User safety
A user is defined as any person who in the course of a veterinary treatment administers a veterinary medicinal product, has contact with veterinary medicinal product or constituents thereof or comes in close contact with a treated animal. This includes professionals or trained users like veterinarians, veterinary technicians, assistants, farmers or farm workers as well as non-professional users like pet owners and their household members.
During the marketing authorization procedure health risks to users due to exposure to a veterinary medicinal product during intended use and foreseeable accidents are assessed in order to identify whether risk mitigation measures are required. If so, these measures are recorded in the product information (for professional users) and the package leaflet.
The evaluation of health risks of a veterinary medicinal product to users is carried out in accordance with the current version of respective EMA Guidelines, i.e. "Guideline on user safety for pharmaceutical veterinary medicinal products" (EMEA/CVMP/543/2003 Rev. 1) and "Guideline on user safety of topically veterinary medicinal products" (EMA/CVMP/SWP/721059/2014). It is carried out both quantitatively and qualitatively.
The quantitative risk assessment is based on the comparison of a possible exposure with toxicological reference values derived from pharmacological, toxicological and, where appropriate, microbiological studies for the veterinary medicinal product, the active substance or individual constituents of the veterinary medicinal product, e.g. the so-called "No observed (adverse) effect level", NO(A)EL. This term refers to the highest tested dose of a substance that had no (adverse) effect on the investigated organism in a study. For risk assessment, a NO(A)EL with respect to the most sensitive (adverse) effect in the most sensitive species (including humans) is usually used.
For the assessment of realistic exposures that might occur when handling the veterinary medicinal product and administering it to an animal, the following aspects are considered within the authorization procedure: who will use the veterinary medicinal product, the route of exposure (oral, dermal, inhalation), the pharmaceutical form (e.g. solution, ointment, spray), and the likelihood and frequency of exposure, including accidental exposure (e.g. spilling, self-injection, ingestion, hand-to-mouth, hand-to-eye) or contact after administration (e.g. stroking a treated animal). When assessing unintentional exposure, possible risks to children are given special consideration.
The relation between exposure level and NO(A)EL is referred to as Margin of Exposure (MOE). If the exposure is below the relevant NO(A)EL with a sufficiently high factor (at least 100), a low health risk for users can be assumed. However, if the exposure is close to or even above NO(A)EL – the MOE is ≤ 100 – risk mitigation measures should be taken.
The qualitative risk assessment is performed for local effects, such as skin sensitization or skin and eye irritation. This assessment shall be based on the likelihood of exposure which will addressed by means of risk mitigation measures (for example, the recommendation to wear gloves when administering the veterinary medicinal product).
Risk mitigation measures include, for example, the reduction of package sizes, the use of a dosing unit or the use of child-resistant closures. In addition, precautionary measures and safety warnings may be determined to prevent health hazards. Furthermore, when formulating safety warnings their practicability should always be taken into account.