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Тарасенко О.А. Биоэквивалентность и ее роль в обеспечении качества жизни населения.
13.10.2014, 23:03

Резюме
Тарасенко О.А. Биоэквивалентность и ее роль в обеспечении качества жизни населения.
Лекарственные препараты должны не только влиять на текущее состояние пациентов, но и повышать качество их жизни, способствовать полной социальной адаптации. Это возможно только при условии использования лекарственных средств высокого качества. Одним из методов доказательства качества генерического лекарственного препарата является изучение биоэквивалентности. Статья посвящена обзору международных и национальных документов, регламентирующих проведение исследований биоэквивалентности. Содержит детальное описание требований к проведению исследований биоэквивалентности лекарственных препаратов. В статье раскрываются понятия «биодоступности» и «биоэквивалентности», приведены нюансы, которые необходимо учитывать при проведении клинической фазы исследований биоэквивалентности. Описаны общие принципы процесса регистрации воспроизведенных лекарственных препаратов и законодательство Украины в области биоэквивалентности.
Ключевые слова: биодоступность, биоэквивалентность, требования к проведению исследований биоэквивалентности, законодательные акты в области биоэквивалентности.
Резюме
Тарасенко О.О. Біоеквівалентність та її роль у забезпеченні якості життя населення.
Лікарські препарати повинні не тільки впливати на поточний стан пацієнтів, але і підвищувати якість їхнього життя, сприяти повної соціальної адаптації. Це можливо тільки за умови використання лікарських засобів високої якості. Одним з методів доказу якості генеричного лікарського препарату є вивчення біоеквівалентності. Стаття присвячена огляду міжнародних та національних документів, що регламентують проведення досліджень біоеквівалентності. Містить детальний опис вимог до проведення досліджень біоеквівалентності лікарських препаратів. У статті розкриваються поняття «біодоступності» і «біоеквівалентності», наведені нюанси, які необхідно враховувати при проведенні клінічної фази досліджень біоеквівалентності. Описано загальні принципи процесу реєстрації відтворених лікарських препаратів і законодавство України в області біоеквівалентності.
Ключові слова: біодоступність, біоеквівалентність, вимоги до проведення досліджень біоеквівалентності, законодавчі акти в області біоеквівалентності.

Summary
Tarasenko O.A. Bioequivalence and its role in ensuring quality of the population life.
Medicines should not only affect the current state of the patients, but also to improve their quality of life, promote their full social adaptation. It is possible only when high quality drugs used. One of the methods for proving the quality of the generic drug is bioequivalence study. The article provides an overview of national and international documents regulating the conduct of bioequivalence studies. Contains a detailed description of requirements for bioequivalence drugs studies. The article describes the concept of “bioavailability” and “bioequivalence”, given the nuances that need to be considered during the clinical phase of bioequivalence studies. Describes the general principles for the registration process of generic drugs and the Ukraine legislation in the field of bioequivalence.
Key words: bioavailability, bioequivalence requirements for bioequivalence studies, legislative acts in the field of bioequivalence.

Рецензент: д.мед.н., проф. В.А. Мороз

УДК 615.014.2/038/036.8

Национальный фармацевтический университет (Харьков)

National University of Pharmacy (Kharkov)

olga.tar.rogan@mail.ru

In the past few decades Ukraine has suffered from a demographic crisis. This crysis is a reflection of both the economic problems and problems in the domain of healthcare, as well as of the absence of healthy lifestyle practice.

Drugs must not only influence patients’ current condition, but also improve quality of their lives and facilitate their complete social adaptation. That is possible only under condition of using of high-quality drugs. Administration of drugs with unproved effectiveness and safety leads to a decline in efficiency of therapy of socially significant diseases (tuberculosis, acquired immune deficiency syndrome, oncology diseases, cardiovascular pathology etc.) and growth of number of cases of complications or disability.

On of methods for proving the generic drug quality is the study of its bioequivalence. At the present time it is a key parameter determining the possibility of registration of a generic drug in the USA, Canada, Japan, and European Union. Bioequivalence study is performed in three stages: clinical stage, bioanalytical stage, and pharmacokinetic and statistical analysis. Generally, the test subject is a healthy human, so the requirements for these trials are the same as for the other clinical trials.

Pharmacotherapeutic effect of a drug depends on many factors. Therefore, at bioequivalence study it is necessary to select the subjects scrupulously. According to recommendations, the group of test subjects must answer to the following requirements: it must be homogeneous to the utmost, have no subjects with diseases, consist of men and women, correspond to exact entry criteria, and preferably include no smokers. According to the international regulations, the number of subjects should be not less than 12. Usually the bioequivalence study is performed into 18 or 24 healthy volunteers.

The gold standard of bioequivalence study design in our country is the randomized cross over clinical study. In bioequivalence study the provision of standard conditions for test subjects during the trial is of high importance. Diet, physical activity, day regimen, the absence of concomitant therapy, time of residence in clinical facility, and trial completion time are to be standardized.

Bioequivalence study provides for comparative trials. The list of reference drugs is drawn up by WHO, ЕМЕА, FDA and is approved by order of Ministry of Health of Ukraine in our country.

The establishment of two drugs bioequivalence consists in comparison of rate and extent of drug absorption, and of pattern of drug distribution in body tissues and fluids and the specific features of its recovery. During the study of drug pharmacokinetics the concentration of either active substance directly or of its metabolites in biological matrices is measured at exact moments of time, which is followed with plotting of pharmacokinetic curve that represents the dependence of concentration on time. Blood, urine, mucus and other fluids can be used as biologic substrate for determination of active substance content and its metabolites. All the bioanalytical methods that are used for establishment of content of active substance or its metabolites must be clearly characterized and completely validated. Bioanalytical part must be performed in compliance with the preliminary approved SOP and the requirements of good laboratory practice.

The drugs are considered as bioequivalent, if the 90% confidence interval for ratio of mean ln-transformed values AUC0-t and Cmax lies within the range of 0,8000÷1,2500 (80,00÷125,00 %). Bioavailability or bioequivalence study report is completed in compliance with the requirements of ICH GCP for clinical trial reports.

In the developed countries the generics and the original drugs have the same requirements for entry into market. If the generic is approved, it means that it complies with stringent standards established in regards to drug identification, dosage, quality, purity and effectiveness. The situation in Ukraine is quite different. The information on drugs replaceability either does not exist due to non-performing of undertaken bioequivalence studies, or it is unavailable for wide range of specialists.

Nevertheless, today in Ukraine certain steps are taken to protect its citizens from poor-quality products: there functions a number of clinics and pharmacokinetic laboratories, and the required regulatory framework is created. However, the requirements for quality of clinical trials and their legal and procedural framework get more and more stringent and require further work in this direction. Domestic manufacturers have to keep up with the times and confirm quality of their drugs with respect to provisions of evidence based medicine, and the authorized authorities officers have to strengthen control over effectiveness, safety and quality of drugs.

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