STATE PHARMACOPOEIA OF THE REPUBLIC OF UZBEKISTAN: HISTORY AND LEGAL BASIS

The history of pharmacopoeia goes back a long time. The term "pharmacopoeia" was formed in the field of health care much earlier and literally translates as "preparation of medicines" (in Greek φαρμακον – medicine, poison, etc. ποιη – I do, I prepare). The recognition of pharmacopoeia as a document of national importance, mandatory for the entire national health care system, occurred only in the second half of the 18th century. Prior to that, this task was performed by various works, including instructions on the sets of medicines used in the treatment of various diseases, the technology of their preparation and methods of application.

The first manifestations of pharmacopoeia have been created since ancient times and are found in one form or another in almost all civilizations and cultures. Many of these works that have come down to us are historical Significantly, some aspects of them have not lost their relevance even today.

The earliest examples of pharmacopoeia include ancient Egyptian "medical" papyri. They contain information about various diseases, as well as methods and means of treating them (there are currently around ten such papyri). For example, the Edwin Smith Papyrus (known as the "surgical" papyrus), which dates from 1500 BC and is considered an incomplete copy of a text created approximately 2686-2181 BCE, provides insight into the diagnosis, methods, treatments, and projected outcomes of diseases caused by 48 injuries.

In ancient Greece, the views on the treatment of diseases and the use of medicines were formed under the influence of philosophical teachings - dialectics, materialism, etc. For example, Hippocrates (c. 460-370 BC), the so-called "Father of Medicine", understood the organism and the processes that take place in it in a holistic whole. The so-called "Corpus Hippocraticum" ("Hippocratic Collection") that has come down to us contains descriptions of many diseases, as well as information on the methods of preparing remedies of various forms (hard, liquid, soft, etc.), as well as their dosage. The collection mentions a drug of 250 plant nature and about 50 of animal origin.

Among the forms of hard medicines, powders made from plant, animal and chemical (mineral) raw materials, "kulchas" (a hard-dosed form used for many centuries), tablets, etc., were common. From liquid forms, mainly solutions, tinctures, decoctions and suspensions were used. It was recommended to prepare decoctions made from plants in water, wine or goat's milk. Instructions for the preparation of soft forms intended for external use – ointments, plasters, candlesticks, primates, etc. – were also distinguished by their detail. Each physician had a reserve of ingredients necessary for the preparation of remedies and kept them in a room called άποθήκη or apotheca (i.e., warehouse, place of storage) specially reserved for this purpose. This is where the term "pharmacy" came from.

The views on the preparation and application of remedies, which were widespread in Ancient Greece, continued to develop steadily in Ancient Rome. In particular, Pedanius Dioscorides (c. 40-90 CE), who served as a physician in the Roman army and visited many countries, in his treatise "De materia medica" ("On Medicines"), described the systematic nature of many remedies (about 1000 names) of plant, animal, and chemical (mineral) origin that were popular at that time

He gave a description. He described in detail the methods of their preparation, as well as the methods of technological processing (driving, distillation, crystallization) of the corresponding ingredients. In the same work, Dioscorides described about 600 plants and divided them into 4 groups: aromatic, food, healing (medicinal) and winemaking plants.

A number of fundamental works, rightly recognized as the predecessors of pharmacopoeia – "De simplicium medicamentorum tempeamentis et facultatibus" ("On simple medicines and their properties"), "De compositione medicamentorum secundum locos" ("On complex drugs"), "De compositione medicamentorum secundum genera" ("On locally applied complex medicines"), "De Antidotis" ("Remedies against poisons") – the famous physician of ancient Rome, Galen (129–199 CE, according to other sources, 216 AD) is a Greek philosopher and scholar. For example, "De simplicium medicamentorum..." The brochure describes more than 300 medicinal plants, giving them two different properties – one positive, healing, and the other useless or even harmful. On this basis, it was recommended to carry out the necessary processing of plant raw materials in order to isolate the "beneficial" agents (the main technological methods were "cutting, grinding, crushing, rubbing, dripping, boiling, thawing, etc."). Centuries later, during the Renaissance, preparations obtained in this way from plant and animal raw materials were called "galen preparations" ("medicamenta galenica"), which later paved the way for the development of phytochemistry, pharmaceutical chemistry, phyto- and organotherapeutic technology. Galen divided the remedies into four groups according to the level of exposure to the body: the first is the one that has a palpable effect, the second is the one that has a significant effect, the third is the strong one, and the fourth is the means of harmful effects. In the use of remedies, Galen considered the ability to use these subtle differences in prescribing medications according to available instructions to be the most important. He also proposed a classification of remedies similar to those of modern times: diarrhea-stimulating, urinary stimulant, twisting, softening, blood drive, and blood stopper, painkiller, and so on. However, Galen understood their mechanisms of action in an idealistic way – he believed that diarrhea drugs have an effect because they have a "diarrhea power," while opium has a "sleeping power." Galen, who ran a pharmacy called "Officina," set out to make medicines according to his own standardized prescriptions. This was the basis for the emergence of the term "official medicines" later. Galen's works were first published in the Near (Arab) East and Central Asia, and later in Europe

It was also widely disseminated. They were translated into Latin and then into other languages and reprinted many times.

Among the scientific works of Abu Rayhan Beruni (973-1048), a mature encyclopedic scientist of his time, the most important and the largest in terms of volume is the book "Kitap as-saydana fit-tibb" (Pharmacognosy in Medicine). This work contains information about 674 medicinal plants and 90 medicinal plant products used in oriental medicine at that time. The names of medicinal plants mentioned in the "Saydana" reach 750.

One of the famous physicians of Central Asia, a prominent figure of his time – Abu Ali al-Husayn ibn Abdallah ibn al-Hasan ibn Ali ibn Sina (c. 980-1037), known to us as Abu Ali ibn Sina or Avicenna, made a great contribution to the creation of the main foundations of pharmacopoeia. Despite the fact that the "Laws of Medicine" were published 1000 years ago, the article pharmacopoeia used in modern pharmacy highlights the standards that determine quality, including appearance, organoleptic indicators, purity, sampling, and must be followed.

The second book of this work is devoted to the description of medicines of plant and animal origin, and the fifth book is devoted to complex preparations, poisons and antidotes. The pamphlet contains information about medicines, including drugs with narcotic and pain-inducing effects (belladonna, cinnamon, mandragora, opium, etc.), their various forms (hard, soft, liquid, etc.), the technology of preparation and the procedure for use. In addition, the healing properties of mercury, silver, sulema are described (the idea of using mercury preparations in the treatment of mercury is considered to have been borrowed from Ibn Sina).

In general, the work "The Laws of Medicine" describes about 800 medicines of herbal, animal, and chemical (mineral) origin, of which 150 are still in use today. In all the works of Ibn Sina, about 2,600 medicinal remedies are mentioned, of which at least 1,400 are derived from plants. Importantly, he was the first to put forward the idea of pre-testing the effects of drugs on animals (this is one of the main elements of modern preclinical testing of drugs). It is noteworthy that in the work "The Laws of Medicine" Galen's experiment is repeatedly referred to. In the 12th century, the work "The Laws of Medicine" was translated into Latin, and later into many other languages. Over the course of several centuries, it was reprinted and became a true musical work on various health problems, including pharmacy.

Thanks to the accumulated practical knowledge of mankind over the centuries and continuous efforts to improve the healthcare system, created the basis for the systematization of the composition, quality criteria and rules of use of medicines, as well as the creation of regulatory documents aimed at ensuring their safety and effectiveness.

Pharmacopoeia in modern pharmacy is a set of standards that must be observed by law to ensure the quality of medicines used in a particular country or a certain territory, the main task of which is to establish modern and highly effective general requirements for the quality of medicines, as well as separate quality standards for active pharmaceutical substances, finished medicines, excipients, reagents, reagents and the like.

According to the World Health Organization, to date, a total of 57 pharmacopoeias have been registered, including 3 territorial, 1 international and national pharmacopoeias. The structure of the existing pharmacopoeia differs in the extent to which the articles covered in them are widely represented, the requirements for the standards, the level of established norms.

With globalization and increased cooperation, the goal of achieving broad harmonization of quality indicators globally for selected pharmaceutical products, excipients and drug forms has emerged. The history of these approaches can be traced back to 1902-1925, when the concept of "United Pharmacopoeia" was formed as a result of international agreements. In 1929, the "Brussels Agreement" imposed on the League of Nations the obligation to carry out administrative tasks in the field of pharmacopoeia. Eight years later, in 1937, the first meeting of the "Technical Commission of Pharmaceutical Examiners" was held.

An important date in the history of quality assurance of medicines is 1948. In 1948, the first World Health Assembly (WHO) established the International Pharmacopoeia Secretariat and the "World Health Organization's Expert Committee on the Integration of Pharmacopoeias" by resolution WHA1.27. In 1949, the WHO renamed it the International Committee of Experts on Pharmacopoeia. This committee later became the "Expert Committee on Drug Specification" (ECSPP).

Representatives of the International Conference Sessions of the Medicines Regulatory Authorities (ICDRA), including representatives of the Council of Europe, Pharmacopoeia (USP) of the United States, Brazil, the Russian Federation, China, India and others, contacted by telephone to emphasize the need for a world-wide approach to pharmacopoeia standards and extensive work has been undertaken.

International Pharmacopoeia (Ph. Int.) \u2012 consists of a set of analyses and specifications recommended for the identification of pharmaceutical substances (active pharmaceutical ingredients) and drug forms, and is intended to serve as a reference or reference material for adaptation by any WHO Member State for the establishment of pharmaceutical requirements. Pharmacopoeia or any part thereof shall have legal status in cases where it has been formally incorporated into relevant legislation by a national or regional authority.

The origins of international pharmacopoeia can be traced back to 1874, at which time the need to standardize terminology and prescribe the dosage and composition of medicines laid the groundwork for the creation of this international pharmacopoeia collection.

International pharmacopoeia is based on the WHO's ECSPP recommendations and decisions, and pharmacopoeia articles are recommended for adoption in accordance with its decision. International pharmacopoeia gives priority to medicines included in the WHO's sample list of essential medicines, as well as medicines that are important to WHO's health programs and whose trial properties are not proposed in other pharmacopoeias. The quality control specifications published in the International Pharmacopoeia are developed independently through discussion by international experts. This takes into account the needs of developing countries. The main objective of the International Pharmacopoeia is to provide quality control criteria and characteristics to ensure access to quality medicines worldwide.

The pharmacopoeia developed and published in accordance with the current understanding of pharmacopoeia are: Russian pharmacopoeia in 1778, Polish pharmacopoeia in 1817, United States pharmacopoeia in 1820, British pharmacopoeia in 1864, Hungarian pharmacopoeia in 1871, German pharmacopoeia in 1872, Japanese pharmacopoeia in 1886, Argentine pharmacopoeia in 1898, International Pharmacopoeia (WHO) in 1951, Chinese pharmacopoeia in 1953, Korean pharmacopoeia in 1958, Indian pharmacopoeia in 1960, and European pharmacopoeia in 1969.

Pharmacopoeias are the official source containing national and international regulations to be legally and scientifically followed with respect to substances, materials, drugs, drugs, devices and methods used in the pharmaceutical field and in the production of medicines.

In the European Union (EU), the concept of pharmacopoeia has been incorporated into legislation and is enforced by regulatory bodies. European Pharmacopoeia (Ph. Eur.) It was developed in 1964 by eight member states and is now officially used by 39 member states as well as the European Union (EU).

The EU Directive (2001/83/EC) states: "The monographs of the European pharmacopoeia are required to apply to all substances, preparations and forms of pharmaceutical medicines contained therein. With regard to other substances, each Member State may require compliance with its national pharmacopoeia." "Compliance with the monograph of the pharmacopoeia of a third country may be adopted if the starting and raw materials, active ingredient(s) or excipients(s) are not described in the European Pharmacopoeia and in the pharmacopoeia of the Member State.". These Directives have been incorporated into the national legislation of the Member States of the European Union. For example, the Medicines Used in Medicine Regulations (UK), passed on August 14, 2012, the Reasonable Use Guarantees Act (Spain), the Drugs and Medical Products Act (Serbia), the Food, Drug, Federal and Cosmetic Act (USA) and so on.

Members of the European Pharmacopoeia have different approaches to the application of pharmacopoeia standards. For example, Sweden and Finland have abolished their national pharmacopoeia and chosen to implement only the requirements of the European pharmacopoeia. In France, however, the European Pharmacopoeia and the French Pharmacopoeia are jointly recognized as the official standard. Switzerland – Ph. Eur. and Ph. Helv. (Swiss Pharmacopoeia) apply together. In the United Kingdom, however, the British Pharmacopoeia (BP) has fully harmonized the Ph. Eur. standards.

National/regional legislation has largely provided for references to other pharmacopoeias in cases where their own pharmacopoeia texts do not exist, and historical and linguistic links are also important. For example, the European pharmacopoeia is conducted in English and French, while the Portuguese pharmacopoeia has also been adopted in the legislation of other countries where Brazilian and Portuguese are the official language (e.g., Mozambique, Guinea or São Tome e Principeia). The WHO's International Pharmacopoeia is mentioned in a number of national legislation due to its "ready-to-use" status by Member States.

Brazil, Argentina, and Mexico have their own national pharmacopoeias, which can refer to Europe, the United States, the WHO, and other international pharmacopoeias. For example, in Brazil, ANVISA (National Health Surveillance Agency) recognizes international pharmacopoeias and allows them to be applied to regulatory processes.

The "General Health Law" in Mexico states: The quality characteristics of drug supplements, preparations, and medicines are indicated in the current edition of the Mexican Pharmacopoeia. If it does not have data, one can use pharmacopoeias from other countries (or other internationally recognized scientific sources).

Pharmacopoeias are frequently mentioned in the laws and regulatory acts of countries of the world to help ensure the quality, safety and effectiveness of medicines, such as:

The U.S. Pharmacopoeia and the National Formulary (USP–NF) is published by the USP Convention (a non-U.S. government, nonprofit organization). The USP-NF is recognized as an official collection under the Federal Food, Drug, and Cosmetic Act (FD&C Act). For example, the 501(b), 502(e)(3)(b), and USP general notes are listed in Section 2.30.

European Pharmacopoeia (Ph. Eur.) Published by the European Directorate for Health and Drug Quality (EDQM). In accordance with European Union (EU) Directives 2001/82/EC and 2001/83/EC, medicines used in medicine and veterinary medicine are the mandatory standard of the European Pharmacopoeia.

The British Pharmacopoeia (BP) is published by the British Pharmacopoeia Commission under the guidance of the Medicines and Healthcare Products Regulatory Agency (MHRA). BP has been approved under the terms of the Medicines Act 1968 (Section 99) and has instead been incorporated into the Medicines Used in Medicine Regulations 2012 (section 317(1)).

The Japanese Pharmacopoeia (JP) is published by the Government of Japan through the Ministry of Health, Labor, and Welfare (MHLW) by order of the Ministry. The JP is published in accordance with the Law on Ensuring the Quality, Efficacy, and Safety of Medicines and Medical Devices. It is the most basic legal document of pharmaceutical regulation in Japan.

The Chinese Pharmacopoeia (ChP) is published by the China Pharmacopoeia Commission through the National Medical Products Administration (NMPA, formerly CFDA). The ChP operates in accordance with the laws enacted by the Ministry of Health in 1950. According to the Drug Administrative Management Act, enacted by the National People's Congress in 2001 and updated in 2015, the drug standards issued by the ChP and the Drug Regulatory Unit under the Council of State are valid as national drug standards. The Drug Registration Regulation of 2007 (issued by the CFDA) defines the ChP's role as a regulator.

The Indian Pharmacopoeia (IP) is published by the Pharmacopoeia Commission of India on behalf of the Ministry of Health and Family Welfare. The process is monitored by the Central Drug Standards Control Organisation (CDSCO). IP has legal status under the Indian Medicines and Cosmetics Act, 1940 and the Regulations, 1945.

The Pharmacopoeia of the Russian Federation (GF RF) is published by the Ministry of Health (Minzdrav Rossii) of the State Pharmacopoeia of the Russian Federation (GF RF) and is officially a competent federal executive body.

State pharmacopoeia is a set of modern requirements that determine the quality of medicines and medical products, which, on the one hand, is a factor that indicates the degree of development of the pharmaceutical industry in a particular state, and on the other hand, is the basis for further improvement and improvement of the quality of medicines in this state.

From the above information can be seen that today most countries do not have their own national pharmacopoeias, that is, they contain strict requirements and control methods for the quality of medicines and medical devices put into circulation, limited to adopting and applying those established in different countries of manufacture of the product.

This, in turn, may lead to the establishment of different criteria for the quality of the same type of products produced in different countries, the introduction into circulation of products with low quality indicators, and other similar adverse situations.

The set of requirements for the quality indicators of medicines and medical products is reflected in the State Pharmacopoeia. This makes it urgent to develop the State Pharmacopoeia in cooperation with experts in the relevant field on a regular basis on the basis of modern scientific achievements, improve it and introduce it into practice. The competence of the Ministry of Health includes the implementation of quality control and standardization work of medicines and medical products, as well as the organization of approval and publication of the State Pharmacopoeia.

Currently, the organization, approval and implementation of the State pharmacopoeia of the Republic of Uzbekistan is another proof of the special attention paid by the President to the pharmaceutical sector, which includes medicines and medical products produced by local pharmaceutical enterprises, including new, original products created in the Republic

plays an important role in the presentation of pharmaceutical products for use in international medical practice.

The basis for the publication of the State Pharmacopoeia of the Republic of Uzbekistan is reflected in the Law of the Republic of Uzbekistan dated January 4, 2016 No. ZRU-399 "On medicines and pharmaceutical activities", Article 8 of which states that "State pharmacopoeia is an official publication, which is a collection of documents containing requirements for medicines and medical products, general pharmacopoeia articles, pharmacopoeia articles, quality control of medicines and medical products." .

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The General Pharmacopoeia article defines general requirements for the quality of medicines, medical products, medicinal herbal raw materials, methods for their quality control, standard samples used in the quality control of medicines, reagents, location-packaging materials used in the manufacture of medicines.

Article of Pharmacopoeia defines requirements for the quality of a particular medicinal product, medicinal herbal raw material, excipient.

Development of general pharmacopoeia articles, articles of pharmacopoeia and their inclusion in the State pharmacopoeia is carried out in the prescribed manner by the Ministry of Health of the Republic of Uzbekistan.

The State Pharmacopoeia is published by the Ministry of Health of the Republic of Uzbekistan at least once every five years. In the period between reprints of the State Pharmacopoeia, appendices to the State Pharmacopoeia will be published."

In accordance with the foregoing, in accordance with the Decree of the President of the Republic of Uzbekistan dated April 10, 2019 No. UP-5707 "On measures for further accelerated development of the Republic's pharmaceutical industry in 2019-2021", the tasks of developing and approving the State pharmacopoeia are instructed to develop and approve the State Pharmacopoeia taking into account modern international requirements for the quality of pharmaceutical products and methods of their quality control.

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The following is noted: "On the activities of medicines and pharmaceuticals" (Decree No. ZRU-399 of 04.01.2016); "On standardization" (No. ZRU-800 of 03.11.2022); "On certification of products and services" (No. 1006-XII of 28.12.1993); "On Metrology" (No. 1004-XII of 28.12.1993); In accordance with the Law "On Technical Regulation" (No. ZRU-819 of 27.02.2023), the Ministry of Health of the Republic of Uzbekistan and its territorial governing bodies within the following competences within their competence in: treatment of medicines; standardization; certification; metrological support; technical regulation; The issues of determining the content of substances harmful to humans in the composition of medical products, including medicines, medical devices, medical equipment, as well as products manufactured in the Republic of Uzbekistan, including imported products.