Generic Medicinal Products Research Articles

FACTORS AFFECTING THE WITHDRAWAL PERIOD OF AMOXICILLIN FROM VETERINARY MEDICINAL PRODUCTS USED IN FOOD-PRODUCING ANIMALS

The withdrawal period of active substance residues from the animal’s body which products are intended for human consumption is an important criterion for the safety of veterinary medicinal products. This products cannot be authorized without establishing this important parameter. There are a number of veterinary medicinal products on the market of Ukraine and EU member states, which have the same active substance in the same concentration and pharmaceutical formulation, but the withdrawal period can differ significantly.
 The goal of our study was to determine the influence of various factors on the withdrawal period of amoxicillin from single-component oral (powders) and injectable (suspensions, long acting suspensions) dosage forms, which are included in the State Register of Veterinary Medicines of Ukraine and EU product database (UPD).
 As is known, amoxicillin is widely used for the treatment of infectious diseases in humans and animals, in particular food-producing ones, which are a source of food products intended for human consumption. From the point of the hazard of development acquired antimicrobial resistance when consuming products of animal origin contaminated with residues, the duration of the established withdrawal period is a question of great importance.
 As shown in the study results, the pharmacokinetic parameters of veterinary medicinal products, in particular bioavailability, as well as clinical characteristics of the disease, have a significant impact on the duration of the withdrawal period. Usually, the withdrawal period depends on the type of dosage form, and the amount and nature of excipients, because oral and injectable pharmaceutical formulations of the same veterinary medicinal product differ in terms of bioavailability from the systemic circulation and the site of injection. It was also defined that the duration of the withdrawal period depends on the amount of the administered dose of the veterinary medicinal product, the treatment duration, the target animal species, fasting conditions (before or after feeding), and the substrates used for feeding (dissolving in water or mixing with feed), analytical methods used to determine active substances or their metabolites, methods of the statistical processing results and differences between individual values established in a group of animals involved in the study.
 The importance of approving the withdrawal period for generic veterinary medicinal products manufactured by different companies is confirmed by studies carried out by the European Medicines Agency order at the request of the Competent authorities of individual EU countries in connection with the detection of the overestimated residue level compared with the established maximum limits over time, defined as the withdrawal period specified during product authorization.
 In two cases, changes were made to the Summary of Product Characteristics and package leaflets, regarding the extension of the withdrawal period of amoxicillin from certain tissues and for different target animal species. Marketing authorization holders are recommended to harmonize the withdrawal period for generic products with the established value for the reference veterinary medicinal products.

Antimicrobial activity and pathogen mutation prevention of originator and generics of cefepime, linezolid and piperacillin/tazobactam against clinical isolates of Staphylococcus aureus

Although generic medicinal products are required to have the same qualitative and quantitative composition of the active substance as their reference originator product, patients and health care professionals express concerns about their interchangeability and safety. Therefore, the present study investigated the antimicrobial activity and pathogen mutation prevention of original and generic cefepime, linezolid and piperacillin/tazobactam against Staphylococcus aureus. Two generic formulations of cefepime, linezolid and piperacillin/tazobactam were tested against their respective originator products. Susceptibility testing was performed with twenty-one clinical isolates of S. aureus and ATCC-29213 using broth microdilution. Time kill curves (TKC) were performed with ATCC-29213 at drug concentrations above and below the respective minimum inhibitory concentrations (MIC). Mutation prevention concentration was determined for each drug formulation against ATCC-29213. All experiments were performed in triplicate. Mutant colonies from mutation prevention concentration (MPC) experiments were genotypically tested by sequence analysis. MIC ratios between contiguous originator and generic drugs were similar for each isolate. No visual differences were observed in TKCs between originator and generic substances. The MPC did not differ between different formulations of the same substance. Although sequence analysis of mutant colonies revealed genomic differences compared with the original ATCC-29213, no differences in mutation frequencies were observed between clinical isolates and ATCC-29213 treated with originator or generic substances. Similar antimicrobial activity and pathogen mutation prevention was observed between contiguous substances. These results support the interchangeability of generic and originator drug formulations with the same active ingredient.

Health professionals' perceptions on local production and bioequivalence study of generic medicines: A cross-sectional survey of physicians and pharmacy professionals in Addis Ababa, Ethiopia.

Local production of generic medicines in developing countries has a critical role to meet public health needs by ensuring the availability of essential medicines and providing patients' relief from the burden of unaffordable medical bills. Compliance with bioequivalence (BE) requirements increase the quality and competitiveness of generic drugs regardless of the source. In this regard, a regional BE center has been established in Addis Ababa, Ethiopia to serve the needs of Ethiopia and neighbouring countries. The present study aimed to assess the knowledge and perceptions of health professionals working in Addis Ababa regarding local production and BE studies of generic medicines. A cross-sectional survey was employed and physician participants working at public hospitals and pharmacists from various practice settings were selected using convenient sampling technique. Data was collected using self-administered structured questionnaire. Descriptive statistics was used to summarize the data and multinomial logistic regression analyses was used to assess predictors of health professionals' perception towards the source of drugs. Statistically significant association was declared at p-value < 0.05. A total of 416 participants responded and 272 (65.4%) of them were male. Nearly half of the study participants (n = 194) preferred the imported products. Compared to physicians, participants with diploma (AOR = 0.40; 95%CI: 0.18-0.91, p = 0.028) and bachelor degree and above holders (AOR = 0.32; 95%CI: 0.15-0.68, p = 0.003) in pharmacy were more likely to prefer locally produced products. Participants who practiced in pharmaceutical industries (AOR = 0.40, 95%CI: 0.22-0.77, p = 0.006) preferred locally manufactured products as compared to those practicing in the hospital. While a majority (321, 77.2%) believed in the advantages of doing BE studies locally, only 106 (25.5%) recognized that local pharmaceutical manufacturers did not implement BE studies for their generic products and lack of enforcement by the national regulatory body was raised as a reason for not conducting BE studies by most of the participants (67.9%). The present study revealed a modest preference by physicians and pharmacy professionals towards locally produced products. Majority of participants supported the idea of doing BE studies locally. However, manufacturers and regulators should devise ways to increase health professionals' confidence in local products. Strengthening local BE study capacity is also highly recommended.

A Pharmacoeconomic Outlook of the Biological Drugs Marketed in India: A Cost Variance Analysis.

Introduction Biologic drugs are used to treat various illnesses like autoimmune diseases, cancers, hormonal irregularities, anemia, etc., and to prevent various diseases as vaccines. Though various biologic drugs are already available, they are still not within reach of the common man due to financial constraints. Through many search engines, studies evaluating the cost variation of different brands of biologics were investigated; however, only a few studies that address this problem were found. Hence, this study was planned with the objective of addressing the cost variation of various brands of biologic medicines available in the Indian market. Methods The website for the Current Index of Medical Specialties (CIMS) for India's location was used to obtain the prices of the different brands of biologic medicines in Indian National Rupee (INR) currency, which different manufacturers market with identical forms in strength and dosage. The percentage cost variation and cost ratio were calculated with the help of the minimum and maximum prices of various brands of biologic drugs. Results The prices of biologics belonging to six different classes that are available in 23 formulations were analyzed. The highest cost variability was shown by pegfilgrastim 6 mg at 1,022.92%, and the minimum-cost variation was shown by darbepoetin alfa 200 mcg at 13.07%. Conclusion Our research found a vast variance in the costs of various brands of biologic medicines in India. The government should address this cost variation problem by developing various policies, such as breaking the monopoly of manufacturers, providing tax incentives to nonprofit generic medicine manufacturers, and incorporating more biologic drugs under the protection of the Drugs Prices Control Order (DPCO).

RISK-ORIENTED APPROACH TO OPTIMIZATION OF PHARMACEUTICAL DEVELOPMENT PROCESS OF MEDICINAL PRODUCTS

Abstract. The modern regulatory requirements for pharmaceutical development, stricter of requirements of medicinal products (MP) quality standards, the experience of manufacturers and development companies in terms of MP pharmaceutical development revealed need to create solutions that minimize the risk of medicinal product quality deviations, guaranteeing the release of effective and safe MP with the planned quality. The aim of these study is to form solutions for optimization of generic medicinal products pharmaceutical development process. For the study, according to the proposed algorithm, a generic drug in a liquid for inhalation dosage form was developed. The pharmaceutical development of MP according to created model contributes to reducing the financial and time costs of the developer company related to repeated research of PD, eliminating inconsistencies in the reproducibility and control of the technological process, maintaining the goals of the company's PQS in terms of the development and circulation of medicinal products, guaranteeing efficiency, safety and quality of the developed generic medicinal products.

An IPRP survey of the regulatory requirements for the waiver of in vivo bioequivalence studies of generic medicinal products in certain dosage forms

Medicines regulatory authorities aim to address rising healthcare costs and promote access to medicines worldwide through review and approval of quality generic drug products that are interchangeable with the corresponding reference medicinal product.

Pharmaceutical nationalism as an instrument to ensure the access to medicines

Keywords: pharmaceutical nationalism, access to drugs, compulsory licensing, governmentuse, exclusion from intellectual property rights&#x0D; The article concerns the emergence of the phenomena of«pharmaceutical nationalism» in the year of the COVID-19 pandemic. Pharmaceuticalnationalism is manifested in the qualitative and quantitative aspects. In the contextof a qualitative manifestation of pharmaceutical nationalism, we presume the politicalwill on establishing of a new state protectionist policy to local manufacturers ofmedicines, the establishing of preferences, exemptions of the patent monopoly basingon international legal instruments (TRIPS-flex). The quantitative aspect of pharmaceuticalnationalism is the primacy of satisfaction of the needs of the domestic marketof medicines in quantities that could ensure the biological security of individually foreach state, independently of the interests of others. The article also raises the issue ofthe need and means of forming pharmaceutical nationalism in Ukraine.The world community is calling for the demonopolization of research results on theprevention and treatment of COVID-19. WHO invites developers and companies towork together to ensure the disclosure of treatments and methods if they prove effective.International Federation of Library Associations and Institutions also presentedan open letter to WIPO urging WIPO to use all available flexible intellectual propertymechanisms to maximize global access to information (research data) on the treatmentof COVID-19. Canada, Israel and the EU are working to prevent the monopolizationof COVID-19 prevention and treatment.Ukraine should actively work to develop legislation in the field of compulsory licensing,as provided for in Art. 31 TRIPS Agreement. From a political point of view, itis the historical chance of Ukraine to become «he second India» or «the first Ukraine»in Europe in the production of generic medicines and biosimilars.

WITHDRAWN: Cloud computing based generic medicine recommendation system for advanced E-Healthcare

Many health institutes manually record and collect patients' data may be misunderstood and at times, inconsistent. Also, patients' alienation from medical details leaves them unaware of the necessary medical costs and inevitably causes them to pay long and ineffective bills. Therefore, it is very important and important to consider the consumers of generic medicinal products – medicinal products of the same chemical composition, but available at low cost. This device proposes a method for sensing the physical wellbeing of patients using sensors after they are admitted to the hospital. This is added to a “cloud” server that stores the health parameters of patients and accesses them whenever possible. The patient's cloud-based databases also include the medicine prescribed by physicians, the diagnosed condition of the patient and the tests suggested by the doctors. The software interfaced between the cloud and the patient data entry displays the results of 'cost-effective generic drugs,' the necessary tests needed for the patient and the hospital to be qualified for further treatment, which are shown to the patients or their associates. Few well-equipped healthcare facilities follow data centralization and database approaches, but their accuracy remains a matter of reliability. Our proposed system offers a way for patients to track their medical costs within their boundaries, using sensors and cloud computers as their technological resources.

A Survey of the Regulatory Requirements for the Waiver of In Vivo Bioequivalence Studies of Generic Products in Certain Dosage Forms by Participating Regulators and Organisations of the International Pharmaceutical Regulators Programme.

The requirements to waive in vivo bioequivalence studies for immediate release solid oral dosage forms based on the Biopharmaceutics Classifications System (BCS) are well known, and biowaivers[1] for other types of oral dosage forms based on pre-defined criteria may also be acceptable. Similarly, biowaivers for dosage forms such as injectable products may also be allowed if certain criteria are met. The current paper summarises the biowaiver requirements for oral solutions and suspensions, soft gelatin capsules and injectable products (intravenous injections, subcutaneous and intramuscular injections, emulsions for injection and micellar solutions for injection) among the participants of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Programme (IPRP). A review of the requirements indicated that there was a trend towards convergence when the dosage form became less complex; however, the most common approach used by each of the jurisdictions was a case-by-case approach given that most jurisdictions do not have well defined guidelines to support all possible scenarios. Even in the simplest case of intravenous solutions, the acceptability of qualitative changes in excipients differ between the IPRP members. Notwithstanding the differences, the dissemination of the information is a first step towards regulatory convergence regarding biowaivers for certain dosage forms and should be useful for pharmaceutical companies currently developing generic medicinal products for IPRP jurisdictions.

Monitoring the manufacturing and quality of medicines: a fundamental task of pharmacovigilance.

The collection and assessment of individual case safety reports (ICSRs) is important to detect unknown adverse drug reactions particularly in the first decade after approval of new chemical entities. However, regulations require that these activities are routinely undertaken for all medicinal products, including older medicines such as generic medicinal products with a well-established safety profile. For the latter, the risk management plans no longer contain important risks, considered important safety concerns, on the basis that routine pharmacovigilance activity would not allow their further characterisation. Society assumes that unexpected adverse reactions causally related to pharmacological activity are very unlikely to be detected for such well-established medicines, but important risks can still occur. For these products, a change in the safety profile which is brand or source specific and usually local in nature, associated with failures with the adequate control of quality of manufacturing or distribution are important safety issues. These may be the consequence of manufacturing and pharmacovigilance quality systems that are not fully integrated over the product life cycle (e.g. inadequate control of quality defects affecting one or multiple batches; inadequate impact assessment of change/variation of manufacturing, quality control testing, storage and distribution processes; inadequate control over the distribution channels including the introduction of counterfeit or falsified products into the supply chain). Drug safety hazards caused by the above-mentioned issues have been identified with different products and formulations, from small molecules to complex molecules such as biological products extracted from animal sources, biosimilars and advanced therapy medicinal products. The various phases of the drug manufacturing and distribution of pharmaceutical products require inputs from pharmacovigilance to assess any effects of quality-related issues and to identify proportionate risk minimisation measures that often have design implications for a medicine which requires a close link between proactive vigilance and good manufacturing practice. To illustrate our argument for closer organisational integration, some examples of drug safety hazards originating from quality, manufacturing and distribution issues are discussed.Plain language summary Monitoring the manufacturing and quality of medicines: the fundamental task of pharmacovigilance Pharmacovigilance is the science relating to the collection, detection, assessment, monitoring, and prevention of adverse reactions with pharmaceutical products. The collection and assessment of adverse reactions are particularly important in the first decade after marketing authorisation of a drug as the information gathered in this period could help, for example, to identify complications from its use which were unknown before its commercialization. However, when it comes to medicines that have been on the market for a long time there is general acceptance that their safety profile is already well-established and unknown adverse reactions unlikely to occur. Nevertheless, even older medicines, such as generic drugs, can generate new risks. For these drugs a change in the safety profile could be the result of inadequate control of their quality, manufacturing and distribution systems. To overcome such an obstacle, it is necessary to fully integrate manufacturing and pharmacovigilance quality systems in the medicine life-cycle. This could help detect safety hazards and prevent the development of new complications which may arise due to the poor quality of a drug. Pharmacovigilance activities should indeed be included in all phases of the drugs’ manufacturing and distribution process, regardless of their chemical complexity to detect quality-related matters in good time and reduce the risk of safety concerns to a minimum.

Current Challenges in Labelling for Generic Medicinal Products: Company Core Data Sheet (CCDS) Development and Maintenance.

Labelling of pharmaceutical products plays a vital role in the safe and effective use of approved medicinal products. This information may be provided to end-users including patients and/or prescribers, and it needs to be made available in multiple formats including printed forms (patient information leaflets, pack inserts, etc.) or web portals of the product, based on national authority guidelines. The Company Core Data Sheet (CCDS) serves as a key document representing the pharmaceutical company’s position on the product and is used as a reference document for national labels. Content from national labels may differ from the CCDS for different reasons including implementation of national authority requirements in the serving market and findings from local markets. In the current article, we discuss the process, challenges and key concepts in creating and maintaining CCDS documents for generic products. We highlight key parameters that are worthy of process improvement in generic products’ CCDS updates. In addition, we argue that labelling harmonisation across multiple regions, especially safety section-related information, plays a key role in promoting end-user safety and would help communicate risks. We also strongly believe that the topic is worthy of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) consideration, and propose that this is the key area that requires standardisation and harmonisation.

Bioequivalence study of the medicinal products Flutrixan and Nexavar

А replicate designed open-label, randomized, crossover single-dose bioequivalence study using three periods and three sequences was conducted to assess the comparative bioavailability of the sorafenib-containing medicinal products Flutrixan (200 mg tablet, Institute of Bioorganic Chemistry of NAS of Belarus, Belarus) and Nexavar (200 mg tablet, Bayer Pharma AG, Germany), in healthy volunteers under fasting conditions. It was shown that all criteria used to assess the bioequivalence of compared medicinal products were fulfilled. The Test/Reference geometric mean ratios obtained for the pharmacokinetic parameters C max and AUC 0-72 and the corresponding 90 % confidence intervals were within the acceptance range of 80.0-125.0 %. Both sorafenib products were well tolerated and had a favorable safety profile. Therefore, it can be concluded that the generic medicinal product Flutrixan is bioequivalent to the reference medicinal product Nexavar.

Corrigendum to: Oral anticoagulation in patients with non-valvular atrial fibrillation and a CHA2DS2-VASc score of 1: a current opinion of the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy and European Society of Cardiology Council on Stroke and Low quality of some generic cardiovascular medicinal products represents a matter for growing concern.

Corrigendum to: Oral anticoagulation in patients with non-valvular atrial fibrillation and a CHA2DS2-VASc score of 1: a current opinion of the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy and European Society of Cardiology Council on Stroke and Low quality of some generic cardiovascular medicinal products represents a matter for growing concern.

Discrepancies Between the Labels of Originator and Generic Pharmaceutical Products: Implications for Patient Safety.

BackgroundAll drug marketing authorization holders have the legal obligation to collect data on the use of the products they market and to keep the labels of those products updated. As demonstrated by previous studies, many generic products have labels that are discrepant from the labels of their reference (originator) products. This fact may cause inconsistent messages to be disseminated to healthcare professionals and patients for the same active ingredient.ObjectiveThese potential label discrepancies led us to investigate the degree of difference between labels for generic and originator products, the possible consequences of this discrepancy for patients, and its implications for risk minimization.Products and MethodsDrugs from different Anatomical Therapeutic Chemical classes were randomly selected from the Electronic Medicines Compendium. For each drug, the consistency and discrepancies between the summaries of product characteristics (SmPCs) for originator and generic products were analyzed for each safety-relevant section of the SmPC separately as well as across all of its sections. The percentile distribution of discrepancy classifications was calculated. The same method was applied when determining the potential impact of label discrepencies on patients.ResultsAmong the 50 drugs selected initially, 31 were eligible for the study and were analyzed further. Of those 31 drugs, 13 (41.9%) presented critical label differences between originator and generic products, 6 (19.4%) showed major label differences, 7 (22.6%) exhibited minor label differences, and 5 (16.1%) showed very minor label differences. Over 60% of the selected drugs (19, 61.3%) presented important (critical, major) label differences between originator and generic products. None of the selected drugs had fully aligned labels of originator and generic products. Label misalignments that could potentially have a fatal or life-threatening impact on the patient were observed for 4 (12.9%) of the selected drugs. Label misalignments that could have a severe patient outcome were noted for 11 (35.5%) of the selected drugs, and label misalignments that could have a medium impact on the patient were seen for 6 (19.35%) of the selected drugs. The label misalignments observed for 10 (32.25%) of the selected drugs would potentially lead to only a minor or no effect on the patient. Almost half (15, 48.4%) of the selected drugs presented label misalignments that could have a critical (fatal, life-threatening, severe) influence on the patient.ConclusionsIn this sample, SmPC alignment between generic and originator medicinal products was found to be inefficient for established drugs, and could lead to the diffusion of discrepant messages to healthcare professionals and patients. In order to address this SmPC alignment problem, health authorities such as the EMA and the FDA must conduct retrospective analyses of all drugs on the market as a first step towards realigning labels. These analyses could be performed during the evaluation of aggregate reports.

Razvoj SPE-HPLC-DAD metode za određivanje florfenikola i florfenikol amina u cerebrospinalnoj tekućini svinja

A study of florfenicol (FF) and its metabo- lite florfenicol amine (FFA) in pig cerebrospinal fluid was conducted following repeated intramuscular administration of the original (reference) and a generic veterinary medicinal product (VMP) under the same experimental conditions (20 mg FF/kg body weight, 48-hour interval). Both VMPs are solutions for injection containing FF as an active substance in the concentration of 300 mg/mL and have been authorized in Croatia for use in cattle and pigs. In this study, clinically healthy pigs were randomly divided into three groups. The first group was treated with the reference VMP, the second with the generic VMP, while the third served as the control group. Animals were sacrificed at 216, 288 and 384 hours after the first drug administration. Cerebrospinal fluid samples were analysed by the optimized and validated high-performance liquid chromatography-diode array detector method (HPLC-DAD). The solid-phase extraction (SPE) technique was chosen for sample preparation. The HPLC-DAD method provides good linearity over the concentration range of 0.05 to 5.00 μg/mL for FF and FFA. Limits of detection were 0.0023 μg/mL for FF and 0.0100 μg/mL for FFA. Extraction recoveries of FF were from 86.6% to 111.8%, and of FFA from 91.7% to 98.8%. The SPE-HPLC-DAD method has been demonstrated to be a selective, sensitive and suitable analytical method for the determination of FF and FFA in cerebrospinal fluid. The present study was based on a preliminary study that quantified FF in pig plasma at 216 hours after the first application of reference or generic VMP. However, FF and FFA were not detected in any of the cerebrospinal fluid samples during the experimental period. According to the nature of biological fluids, the SPE-HPLC-DAD method can be suitable for further pharmacokinetic studies of FF in pig plasma and serum after intramuscular administration of VMPs.

Conventional and Multivariate Statistical Methods for Evaluation of &amp;lt;i&amp;gt;In vitro&amp;lt;/i&amp;gt; Dissolution Similarity of Bisoprolol Film-coated Tablets

<i>In vitro</i> dissolution testing is an important tool used for pharmaceutical development and approval of generic medicinal product, playing a pivotal role in regulatory decision-making. This study includes evaluation and comparative analysis of <i>in vitro</i> dissolution profiles of Bisoprolol film-coated tablets and <i>in vitro</i> dissolution profile of a reference medicinal product, using several model-independent and model-dependent statistical methods. The evaluated medicinal product belongs to BCS Class I (high solubility, high permeability). The similarity testing of dissolution profile is performed on the highest strength of the dosage form, in accordance with the regulatory requirements for bioequivalence study. Obtained results have shown that <i>in vitro</i> comparative dissolution analysis using pair-wise independent-model procedures, such as difference (<i>f₁</i>) and similarity (<i>f₂</i>) factors are not suitable, because one of the requirements (not more than one mean value dissolves more than 85%, for any of the formulations) was not fulfilled. Therefore, the comparison of the similarity of dissolution profiles was performed using Ratio test methodology and multivariate model-independent approach based on generalized statistical distance (Mahalanobis distance). Furthermore, other model-dependent approaches coupled to multivariate statistics (Weibull) were applied. The obtained results from the performed analysis indicated a significant similarity of the compared <i>in vitro</i> dissolution profiles between the tested batches from bisoprolol film-coated tablets and reference medicinal product). Implemented statistical methods can be considered as a regulatory accepted concept for evaluation of <i>in vitro</i> similarity of generic medicines.

Проблеми правового регулювання спрощеної реєстрації ветеринарних препаратів в Україні

Статтю присвячено дослідженню особливостей правового регулювання спрощеної реєстрації ветеринарних препаратів у світлі гармонізації законодавства України із законодавством ЄС. Відзначено, що у зв’язку зі складністю підготовки повного реєстраційного досьє в законодавстві багатьох країн, в тому числі країн Євросоюзу передбачено низку можливостей для спрощеної реєстрації ветеринарних препаратів шляхом подачі скороченого переліку матеріалів реєстраційного досьє.&#x0D; Здійснено аналіз відповідного законодавства ЄС, зокрема положень Директиви 2001/82 щодо спрощеної реєстрації ветеринарних препаратів. Визначено, що в праві ЄС передбачено можливість подачі неповного досьє у випадках реєстрації генеричних чи гібридних ветеринарних препаратів, ветеринарних препаратів з добре вивченим ветеринарним застосуванням, ветеринарних препаратів з фіксованою комбінацією, ветеринарних препаратів, що реєструються за інформованою згодою. Доведено, що на сьогодні правове регулювання такої реєстрації в Україні потребує вдосконалення.

Low quality of some generic cardiovascular medicinal products represents a matter for growing concern.

Generic medicinal products (GMPs) are low-priced copies of off-patent medicines that reduce healthcare costs and broaden access to healthcare. Thus, healthcare authorities, professionals, and providers recommend their use. In recent years, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved hundreds of GMPs based on specific bioequivalent trials. The question is whether the brand name drugs and GMPs or the different GMPs similar in purity, efficacy, and safety. We have reviewed the progressive increasing recalls and warning letters of cardiovascular GMPs issued recently by the FDA/EMA. Both Agencies found numerous irregularities in the purity, safety, effectiveness, and current good manufacturing practices in some GMPs widely used in cardiovascular therapy. This evidence and the recent identification of nitrosamine impurities classified as probable human carcinogens in several angiotensin receptor blockers confirm that the presence of low-quality/substandard GMPs represents a serious public health problem with significant impact on national clinical and economic burden. A global strategy that unifies the efforts of all the stakeholders, including drug manufacturers, healthcare providers, governments, health professionals, patients, and judicial systems are needed to protect the drug chain supply and ensure that only high-quality GMPs are available for use.

Overview of the European Medicines Agency's Experience With Biowaivers in Centralized Applications.

The waiver of the in vivo demonstration of bioequivalence (biowaiver) is an established tool in drug development and regulatory assessment. This study reviews the use of different biowaiver approaches in centralized applications for marketing authorization to the European Medicines Agency for generic and innovator medicinal products in 2016 and 2017. The focus was to provide insight into the applicability of biowaivers for medicines development. The results show that as expected, biowaivers were most frequently used in applications for generic medicines, in particular for the approval of additional strengths when in vivo bioequivalence has been demonstrated using a single, usually the highest, strength. Biowaivers have, however, also been used in applications for innovator medicines in different phases of clinical development. This review confirms the existing key roles and further potential for biowaivers in regulatory submissions in that they are useful in streamlining the often challenging processes of clinical development.

Generic medicinal products: if you know them, you do not avoid them

Although equivalent (generic) medicinal products have been introduced in the Italian market since decades, Italy is still among the latest for prescription of equivalent medicinal products. Several reasons may explain this behavior such as a scant familiarity with equivalent medicinal products, a general skepticism toward "not branded-named" medications and an "indolent laziness" both by specialists and general practitioners. Yet, the wider use of the generic drug could: (i) save economical resources for the National and Regional Health Services and allow to allocate them in clinical research and development of new therapies; (ii) reduce the economic burden for the patients by saving the brand drug-related co-payments, especially if they are on polytherapy. Moreover, given that current resources for our health system are limited, preferring drug with expired patent should be an "ethical" issue and a mandatory duty. The purpose of this brief review is to propose a concise but exhaustive analysis on equivalent medicinal products, in order to clarify still existing doubts and to remove remaining cultural obstacles to their use, if any, in the field of clinical cardiology.