WORK ON THE INTERACTION OF THE STATE PHARMACOPOEIA OF THE REPUBLIC OF UZBEKISTAN WITH THE WORLD'S LEADING PHARMACOPOEIA

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The main factor in the development of trends in the field of drug circulation is the increasing globalization of the development, research, production, sale and application of pharmaceutical preparations. Globalization, in turn, strengthens the international harmonization of the requirements for the safety, efficacy and quality of medicines, as well as the forms of verification of compliance with these requirements.

In the various mechanisms of harmonization, on the one hand, it is possible to distinguish global, generally used mechanisms: the World Health Organization – WHO, the International Federation of Pharmaceuticals – FIP, the World Medical Association, the International Council of Scientific Medical Organizations – CIOMS, on the other hand, regional, more or less exclusive forms of cooperation within the framework of the European Union and the Council of Europe, Pharmaceutical Inspection Cooperation Schemes – PIC/S; Organizations such as the International Society for Pharmaceutical Engineering – ISPE, the International Conference on the Harmonization of Technical Requirements for the Registration of Human Pharmaceutical Products (ICH).

The globalization of the pharmaceutical industry on a global scale and the issues of meeting the needs of the population for medicines create the need to harmonize the requirements established in regional and local pharmacopoeias. In particular, the unification of standards for the quality of medicines, harmonization with international norms and the integration of regulatory requirements have become one of the most important tasks in the pharmaceutical industry today.

The process of harmonization of international pharmacopoeias began in 1948, when the Secretariat of the World Health Organization (WHO) gained the appropriate authority. The first volume of the first edition of the International Pharmacopoeia was published in 1951. Its goal was to harmonize the requirements for the quality of pharmaceuticals around the world.

According to the WHO Charter (Constitution), among the tasks of the WHO is to establish international standards, in particular with regard to food, pharmaceutical, biological and other products. WHO normative documents are not binding; the nature of their use (compulsory, recommendatory, etc.) is determined at the national level, that is, by the decision of each WHO member state. The WHO establishes expert committees and directs their work. These committees prepare recommendations, methodological guidelines and reports on the work carried out.

Since 2012,  under the leadership of the World Health Organization (WHO) Expert Committee on Drug Specification (ECSPP), pharmacopoeia representatives  have developed the WHO standard "Necessary Pharmacopoeia Practice" (GPhP)  in order to achieve global harmonization.

The main objective was to identify approaches and policies for setting pharmacopoeia standards, with particular emphasis on harmonization. The set of principles outlined in the GPhP provides guidance for the design, development and support of pharmacopoeia standards for national, regional and international pharmacopoeias. Although the GPhP initially focused on pharmaceutical ingredients and medicines, it later also focused on pharmacopoeia articles for pharmacopoeia preparations and pharmacopoeia articles for medicinal plant-based preparations prepared in pharmacies. These chapters are published in the WHO ECSPP 52nd Report (Annexes 6 and 7, respectively).

The main objectives of the WHO GPhP  standard are:

– ensuring the quality of medicines on a global scale through the adoption of pharmacopoeia standards;

– promoting the recognition of global pharmacopoeia activities;

– increasing regulatory authorities' confidence in pharmacopoeia standards of quality of medicines on a global scale;

– strengthening cooperation between all stakeholders (national and regional pharmacopoeia committees and other organizations, regulatory bodies, representatives of the pharmaceutical industry) and reducing costs associated with the development of pharmacopoeia standards for the quality of medicines;

– simplification of the process of harmonization and recognition of pharmacopoeia standards for the quality of medicines on a global scale;

– assisting the Pharmacopoeia Committees of the Member States in their work on creating harmonized pharmacopoeia standards for the quality of medicines.

The WHO GPhP standard should be a guide for national and regional pharmacopoeia committees and other organizations for the development, publication and dissemination of pharmacopoeia requirements. The principles and approaches for the development of pharmacopoeia articles (monographs) set forth therein relate to:

– pharmaceuticals;

– medicinal raw materials of natural (plant, animal) origin;

– medicines;

– biological preparations;

– extemporal medicines;

– standard samples used in drug testing.

An example of effective efforts to harmonize pharmacopoeias  is the Pharmacopoeia Discussion Group (PDG).

The main goal of the PDG is to harmonize the quality standards of medicines, primarily the requirements of regional and national pharmacopoeias, at a time when the world pharmaceutical market is rapidly undergoing globalization.

The PDG Group was established in 1989 by the European Pharmacopoeia (Ph. Eur.), the Japanese Pharmacopoeia (JP) of the Ministry of Health, Labour and Social Security of Japan (MHLW/PMDA), and the US Pharmacopoeia Convention (USP) of the European Directorate for Drug Quality (now EDQM) of the Council of Europe. The WHO joined as an observer in May 2001 and the group continued to work in this configuration until the launch of an expansion pilot project in late 2021. This experience is an important first step towards PDG's commitment to expanding the recognition of harmonized pharmacopoeia standards with the aim of harmonizing standards worldwide. To ensure that PDG can continue to operate efficiently and produce high-quality, harmonized standards, it has set out clear entry criteria and a detailed structure for the testing phase. Thereafter, the PDG reviewed the applications and agreed with the Pharmacopoeia Commission of India (IPC) to commence a one-year trial phase, which began in October 2022. At the PDG's annual meeting held in Hyderabad in October 2023, the IPC was accepted as a member of the PDG.

The main objective of the PDG is to protect public health by harmonizing pharmacopoeia standards and maintaining scientific excellence at a high level. The PDG also plans to expand the scope of its activities internationally by incorporating non-member pharmacopoeia into its membership.

The State Pharmacopoeia of the Republic of Uzbekistan is working on the harmonization of pharmacopoeia articles within the framework of bilateral signed memorandums and agreements with the European Pharmacopoeia (Ph. Eur.), the US Pharmacopoeia (USP). It also participates in regular discussions within the framework of the International Meeting of World Pharmacopoeias (IMWP) with the aim of strengthening coordination and cooperation between international pharmacopoeias.

The International Meetings of World Pharmacopoeias (IMWP)  was first established by the WHO in 2012 and brings together pharmacopoeias from around the world with the aim of promoting international cooperation and harmonization. This goal is achieved by encouraging effective discussions and information exchange. Representatives of national, regional and international pharmacopoeias participate in the regular meetings of the IMWP. These meetings are an important platform for standardizing the production and testing processes of medicines on a global scale. During the meetings, issues of development and improvement of pharmacopoeias standards by the WHO are discussed. At the same time, the participants sought to harmonize global standards, ensuring that they are clear and effective for regulators and manufacturing entities. In addition, strengthening mutual recognition of pharmacopoeia requirements and strengthening cooperation between pharmacopoeias are also seen as one of the priorities on the agenda. IMWP meetings also serve to improve coordination mechanisms between international pharmacopoeias. This, in turn, contributes to improving drug safety, quality control, and access to effective treatment for patients. The development of the necessary pharmacopoeia practice (GPhP) to encourage future harmonization is one of the significant achievements of IMWP to date.

The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) – established in 1990, is a coordinating council for international scientific and technical requirements for pharmaceutical products to ensure the quality, safety and efficacy of medicines. Today, the ICH has 19 full members and 37 participants with observer status, the main of which are the regulatory bodies of the United States, the European Union, Japan, as well as several international organizations.

Like other organizations, ICH is on a path of adaptation to the increasingly globalized drug manufacturing industry. A key means of achieving its harmonization is the ICH guidelines, which are developed through a process of scientific consensus and collaboration between regulatory bodies and industry experts.

The ICH Assembly, as the supreme governing body of the organization, includes all members and observers of the ICH Association.

The objectives of the ICH are:

• more efficient use of human, biological and material resources;

• eliminate excessive delays in the overall process of introduction of innovative medicines;

• increase the indicators of consumer consumption of new medicines by the population, observing all guarantees of quality, effectiveness and safety.

Working groups within the ICH address issues of preclinical toxicity and related testing; engage in clinical trials and safety monitoring programs; review communication issues for the control and planning of toxicity studies with clinical trials in mind; and discuss pharmaceutical developments and specifications.

The ICH harmonization process is carried out in the following ways:

• Technical Discussion (EWG);

• state control agreement;

• advice within the IC;

• formalization of the text and approval of decisions of the ICH;

• Adoption of ICH decisions by national authorities.

The main work is carried out in three areas: Quality (Q – documents with a quality index), Efficiency (E – documents with an efficiency index) and Security (S – documents with a safety index).

The Centre for Pharmaceutical Product Safety (hereinafter the Centre) has been admitted to the International Organization of Pharmaceuticals (hereinafter the Centre) as an official observer and is collaborating towards the harmonization and implementation of regulatory documents relating to the industry from 2024 onwards. This collaboration is important to ensure that the articles of the National Pharmacopoeia are harmonized with current regulatory requirements and future regulatory needs. The Centre is also a member of the Programme of International Pharmaceutical Regulatory Authorities (IPRP). Membership in the PRP provides Uzbekistan with a unique opportunity to collaborate and exchange experience with the world's leading regulators, including the FDA (USA), EMA (European Union), PMDA (Japan), MHRA (UK), Health Canada (Canada), ANVISA (Brazil) and other agencies from more than 30 countries. IRPR also brings together regional and international organizations by harmonizing the requirements for the safety, efficacy and quality of medicines.

Harmonization of pharmacopoeia standards is one of the most complex types of global pharmacopoeia activities. It can be implemented according to retrospective and perspective, complete and selective (partial) mechanisms. Retrospective harmonization refers to pharmacopoeia articles (monographs) included in pharmacopoeia. Prospective harmonization covers testing methods (methodologies) and drugs (excipients) that were previously not the object of pharmacopoeia standardization.

A complete mechanism involves mastering the entire scale, excluding any significant changes. A selective (partial) mechanism, on the other hand, is based on mastering selected parts with an agreed change in mind.

In contrast to the first type of harmonization, the second has the possibility of setting stricter or more lenient requirements for product quality than those established in other harmonizing states. This is usually accomplished through mutual recognition and application of uniform standards, which allows control to be exercised in the country where the drug is manufactured. In this way, it eliminates the need for repeated control in harmonizing states, simplifying and cost-effective the control process.

The harmonization of the State Pharmacopoeia of the Republic of Uzbekistan with the world's leading pharmacopoeia has its own characteristics and is carried out through various mechanisms. The European pharmacopoeia provides for the application of a promising type of harmonization and its full mechanism. Such an approach implies that the texts of the European pharmacopoeia are not changed in the text, the style of presentation, the numbering and titles of chapters and monographs are preserved. The US Pharmacopoeia provides for the implementation of promising and retrospective harmonization in terms of both complete and selective mechanisms. It is envisaged that the texts that have undergone harmonization will be marked with the "USP" symbol.

In the process of developing state pharmacopoeia the harmonization is mainly perspective, but at the same time, certain selective mechanisms were used, taking into account local conditions for certain pharmacopoeia articles and texts, using the method of retrospective harmonization.

In the process of preparing the State Pharmacopoeia for publication, special attention was paid to the harmonization of the general and private pharmacopoeia articles and other relevant texts included in it with the European pharmacopoeia. These activities were carried out in the direction of the adoption of the articles cited in the European Pharmacopoeia as they were or in part, the introduction of appropriate changes, additions and additions, or the adaptation of the general requirements of the European Pharmacopoeia in the revision of monographs that do not exist in the European Pharmacopoeia, etc.

Today, taking into account the globalization processes taking place internationally in the field of pharmaceuticals, attention is paid to the improvement of methods of quality control of medicines and medical products, in order to facilitate the export of domestic pharmaceutical products to foreign markets, the texts of the main monographs included in the State Pharmacopoeia and will be included in the future are additionally recognized with the world's leading pharmacopoeia – International Pharmacopoeia, European Pharmacopoeia (Eur. Pharm.), US Pharmacopoeia (USP), British Pharmacopoeia (BP), Japan Pharmacopoeia (JP), Russian Pharmacopoeia (GF RF), Belarusian Pharmacopoeia (GF RB), Kazakhstan Pharmacopoeia (GF RK), Ukrainian Pharmacopoeia (DFU) and others.