Outsourcing Formulation Development & Manufacturing: Going Beyond the Science to Become True Partners
Contract Development and Manufacturing Organizations (CDMOs) are critical partners for pharma and biotech companies when it comes to providing innovative solutions that advance the next generations of therapies. To that end, CDMOs are seeking to modify contracts to maintain competitiveness and maximize revenue growth. The top three contract modification priorities are adding more indices, extending contract durations, and ensuring adaptability to shifting market requirements.
The global large-molecule CDMO market was valued at $11.6 billion in 2023 and is expected to jump to almost $20 billion in 2029. This market revolves around biologics, monoclonal antibodies, therapeutic proteins, and biosimilars.
In this exclusive, annual report, leading CDMOs speak with Drug Development & Delivery about how they are adapting to bio/pharma client needs, their capabilities in handling complex molecules, and how they are transforming from specialist contractors to true partners.
Abzena: A Two-Pronged Approach to Formulation
Abzena offers a customer-centric approach across a range of formulation and manufacturing services that support a biopharmaceutical product throughout its entire lifecycle, from the initial preformulation and generation of a formulation to support toxicology and first-in-human (FIH) clinical trials through to clinical in-use studies, formulation optimization, robustness, and device interaction studies. This enables customers to utilize a single organization for all their formulation and manufacturing requirements, which streamlines and de-risks the process and allows any experience and learnings to be shared across teams, says Gary Watts, PhD, Senior Manager of Analytics at Abzena. This first-hand knowledge of the product can then be applied to rapidly solve any complex problems that may arise downstream.
Broadly speaking, Abzena applies two approaches to formulation studies: First-in-Clinic approach, which is a streamlined methodology focused on enabling the customer to obtain FIH results in the shortest time possible; and a Best-in-Clinic approach, focused on providing a superior product format to the competitors, often applied after Phase 1.
“A practical example of these approaches is where a customer applies the streamlined approach to get to the clinic quickly using a simple formulation at low drug concentration (for intravenous administration), utilizing frozen storage,” explains Dr. Watts. “The aim is to ensure there are no adverse events when the drug is administered. The same drug would then be reformulated to provide a ‘best-in-clinic’ product once known to be safe and efficacious, which could involve concentration of the drug to allow for subcutaneous administration, and optimization of the formulation to maintain a viscosity that is readily injectable, and a product stable to long-term storage at refrigerated temperatures.”
He describes how one customer acquired a novel monoclonal antibody (mAb) that was formulated at another CDMO where the approach did not assess the fundamental properties of the mAb. This resulted in phase separation and gelation during refrigerated storage. “These issues were resolved by warming to room temperature (without any apparent impact on quality), however, this was not ideal from a regulatory perspective or for patient administration,” Dr. Watts says.
A study was designed to evaluate the fundamental factors crucial to formulation stability and an optimal formulation was identified that showed the desired physical and chemical stability, and was clear, colorless, and free of visible particles after >6 months storage at 2-8°C. In addition, Watts says solubility was sufficiently improved to allow the concentration to be increased to 100mg/mL from 50mg/mL, in line with the customer’s requirements.
Over the last couple of years, the proportions of projects based on antibody-drug conjugates (ADCs), multi-specifics, and vaccines have increased noticeably, making it more important for suppliers to offer customers a streamlined approach to the clinic. “To that end, Abzena’s mission is to move new medicines forward to patients faster and we’ve been investing in our capabilities and forming strategic partnerships to support that,” says Dr. Watts.
For example, for the newly launched cell line development platform, AbZelect™, Abzena forged a partnership with ProteoNic Biosciences BV to license their premium protein expression technology, 2G UNic®. This vector technology will significantly improve the production of high-yielding CHO cell lines for Abzena’s customers, he says. “By partnering with ProteoNic, we further enhance our existing offering by providing customers with a premium solution that increases the production levels for even the most challenging and complex proteins.”
For customers with complex biologics in discovery, the DRIVE-Bio partnership with OncoDesign Services offers an ecosystem of support. Dr. Watts says: “DRIVE-Bio leverages the skills and expertise to develop antibodies in oncology and inflammation through a privileged collaboration that combines Abzena’s discovery, development, and manufacturing support of biologics and ADCs with OncoDesign Services’ capabilities in optimization to lead selection of naked or pay-loaded preclinical candidates vs target product profile.”
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