For a biotech company, discovering a new therapeutic candidate is a years-long, herculean achievement. A crucial question post-discovery is, can the drug be manufactured at scale? Companies must ensure that they can procure enough of a new therapy for clinical trials and eventually be able to meet commercial supply needs post-FDA approval. In addition to being able to provide a new drug at sufficient quantities, the company (or the contract manufacturer hired by the company to produce the drug) must also ensure that the same process is followed for each batch to create safe and effective therapies.
Manufacturing processes vary depending on the type of drug being developed. There are three overarching categories of drugs: small molecules, biologics, and cell and gene therapy (C>). Small molecules (think everyday drugs like aspirin or cholesterol-lowering Lipitor) are manufactured using common synthetic chemistry methods; their structures are well-known and consistency across batches is easily achieved. The manufacturing of biologics, (including monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs)), as well as C> (an emerging, more complex class of biologics), is generally more complicated, costly, and time-consuming.
Despite the inherent manufacturing complexities, researchers and investors are hopeful that the clinical benefits of novel biologics and C> will outweigh the challenges of producing them, which will eventually lead to more commercially-available advanced biologics. As a result, the biologics market is expected to grow at an 8.4% CAGR from $300B in 2020 to $568M in 2028. Thus, manufacturing biologics and C> — or biomanufacturing — is an exciting growth opportunity poised to support the advancement of new medicines.
What is Biomanufacturing?
Biomanufacturing involves using living systems, such as cells or other microorganisms, to produce a desired product. In the case of monoclonal antibodies such as Humira or Keytruda, Chinese hamster ovary (CHO) cells are engineered to produce antibodies, which are expanded and purified through a series of highly precise steps. Separately, in the case of cell therapies, the engineered living cells are the drug. In almost all cases, biologics and C> are manufactured using these living systems, a distinction from the synthetic chemistry methods utilized for small molecule production.
The science and technology underpinning biologics and C> have advanced in the last two decades. As a result, these new drugs are ready to move out of small experimental labs and into larger-scale production as they progress through late-stage clinical trials and into the commercial landscape. However, technical challenges still exist, especially for C> manufacturing. Safety and durability of response remain key hurdles for these therapies, and biotech companies are working ferociously to address these challenges. We believe the science will continue to improve and that there will be significant commercial demand for C> as the number of approved products increases and as advanced biologics become safer, more efficacious, and cost-effective.
Separately, the pharma industry often lacks the manufacturing capacity to produce these complex drugs, requiring companies to seek third-party manufacturers to help meet clinical trial and commercial supply needs. In these cases, outsourcing fills the gaps for everything from R&D to manufacturing and packaging. The global pharmaceutical R&D market reached nearly $200B as of 2020 and is growing at a 3-4% CAGR — the need for outsourced manufacturing will grow in tandem with increased R&D spend. As such, the global biologics CDMO market is expected to top $30B by 2030, growing at a 10.3% CAGR.
Types of Biologics
Investors and industry leaders can track emerging biopharma trends by keeping a keen eye on the types of drugs entering preclinical and clinical trials. Chemical & Engineering News (C&EN) explains that even though the FDA has approved only a handful of cell and gene therapies, there are more than 1,200 candidates in development, with more than half of those in Phase 2 clinical trials. C&EN points out that this creates a demand for pharmaceutical services that “far outstrips supply.”
The opportunity to meet the industry’s manufacturing needs is here and now. There are several sub-categories within biologics and C>. Here, we’ll briefly introduce classes of advanced biologics that we’re excited about today.
Next-Generation Antibody-Based Biologics
Monoclonal antibodies (mAbs, or synthetic proteins that act like human antibodies in the immune system) have greater than 30 years of clinical use. The FDA has approved more than 600 biologics products, of which over 100 are monoclonal antibodies. Building on the science used to develop the first-generation mAbs, companies are rapidly advancing newer versions of biologics, two of which are described below:
- Antibody-drug conjugates (ADCs) are biologics consisting of a monoclonal antibody linked to a small molecule drug. As of September 2021, the FDA approved 11 ADCs, while more than 80 are being evaluated in 150 clinical trials. The goal of these drugs aims to offer a more precise therapy, in which the mAb binds to a biological target of interest in order for the small molecule to do its job at a specific, desired site and avoid off-target toxicities.
- Bi-specific antibodies (bsAb) are antibodies with two binding sites directed at two antigens, or two epitopes on the same antigen. As of March 2022, there were four FDA-approved bsABs, with 50 being investigated in clinical trials and 180 in preclinical development.
Advanced Biologics – Cell & Gene Therapy (C>)
The field of C> continues to make progress, expanding the tools available to treat disease – please read our primer on C>. Manufacturing these therapies with safe, scalable, and cost-effective processes are essential to their commercial adoption. To enable the advancement of these processes, software will be deeply embedded in future C> manufacturing solutions. Gene sequencing costs have come down dramatically in the last 20 years, resulting in more genomic data that can be leveraged to understand the cause of certain diseases – these data then feed constantly-improving computational tools to more accurately design, develop, and manufacture novel C>.
We hope to support the companies aiming to solve the toughest challenges in the field of C> biomanufacturing, providing a sustainable supply chain for these life-changing medicines.
What’s Happening Now
We’re at a turning point in the industry. Biotech companies and investors are committed to rapidly advancing safe and effective advanced biologics that will have a tangible impact on human health. This could solve unmet medical needs, which is an opportunity to improve people’s lives. While technical and economic challenges remain, we’re excited to partner with companies committed to addressing these obstacles and creating scalable biomanufacturing businesses.
The science and technology surrounding advanced biologics and C> are maturing, and now manufacturing is catching up. We’re in the early stages of figuring out what a global, scalable biomanufacturing facility looks like and how we can stand up enough capacity to make these solutions broadly accessible to patients in need. The supply chain for ADCs, bispecific antibodies, and C> is still emerging, and we must make sure that we continue developing biomanufacturing capacity in a way that effectively serves the biopharma industry so that patients can access new therapies when they need them.