EXECUTIVE INTERVIEW - Lifecore Biomedical: Capacity to Keep Pace With Biologics Growth

With a 40+ year regulatory track record, Lifecore is a fully integrated CDMO with highly differentiated capabilities in the development, fill and finish of sterile injectable pharmaceuticals, including 20+ commercial products. Drug Development & Delivery recently interviewed Thomas Guldager, Vice President, Operations at Lifecore.

Mr. Guldager recently joined U.S.-based Lifecore Biomedical after leading manufacturing at Xellia Pharmaceuticals, a Danish API manufacturer and wholly owned subsidiary of Novo Holdings A/S. During his tenure, he also served as Director of Business Excellence and Director of Operational Excellence.

His career has also included a tenure as Chief Operating Officer of Vertanical, a Germany-based biopharmaceutical company, Supply Chain Controller for ReckittBenckiser, a British-Dutch multinational consumer goods company, and Finance Officer for GlaxoSmithKline.

Q: Many industry reports cite that biologics are a rapidly growing area of the pharmaceutical market. Does that hold true for injectable products?

A: Yes, in recent years the FDA approvals for injectables have been led by biologics. Although those numbers only represent the US market, we’ve seen an increase in the number of global opportunities related to biologics, and we expect that trend to continue.

Q: What biologic products can Lifecore support?

A: Our facility infrastructure and Quality Management System (QMS) can support a range of biologics including monoclonal antibodies (mAbs), therapeutic proteins, peptides including GLP-1s, mRNA/lipid nanoparticles, and others. Our QMS also incorporates requirements across product types and geographies, providing flexibility for specific customer needs.

In addition, our development team has prior industry experience in the biologics space and has been able to share knowledge to help Lifecore continue expanding within biologics.

Q: How is handling biologics similar to small molecules?

A: Biologics are more complex, and this complexity can add sensitivities that need to be understood and mitigated during production. However, in many ways, the fill/finish of a biologic is not unique. The manufacturing steps are virtually the same. All sterile injectable production requires stringent aseptic techniques to prevent contamination throughout manufacturing processes and environments.

Q: So, what is special about biologics from a development and fill/finish perspective?

A: Shear sensitivity is a major consideration. To preserve the critical structure-function relationship of biologic molecules, manufacturing equipment trains must be designed to minimize exposure to shear stress. In fill/finish activities, this involves special considerations for mixers and filling pumps. For example, peristaltic pumps are often preferred over rotary piston pumps because they cause less shear when operating.

A second major area is sterilization. Due to their nature, biologics must undergo sterile filtration as opposed to terminal sterilization. This can be challenging, especially since formulations with higher concentrations of biologics result in an increase in viscosity. Lifecore has proprietary technology that enables sterile filtration of high-viscosity formulations to address this challenge.

Also, biologic APIs are typically more expensive, so minimizing loss is important. When developing a manufacturing process, short distances between fill tanks and fillers are preferred. The amount of drug product used during development/engineering runs should be minimized as well.

That said, many of the sensitivities associated with biologics are also present with complex small molecules, i.e., light sensitivity, and time-out-of-refrigeration (TOR) constraints. As a producer of a variety of ophthalmic products which have requirements that can be stricter than biologics, such as particulate size limitations, Lifecore is used to adjusting for molecular sensitivity.

Q: What about from an analytical testing perspective?

A: Characterization of large molecules is more challenging, typically requiring the development of multiple analytical techniques to analyze structure, purity, and other physical and chemical characteristics. There is some overlap between commonly used equipment but, at times, we acquire different instruments to support biologics.

Q: Can Lifecore support biologics from a regulatory standpoint?

A: Among the types of products we handle, requirements for biologics and small molecules are similar. Lifecore is well-positioned to comply with biologic requirements due to our infrastructure and processes for other complex products. Plus, we have strong relationships with global regulatory bodies to help move customer products across the finish line.

Q: What capacity do you have to support the growing biologics market?

A: With the recent installation of our high-speed, 5-head isolator filler, we doubled our capacity to support all types of injectables in vials, syringes, and cartridges. Plus, this filler offers several benefits that are especially valuable for biologics, including optimization of filling parameters to reduce losses at start-up, during production, and at the end of a batch, as well as non-destructive, in process weight checks.

For those who haven’t fully developed their platform, our pilot laboratory is well-equipped to produce engineering batches and pre-clinical study material. We also have on-site laboratories, an ICH stability program with a range of conditions that accommodate biologics, and in-house secondary packaging.

Q: What trends do you see related to biologics?

A: From a container perspective, we are seeing a need to move away from traditional vials early in the development cycle toward combination products that can support the use of large volume, wearable devices. Also, we see the application of technologies to increase dosage concentration while maintaining sub-cutaneous administration. Again, Lifecore is well-positioned to support these trends with our increased capacity, infrastructure, and capabilities.

“Many of the special considerations and modifications that need to be made in the process development and fill/finish of biologics are the same things we address for complex, small molecules. Every process is designed and built around the molecule, no matter the type.”