The Logistics of Outsourcing Biologics

Bio/pharmaceutical companies operate in an industry known for its rigorous, exacting standards; companies place significant, implicit trust in any outside party they involve in their supply chain. Consequently, one could be forgiven for thinking that outsourcing materials for biologics production, which by design are much more complex than their small-molecule counterparts, would be infrequent because of concerns regarding quality control.

However, biologics outsourcing is a major industry that is, in concert with the rising demand for biologics throughout the industry, poised for rapid growth. A market report from IQ4I Research & Consultancy forecasted that this niche is expected to grow at a double-digit compound annual growth rate from 2022 to 2030. Additionally, the authors anticipated the industry reaching a $106.7 billion valuation by 2030 (1).

Outside of the growing demand for biologics, one can point to various reasons for this rise. For one, building a new biopharmaceutical manufacturing facility takes, on average, 5–10 years before it is operational, and can cost up to $2 billion (2). For small-to-mid-sized organizations, this cost is already an untenable expense, especially for products that are still in early-to-mid development phases. That said, even companies who have their own manufacturing facilities tend to dabble in outsourcing, as it allows them to leverage a contract manufacturing and development organization’s (CDMO’s) existing knowledge and experience with biologics production—for many companies, this is uncharted waters. In this vein, outsourcing can ultimately smooth out production irregularities and reduce time-to-market.

This begs the question: what is the state of this emergent industry? BioPharm International® spoke with Kasper Møller, chief technical officer at AGC Biologics, a CDMO specializing in protein-based biologics and advanced therapies, to outline the keys to a successful outsourcing platform, explore ongoing trends in biologics outsourcing, and much more on the topic.

The importance of flexibility

When speaking with Møller, the core mantra that he repeatedly stressed was that biologics CDMOs need to be flexible. Because outsourcing companies are working with various companies on wildly different biologics requiring often disparate approaches—for instance, the needs of mammalian-derived therapeutics are different than those of microbial-derived proteins—versatility must be built into the framework of one’s solutions.

“Flexibility is key to adding value to each project and within each modality, facility, and manufacturing line,” said Møller. “Longer-term planning for projects can help address [this problem], but potentially more important is the use of flexible technology systems. With single-use technology and materials, it is possible to change the configuration of a manufacturing line, exchange or add unit operations, and cover various scales of operation.”

In Møller’s case, AGC Biologics developed “the 6-Pack single-use manufacturing concept,” which helps vary batch sizes within the same manufacturing line. This is achieved through combining harvests of parallel 2000-L single-use bioreactors, allowing the company to run anywhere from 2000-L–12,000-L batches at a time. Varied batch sizes allow customers to scale at their own pace, providing more time to evaluate product demand.

Møller also noted that this flexibility should also extend manufacturing agreements. For instance, in cases where high capacity is needed but the timing is uncertain, customizing a deal to provide a fully dedicated line, a partially dedicated line, or a line based off of a “rolling forecast” where products can be exchanged and manufacturing slots moved via a forecasting mechanism (Møller likened the last one to commercial manufacturing), can be helpful for fulfilling customer expectations while maintaining peak operational efficiency.

How demands shape businesses

While biologics come in many forms—vaccines, recombinant proteins, gene therapies, etc.—Møller emphatically stated that he believes protein therapeutics will continue to be the top dog for years to come. Monoclonal antibodies (mAbs) in particular, he stressed, are something that AGC is focused on supporting, which the company facilitated by expanding its existing facilities in Copenhagen, Denmark in 2021 (3). According to Møller, this investment doubled their mammalian single-use system capacity at the site, adding a new manufacturing line with eight 2000-L single-use bioreactors for mammalian protein projects, a new 500-L perfusion bioreactor, and two downstream purification lines. Similarly, the company acquired a commercial-grade large-scale 20,000-L mammalian protein manufacturing facility in Boulder, Colo., in 2020 (4).

However, while mAbs are the king of the hill, they are not without competition. A key area of growth that Møller identified was cell and gene therapies, particularly in North America. In 2022 alone, FDA approved five novel cell and gene therapies, including Zyntelgo (betibeglogene autotemcel), Hemgenix (etranacogene dezaparvovec), Skysona (lisocabtagene maraleucel), Adstiladrin (nadofaragene firadenovec), and Carvykti (ciltacabtagene autoleucel); these 2022 approvals comprise roughly one-fifth of the total number of FDA-approved cell and gene therapies to date (5).

Møller’s observations are mirrored by many others in the industry: in BioPharm’s annual survey of bio/pharma workers, approximately half of them felt the biggest opportunity in the entire industry lay in cell and gene therapies (6). As companies race to compete in this rapidly growing niche, biologics-oriented CDMOs such as AGC will move to accommodate them. In the case of AGC, one such decision the company made was the acquisition of a of an established Italian cell and gene company, MolMed, in 2020 (7), as well as a Colorado facility containing viral vector and cell therapy production and manufacturing capabilities in 2021 (8).

Tips for CDMO partners

While the exact needs of any company are typically unique in some form or fashion, Møller noted that are two core themes he finds himself telling his potential partners. “Two of the biggest considerations AGC Biologics focuses on with drug developers of any size is reducing cost and process robustness,” he said. “As an outsourcing partner, these are key areas that we advise our customers to watch closely.”

While few skimp on the actual development of the treatment, according to Moller, companies often neglect the design of robust manufacturing processes and analytical methods in the early stages of development in an effort to reduce costs and hasten time-to-market. However, this short-term outlook can present problems down the line.

Regardless of a treatment’s effectiveness, if there isn’t a scalable manufacturing process associated with it, there will almost certainly be delays when the time comes for commercialization. By taking the time to consider the design of manufacturing processes early on, companies can ultimately save themselves time and money.

References

1. IQ4I Research & Consultancy. Biologics Outsourcing Global Market–Forecast to 2030; November 2022.

2. Longo N. Setting up a Pharmaceutical Manufacturing Supply Chain Is a Complex and Lengthy Process. Catalyst.phrma.org, May 14, 2020.

3. AGC Biologics. AGC Biologics Announces the Groundbreaking of its New Facility at its Copenhagen, Denmark Site. Press Release, Aug. 20, 2021.

4. AGC Biologics. AGC Acquires Biopharmaceutical Commercial Facility in Colorado, USA. Press Release, June 2, 2020.

5. FDA. Approved Cellular and Gene Therapy Products. FDA.gov/vaccines-blood-biologics (accessed Feb. 10, 2023)

6. Playter G. Crossing the Same River Multiple Times. BioPharm International. 2023 36 (1).

7. AGC Biologics. MolMed S.p.A Becomes AGC Biologics S.p.A Following the July Acquisition. Press Release, Oct. 27, 2020.

8. AGC Biologics. AGC Biologics Enters Agreement to Acquire Facility in Longmont, CO, Eyeing to Significantly Expand Their Cell and Gene Therapy Capabilities and Offerings. Press Release, July 1, 2021.

About the author

Grant Playter is associate editor for BioPharm International.

Article details

BioPharm International
Vol. 36, No. 3
March 2023
Pages: 30–36

Citation

When referring to this article, please cite it as G. Playter. The Logistics of Outsourcing Biologics. BioPharm International 2023 36 (3).