Based on its recent analysis of the global contract manufacturing services market for antibody-drug conjugate or ADCs, Frost & Sullivan has awarded China-headquarter MabPlex with the 2019 Global Growth Excellence Leadership Award.

ADCs are highly targeted biopharmaceutical drugs that combine monoclonal antibodies specific to surface antigens present on particular tumor cells with highly potent anti-cancer agents linked via a chemical linker.

With five approved drugs on the market, ADCs have become a powerful class of therapeutic agents in oncology and hematology. However, academic laboratories and biopharmaceutical companies are developing antibody-drug conjugates for treatment beyond cancer.

Outsourcing of development and manufacturing
In-house manufacturing of ADCs by pharmaceutical and biotechnology companies remains rare. In various discussions with senior managers in both the pharmaceutical and biotechnology industries during a recent industry meeting focusing on ADCs, reveals that nearly 70% of ADC manufacturing is currently outsourced to Contract Development Management Organizations (CDMOs). The expectation is that this will not necessarily change in the near future.

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Manufacturing of ADCs offers a particular challenge. The complex nature of ADCs requires both clean room biologic and high containment cytotoxic facilities designed for safe handling and manipulation of very low Occupational Exposure Limit (OEL; below 50 nanograms/m3) compounds while maintaining aseptic conditions and GMP compliance.[1]

In order to meet current Good Manufacturing Practice or cGMP requirements, the aseptic process in the production ADCs must be run in positive pressure, while, at the same time specifically trained operating personnel needs be actively protected from the manufactured agents. [1]

The technical complexity in the manufacturing of ADCs requires specialized facilities. While this is often one of the primary reasons for outsourcing, building these facilities necessitates large investments.

However, with a sharp fall in earnings growth over the past few years, the industry experts ADC Review interviewed believe that the (bio) pharmaceutical sector prefers outsourcing over in-house development and manufacturing. This approach, they say, not only limits investments, but enhances operational efficiencies, helps expand geographical presence, and increase therapeutic expertise. As a result, outsourcing, especially in the development and manufacturing of highly complex innovative agents such as ADCs, is expected to be one of the major trends in the coming decade.

In addition to cost savings, which still remains a key reason for outsourcing, experts also believe that added expertise, improved quality and reduced time-to-market are also among the major motivations for outsourcing to a specialized CDMO.

For small biotech, academic institutions and spinout companies formed by academic scientists, the decision to outsource is often based on operational and financial ability vs. the choice of focusing on the discovery process. And in most cases, their focus remains on the discovery process wins.  However, outsourcing  becomes critical, especially when drug development moves from preclinical research into larger, multi-centered advanced human clinical trials.

Outsourcing provides additional expertise in a particular area of drug development, smaller organizations focusing on the discovery process may not necessarily have.

For example, in the early preclinical phase they may lack the ability or the expertise to analyze the developability and manufacturability of a complex compound such as an ADC.  In this phase expert CDMOs may provide specific services to assess the chemical degradation pathways, post translational modifications including deamidation (which may lead to potential changes in protein structure, function, stability and immunogenicity), oxidation and glycosylation, potential physical stability issues, and protein aggregation.

Fully integrated
MabPlex is one of the few fully integrated CDMOs, offering an advanced biologics platform with a comprehensive, integrated solution for global biopharmaceutical developers.

Founded in 2013, MabPlex currently operate state-of-the-art facilities in two sites in China (Yantai and Shanghai) and one site in the United States (San Diego, CA) offering high quality services from biologics drug development to commercial manufacturing for antibodies, recombinant proteins, and ADCs.

According the business analyst at Frost & Sullivan, a business consulting firm involved in market research and analysis, MabPlex emerges as one of the few large-scale, end-to-end ADC producers, providing services from early-stage development to commercialization. The company’s proprietary conjugation platform and innovative technologies deliver novel and clinically effective ADCs for cancer therapeutics around the world.

Khushbu Jain, Industry Analyst at Frost & Sullivan

“While rapidly expanding its operations in China, MabPlex also established a center of excellence in the United States. Its first manufacturing facility (M1) in Shandong provides an integrated solution supporting early-stage clinical manufacturing of antibodies, recombinant proteins, and ADCs,” noted said Khushbu Jain, Industry Analyst at Frost & Sullivan.

“MabPlex’s second Shandong-based facility (M2) opened in 2018 as it anticipated the advancement of ADCs in later-stage development encouraged by the rising global bio-manufacturing capacity demand,” Jain added.

“M2 has built upon the current process development facility by adding six new cell culture (upstream) suites, and all single-use stirred-tank bioreactors,” she further noted.

United States
Meanwhile, the company’s San Diego, CA, facility in the United States has a dedicated team that engages early with clients and communicates with pharmaceutical partners in Europe, the US, and the rest of the Western market.

MabPlex’s services cover the entire spectrum—from gene sequencing to cell line development, process characterization, conjugation optimization to current Good Manufacturing Practice (cGMP) clinical and commercial manufacturing of final drug product for biopharmaceutical companies.

The San Diego facility currently has a scale-up capacity of up to 200 liters and provides an exceptional integrated solution supporting cell-line development, upstream and downstream process development, ADC, analytical testing, and formulation development.

MabPlex’s solution minimizes external touch points and facilitates timely interfacility communication. A unified supply chain ensures efficiencies across the board, allowing MabPlex to save scheduling and testing time, eliminate rescheduling due to supply chain delays, limit inventory and logistical management concerns, and reduce product transfer related risks. These enhanced efficiencies lower the company’s overhead costs, which gives it one of the most competitive pricing models in the industry.

“MabPlex’s technology enables consistent drug-to-antibody-ratio for each manufacturing lot,” Jain noted.

“In the US, its focus is on ADC pipeline growth, client engagement, and co-development partnerships specializing in ADC development. Overall, its ability to deliver quality manufacturing services while lowering time to market makes it the partner of choice for ADC development,” she concluded.

Global Growth Excellence Leadership Award
Each year, Frost & Sullivan awards a company that demonstrates excellence in growth and customer value. It recognizes the superiority of the product/service as well as the overall customer, purchase, ownership, and service experience offered, which has historically resulted in the recipient company seeing above-market growth.

Frost & Sullivan Best Practices awards recognize companies in a variety of regional and global markets for demonstrating outstanding achievement and superior performance in areas such as leadership, technological innovation, customer service, and strategic product development. The organization’s industry analysts compare market participants and measure performance through in-depth interviews, analysis, and extensive secondary research to identify best practices in the industry.

[1] Denk R. The Challenge of cGMP in the Manufacturing of Antibody-drug Conjugates J. ADC. April 4, 2016. doi: 10.14229/jadc.2016.04.02.001 Online. Last accessed October 10, 2019.

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