Key Components of Bioequivalence Assessment of Medicinal Products for Veterinary Use

Veterinary medications play an important role in ensuring the health and welfare of animals. However, in order to introduce a new pharmaceutical to the market, the registration process can be quite extensive and complex. In recent years, simplification of the registration procedure for veterinary medicines has become a hot topic for discussion, especially since major changes in veterinary legislation also contribute to some simplification of such procedures

A simplified procedure for registration of veterinary drugs, based on the principle of bioequivalence, allows reducing the time and costs associated with research and testing. This is especially important for small and medium-sized manufacturers, who may not have sufficient financial resources to conduct extensive clinical trials

One of the key concepts related to the simplified registration procedure is bioequivalence. Thus, the legislation allows providing bioequivalence studies in the registration dossier instead of a clinical trial report (confirming the clinical and therapeutic effectiveness of the medicine under investigation). However, the concept of bioequivalence itself is a complex, composite concept

Recently, in international and national databases of scientific publications, there has been a growing number of publications describing the similarities in the pharmacokinetics of several pharmaceuticals, after which a conclusion is made about their bioequivalence, which is a rather controversial issue requiring discussion

The main goal of the study is to analyze national and supranational legislation in the field of drug bioequivalence studies and identify key points based on which the drugs under study can be considered truly equivalent.

The scientific novelty of the publication lies in the comprehensiveness of the review about the existing regulatory framework in the field of bioequivalence studies of medications. The search and processing of scientific publications was performed in accordance with the recommendations of H. Snyder for writing review articles. The information retrieval methodology was based on such general scientific methods of cognition as: a review of specialized search engines and scientific and research databases (Scopus, WoS, PubMed, scientific electronic library eLIBRARY.RU) over the past 10 years, from which the most informative ones were selected, analysis of identified results, comparing them by relevance. Articles published before 2013 were used only if they contained information critical to the topic that was missing in later publications.

The main guidance documents regulating the conduct of bioequivalence studies of medicinal products for veterinary use are: Rules for regulating the circulation of veterinary medicinal products in the customs territory of the Eurasian Economic Union, Federal Law dated 04/12/2010 N 61-FZ (as amended on 08/04/2023) “On the circulation of medicines” (with amendments and additions, entered into force on September 1, 2023)

Summarizing the above regulatory documents, we can conclude about the structure of a multi-stage study that allows drugs to be considered bioequivalent, namely: the components of bioequivalence include pharmaceutical bioequivalence, pharmacological equivalence and therapeutic equivalence. Each of these components has its own role and significance in the evaluation and comparison of various medicines.

Pharmaceutical bioequivalence is the first step in evaluating the equivalence of medications. It means that two pharmaceuticals containing the same active substance in the same dosage should be as similar in physical and chemical properties as possible. This includes parameters such as tablet size, shape, color, consistency, and other physical characteristics. Pharmaceutical bioequivalence ensures that both drugs have the same pharmaceutical form and properties, which is important to ensure their stability and safety. In this study, the most debatable issue is the influence of excipients on the overall conclusion of pharmaceutical bioequivalence. The key to this issue is to compare the solubility/degradability of the dosage form or a reference to other forms of equivalence.

Pharmacological equivalence is the next step in bioequivalence assessment. It suggests that two medicines that are pharmaceutically equivalent should have a similar pharmacokinetic profile. This means that after taking the medication, it must be adequately absorbed, distributed, metabolized and eliminated from the body. Pharmacological equivalence ensures that both drugs have the same bioavailability and effect, which is important for achieving the desired therapeutic effect.

Therapeutic equivalence is the final step in assessing bioequivalence. It assumes that two pharmaceuticals that are pharmacologically equivalent should have similar therapeutic effects. This means that they must have the same efficacy and safety when used in clinical practice. Therapeutic equivalence ensures that medicine can be used interchangeably and still achieve the expected outcome for the patient.

All the components of bioequivalence are interconnected and interdependent. Pharmaceutical bioequivalence is the basis for assessing pharmacological equivalence, and therapeutic equivalence includes both pharmaceutical and pharmacological equivalence. The coincidence of only one type of equivalence does not allow us to draw a conclusion about the general bioequivalence of the drugs under study.

In conclusion, the components of bioequivalence — pharmaceutical bioequivalence, pharmacological equivalence, and therapeutic equivalence — are key elements in the evaluation and comparison of different drugs. Their comprehensive consideration makes it possible to determine how similar the medications are to each other and how they can be interchangeable in clinical practice. This is important to ensure the safety and effectiveness of pharmaceutical treatment.

Interest in bioequivalence studies continues to grow, since the development of new pharmaceuticals and their analogues requires mandatory verification of identity and the acceptability of substitutions. Thanks to these studies, both animals and veterinary professionals can be confident in the quality and safety of the medications they use.