Considerations for setting occupational exposure limits for novel pharmaceutical modalities

Abstract

In order to develop new and effective medicines, pharmaceutical companies must be modality agnostic. As science reveals an enhanced understanding of biological processes, new therapeutic modalities are becoming important in developing breakthrough therapies to treat both rare and common diseases. As these new modalities progress, concern and uncertainty arise regarding their safe handling by the researchers developing them, employees manufacturing them and nurses administering them. This manuscript reviews the available literature for emerging modalities (including oligonucleotides, monoclonal antibodies, fusion proteins and bispecific antibodies, antibody-drug conjugates, peptides, vaccines, genetically modified organisms, and several others) and provides considerations for occupational health and safety-oriented hazard identification and risk assessments to enable timely, consistent and well-informed hazard identification, hazard communication and risk-management decisions. This manuscript also points out instances where historical exposure control banding systems may not be applicable (e.g. oncolytic viruses, biologics) and where other occupational exposure limit systems are more applicable (e.g. Biosafety Levels, Biologic Control Categories).

Keywords: Engineered bacteria; Exposure control band; Occupational exposure limit; Occupational health; Oncolytic virus; PET Tracer; Pharmaceutical modalities; Protein therapeutic; Vaccine safety; Worker safety.

Graphical abstract

Fig. 1

Occupational Exposure Control Banding Decision Tree for Therapeutic Modalities. Use of this decision tree, and the potencies included herein, should be considered as a rough guide for initial band selection. Ultimate selection of the band should come from a qualified occupational toxicologist, and rely on the consideration of a number of additional criteria such as the innate hazard of the therapeutic, its pharmacokinetics, and pharmacodynamics, among others. For example, an additional safety factor may need to be applied for compounds which are mutagenic or teratogenic, resulting in a more restrictive band. Footnotes: ^a ADC banding is generally driven by the warhead potency; ^b Follow guidance for radiolabeled compounds, banding is based on the API; ^c Biologic materials made through biological processes (i.e. cell culture); ^d This biologically significant effect should also be clinically relevant; ^e Note that for live viruses, enhanced control measures may be required. Abbreviations: aa = amino acids; sc = special case.