In our earlier discussion, we delved into the intricacies of the classic Permitted Daily Exposure (PDE) and its functioning (click here for an in-depth exploration!). However, the application of PDE extends beyond human pharmaceuticals, finding relevance also in veterinary drugs, particularly those manufactured in shared facilities.
As a quick recap, the PDE servs to determine the acceptable levels of exposure to a drug or its residues without compromising the well-being of animals (or humans).
In this article, our focus will be on scenarios involving shared facilities. These are places that produce both human and veterinary drugs; which are becoming increasingly common. As one may think, this coexistence necessitates rigorous protocols to prevent cross-contamination and ensure safety for all, humans and animals alike.
Calculating PDE for veterinary drugs in such facilities becomes more intricate due to the coexistence with human pharmaceuticals. Nevertheless, this value is a crucial factor in ensuring the safe use of these medications.
These facilities present unique challenges in terms of PDE calculation and management, such as:
- Distinct PDE Requirements: Human and veterinary drugs often have vastly different PDE values.
- Risk of Cross-Contamination: Cross-contamination is a significant concern in shared facilities. Traces of veterinary drugs must not inadvertently find their way into human pharmaceuticals, or vice versa. This requires stringent processes for cleaning and sanitation.
As a general rule, according to the “Guideline on setting health-based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities”, PDEs should be derived assuming human exposure, even when the product that will be contaminated is a veterinary medicinal product. Nevertheless, veterinary guidelines also need to be taken into account. In particular, the PDE evaluation can be molded according to Appendix 3 of VICH GL 18 “Residual solvents in new veterinary medicinal products, active substances and excipients (Revision)”.
In principle it would be possible to use the PDE approach to establish different limits for different target species, but this would be highly impractical. Consequently, it is considered pragmatic that PDEs should be derived assuming human exposure, in line with the approach taken in VICH GL 18, in which human PDEs are used to calculate residual solvent limits applied for veterinary medicinal products.
What about the formula?
The formula to derive the PDE to be applied in shared facilities and concerning veterinary products is very similar as the one for pharmaceutical products. For a deep-dive on the formula’s values, please check our previous post by clicking here, as we will focus mainly on the differences between the two formulas.
In fact, some slight differences have to be highlighted, In particular the weight. In fact for veterinary products the PDE should be calculated on a mg/kg bw basis (i.e. without a weight adjustment) rather than on a per person basis. This is due to the fact that animals come in different shapes and forms, and thus different weights. We have to remember that yes, in shared felicities the cross-contamination can happen between veterinary and human products, but also between two different veterinary products. In alternative a value of 1 kg can be considered as worst case scenario, obtaining a PDE expressed in mg/day.
Also the modifying factor F2 can be a little bit tricky when dealing with veterinary products. This modifying factor takes into account the extrapolation between species, but not such standardized values are present in the open literature, especially if we take into account companion animals. Accordingly, either a specific PDE is derived for a specific species, but this approach as we mentioned before can be complicated, time consuming and it is not advised by the relevant guidelines. A solution could be applying a default value of 10, to take into account all possible different animal species the veterinary products residues can encounter, and humans as well.
Moreover, another scenario has to be taken into account: the possible contamination of a veterinary medicinal product for administration to food producing animals. In this case, the limit applied must take into account not only the target animal species, but also consumer safety, assessing that neither the target animal nor the consumer will be exposed to residual active substance levels exceeding the PDE.
In conclusion, the calculation and application of Permitted Daily Exposure (PDE) are integral to ensuring the safe use of veterinary drugs, particularly in shared facilities where human and veterinary pharmaceuticals coexist. The application of PDE in shared facilities is guided by both human and veterinary considerations, adding layers of complexity to the calculation process, that’s why it is crucial for companies to choose experienced safety assessors with a deep understanding of both human and veterinary pharmaceuticals.
Our team at ToxHub brings a wealth of expertise to the table, ensuring a comprehensive approach to PDE calculations in shared facilities. With a track record of navigating the intricacies of cross-contamination risks and adhering to stringent regulatory guidelines, we offer a reliable solution for companies seeking to uphold the highest safety standards.
Article issued by Chiara Gazerro