How do I apply an OEL Fastrac ADE to a veterinary ADE?

OEL Fastrac® documents from Affygility Solutions (Affygility) provide an occupational exposure limit (OEL) and an acceptable daily exposure (ADE) for the pharmaceutical of interest.  Unless otherwise indicated in the specific monograph, the reported values (OEL and ADE) are for adult humans.  The ADE is the daily dose of a substance below which no adverse effects are anticipated by any route, even if exposure occurs over a lifetime. In addition, as previously indicated by the EMA, the terms ADE and PDE are equivalent.

How does one apply this information to obtain a relevant veterinary ADE?

The European Medicines Agency (EMA) has provided guidance as to how to set ADE/PDE for veterinary medical products ^(1,2,3).  How to use the information provided in an Affygility OEL Fastrac® document for your particular veterinary application is described in the paragraphs below.

The first thing to consider is that the ADE found in the OEL Fastrac ^® document is based on an adult human body-weight.  To determine the ADE, Affygility uses the conservative 50 kg as provided in the EMA guidance.  For general veterinary products, the typical weight of the treated animal, however, is not so clear.  Cats, for example, could easily range from 5 lbs (2.2 kg) to 25 lbs (11 kg) and dogs could range from 3 lbs (1.3 kg) to over 200 lbs (~90kg).

The EMA guidance is to convert the human ADE (based on 50 kg) to the body weight of the of the potentially affected veterinary animal.  A conservative assumption for both cats and dogs is to use 1 kg body weight since this is at the lower end of the range for both species. 

To calculate a veterinary ADE, divide the OEL Fastrac® ADE by 50 kg as shown in the equation below;

(human ADE)/50 kg = veterinary ADE on a per kg body weight basis

This can be used to determine the ADE based on the body weight of the species to be treated (OEL Fastrac® ADE/(50 kg body weight) * species weight).  A 1 kg species body weight is used for a conservative calculation and that value is simply the human ADE divided by 50.

Be aware of animal- and breed- specific toxicity

It is important to recognize that some human pharmaceuticals are not appropriate for certain animals, and this should be considered when deriving a veterinary ADE.  For example, some breeds of dogs and cats are sensitive to avermectins such as ivermectin, selamectin and others. In addition, horses can be susceptible to monensin.   In these cases, the ADE should take into consideration knowledge of the specific animal toxicity when evaluating products manufactured in a shared facility or equipment.  It is not relevant in those cases to use the human ADE directly without further consideration.

Do NOT use the above methodology to calculate human pediatric ADE

For human pediatric ADEs, there is typically more human specific data than for animals. This information should be reviewed by an expert toxicologist to determine the human pediatric ADE.

References

1. European Medicines Agency (2010) VICH GL 18 residual solvents in new veterinary medicinal products, active substances and excipients. 30 Churchill Place, Canary Wharf, London, UK.
2. EMA (2014). Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities (EMA/CHMP/ CVMP/ SWP/169430/2012)
3. EMA (2018). Questions and answers on implementation of risk-based prevention of cross-contamination in production and ‘Guideline on setting health-based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities’ (EMA/CHMP/CVMP/SWP/169430/2012).