Transition of Veterinary Manufacturers to the EAEU GMP Rules

0
28

In October 2020, the Federal Service for Veterinary and Phytosanitary Surveillance (Rosselkhoznadzor) announced that from January 1, 2021, the Rules of Good Manufacturing Practice of the Eurasian Economic Union, approved by the Resolution of the Council of the Eurasian Economic Commission of November 3, 2016 No. 77, will come into force, in relation to medicinal products for veterinary use.  Compliance with these Rules will be taken into account when issuing permits (licenses) to manufacturers of medicinal products for animals for these activities, as well as when inspecting them [1]. In this short overview, we’ll look at some of the articles, presentations and documents that veterinary manufacturers may find useful.

EAEU GMP RULES

The text of the Rules of Good Manufacturing Practice of the Eurasian Economic Union (the EAEU GMP Rules) is published on the website of the Eurasian Economic Commission (EEC) in the section “Resolutions of the Council of the Eurasian Economic Commission” [2]. The EAEU GMP rules were approved in 2016. They entered into force in 2017, with the exception of the provisions of these Rules concerning the requirements for the production of veterinary medicinal products.

The requirements of the EAEU GMP Rules for the manufacture of veterinary medicinal products are the same as for the manufacture of medicinal products for human use. Special requirements of these Rules for veterinary medicinal products and immunobiological veterinary medicinal products are set out in the Annexes No. 4 and 5. Part II of the EAEU GMP was developed based on the ICH guidelines published as an ICH Q7A document for active pharmaceutical ingredients. This part applies both to medicinal products for human use and veterinary medicinal products.

According to Dmitry Rozhdestvensky, Head of the Division for Coordination of Common Market for Drugs and Medical Devices Formation, Technical Regulation and Accreditation Department of the EEC and Andrey Meshkovsky, associate Professor of the Department of organization of production and sale of medicines of the Sechenov First Moscow State Medical University, authors of the article “On the Application of GMP Rules in the EAEU Member States” published on the GMP News internet portal in February 2020, a comparison of the texts of the EAEU GMP Rules and the Rules of Good Manufacturing Practice approved by the Order of the Ministry of Industry and Trade of Russia dated June 14, 2013 No. 916 (the GMP Rules of the RF) [3] does not reveal fundamentally important discrepancies between them [4].

On the website of the Federal State Institution “State Institute of Drugs and Good Practices” (FSI “SID & GP”) subordinated to the Ministry of Industry and Trade of Russia, in the section “Inspection” there is a presentation “Main differences between the GMP Rules of the RF, the EAEU GMP Rules and the EU GMP Rules (Information note)” [5]. This presentation covers the main differences between the GMP Rules of the RF and the EAEU GMP Rules, as well as an overview of changes in the EU GMP Rules: Volume 4 of “The Rules Governing Medicinal Products in the European Union” [6].

In August 2020, an article by the GMP expert of IBA Elena Zelinskaya and the QC Head of JSC “Tatchempharmpreparaty”, Elena Sadykova, entitled “Comparison and Analysis of the GMP Requirements of the Russian Federation and the EAEU” was published on the GMP News internet portal [7]. Both the GMP Rules of the RF and the GMP Rules of the EAEU are a translation of the EU GMP Rules. However, they also have differences. The EAEU GMP Rules are closer in structure and translation accuracy to the original. They also include Part III “GMP related documents”. The GMP rules of the RF were developed in 2013, and the last amendments to Part I of the EU GMP Rules were introduced in 2015, accordingly, the EAEU GMP Rules included these changes. The authors of this article set out to compare Part I of both documents and presented a comparative table.

Interesting discrepancies in the text of the GMP Rules are found by the Head of the Validation Department of LLC “LabPromEngineering” Alexander Belinsky in the article “Regulatory quests and labyrinths, or who lives well in Russia: an old fairy tale in a new way with a pharma accent” which was published on the PharmaPharm internet portal in 2019. For example, he draws attention to some differences between the paragraphs of Chapter 3 “Premises and equipment” and Annex No. 4 regarding veterinary medicinal products, in the context of dedicated and self-contained facilities [8].

It is important to understand that the EAEU GMP Rules, like the EU GMP Rules, will be regularly reviewed to reflect the continuous improvement of quality management practices. This applies to both the Rules themselves and their Annexes. The purpose of regulating the EAEU GMP Rules is to establish uniform approaches and eliminate differences in the requirements of the pharmaceutical inspectorates of the Eurasian Economic Union Member States when conducting pharmaceutical inspection and confirming the stability of the quality of products.

ANNEX 15

In June 2020, an article titled “The EAEU will establish uniform requirements for qualification and validation in pharmaceutical production” was published on the GMP News internet portal [9]. This article describes the proposed changes to Annex 15 to the EAEU GMP Rules “Requirements for qualification and validation”, including: introduction of terms such as “User Requirements Specification (URS)”, “Factory Acceptance Testing (FAT)”, “Site Acceptance Testing (SAT)”; introduction of new approaches to process validation, including continuous process verification, hybrid approach, ongoing process verification during lifecycle, justified application of the bracketing approach for new products; new sections related to verification of transportation, validation of packaging; establishment of limits for the carryover of product residues during cleaning validation based on a toxicological evaluation, etc. Among the most important proposed changes – retrospective validation is no longer considered an acceptable approach.

The text of the draft updated version of Annex 15 has already been preliminarily agreed upon at the level of EAEU expert groups and published on the EEC website in the section “Projects of the working group on the formation of common approaches to the regulation of drug circulation within the Eurasian Economic Union” [10]. At present, the final approval of the draft document is expected.

ANNEX 16

At the current moment, the EAEU GMP Rules contain Annex 16 which is based on the translation of Annex 16 to the EU GMP Rules, published in 2001 and entered into force in 2002. In 2015, Annex 16 to the EU GMP Rules was revised and its updated version entered into force in 2016.

A presentation by Vladimir Orlov, who is currently the Director of the International Society for Pharmaceutical Engineering of the Eurasian Economic Union – Eurasian ISPE Affiliate, is posted on the website of FSI “SID & GP” in the section “Inspection” on the topic “Overview of the main innovations in the new version of Annex 16 to GMP rules – “Requirements for confirmation by a Qualified person of compliance of a product batch for release” [11]. This presentation covers the requirements of the regulatory framework of the Russian Federation and the European Union, the new version of Annex 16 to the EU GMP Rules and some key changes in the content of the updated version of Annex 16 on the example of a draft translation of the specified document for the EAEU GMP Rules.

On September 30, within the framework of the V All-Russia GMP Conference with international participation held online, a round table “Current trends in global legislation and global harmonization” was held. At this round table, Tatiana Vyazmina, the Quality Director of R-Pharm Group, made a presentation on the topic “General provisions of the new version of the draft Annex 16 of the EAEU GMP from the perspective of the GMP requirements and the Qualified person at pharmaceutical enterprise” [12]. She provided some comparisons of the current version and the draft of the new version of Annex 16. In particular, the project involves the introduction / correction of terms and definitions (“Batch certification”, “Marketing authorization holder”, “Certification of compliance for individual stages of drug product manufacturing process”); the provision that the key responsibility for safety, quality and efficacy of a medicinal product rests with MAH throughout the whole product lifecycle; the provision that the evidence of certification for a batch of medicinal product is documented by QP in a register or in a similar document intended for this purpose, etc.

INSPECTION

In October 2020, on the Federal Portal of Draft Normative Legal Acts, the draft “On amendments to the Order of Rosselkhoznadzor No. 755 of October 18, 2016 “On approval of the application form related to determination on manufacturer (foreign manufacturer) of medicinal products for veterinary use compliance with the requirements of the Rules of Good Manufacturing Practice, the form of an inspection report on the results of inspection of manufacturer (foreign manufacturer) of medicinal products for veterinary use with respect to its compliance with the requirements of the Rules of Good Manufacturing Practice, and the form of conclusion on the compliance of the manufacturer (foreign manufacturer) of medicinal products for veterinary use with the requirements of the Rules of Good Manufacturing Practice ” was posted [13].

The text of the normative legal act, finalized following the results of public discussions, includes the following changes:

  • In the form of an inspection report on the results of inspection of manufacturer (foreign manufacturer) of medicinal products for veterinary use with respect to its compliance with the requirements of the Rules of Good Manufacturing Practice, approved by the Order, footnote <2> shall be stated as follows: “<2> All identified nonconformities are assessed in accordance with the requirements of the Rules of Good Manufacturing Practice of the Eurasian Economic Union approved by the Resolution of the Council of the Eurasian Economic Commission of November 3, 2016 No. 77 (official website of the Eurasian Economic Union, November 21, 2016)”, with references to the clauses of the act constituting the law of the Eurasian Economic Union;
  • In the form of conclusion on the compliance of the manufacturer (foreign manufacturer) of medicinal products for veterinary use with the requirements of the Rules of Good Manufacturing Practice, approved by the Order, the words “the Rules of Good Manufacturing Practice approved by the Order of the Ministry of Industry and Trade of Russia dated June 14, 2013 No. 916” shall be replaced by the words “the Rules of Good Manufacturing Practice of the Eurasian Economic Union approved by the Resolution of the Council of the Eurasian Economic Commission of November 3, 2016 No. 77 (official website of the Eurasian Economic Union http://www.eaeunion.org/, November 21, 2016)”; after the words “the Rules of Good Manufacturing Practice” add the words “Eurasian Economic Union”;
  • This order comes into force on January 1, 2021.

On October 8-9, 2020, on the basis of the Federal State Budgetary Institution “The All-Russian State Center for Quality and Standardization of Veterinary Drugs and Feed” (FSBI “VGNKI”) subordinated to Rosselkhoznadzor, a training seminar was held. In the training program, the specialists of the FSBI “VGNKI” paid special attention to a comparative review of the EAEU GMP Rules and the GMP Rules of the RF [14].

TO BE CONTINUED

What other events and activities planned for the already ending 2020 can be recommended to manufacturers of veterinary medicinal products?

The “PHARMSTRATEGY” company and FSI “SID & GP”, within the joint program of promoting implementation of the best practices in the Russian pharmaceutical industry, have come up with the initiative of the “SOLIDARY TRAINING PROGRAM” project. Since September 2020, they have been hosting corporate webinars for companies with an “open-door policy”. At the same time, the company for which the event is held provides all interested employees of the industry with the opportunity to take part in it free of charge, thus showing industry solidarity and contributing to the achievement of common and not exclusively internal corporate interests. One of the prerequisites for the project is the introduction of Eurasian GMP standards and preparation for the start of inspection of Russian enterprises for compliance with the requirements of the EAEU GMP Rules [15].

On December 16, 2020, the Eurasian ISPE Affiliate will hold an online preconference, within which international experts and regulators of the Eurasian market will discuss the specifics of pharmaceutical engineering and regulatory trends in an unstable environment [16]. In particular, Jean François Douliere, Pharmaceutical Senior Expert, Chair ISPE France Affiliate will talk about the changes in Annex 1 to the EU GMP Rules (review of the second version of the draft document dated December 2020); Dmitry Rozhdestvensky will give an overview of the current changes in the EAEU regulatory legal acts regarding the circulation of medicinal products for 2020; the Head of the Department for Inspection of Good Pharmaceutical Practices of the Scientific Centre of Drug and Medical Technology Expertise of the Ministry of Health after Academician Gabrielyan (Republic of Armenia) Mkrtich Shakaryan will give practical advice on the application of the EAEU regulatory legal acts in the field of GM(D)P, etc.

The presented material was prepared using data published on the official websites, as of early November 2020. Manufacturers of veterinary medicinal products are advised to follow the constantly updated information and are seriously preparing for the start of an inspection for compliance with the requirements of the Rules of Good Manufacturing Practice of the Eurasian Economic Union.

Konstantin Morozov, GMP Specialist of Ceva Sante Animale LLC


REFERENCES:

  1. Россельхознадзор / Новости / С 2021 года изменятся требования к соискателям и лицензиатам, осуществляющим деятельность по производству лекарственных средств для ветеринарного применения. URL: https://fsvps.gov.ru/fsvps/news/38067.html (дата обращения 02.11.2020)
  2. Решение Совета Евразийской экономической комиссии от 03.11.2016 г. № 77 «Об утверждении Правил надлежащей производственной практики Евразийского экономического союза». URL: https://docs.eaeunion.org/docs/ru-ru/01411921/cncd_21112016_77 (дата обращения 02.11.2020)
  3. Приказ Минпромторга России от 14.06.2013 № 916 (редакция от 18.12.2015) «Об утверждении Правил надлежащей производственной практики». URL: http://www.consultant.ru/document/cons_doc_LAW_152004/ (дата обращения 02.11.2020)
  4. Новости GMP / Новости / О применении правил GMP в государствах-членах ЕАЭС. URL: https://gmpnews.ru/2020/02/o-primenenii-pravil-gmp-v-gosudarstvax-chlenax-eaes/ (дата обращения 02.11.2020)
  5. ФБУ «ГИЛС и НП» / Документы / Инспектирование / Основные отличия GMP РФ, GMP ЕАЭС, GMP ЕС (Информационная справка). URL: https://gilsinp.ru/?wpfb_dl=368 (дата обращения 02.11.2020)
  6. EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use. Volume 4. URL: http://ec.europa.eu/health/documents/eudralex/vol-4/index_en.htm (дата обращения 02.11.2020)
  7. Новости GMP / Статьи / Сравнение и анализ требований GМP Российской Федерации и ЕАЭС. URL: https://gmpnews.ru/2020/08/sravnenie-i-analiz-trebovanij-gmp-rossijskoj-federacii-i-eaes/ (дата обращения 02.11.2020)
  8. Объединенный фармацевтический портал PharmaPharm / Статьи / Статьи экспертов / Регуляторные квесты и лабиринты, или кому на Руси жить хорошо: старая сказка на новый лад с фарма-акцентом. URL: https://pharmapharm.ru/stati/regulyatornye-kvesty-i-labirinty-ili-komu-na-rusi-git-chorosho-staraya-skazka-na-novyy-lad-s-farma-akcentom/ (дата обращения 02.11.2020)
  9. Новости GMP / Новости / В ЕАЭС установят единые требования к квалификации и валидации на фармпроизводстве. URL: https://gmpnews.ru/2020/06/v-eaes-ustanovyat-edinye-trebovaniya-k-kvalifikacii-i-validacii-na-farmproizvodstve/ (дата обращения 02.11.2020)
  10. Изменения в Правила надлежащей производственной практики​. URL: http://www.eurasiancommission.org/ru/act/texnreg/deptexreg/LS1/Pages/WP_LA_projects.aspx (дата обращения 02.11.2020)
  11. ФБУ «ГИЛС и НП» / Документы / Инспектирование / Обзор основных нововведений в новой версии Приложения №16 к правилам GMP – «Требования к подтверждению Уполномоченным лицом соответствия серии продукции с целью ее выпуска». URL: https://gilsinp.ru/?wpfb_dl=369 (дата обращения 02.11.2020)
  12. Новости GMP / Новости / Современные тренды мирового законодательства: что изменится в отношении УЛ и владельцев РУ? URL: https://gmpnews.ru/2020/10/sovremennye-trendy-mirovogo-zakonodatelstva-chto-izmenitsya-v-otnoshenii-ul-i-vladelcev-ru/(дата обращения 02.11.2020)
  13. Федеральный портал проектов нормативных правовых актов. О внесении изменений в приказ Россельхознадзора от 18.10.2016 № 755 «Об утверждении формы заявления о выдаче заключения о соответствии производителя (иностранного производителя) лекарственных средств для ветеринарного применения требованиям правил надлежащей производственной практики, формы инспекционного отчета по результатам инспектирования производителя (иностранного производителя) лекарственных средств для ветеринарного применения на соответствие требованиям правил надлежащей производственной практики и формы заключения о соответствии производителя (иностранного производителя) лекарственных средств для ветеринарного применения требованиям правил надлежащей производственной практики». URL: https://regulation.gov.ru/projects#npa=109167(дата обращения 02.11.2020)
  14. ФГБУ «ВГНКИ» / Пресс-центр / Новости / В ФГБУ «ВГНКИ» прошел семинар о правилах надлежащей производственной практики евразийского экономического союза. URL: http://www.vgnki.ru/v-fgbu-vgnki-proshel-seminar-o-pravilah-nadlezhashhej-proizvodstvennoj-praktiki-evrazijskogo-ekonomicheskogo-soyuza.html (дата обращения 02.11.2020)
  15. Совместная программа содействия внедрению лучших образцов надлежащих практик в российской фармацевтической отрасли / Открытые семинары и вебинары. URL: https://www.goodpractices.ru/anonce/ (дата обращения 02.11.2020)
  16. Новости GMP / События / Что войдет в повестку предконференционного дня ISPE ЕАЭС? URL: https://gmpevents.ru/chto-vojdet-v-povestku-predkonferenczionnogo-dnya-ispe-eaes/ (дата обращения 02.11.2020)