In the pharmaceutical manufacturing, and contract development and manufacturing organization (CDMO) industry, preventing cross-contamination and protecting pharmaceutical manufacturing employees from occupational exposure to active pharmaceutical ingredients (API)s is imperative and is a regulatory requirement. In addition, failure to do so can result in costly pharmaceutical manufacturing delays and the potential for regulatory violations. Since the late 1980’s, pharmaceutical manufacturers have used the concept of occupational health categorization and control banding to protect their employee from unwanted exposures to active pharmaceutical ingredients. Furthermore, the majority of credible CDMOs will not be able to accurately bid a project until an occupational health categorization report by a qualified occupational toxicology firm has been obtained. If your company is developing a “potent compound” and a CDMO doesn’t ask for an OHC report, your company should run away from them, because they don’t have the base knowledge to understand that handling highly potent compounds require proper onboarding and risk evaluation.
What is an Occupational Health Categorization?
While the term “Occupational Health Categorization” (OHC) can be used synonymously with “control band” or “occupational exposure band” (OEB) assignment, an occupational health categorization can be defined as “a process intended to quickly and accurately assign chemicals [and APIs] into specific categories (bands), which correspond to a range of exposure concentrations designed to protect worker health” (Contract Pharma, April 2022, p. 66).
OHC reports are typically intended for active pharmaceutical ingredients that are early in the pharmaceutical development process (less than Phase 2B) where there is limited toxicological data. At this stage in the development process, the anticipated human therapeutic dose and adverse effects have not yet been fully determined, making it difficult to determine a specific numerical occupational exposure limit (OEL.) OHC assignments are not a precise number, but a range of airborne concentrations called a “control band.” It is expected that OHC assignments are fairly conservative and will change as the API continues down the development path. An assignment into a company-specific OHC works well for most CDMOs since they will be handling the API for a limited duration. Depending upon the number of engineering control options that a company may have, control bands can range from 3 to 6 bands or more. It is important to recognize that there is not a standard number of control bands in the pharmaceutical industry. It really depends upon how many engineering control options are available in your company. The majority of occupational toxicology requirements throughout the drug development process are shown in Table 1.0 below.
What is an Occupational Exposure Limit (OEL) report?
Occupational Exposure Limit (OEL) reports are intended for APIs that are in the later stages of development (>2b) where the therapeutic indication and the human therapeutic dose have been well defined. At this point, the API should have a well-developed investigators’ brochure (IB) and other toxicological data necessary to support a fully developed occupational exposure limit monograph. An OEL report defines a specific numerical occupational exposure limit. Here at Affygility Solutions, since the toxicology information is the same, we also include the derivation of an acceptable daily exposure value in our reports.
Companies that are developing API products that are either already on-market or in post-market development for different indications or formulations should look at acquiring an OEL Fastrac report. This is the most cost- and time-efficient way of obtaining an OEL/ADE report.
When do you need a Safety Data Sheet?
Safety Data Sheets (SDS)s, otherwise known as MSDSs, are required once a specific API leaves the “discovery” site. In the early stages of development, the SDSs may contain little information, and many of the fields will be “not known” or “undetermined.” Nonetheless, an SDS is still required and will need to be updated as the API moves down the development path. As the compound moves down the development path, the SDS will need to be updated.
Affygility Solutions can help.
For over 20 years, Affygility Solutions has provided expert occupational and product quality toxicology services to the pharmaceutical industry. Our OEL and ADE reports (known as Relatórios de PDE in Brazil) are prepared by pharmaceutical industry experts and are compliant with FDA, EMA, PIC/s, and ANVISA requirements. We have provided these services to over 800 clients in 74+ countries. For more information please contact us.