The European Medicines Agency's Committee for Medicinal Products for Veterinary Use (CVMP), which is the committee responsible for preparing opinions on all questions concerning veterinary medicines in the European Union, has reviewed and given an opinion on the risk to consumers from the use of diethanolamine in veterinary medicines. The CVMP considered that it is not appropriate that the excipient is included in the list of substances considered as not falling within the scope of Regulation 470/2009 (the ‘out of scope’ list); this Regulation legislates for the use of substances that are administered to food-producing animal species (the maximum residue limit legislation). The opinion of the CVMP on 19 July 2018, which is directed at all EU Member States, is that it is not possible to rule out a risk for consumers of food produced from animals treated with veterinary medicinal products containing diethanolamine.
Consequently, as a precautionary measure, the HPRA commenced a review process, which commenced on 27 July 2018, and which included consideration by the HPRA of representations from the companies that were directly concerned by this opinion of the CVMP, as well as consideration of the matter by the HPRA’s independent expert advisory committee, the ACVM.
The review, which involved 6 products is now complete and the following actions have been taken:
Marketing authorisation number
Marketing authorisation holder
Finadyne 50 mg/ml Solution for Injection.
Intervet Ireland Limited. The marketing authorisation has been varied to remove diethanolamine from the product.
Cronyxin Injection 50 mg/ml Solution for Injection
Bimeda Chemicals. The marketing authorisation has been suspended with effect from 16 September 2019, pending approval of a reformulation to remove diethanolamine from the product.
Flunazine 50 mg/ml Solution for Injection for cattle, horses and pigs.
Cross Vetpharm Group Limited. The marketing authorisation has been suspended with effect from 16 September 2019, pending approval of a reformulation to remove diethanolamine from the product.
10999/069/001 (VPA number since changed to 22664/46/1)
Norbrook Laboratories Limited. The marketing authorisation has been varied to remove diethanolamine from the product.
Dugnixon 50 mg/ml solution for injection for cattle, pigs and horses
Global Vet Health Sl. The marketing authorisation has been suspended with effect from 16 September 2019, pending approval of a reformulation to remove diethanolamine from the product.
Tribrissen Oral Suspension.
Intervet Ireland Limited. The marketing authorisation has been withdrawn.
Problem Or Issue:
Diethanolamine has been used as an excipient in certain veterinary medicinal products for many years. In January 2018, the CVMP removed diethanolamine from the list of substances considered as not falling within the scope of Regulation (EC) No. 470/2009, with regard to residues of veterinary medicinal products in foodstuffs of animal origin (also known as the ‘out of scope’ list), on the basis of concerns relating to carcinogenicity and genotoxicity: diethanolamine has been shown to have carcinogenic potential in mice and the available genotoxicity data did not allow a conclusion to be drawn on the relevance of the findings for humans.
The removal of diethanolamine from this ‘out of scope’ list meant that there were veterinary medicinal products for food producing animals on the market that contained a substance for which the MRL status is not addressed. On 7 March 2018, Belgium presented to the European Medicines Agency a request for an opinion in accordance with Article 30(3) of Regulation (EC) No 726/2004 from the CVMP on the potential risk for the consumer resulting from the use of diethanolamine as an excipient in veterinary medicinal products for food-producing species.
A public consultation was initiated by the CVMP on 16 March 2018 in order to seek scientific data for use in the review of the consumer safety assessment of the substance.
That European review procedure concluded on 19 July 2018 with the CVMP confirming its original view. While the newly available data indicates that diethylanolmine is not likely to be a DNA reactive carcinogen, when adopting conservative estimates of exposure in a worst case scenario, calculations indicate that diethanolamine could represent an unacceptable risk to consumers. If the substance is to be further used in veterinary medicinal products, the substance will need to be approved as safe for consumers in accordance with Regulation (EC) No. 470/2009. The CVMP assessment report is available here.