StemCell Therapy

Pharma and biopharma companies dont want to work on their relationships. These companies want their relationships to work for them. Fair enough. Still, when it comes to relationships with contract manufacturing and drug development organizations (CDMOs), pharma and biopharma companies cant avoid intimacy. These relationships are rewarding to the extent pharma and biopharma companies are clear about their needs and the kinds of associations consistent with those needs.

Typically, the most pressing need is keeping costs down. But other needs are important, too. These include expertise with specialized technologies, challenging drugs, and complex formulations. Identifying needs will help pharma and biopharma companies decide whether their CDMOs should help with discrete activities or provide complete, end-to-end services. Pharma and biopharma companies may also want their CDMOs to help with business strategy and regulatory compliance.

Besides identifying potentially compatible CDMO partners, pharma and biopharma companies need to build CDMO relationships characterized by mutual trust. Here again, clear communication is essential. It can help both parties in a CDMO relationship resolve misunderstandings and overcome unanticipated challenges together. For a fuller discussion of the ways CDMO relationships can benefit from clear communication, see the rest of this article, which presents various pointers and perspectives from CDMO experts.

Thierry Cournez is head of end-to-end solutions at MilliporeSigma, which offers a comprehensive portfolio of high-quality products and services, including testing services, for biopharmaceutical development. According to Cournez, most emerging biotech companies that have very early data and need to take their molecule to commercialization dont have all the expertise in-house that they need to navigate the entire process. One major trend is complete services, as opposed to la carte offerings.

MilliporeSigmas Plug & Play Upstream Development Service eliminates the need to work with multiple vendors for upstream development, relieving bottlenecks and reducing time to clinic. The service covers cell line development from DNA transfection to cell banking. Process development activities, which run in parallel, start when the company receives material from the first clones.

Cournez says that two services that will continue to be important in pharmaceutical development are process development and analytical services. A robust process is critical for manufacturing success, he explains, and analytical services are the foundation that supports the entire life cycle of biologics.

A trend toward all-in-one CDMO services has also been observed by Richard Shook, director of drug product technical services and business integration at Cambrex. Any time a client has to go to multiple vendors, it creates a lot of seams and communication problems, he points out. A lot of dots are not connected. Critical items can be lost, especially internal knowledge. When a client works with a single vendor, he stresses, the partners create a knowledge base that can be carried forward with the project. Cambrex provides drug substance, drug product, and analytical services across the entire drug lifecycle.

Fujifilm Diosynth Biotechnologies (FDB) is a division of Fujifilm that focuses on biopharmaceutical contract manufacturing, especially drug substances for biologics. That includes cell culture and fermentation, development and manufacturing, and advanced therapies like gene therapy. Fujifilms director of strategic business development, Daniel DeVido, PhD, says there is growing interest in gene therapy products and gene modified cell therapies.

In the area of viral vectors, new products on the market such as Luxturna (from Spark Therapeutics) and Zolgensma (from Novartis) have moved that sector of the industry forward. Newly approved chimeric antigen receptor (CAR) T-cell therapies, such as Kymriah (from Novartis) and Yescarta (from Kite Pharma) are also injecting energy into the field. And monoclonal antibodies have been going strong for the last 10 to 15 years, with approximately 80 therapies approved and on the market.

The industry is well funded right now, DeVido points out. A lot of companies are pushing candidates forward.

That increased demand for cell culture services brings new technical challenges. Everybodys looking for increased titers, DeVido emphasizes. For gene therapy, yields and titers are much less than they are for cell culture, so everybodys looking for the next thing that will get gene therapy to produce on the scale that monoclonal antibodies are on now.

Lonza offers a range of CDMO services. Karen Fallen, the companys head of mammalian and microbial development and manufacturing, says that Lonza works with companies from several different segments, including small and virtual companies that have limited in-house resources and capabilities. A lot of them are really focusing on the science, she notes. Theyre looking for preclinical and clinical services.

In Lonzas view, some of the trends among the smaller companies are due to larger Series A financings. In past years, Series A deals would have been $10 or $15 million, but now they are running higher, up to $70 or $80 million. They have different ambitions now, Fallen points out. They want and are able to take the molecule further along the supply chain, even to launch. They want to stay with Lonza longer before they partner up with large pharma and/or out-license these molecules. She adds that Lonzas customers also have more complex molecules in their pipelines.

Lonzas other big segment consists of large pharma companies. They have assets, and they have experience, she says. What theyre looking for now is newer technologies, with newer modalitiesbioconjugation, highly potent small molecules, or cell and gene therapies, for example.

Almac Group provides an extensive range of contract development and manufacturing services across the drug development life cycle. The increased interest in pediatric formulations is driving a demand for mini-tablets, especially those in stick-pack dosage form. The rapidly expanding oncology space, by its nature, creates a need for CDMOs that have extensive capabilities in processing highly potent active pharmaceutical ingredients at the small-to-medium scale.

Were seeing an industry trend toward higher value, lower volume products, says Jonas Mortensen, vice president of business development at Almac. Our clients are asking us to take on commercial supply of their product, often at, or close to, the same scale we had previously provided for their clinical studies.

To meet these new needs, Almac has installed multiple stick-pack machines across its sites in the United Kingdom and the United States. Almac is also finalizing the qualification of a dedicated suite of eight processing rooms and equipment solely designed for, and dedicated to, processing of highly potent active pharmaceutical ingredients.

Mortensen anticipates that some near-term trends in CDMO services will include supply chain risk mitigation, end-to-end services, and GMP floor space. CDMOs, he points out, are increasingly being asked to demonstrate their ability to support multisite supply strategies through global facilities or act as a secondary site of manufacture.

Communication is a common theme when it comes to recommendations for working with a CDMO. MilliporeSigmas Cournez says that biotech companies should choose a CDMO that has the most experienced people in-house. Doing so can help biotech companies avoid having to deal with multiple vendors. He also recommends having a dedicated project manager who can provide transparent communication with the vendor and connect with subject matter experts in case of unexpected changes.

Good communication also contributes to transparency in a project. Project transparency is really important, insists Cambrex Shook. That can be limited due to the competitive landscape of the project.

If problems arise during project execution, ownership and communication is really important. If its not there, losses occur and there are timeline setbacks. This could impact the scope, and once you get off scope, [it takes] money and resources to get back on track.

An illustration of the importance of communication comes from Catalent, a company that offers a range of CDMO services, including its recently introduced GPEx Boost technology for cell line development. Michael Riley, vice president and general manager of biologics at Catalent, says that in a program the company is currently working on, a customer was on a highly accelerated path to a product filing for a fast-track product. Catalent was working with regulatory authorities to characterize the companys manufacturing process and move toward validation of that process. To do that, Riley explains, we had to have very robust conversations between multiple functions within our organization and their organization from a quality and development standpoint.

Trust can be a delicate issue in relations between a CDMO and a customer. To illustrate this point FDBs DeVido describes a face-to-face discussion that the company had with one of its customers. This discussion, which took place in FDBs office in Cambridge, MA, resolved some contractual disagreements. We were able to sit around the table and go through the legal issues, DeVido recalls. We cleared up a lot very quickly.

When you sit down face to face and have good discussions, he says, everyones a little more comfortable. Even though people may feel theyre not completely safeguarded from a one-in-a-million occurrence, they may feel comfortable the two parties are going to work together through whatever the issue is.

DeVido said that once youve selected a CDMO, its important to be transparent and trust the company. Youve done your due diligence, he proposes. Now trust your selection and the system theyre operating in.

Benefits of working with an experienced vendor can go beyond development and manufacturing. Cournez says that in one instance, an emerging biotech customer had the opportunity to engage in licensing discussions with a large pharmaceutical company. Because the emerging biotech was small, we hosted the large pharma company at one of our sites and ran the due diligence, which was a great success, he relates. This former emerging biotech now funds many different programs because of the success of their first molecule.

Some vendors warn that business strategies can backfire. Focusing too much on price and speed to market can be risky when researching or working with CDMO/CMO partners, according to Cournez. The service provider must simplify the process and reduce touchpoints throughout the process.

Mortensen says that due to the significant investment required in resource and training, many smaller biopharma companies often do not have a regulatory affairs department of their own. Therefore, its critical for sponsors to recognize the consultative benefit CDMOs bring to the table as an extension of their company to help fill in any regulatory knowledge gaps. This timely advice, integrated with early- and late-stage development, can enable a sponsor to adequately prepare, ensuring little or no delay when bringing its products to market.

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Making the Most of a CDMO Relationship - Genetic Engineering & Biotechnology News

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