Applying Occupational Exposure Banding to Antibody Drug Conjugates
Occupational Exposure Banding (OEB), also known as hazard banding, is a process used for assigning chemicals into categories based on toxicological potency and potential health hazard. OEB has been used to help organizations define and identify worker health exposures since the mid-1990s and has primarily focused on small-molecule chemicals, which make up most market pharmaceuticals. However, new modalities have been developed, and with increasing use across segments such as oncology, cardiovascular conditions, and autoimmune diseases, these modalities often lack occupational exposure limits.
In 2020, Graham, Hillegrass, and Schulz published an article reviewing the potential use and benefit of applying OEB to novel modalities outside of small-molecule pharmaceuticals. Of these modalities, one has shown active application of OEB throughout the pharmaceutical industry—antibody-drug conjugates (ADCs). While not a new idea, ADCs are becoming increasingly popular treatments in oncology and other health segments and are projected to have a potential market worth nearly $10 billion by 2025 (Hotha, 2023). ADCs are unique in that they are substances composed of an antibody linked to a toxic payload designed to bind to and kill specific cells without harming surrounding cells. Due to the inherently variable nature of ADCs and the toxicity levels of the payloads, consistent assessment and safety protocols need to be in place to ensure worker safety. This article will review the history and development of using OEB, potential worker exposures to ADCs, and how OEB can be applied to the emerging market of ADC products.
Background of OEB:
Creators of pharmaceutical banding developed the process along the lines of the CDC/NIH (Centers for Disease Control/National Institutes of Health) Biological Safety Level system. In this scheme, biological organisms are classified or categorized -- based on their potential hazard -- into categories or Levels 1 through 4 or 5. Predetermined and accepted safety measures could then be implemented for handling all organisms at the same level. The same holds true for pharmaceutical products. Pharmaceutical companies can set their bands and can even specify their safety measures and criteria within those bands.
While most large pharmaceutical companies rely on something similar to the original systems published in the mid-1990s, many have tailored their own classification system to their specific products and facilities.
Most large pharmaceutical companies use a 4 or 5-band system based on semi-firm criteria for categorizing hazards presented by the compound. These usually include factors such as acute health effects (e.g., irritation), potency, toxicity, likelihood of chronic effects (e.g., cancer or reproductive harm), and several others. Along with the criteria for establishing compound hazards or class levels, criteria for protective measures are also placed into these categories. Such protective measures can range from completely isolating workers from the compound to wearing basic personal protective equipment. The combined hazards and protective measures form the matrix which is the banding system’s foundation. Typically, a Class 1 compound poses the least potential for harm, and thus, the required containment and protective measures are relatively minimal.
In many systems, Category 4 or 5 classifications are normally reserved for products that are considered highly toxic, carcinogenic, or teratogenic (i.e., known to cause birth defects). Since most products fall somewhere in between, deciding where in the continuum they fall and the level of appropriate protective measures to apply is often challenging.
Use of OEB on ADCs:
According to the National Cancer Institute (cancer.gov, 2024) an antibody-drug conjugate is a substance made up of a monoclonal antibody that is chemically linked to a drug. This antibody binds only to specific types of cells and not others. In practice, the linked drug enters and kills the targeted cells without harming other non-targeted cells. ADCs are primarily being tested and used to treat a variety of cancers but are also being studied for their efficacy in treating other diseases. As of June 2023, there are 11 ADCs that have been FDA-approved and are on the market (Gogia et al., 2023). According to Maecker et al. (2023), there are over 260 ADCs that have been clinically tested for various oncology indications and 77 active clinical trials, with another 191 studies still recruiting participants (clinicaltrials.gov, 2024).
For over twenty years, the life science industry has recognized that ADCs present challenges to worker safety. The overall concern has been that these types of molecules are highly potent, and the payload component has a toxic nature. According to Graham, Hillegrass, & Schulz (2020), potential routes of workplace exposure to the intact ADC or its respective components include inhalation, ingestion, and dermal contact.
OEB recommendations are based on the inherent hazards associated with exposures to each component of the ADC manufacturing process. The OEB can be utilized for payload and the payload plus linker, the intact ADC, and the linker molecules. While the intact antibody components would be assigned a Biologic Control Category for hazard identification and protection instead.
While the OEB has historically been used for small-molecule pharmaceuticals, applying the OEB process for ADCs may help companies identify and establish safe work practices during the development of these potentially lifesaving products. According to Graham, Hillegrass, and Schulz (2020), several other modalities, including peptides, oligonucleotides, and positron-emission tomography tracers, may also benefit from the OEB process or use the OEB with slight adjustments. These modalities include peptides, oligonucleotides, and positron-emission tomography tracers.
As the Life Science industry evolves, it is critical to have exposure assessments for worker safety and health evolve too. The application of OEB to ADCs supports a proactive approach to occupational health and a progressive step in pharmaceutical development, helping ensure that workers are protected from the unique hazards of increasingly potent therapeutic agents.
Authored by Medora West, Berkley Life Sciences, Senior Life Sciences Risk Management Specialist
