Outsourcing: A Viable Solution for Monoclonal-Antibody Production

Abstract

Broadly stated, a biotherapeutic is a medicine developed from biological products or processes. In the timely journey to bring to market a biotherapeutic product—whether a monoclonal antibody, small molecule or protein product, researchers are increasingly turning to contract manufacturing organizations (CMOs) and contract development and manufacturing organizations (CDMOs) to accelerate their workflow. Contract organizations provide unique and specialized services and the expertise and experience needed to assist researchers with the challenges of target-protein bioproduction and bioprocessing. Here we speak with experts to identify key considerations in selecting and partnering with a CMO for a specific project.

Broadly stated, a biotherapeutic is a medicine developed from biological products or processes. In the timely journey to bring to market a biotherapeutic product—whether a monoclonal antibody, small molecule or protein product, researchers are increasingly turning to contract manufacturing organizations (CMOs) and contract development and manufacturing organizations (CDMOs) to accelerate their workflow. Contract organizations provide unique and specialized services and the expertise and experience needed to assist researchers with the challenges of target-protein bioproduction and bioprocessing. Here we speak with experts to identify key considerations in selecting and partnering with a CMO for a specific project.

An increasing number of companies in the biotherapeutics field have turned to contract organizations. According to the 2016 Nice Insight Contract Development & Manufacturing Survey, which included nearly 600 biopharmaceutical professionals, one major trend is “escalating spending by pharmaceutical and biotech companies for outsourcing services.” The survey noted: “CMOs/CDMOs are trying new technologies, such as advanced expressions systems, improved bioprocessing systems, and single-use technologies to lower costs and meet demand more efficiently. And they are doing so at a greater rate than biotherapeutic developers, who are slower to switch from their current systems.”

As an example, Catalent Biologics offers advanced technologies and tailored solutions to biologic and biosimilar development; this ranges from DNA to clinical supply. To provide these services, the company relies on a technology platform that includes its GPEx cell-line engineering and SMARTag protein-conjugate technology. Other CMOs also use their own proprietary technologies to produce the proteins needed in the biotherapeutics market.

CMOs for everyone

When asked the key reasons to use a CMO for monoclonal-antibody production related to generating biotherapeutics, Min Park, group product manager at Catalent Pharma Solutions, says, “A large percentage of new product developments are being driven by smaller companies with limited infrastructure.” He adds, “These companies can accelerate a path to the clinic by leveraging the established capabilities and expertise of a strong CDMO partner.”

The benefits of using a CMO or CDMO, however, extend beyond small companies. “Larger companies are also finding the ability to gain speed and flexibility by conducting development and manufacturing externally, and [they] are also able to access new technology and expertise that they may not have in-house,” Park explains.

For monoclonal-antibody production, Park recommends several features to look for in a contract manufacturer. These include a successful track record, financial stability and overall capabilities. He adds that “top priorities for our partners are quality, reliability and technical expertise, which will continue to be a ‘ticket to play’ in our industry.”

Even those features are not always enough in this changing industry. As Park explains, “We are also seeing increasing demands for flexibility and responsiveness—as clinical time lines accelerate—and the ability to handle more complex molecules.”

Picking a partner

Referencing the 2016 Nice contract manufacturing survey, Nigel Walker, managing director of That’s Nice LLC/Nice Insight, says: “Regardless of the type of project being pursued, when choosing CDMO partners, the top selection criteria include regulatory compliance; assured IP protection; an understanding of customer requirements; risk adherence; industry reputation; financial stability; and operational, methodological and therapeutic experience.”

For protein projects in particular, says Walker, “the technical criteria will depend on whether the product is manufactured via a cell-culture or fermentation process, whether it is highly potent or not and what services will be required—for example, only commercial drug substance manufacturing or formulation development through fill/finish and final packaging. … Not all CDMOs can provide support for all of these types of projects.”

The Nice survey found that the top method for identifying and selecting a partner is to conduct industry research. “The next two most often used methods include hiring consultants and seeking referrals/recommendations from colleagues and other industry professionals,” Walker says. “Attending trade shows and other industry events, conducting web searches and checking online directories are less frequently used approaches.”

Adding support

Beyond providing the most advanced biomanufacturing, some contract organizations offer support services. For instance, Umay Saplakoglu, global fast track leader at GE Healthcare Life Sciences, says her company—though not a CMO—offers “a range of supporting services” that “are delivered through a global network of scientists, with the aim of increasing speed to market and enabling the success of our customers’ products.” This offering, she says, includes “three interconnected elements to our service: process development, bridge manufacturing and training.”

These features that go beyond pure technological capabilities reveal the need for broader teamwork between CMOs and customers. “There should be a clear alignment of goals between the service provider and the customer,” says Saplakoglu.

 

In most cases, the key goal is speed—especially speed to market.

“To achieve this, the right decisions need to be made at the right time, a flexible and transparent relationship should be established, a robust and high-quality process should be developed and material for clinical and preclinical studies needs to be manufactured,” Saplakoglu says.

 

Expect evolution

The best CMOs have a depth of experience and a successful track record. “Customers should find a provider who has worked across many different projects with difficult challenges that have been overcome, so that they know how to react to complex problems and can make decisions at the right time during development to avoid such problems transferring to the scaled-up process,” Saplakoglu says. A customer should ask any potential CMO for evidence of such successes, as well as customer contacts who can confirm them.

 

A key part of a successful relationship comes from working together.

“In the ideal flexible working environment, tech transfer of manufacturing processes between customer and provider should be seamless, and having the ability to solve difficult process challenges together should be the norm,” Saplakoglu says. “Solving such challenges means having the right mix of academic and industry experience in addition to experience in regulatory and scientific environments globally.”

 

Developing a productive flow of information also depends on transparency between CMO and customer. According to Saplakoglu, “Any service provider should share all procedures—standard operating procedures—and be able to train the customer’s workforce in parallel with the other services they provide.”

In BioPlan Associates’ “13th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production,” which evaluated responses to crucial issues concerning outsourcing of biopharmaceutical manufacturing to a CMO, nearly 90% of respondents rated establishing a good working relationship as important or very important. More than half the respondents also ranked protecting intellectual property and complying with the customer company’s quality standards as very important. Overall, customers demand “high levels of professionalism, performance and effectiveness, in both managerial and technical areas, from their outsourcing vendors,” says Eric S. Langer, managing partner at BioPlan and an experienced biotechnology strategist.

Ultimately, as biotherapeutics evolve, so must CMOs. “Any customer should expect their supplier to be equipped with latest technologies and knowledge,” Saplakoglu says, and to be “willing to constantly adjust their portfolio in line with new developments and in response to evolving customer needs.”