The Application of the International GXP Standards in the Russian Federation: TEMPO Educational Programs
Dr. Z. Grishina, Yu. Kuznetsova, Dr. Yu. Remnev, Dr. A Zudin.
Noncommercial Partnership “The Center of Modern Medical Technology “ÒÅÌÐΔ.
The main goal of TEMPO educational programs is to influence the development of the basis for drugs and vaccines development, clinical trials and manufacturing in accordance with the international standards GLP, GCP and GMP correspondently. TEMPO works with its members on the application of the international GXP quality standards in the Russian Federation, in particular through training of regulatory affairs specialists. TEMPO has evolved as the Russian training platform for sharing knowledge and experience in regulatory affairs. TEMPO educational program in GLP was developed in 2004 in cooperation with Regulatory Affairs Professionals Society (RAPS) and then recognized by RAPS as fully correspondent to the international educational standards. In 2005, TEMPO successfully launched first Russian GLP training program and realized multiple training sessions for specialists of TEMPO member institutions. TEMPO is currently developing together with RAPS new training program in GMP area.
Introduction
The development and production of pharmaceutical products is dominated by regulatory compliance. Regulatory approval being a prerequisite for market entry demands the generation of experimental data in accordance with standard procedures following stringent quality control regimens and its compilation in predefined documentation formats. Preclinical investigations utilize physiological, pharmacological, biochemical, hematological, morphological and other testing methods in animal models to evaluate of a product’s safety for human use. Good Laboratory Practices (GLP) is the system of standards that exists to ensure the quality and integrity of preclinical data submitted to regulatory agencies in support of new pharmaceutical product approvals, as well as to provide for protection of the rights and welfare of human subjects involved in subsequent clinical studies. After the approval of new pharmaceutical products, the provision of their quality assurance and quality control is supported by Good Manufacturing Practice (GMP) standards.
Currently harmonization of requirements to preclinical trials of drugs is considered as a subject of great importance and significance in whole the world. In the Russian Federation “The Rules of Laboratory Practice” were approved by the Ministry of Healthcare and ratified by the Ministry of Justice in June of 2003 in accordance with Federal Law of the Russian Federation “On Drugs”. The rules are similar to the appropriate International rules and standards (GLP) with discrepancy just in the point of experimental animal use and keeping, as well as standard operating procedures (SOPs). Requirements to organization, planning and carrying out of preclinical trials, including toxicological investigations of drugs, as well as to registration of results of preclinical investigations and their quality assurance are established by this document. However, putting of the rules into practice is embarrassed for several reasons. Clearly, GLP-compliant preclinical capacity in Russia is a critical infrastructure required for a viable Russian biotech / pharmaceutical sector.
For the last 5 years Russian pharmaceutical industry realized the introduction and application of the international standards of drug production - GMP. Domestic GMP Guidelines (the Government Standard of the Russian Federation R 52249-2004) “The rules of Drug Production and Quality Control” have been accepted in 2004 and their observance is obligatory for all pharmaceutical companies in Russia since January 2006. Modernization of existing manufactures and construction of the new enterprises is carried out in accordance with the new requirements.
It is recommended that the gradual introduction of these regulatory documents aimed at creating an environment for the development and production of safe, effective, and quality drugs, begins with the training of laboratory and manufacturing personnel and their reorientation toward the introduction of the GLP and GMP guidelines.
NP “TEMPO” member institutions are developing and manufacturing new drugs and vaccines.
One of the tasks defined by the Charter of TEMPO, and its development strategy is implementation and assistance in development of regulatory systems to ensure drug production quality according to the international GXP standards.
TEMPO member institutions are actively engaged in the discovery of new drugs and vaccines utilizing traditional chemistry as well as biotechnology approaches. As a part of the supply chain of drug discovery and development, integrated through TEMPO, TEMPO institutions perform preclinical investigations including in-vivo and in-vitro efficacy studies, acute and chronic toxicology in support of comprehensive safety evaluations. However, the lack of compliance with GLP in the performance of these preclinical studies is a significant barrier to the acceptance of the experimental data generated, which, in turn, discourages Western pharmaceutical and biotechnology companies from adopting TEMPO members’ drug and vaccine candidates.
Currently TEMPO consists of 17 organizations, including JSC BIOKAD, JSC "Biochimmash" and NPO “Microgene”, which is the largest manufacturer of immunobiological preparations in Russia with 14 pharmaceutical enterprises located in several regions of Russia. In addition, TEMPO member scientific research institutes like SRC VB Vector, FSUI SRI of Highly Pure Biopreparations and IBCh RAS, develop pilot production facilities and facilities for the development and manufacturing of devices for immunochemical and biochemical analyses.
Along with modernization of laboratories and production facilities, other remedial actions such as targeted upgrades of vivaria of TEMPO member institutions (being undertaken through other programmatic mechanisms in cooperation / coordination with TEMPO), are required for the applying drug quality assurance and quality control systems according to the international GLP and GMP. TEMPO works with its members on the application of the international GXP quality standards in the Russian Federation, in particular through training of regulatory affairs specialists.
NP “TEMPO” - the Russian training platform for sharing knowledge and experience in regulatory affairs.
In 2004, with financial and intellectual support of the BioIndustry Initiative Program of the US Department of State, TEMPO has started the project on building of competence system in GLP area. The project has united two largest Russian organizations conducting preclinical trials – M.M. Shemyakin and Yu.A Ovchinnikov Institute of Bioorganic Chemistry of the RAS with its Pushchino Branch, and Research Center for Toxicology and Hygienic Regulation of Biopreparations, and also a leading educational and medical institution - The I.M. Sechenov Moscow Medical Academy. The objective of the Project was to establish the system of post-graduate, internationally recognized and compliant education, and training of regulatory affairs specialists from TEMPO institutional members in the field of organization and performance of preclinical trials.
The project is unique by involving of the international organization RAPS to participate in its realization. The first Russian GLP training course curriculum was developed by the group of experts of TEMPO, IBCh RAS and MMA together with RAPS experts. The curriculum is accredited by the Educational-Methodical Association on Medical and Pharmaceutical Education of Russian high schools (EMA) as the programs of thematic advanced training course. The procedure of program registration by EMA confirms the correspondence of the program to the Russian educational standards and supports the issuance of appropriate Russian State diplomas to the successful trainees in accordance with established Russian legislation. Simultaneously the Curriculum was recognized internationally as being fully corresponding to RAPS’ educational standards in GLP and in accordance with the requirements for the Regulatory Affairs Certification. Besides, RAPS together with TEMPO has performed investigation and has given the recommendation for the addition of methodical literature necessary for ensuring quality of preclinical trials.
In 2005, four sessions of GLP training for experts from TEMPO-member organizations has been performed starting in February 2005. The training sessions were carried out on the basis of Pushchino branch of IBCh, possessing facilities for providing of lectures and practical training. 130 experts attended the training and received MMA diplomas as successfully passed the thematic advanced training course. Detailed information on the TEMPO GLP training and numerous photos illustrating training implementation are placed in the TEMPO promotional booklet “Application of International GLP Standards in Preclinical Trials: Educational Program for the Specialists in Russia”.
TEMPO is currently developing together with RAPS new training program in GMP area basing on the GLP project as a successful model for development and implementation of training programs in GXP area. Training of TEMPO-member institutions specialists, development of methodical materials in cooperation with RAPS, as well as development and fulfillment of the GMP distance training course are planned to be realized within the new TEMPO project.