Background

The first version of the ICH Q3D guidance in 2016 set the standard for controlling Elemental Impurities (EIs) in medicinal products for human use, ensuring these impurities stayed within acceptable limits. Building on that foundation, the EMA released two key documents in 2020 and 2021, introducing risk assessment requirements for EIs in veterinary medicinal products:

1. Implementation of risk assessment requirements to control elemental impurities in veterinary medicinal products.
2. Reflection paper on risk management requirements for elemental impurities in veterinary medicinal products.

These guidelines required a risk assessment for all veterinary medicinal products authorized in the EU by January 2023, with exceptions for immunological products. However, with the European Pharmacopoeia (monograph 2619) already applicable to immunological products, a broader and more inclusive framework has become necessary.

Last October, a new draft that would replace these documents was launched for public consultation until January 2025. All veterinary drugs have been included in the scope, with the exception of herbal drugs, radiopharmaceuticals and, as already established in previous guidelines, elements that are intentionally included for therapeutic benefit.

What’s new? 

This new draft continues to reflect the application of a risk-based approach and the consideration that ICH Q3D PDE values are acceptable to ensure the quality of veterinary medicinal products. EIs can arise from several sources:

• Residual catalysts that are intentionally added in the synthesis.

• EIs present as impurities (interactions with manufacturing equipment, water or other utilities, primary packaging, components of the product itself).

In the case of products for veterinary use, any impurities that may have a toxicological risk for the target species must also be included.

As in previous regulations, the option of justifying levels higher than the PDE in certain circumstances is maintained, considering the route of administration, target species, weight, dose, and duration of treatment, but always subject to approval by the authorities.

For immunological veterinary drugs with known production processes, the risk of EIs being present at levels that pose safety concerns for the species or consumers is generally considered low (EIs are not normally used as catalysts or reagents, are present at very low levels in culture media, significantly removed during further processing, infrequently used in an animal’s life, etc.). However, potential sources in manufacturing such as excipients and other environmental sources should also be considered.

Why does this matter?

• Improved Product Quality: Aligning veterinary medicinal product standards with human medicine ensures comprehensive safety across industries.

• Enhanced Safety for Animals and Consumers: Stricter EI controls protect both target species and consumers of animal-derived products.

• Regulatory Compliance: With these updates, manufacturers must adapt their risk management frameworks to remain compliant.

How can QbD Group assist you?

At QbD Group, we specialize in helping life science companies navigate complex regulatory landscapes. Connect with our experts to ensure your veterinary medicinal products meet these evolving standards seamlessly