Lugano, Switzerland: – Dr. Vítor Sousa, Senior Manager of the R&D Biological Division for pharmaceutical ingredient specialist Cerbios-Pharma SA (Cerbios), says the latest generation antibody drug conjugate (ADC) ‘super molecules’ demand new approaches by manufacturers.

ADCs are advanced chemotherapy treatments in which the cytotoxic payload targets the tumor cell through an antibody carrier. The specificity and affinity of the antibody molecule are the key to a safe delivery of the toxic payload into the cell overexpressing a tumor -associated surface antigen.

Picomolar potency

Interviewed in the latest edition of TeknoScienze’s Pharma Horizon magazine, Dr. Sousa said the current generation of ADC payloads, dominated by Auristatins and Maytansinoids, are now being superseded by new and far more powerful classes of toxins, effective at concentrations in the picomolar range or lower.

“As a CDMO, Cerbios is already experiencing this change as it works with molecules that are becoming more potent every day. Significant new manufacturing challenges are associated with next-generation payloads and CDMOs need to be ready to provide suitable processing solutions,” said Dr. Sousa.

He stated the ‘ADC Revolution’ will require radical change in manufacturers’ development approaches and production processes.

Focus on conjugation process and novel targeting agents

“One of the drawbacks of the monoclonal antibodies used to treat solid tumors is their poor tissue penetration and the consequent ineffective delivery of the cytotoxic payload. One way to overcome this problem is to reduce the size of the antibody,” Dr. Sousa notes.

“It is remarkable how, in new ADCs, both the main components (payload and protein) generate significant increases in overall manufacturing costs, which is prompting CDMOs to develop more efficient process, switching the focus from the final product to the conjugation process” .

Integrated process

“Consequently, the process development approach we are using follows the principles of Quality by Design (QbD) accompanied by Design of Experiments (DOE) and the implementation of Process Analytical Technologies that are now a regular part of good practices and have even been incorporated into current guidelines,” Dr. Sousa explained.

In his interview he focused on the essential role of an integrated supply chain in further reducing manufacturing and development costs: a solution that Cerbios makes available through the PROVEO® alliance, where protein scaffolds for the ADCs are provided directly in conditions suitable for the conjugation step, and include Fill-and-finish of the conjugate either in liquid or lyophilized form within an integrated process.

Combined chemical and biological challenge

Dr. Sousa said ADCs posed a unique manufacturing challenge due to the ‘cross-contamination’ between chemistry and biology for the production of highly potent toxins and their conjugation with proteins.

“The strength of Cerbios lies precisely in the coexistence of these worlds: for 40 years it has housed under the same roof both a Chemical Division for the production of folates, vitamin D derivatives and HPAIs, and a Biological Division for recombinant proteins and probiotics”.

“At Cerbios, ADCs mean applying both our expertise in the development and manufacturing of HPAIs and its experience and knowhow in the production and manipulation of recombinant proteins, on the same site in Lugano – a unique setup,” noted Dr. Sousa.

“The continuous growth of the ADCs currently in the development and early clinical phases, associated with the high added value of these products, represents an excellent opportunity for Cerbios as a CDMO,” he concluded.

About Cerbios-Pharma

Cerbios-Pharma SA is a privately held company located in Lugano, Switzerland, that specializes in the development and manufacture of APIs for its partners worldwide. Cerbios specializes in the development and production of high potency active pharmaceutical ingredients (HPAPIs) in the area of fine chemicals and biologicals.

Beside chemical small molecules, Cerbios also have a Biological Division, offering CDMO services for monoclonal antibodies, recombinant proteins and pharmaceutical grade probiotics.

Cerbios provides full CMC support to its worldwide partners, including the supply of cGMP clinical batches, registration/validation material and commercially manufactured APIs. Paramount to this is the ability to supply all of the technical documentation and support necessary for a successful registration. Cerbios’ commercial products are marketed worldwide but primarily in Europe, USA, Japan and India.

Since 2015, Cerbios has been a member of the ADC manufacture PROVEO™ consortium, forged with AGC Biologics of Denmark and with Germany’s Oncotec.

PROVEO can offer an ADCs end-to-end service from substance development through manufacturing to fill & finish.