Drug Development & Delivery: Outsourcing Formulation Development & Manufacturing

04th June 2024

SPECIAL FEATURE – 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.1

Small-molecule specialized CDMOs with expertise in complex formulations, such as (HPAPIs)are growing in importance. The global small-molecule CDMO market will reach almost $85 billion in 2032, up from $45 billion in 2022.2 While not growing quite as significantly, 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.3

Both play a critical part in process development, complex manufacturing processes, and regulatory compliance. “As we continue to see the industry evolve post-COVID, 2023 continued to be a difficult year when it came to rising inflation impacting biotech funding and M&A,” says Dr. An­drew Lewis, Chief Scientific Officer, Quo­tient Sciences. “One major takeaway from 2023 was evident: with the best science, it’s possible to weather the storm and make truly ground-breaking advance­ments. We are already seeing turnarounds in 2024, with CDMOs increasingly viewed as strategic partners.”

For instance, contractors are provid­ing less off-the-shelf programs, and are instead going deeper to work on the sci­ence needed to enable all parts of a pro­gram. He says: “The scientific acumen of the outsourcing provider and quality of sci­entific output can be the deciding factor in a program’s success or failure.”

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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