Improving risk assessment for pharmaceutical industry workers exposed to chemical active ingredients
Active ingredients are the substances that give medicines their therapeutic properties. The expert appraisal carried out by ANSES focused on chemical active ingredients.
While they are invaluable for treating humans and animals, these active substances nevertheless pose a risk to the pharmaceutical industry workers exposed to them. Trade union representatives from the General Confederation of Labour (CGT), together with the National Federation of Chemical Industries (FNIC), asked ANSES to investigate this issue.
In its expert appraisal, ANSES reviewed the exposure of pharmaceutical industry workers to chemical active ingredients and issued recommendations to facilitate assessment of the hazards and risks. This step is essential to enable effective and appropriate prevention and protection measures to be taken.
Available data on toxicity differ from those for other chemicals
Medicinal substances and the available data on their toxicity are unique for a number of reasons.
Firstly, the regulations on the marketing of medicinal products provide for a benefit/risk assessment that focuses on administration of the medicinal product to a patient or an animal, within the range of therapeutic doses.
Moreover, knowledge of the toxicity of medicines evolves throughout their development. At the beginning, data on the toxicity of the active ingredients are often sparse and incomplete.
Lastly, medicinal products subject to marketing authorisation, pharmaceutical active ingredients and finished medicinal products are exempt from certain provisions of the cross-cutting European REACH and CLP Regulations applicable to chemicals. These exemptions do not constitute a release from the obligations of the Labour Code, but they do limit the production and sharing of information needed to carry out assessments of the risks and hazards to exposed workers.
Harmonising risk management methods in drug development
In the early stages of drug development, pharmaceutical companies typically use a graduated risk management method known as control banding to assess the hazards and risks to the health of their employees. This approach categorises the hazards of active ingredients based on the limited information available on their toxicity. It assigns preventive and exposure monitoring measures to each hazard category, including a provisional occupational exposure limit (OEL) or OEL range.
In its expert appraisal, ANSES noted that the control banding methods used within the pharmaceutical industry are varied and imprecise in how they define the hazard categorisation criteria. The Agency recommends harmonising these methods so that all companies use the same procedures for characterising hazards and managing risks. It also advocates using control banding only on a temporary basis during the early stages of drug development.
Prioritise biological monitoring of worker exposure
When toxicity data become available via drug safety studies, the expert appraisal showed that pharmaceutical companies usually develop OELs. These maximum airborne concentrations are used to assess the health risks to workers exposed to the active ingredients.
While atmospheric and surface monitoring are important for identifying exposure sources and verifying the effectiveness of the protective measures taken, ANSES recommends prioritising the development of biological limit values (BLVs). Since workers are generally exposed via multiple routes (respiratory, dermal and oral), only biological monitoring allows all of these exposure routes to be taken into account.
The Agency also recommends that toxicity characterisation studies of active ingredients be conducted at doses lower than therapeutic doses, to cover the range of potential occupational or environmental exposures.
It reiterates that compliance with the reference values is a minimum objective and that worker exposure must be reduced to the lowest possible level.
Improve information sharing
Lastly, ANSES recommends that manufacturers coordinate with each other to establish common reference values for a given active ingredient and ensure their traceability in a specific, regularly updated report. This document should be made available to occupational physicians and staff representatives. These documented values should be shared with all companies using the same active ingredient, including subcontractors. Within the same company, certain data available in connection with the marketing of the medicinal product should be shared with the departments responsible for occupational risk prevention.
The Agency also calls for closer communication between occupational physicians and general practitioners, to take full account of potential interactions between the active ingredients to which workers are exposed in the workplace and any medication they may be taking on an individual basis.