Recently, at the Russian pharmaceutical market the interest in generics is considerably increased, due to significantly lower costs for the organization of production and bringing to the market compared to the original ones, of new medicinal products. In addition, generic medicinal products are more accessible to the poor social groups, due to the fact that their prices do not include the cost of the development of the medicinal product and its extensive clinical trials. However, generic medicinal products must meet the same standards of quality, efficiency and safety that are imposed to the original MP. In connection with this the number of ongoing studies of therapeutic equivalence dramatically increased, which were considered sufficient all over the world to confirm the identity (or close conformity) of generic to the original medicinal product.
is a medicinal product which is based on the same active ingredient (sometimes they say “active molecule”), that is in the basis of the original medicinal product, and having the same dosage form. The composition of excipients can be identical or different.
Generic should be equivalent to the original on its pharmaceutical, pharmacokinetic and pharmacodynamic properties, which is the evidence base for its therapeutic equivalence (FDA, Electronic Orange Book, Approved Medicinal Products with Therapeutic Equivalence Evaluations, 20th Edition, 2000.)
Thus, for the state registration of generic medicinal product confirmation of its therapeutic equivalence of the original patented medicinal product are required. Also, it is represented in the Federal Law № 61-FZ of 12.04.2010 “On circulation of medicinal products”, article 38, paragraph 2 – “With respect to generic medicinal products for medical use, the studies of bioequivalence and (or) therapeutic equivalence are conducted in accordance with the authorized federal body of executive power”. As it is evident from the phrase, pharmaceutical equivalence does not necessarily imply bioequivalence.
The following types of equivalence of medicinal products are distinguished:
Therapeutic equivalence means generic-medicinal product efficacy and safety analogous to that of the original medicinal product in course of the medicinal treatment. Therapeutic equivalence is a basic requirement of interchangeability of medicinal products. For generic medicinal products manufactured in the form of oral dosage forms, the confirmation of therapeutic equivalence based on the pharmacokinetic equivalence (bioequivalence) is widely accepted.
Determination of bioequivalence: two medicinal products are bioequivalent if they provide equal bioavailability of the medicinal product.
Thus, the two medicinal products are bioequivalent if their bioavailability, maximum concentration and time to achieve it (Cmax and Tmax, respectively), as well as the area under the curve (AUC) after prescription of the same molar dose under the same route of administration, are similar.
What are the limits for the differences for the abovementioned parameters?
Medicinal products are bioequivalent if the boundaries of the parametric two-sided 90% confidence interval for the ratio of geometric mean value of the AUC parameter and Cmax/AUC for the product under study and comparator product are within 80 - 125%; and parameters Cmax - within 70-143%.
Determination of bioequivalence is a basic requirement for registration of generic medicinal products, as bioequivalent medicinal products can be replaced with each other without dosage correction and an additional therapeutic monitoring (with the identity of the indications and instructions for use).
We offer you the services for organization and conduct of bioequivalence studies of generic medicinal products in healthy volunteers. We provide a complete provision of the whole process (the “turnkey study”), and separate the fragments of interest to you, such as:
- Development of the bioequivalence study Protocol
- Preparation of the accompanying documentation (Case Report Form, the researcher’s brochure, informed consent of the patient)
- Selection of a clinical site for the bioequivalence study
- Conduct of monitoring and audit visits to the clinical database
- Organization of the insurance of volunteers participating in the bioequivalence study
- Representation of the interests of the company in the authorized state bodies, etc.
Our company has organized more than 30 such studies and cooperates with professional doctors-researchers who, working with our company, confirmed their professionalism and high level of responsibility. Having applied to us on the organizational matters of bioequivalence studies, you can be assured that you will get a qualitative study, with an impeccable documentation and reliable results, performed exactly as scheduled.