Antibody-drug conjugates have become a strong and promising strategy for the treatment of cancer, and, potentially emerging in therapeutic areas outside oncology and hematology.

Today, there are four ADCs approved and commercially available in the United States, with another 150+ investigational antibody-drug conjugates in development, from early discovery to clinical phase III trials, across both hematologic malignancies and solid tumor indications.

Some of the clinical studies are single-agent trials, while others include combinations of and ADC with other therapeutics. Companies are leveraging on lessons learned from first and second-generation trials to inform on next-generation ADC designs.

Contract manufacturing
One of the lessens learned also include the adoption of different manufacturing approaches. The development and manufacturing of antibody-drug conjugates involves a complex supply chain of multiple, different specialized contracted cGMP facilities.

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Contract Development and Manufacturing Organizations or CDMOs have simplified the overal project and contractual arrangements by either forming supplier collaborations or by acquiring specialized “One-Stop Shop” facilities. However, multiple facility transition steps remain, and some involve long-distance, intercontinental shipments.

Experts as ADC Biotechnology have modeled the typical antibody-drug conjugates process/supply chain with an industry-standard modelling template (BioSolve™) to assess the economic value of integrating the downstream processing of the biologic with the drug conjugation processes.

A useful process technology employed is Lock Release conjugation, the only commercially available system that controls aggregation at source, is scalable and capable of meeting GMP regulatory requirements required to produce materials for use in human clinical trials. Lock Release conjugation has the potential to purify and conjugate a biologic, thereby acting as a link to integrate both processes. A fully disposable flow path operated in a multi-product facility was modeled with supporting information from our own facility build and operational costs. The integrated process eliminates formulation & stability studies, repeated QC analytics, separate scale-up studies & contingency runs, etc of the biologic drug substance.

Direct costs
The associated direct costs of these activities usually subsumed into the biologic API cost and represents the main cost savings; corresponding to 30-50% saving in antibody-drug conjugate cost of goods, $/g, across multiple process scenarios.

An additional 10-14% savings were seen through an overall decrease in the number of unit operations (yield increase) and a reduction of consumables required (10kg ADC campaign scenario).

But perhaps most importantly, the team at ADC Bio noted that the overall project time from master cell bank to preparation of Phase I material could be reduced by 6-9 months.

The results of their work was presented during the 15th annual PEGS: The Essential Protein Engineering Summit which brought more than 2,700 world-renowned experts, visionaries, and influencers from top pharma, biotech, academic, and government institutions to the Seaport World Trade Center in Boston, MA this past April 8-12, 2019.

Noel R. Value Proposition of Integrated ADC Manufacturing Processes –Use of Economic Modelling. poster presented during the 15th annual PEGS: The Essential Protein Engineering Summit held April 8-12, 2019.[Poster]

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