Good Manufacturing Practice for Medicinal Products in Bulgaria: an Analysis of Regulatory Inspection Findings

Background: The manufacture of medicinal products for human use in the European Economic Area is governed by European Directives and Regulations stipulating the relevant principles and guidelines of Good Manufacturing Practice, describing the minimum standard to be fulfilled in the production processes.   Aim: To present analysis of the deficiencies reported following Good Manufacturing Practice inspections in Bulgaria in two consecutive years (2016, 2017) and to compare them with results from similar inspections reported by other EU member states.   Materials and methods: A retrospective study was carried out by reviewing the complete Good Manufacturing Practice inspection reports of all manufacturers conducted by the Bulgarian Drug Agency in 2016 and 2017, according to relevant requirements and applicable local legislation. The items reviewed were scope of inspection, type of companies, classification of deficiencies – ‘critical’, ‘major’ and ‘other significant deficiencies’, their nature and reference to EU Good Manufacturing Practice.   Results: The analyzed data included 55 inspections, revealing 460 various deficiencies, of which 2 were critical and 102 – major. Twenty inspections were performed in 2016 vs. 35 inspections in 2017. The pattern of deficiencies was similar to the findings of other EU regulatory agencies, showing that equivalent requirements were applied. Our analysis showed that Bulgarian Drug Agency inspectors rarely raised deficiencies related to Computer Systems, Qualification/Validation, Personnel and Qualification of Suppliers unlike other EU regulators agents.   Conclusions: Our analysis of Good Manufacturing Practice inspection findings in 2016 and 2017 showed that the Bulgarian Drug Agency demonstrated its ability to detect non-compliances and take necessary regulatory actions. Quality related issues constitute the main reasons for non-compliances with the requirements. Publishing the results from the inspections performed by the national competent authorities enhances the regulatory transparency that can be useful for industry to improve its Good Manufacturing Practice compliance.

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European Union Public Procurement Remedies Regimes

Public Sector Transformation Processes and Internet Public Procurement ◽

10.4018/978-1-4666-2665-2.ch008 ◽

2012 ◽

pp. 162-184

Author(s):

Kai Krüger

Keyword(s):

European Union ◽

Public Procurement ◽

European Economic Area ◽

European Economic ◽

Eu Member States ◽

Eu Directive ◽

Court Of Justice ◽

Economic Area ◽

Set Up ◽

The Eu

The chapter explores the Nordic statutory EU-based remedy regimes. Due to the European Economic Area (EEA) agreement, the EU commitments do not vary between EU member states, Denmark, Finland, and Sweden and (non-members) Norway and Iceland. The legislation on procurement remedies is assumed to be EU/EEA compliant. There are however material differences in the set up for handling disputes and complaints—also subsequent to the 2010-2012 Nordic adaptation of EU Directive 2007/66/EC on enhanced procurement remedies. The pending issue is whether the EU “sufficiently serious breach” principle on treaty infringements applies on liability for procurement flaws. Loss of contract damage has been awarded in all Nordic countries, whereas cases on negative interest (costs in preparing futile tender bids) seem more favorable to plaintiffs. Per mid-2012, there are no Nordic rulings on the effect of the recent somewhat ambiguous EU Court of Justice Strabag and Spijkers 2010 rulings.

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Good Manufacturing Practice: The Role of Local Manufacturers and Competent Authorities

Archives of Industrial Hygiene and Toxicology ◽

10.2478/10004-1254-61-2010-2035 ◽

2010 ◽

Vol 61 (4) ◽

pp. 425-436 ◽

Cited By ~ 1

Author(s):

Siniša Tomić ◽

Anita Sučić ◽

Adrijana Martinac

Keyword(s):

Regulatory Network ◽

Good Manufacturing Practice ◽

Pharmaceutical Product ◽

Vital Role ◽

Medicinal Products ◽

Eu Member States ◽

Eu Membership ◽

European Regulatory ◽

The Eu

Good Manufacturing Practice: The Role of Local Manufacturers and Competent AuthoritiesIn every country, a manufacturer of medicinal products for either human or veterinary use is required to operate in compliance with local legislation. In all EU Member States, legislation is approximated to the effect that they are committed to abide by the same standards. The candidate countries transpose the acquis into their national legislation, including the good manufacturing practice (GMP). Consequently, the local manufacturer is required to strictly comply with GMP and the manufacturing licence, including for medicinal products exclusively intended for export. A vital role is also played by national regulatory authorities, in Croatia by the Agency for Medicinal Products and Medical Devices which issues the manufacturing licence, GMP certificate, and the Certificate of a Pharmaceutical Product (CPP) and conducts laboratory control of products. GMP inspection is carried out by the Pharmaceutical Inspectorate with the Ministry of Health and Social Welfare. Both authorities are responsible only for human medicines. There are legislative issues not yet harmonised with the acquis, but as a country aspiring for the EU membership, Croatia is expected to demonstrate that its industry and competent authorities are able to conform to current requirements and thus fully adhere to the integrated European regulatory network. Hence the importance of strengthening the institutional capacity of the competent authorities, as insufficient resources may have a direct bearing on patients by limiting their access to affordable treatment.

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Assessing the Correlation Between GMP Deviations and Potential Quality Defects of Medicinal Products: the Result of the Survey of Qualified Persons

Drug development & registration ◽

10.33380/2305-2066-2020-9-2-151-158 ◽

2020 ◽

Vol 9 (2) ◽

pp. 151-158

Author(s):

V. A. Orlov ◽

V. N. Shestakov

Keyword(s):

Russian Federation ◽

Good Manufacturing Practice ◽

Class I ◽

Medicinal Products ◽

Main Hypothesis ◽

Risk Class ◽

Regulatory Documents ◽

The Russian Federation ◽

Methodological Guidelines

Introduction. One of the key issues in the field of assessing the conformity of drug manufacturers with the requirements of good manufacturing practice (GMP) is a systematic methodology for classifying revealed deficiencies (deviations, non-conformities) by their level of criticality. Today the information included into regulatory documents regarding the definitions of critical, major and minor (other) deficiencies is not always sufficient for the use in GMP inspection practice, as well as in quality management systems of the pharmaceutical manufacturers. In terms to study approaches to the classification of GMP deviations applied in the practice of the Qualified persons of drug manufacturers in the Russian Federation, a survey was conducted in the form of a questionnaire. This work became a logical continuation of a previous study among employees of the pharmaceutical inspectorate of the Russian Federation.Aim. To identify the correlation between the classification of critical and major GMP deviations and potential class I and II quality defects of medicinal products.Materials and methods. The study was based on a survey of Qualified persons of drug manufacturers (56 respondents) using a questionnaire specially designed. The main hypothesis of the study is that specialists (Qualified persons) who make decisions on the classification of GMP deviations are guided by potential quality defects that may be caused by the indicated deviations. In the framework of the study, authors used the model of gradation of quality defects of the medicinal products into 3 classes (class I, II and III) according to the rate of their significance as indicated in the PIC/S and EMA guidelines. At the same time, for GMP deviations a three-level gradation system is also used: Critical, Major and Minor (Other). In designing of questionnaires for the survey, the focus was made on examples of quality defects of classes I and II and, accordingly, Critical and Major GMP deviations.Results and discussion. The results of the processing and analysis of questionnaires summarize the opinion of the majority of respondents about the direct relationship between product quality defects of the high risk (class I) and critical GMP deviations. Respondents also expressed the opinion that deviations that could trigger the occurrence of the class II quality defects in most cases will be classified as critical. The results obtained during the study also indicate the similarity of existing approaches of the classification of GMP deviations (deficiencies) between QPs of the drug manufacturers and pharmaceutical inspectors.Conclusion. The results of the study show that for the purpose of classifying (determining the criticality) of GMP deviations (deficiencies) , it is possible to use the rating system for the quality defects of medicinal products by the rate of their significance for the patient which is presented in EU regulatory documents and PIC/S guidelines. The results of the study also will facilitate the drawing of conclusions that today, not only from the position of regulatory authorities, but also for the pharmaceutical industry, there is a need to develop methodological guidelines with a focus on a risk-based classification of GMP deviations (deficiencies). These guidelines should take into account the potential impact of the mentioned GMPdeviations on the occurrence of the quality defects of medicinal products and, as a result, threats to the life and health of patients.

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Where culture, language and politics meet: Is there any place for national identity in the EEA legal system?

Unio - EU Law Journal ◽

10.21814/unio.2.9 ◽

2019 ◽

Vol 2 ◽

pp. 108-122

Author(s):

Allan F. Tatham

Keyword(s):

National Identity ◽

Legal Order ◽

European Economic Area ◽

Eu Law ◽

The European Union ◽

Eu Member States ◽

Court Of Justice ◽

Economic Area ◽

Language And Politics ◽

Constitutional Identity

Over recent years, most particularly with the entry into force of the Lisbon Treaty, the protection of national identity or constitutional identity has become a bone of contention between the Court of Justice of the European Union and the courts of EU Member States. While of obvious relevance to the development of the Union legal order, this concept has implications beyond the borders of the Union especially with respect to those EFTA states which are also members of the European Economic Area. With its own court, the EFTA Court, having successfully transposed (to varying degrees) fundamental EU law principles into the sui generis EEA system, this article considers whether or not it might repeat the process with national identity and, if so, the extent to which it might be successful.

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Medicamentos Não Sujeitos a Receita Médica de Dispensa Exclusiva em Farmácia em Portugal: Uma Oportunidade de Acesso Sub-Aproveitada?

Acta Médica Portuguesa ◽

10.20344/amp.7465 ◽

2016 ◽

Vol 29 (9) ◽

pp. 542

Author(s):

Ana Paula Martins ◽

Elizabete Gonçalves ◽

Ana Marcelo ◽

Sergio Vilão ◽

José Aranda Silva

Keyword(s):

Public Health ◽

United Kingdom ◽

Czech Republic ◽

Lower Percentage ◽

Medicinal Products ◽

Medical Prescription ◽

Safety And Efficacy ◽

The Public ◽

Human Use

Introduction: In 2013 medicinal products for human use not subject to medical prescription dispensed exclusively in pharmacy, a subcategory of products not subject to medical prescription was introduced in Portugal. This category of medicinal products promotes the accessibility to treatment, ensuring safety and efficacy, with benefits to public health. This article analyzed the medicines classified as medicinal products for human use not subject to medical prescription dispensed exclusively in pharmacy or equivalent in seven European countries, United Kingdom, Denmark, Sweden, Norway, Italy, Czech Republic and Portugal, and proposes a preliminary list of common international names/ medicines that possess the characteristics that justify their inclusion in Portugal, in this category.Material and Methods: For the selection, common international names /medicines approved in the considered countries were selected if, in at least one of the countries considered, they are classified as medicinal products for human use not subject to medical prescription dispensed exclusively in pharmacy or equivalent, and/ or have the classification of medicinal products subject to medical prescription in Portugal and medicinal products not subject to medical prescription in one of the considered countries.Results: The preliminary list obtained contains 271 different common international names / presentations. About 19% of the selected common international names do not have a valid marketing authorization in Portugal and the majority (42%) is classified in Portugal as medicinal products not subject to medical prescription, a lower percentage (35%) as medicinal products subject to medical prescription, and only 4% as medicinal products for human use not subject to medical prescription dispensed exclusively in pharmacy.Conclusion: Safety is one of the main aspects to be considered in the context of the reclassification of medicines regarding their supply to the public. The results obtained promote a reflection on the relevance of extending the availability of medicines with the classification of medicinal products for human use not subject to medical prescription dispensed exclusively in pharmacy in Portugal, which, due to their characteristics and indications, would benefit from an access without a medical prescription, ensuring the safety in its use.

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Quality standards for biopharmaceuticals: the importance of good manufacturing practice

Generics and Biosimilars Initiative Journal ◽

10.5639/gabij.2020.0903.017 ◽

2020 ◽

Vol 9 (3) ◽

pp. 97-99

Author(s):

Elwyn Griffiths

Keyword(s):

Critical Role ◽

Good Manufacturing Practice ◽

Regulatory Agencies ◽

Medicinal Products ◽

Complex Products ◽

Regulatory Standards ◽

Need Support ◽

Regulatory Convergence ◽

Over 40 Years

Regulatory standards for rDNA derived medicinal products put in place over 40 years ago provided a framework for moving forward with novel biotechnologies and biosimilars leading to their success as highly effective medicines. As biologicals and biosimilars are increasingly developed, licensed and used worldwide less experienced manufacturers and regulatory agencies need support in dealing with these highly complex products. This Commentary highlights the need for regulatory convergence and support, notes the critical role of GMP and draws attention to the comprehensive review by Sia Chong Hock et al. which strongly advocates improving harmonization of regulatory efforts especially in the Association of South East Asian Nations (ASEAN).

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Challenges in diagnosing extrapulmonary tuberculosis in the European Union, 2011

Eurosurveillance ◽

10.2807/ese.18.12.20432-en ◽

2013 ◽

Vol 18 (12) ◽

Author(s):

I Solovic ◽

J Jonsson ◽

M Korzeniewska- Koseła ◽

D I Chiotan ◽

A Pace-Asciak ◽

...

Keyword(s):

European Union ◽

Extrapulmonary Tuberculosis ◽

Diagnostic Procedures ◽

Interferon Gamma Release Assay ◽

European Economic Area ◽

The European Union ◽

Doctor Who ◽

Eu Member States ◽

Economic Area ◽

Release Assay

In the European Union (EU) 72,334 tuberculosis (TB) cases were notified in 2011, of which 16,116 (22%) had extrapulmonary tuberculosis (EPTB). The percentage of TB cases with EPTB ranged from 4% to 48% in the reporting countries. This difference might be explained by differences in risk factors for EPTB or challenges in diagnosis. To assess the practices in diagnosis of EPTB we asked European Union/European Economic Area (EU/EEA) countries to participate in a report describing the diagnostic procedures and challenges in diagnosing EPTB. Eleven EU Member States participated and reports showed that in the majority EPTB is diagnosed by a pulmonologist, sometimes in collaboration with the doctor who is specialised in the organ where the symptoms presented. In most countries a medical history and examination is followed by invasive procedures, puncture or biopsy, to collect material for confirmation of the disease (by culture/histology/cytology). Some countries also use the tuberculin skin test or an interferon-gamma-release-assay. A wide variety of radiological tests may be used. Countries that reported challenges in the diagnosis of EPTB reported that EPTB is often not considered because it is a rare disease and most medical professionals will not have experience in diagnosing EPTB. The fact that EPTB can present with a variety of symptoms that may mimic symptoms of other pathologies does pose a further challenge in diagnosis. In addition, obtaining an appropriate sample for confirmation of EPTB was frequently mentioned as a challenge. In summary, diagnosis of EPTB poses challenges due to the diversity of symptoms with which EPTB may present, the low level of suspicion of clinicians, and due to the difficulty in obtaining an adequate sample for confirmation.

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