I. From the author
The concept of ensuringthestate guarantees of medicines' quality
coming into circulation of public health services and the veterinary service of the Russian Federation should be reflected in many federal laws and, above all, in Federal Law No. 61-FZ "On circulation of medicines", which was approved by the President of the Russian Federation on April 12th, 2010 and continues to be finalized until today.
To my great regret, the prolonged period of searching for optimal directions for creating effective health care in Russia as an important component of ensuring a high life expectancy for all categories of citizens in all regions is mainly due to the imperfection of the legislative and regulatory framework for the creation of a modern system of medicines, which should be the conduction of the instrumental control of biological characteristics of quality, efficiency and safety of one substance and the medicinal products manufactured on their basis.
At the same time, our proposals for the introduction of the most modern logistics supply methods, documentary instrumental control of biological characteristics of medicinal products' quality and temperature monitoring of the observance of the safely safe modes of their storage and transportation from the moment of acceptance to the intended use do not find proper understanding, assessment and support from the leadership of the Ministry of Health of the Russian Federation and federal supervision services.
The proposed concept will allow:
- ensure real compliance with the requirements of Federal Law No. 61-FZ (article 1, paragraph 2) on the priority of state regulation of safety, quality and effectiveness of medicines;
- for the first time in the world practice to provide consumers with documented information not about advertising, but about the real quality of medicines before they are used for their intended use, which fully meets the requirements of Federal Law No. 294-FZ "On Protection of Consumer Rights";
- Ensure the production of drugs of high quality guaranteed by introducing state acceptance of substances and medicines purchased for public health and veterinary medicine;
- cardinally solve the problem of counterfeit medicines coming and being in circulation;
- avoid unreasonable expenses for purchase of medicines of inappropriate quality, efficiency, safety and disposal of knowingly useful medicines;
- to simplify the state registration of existing and newly introduced.
The proposed concept should serve as the basis for the development of the "Cold Chain Supply Regulation and Quality Control of Medicines" as an Appendix to Federal Law No. 61-FZ with its subsequent implementation not only in the Russian Federation but also in interstate supply systems of thermolabile products of medical and social appointment of the Commonwealth states - BRICS, SCO, EAGE, etc.
In recent years, Russia and Commonwealth countries are working to introduce the proper production (GMP) and distribution (GDP) rules
into the pharmaceutical industry, without which the producers of medicines are practically deprived of the right to sell their products in the WTO market. To our great regret, the implemented GMP rules practically do not contain the most important requirements, implementation of which will allow solving the problems of ensuring the quality of medicines, their counterfeiting and falsification.
In our opinion, such requirements are:
- mandatory application of instrument monitoring of determination thevalues of biological characteristics of substances and drugs without which GMP certified enterprises can not confirm the real quality of the produced products;
- determination of reference values of biological characteristics of quality and the life of medicinal products with mandatory use of rapid-control devices;
- organization of a documentary monitoring system for observing the established temperature-time regimes for storing and transportation the medicinal products from the manufacture to the intended use;
- introduction of state acceptance of medicines by quality
- introduction of mandatory certification of medical equipment products used in Cold Chain logistics.
II. Terms and Definitions
1. A drugis a substance or a mixture of substances of synthetic and / or natural origin in the form of a dosage (tablet, capsule, solution, ointment, etc.) used for the prevention, diagnosis and treatment of diseases.
2. State registrationis a state control and supervisory function to determine the reference values of biological characteristics of quality, efficiency, safety, thermal stability of medicinal products depending on the integral effect of natural environmental factors and their suitability for use in public health and veterinary medicine.
All medicines are subjects to compulsory state registration and re-registration. The terms of the scheduled re-registration of medicinal products are determined by the Federal Law and must be conducted at least once in every five years. The timing of an unscheduled re-registration of medicinal products is determined when quality violations are detected during their production and / or when the technology of their production is changed.
3. State acceptance of medicinal products by qualityis a complex of organizational and technical measures to determine the real values of the biological characteristics of the quality of each series of medicines purchased from the manufacturer by comparison with similar characteristics determined in the process of state registration using express quality control devices.
4. The quality of medicinal productsis the correspondence of their biological characteristics of quality, efficiency and safety determined in the process of output production control and at any Cold Chain logistics point, similar to the reference characteristics determined in the process of their state registration.
5. Classification of medicines' quality.
5.1. The reference quality of the medicinal productis the maximum, intermediate and minimum permissible values of the biological quality characteristic of the medicinal product, included in the state register and in the instruction for its use, determined during the state registration.
5.2. A medicinal product of guaranteed qualityis a medicinal product of biological quality characteristics not worse than the reference values.
5.3. A medicinal product suitable for useis a drug that's real biological quality characteristics are not worse than the reference minimum acceptable limit value.
6. The life of the medicinal productis determined in accordance to the accepted methodology, the time interval for which the biological characteristics of the drug quality are guaranteed to be no worse than its minimum permissible value.
7. Thermal lability of medicinesis the feature to lose the initial quality under the influence of natural factors and, above all, the temperature of the environment.
8. Classification of thermolabile drugs by resistance to environmental temperatures.
8.1. A medicinal product, the storage and transportation of which requires the use of low temperatures, is a drug stored and transported in a frozen state, and the application is generally at temperatures above 0°C and below + 10°C.
8.2. Medicinal products that do not allow freezing - a drug, storage, transportation and use of which is carried out at temperatures above 0°C.
8.3. A drug that does not allow freezing and overheating is a medicinal product the storage, transportation and use of which is carried out at temperatures from 0°C and not above the values determined in the process of state registration and included in the instructions for use.
The shelf life of thermolabile medicinal products, indicated on packages, can be recognized as reliable only if there is a documentary, in the calendar and real-time mode, confirming compliance with the temperature-time values established for them during storage and transportation, as determined in the process of their state registration and entered into instructions for use.
9. Cold Chainis a complex of scientifically substantiated and confirmed organizational and technical measures to ensure the optimal safe temperature and time regimes of storage and transportation of medicines within which their suitability for use is guaranteed.
10. Logistics of the Cold Chain Supply and the quality control of medicinesis a set of scientifically grounded and proven methods for preserving the quality of medicines from the effects of natural and other factors from the time they are accepted by quality to their intended use.
11. Express quality control of medicinal productsis an instrumental method for determining the biological characteristics of the quality of medicinal products at the stages of the output production control, their state acceptance by quality, delivery and storage at warehouses and in detecting the negative consequences of their use for the intended purpose.
12. Documentary temperature monitoring of medicinal productsis the organization of a continuous, reliable, documentary, in the calendar and real-time mode, monitoring of compliance with temperature and time regimes of storage and transportation of medicinal products from the moment of state acceptance by quality to the intended use.
13. Proper rules for the production of medicines (GMP) can be considered appropriate if the pharmacopoeia of their production is based on the following conditions:
- manufacturers of medicines have reliable and documented information of input control based on the use of devices for express control of biological characteristics of quality and documentary temperature monitoring of storage and transportation regimes of substances used in their production;
- the real values of biological characteristics of the medicinal products' quality are determined by means of instrumental methods by comparing the values of these characteristics obtained in the process of output production control with similar values obtained in the process of state registration;
- instructions for the use of medicinal products contain information on the values of biological characteristics of their quality, depending on the duration and quantitative values of the ambient temperatures that affect them, as well as recommendations for preventing possible negative consequences of their use and providing necessary medical assistance in this case.
14. Mandatory state certification of operational characteristics of medical equipmentused in Cold Supply Chain and Quality Control logistics is checking the compliance of their operational and technical characteristics with the requirements of approved programs, methods and recommendations of the World Health Organization.
15. The main operational characteristics of products of medical equipment, subject to mandatory certification.
15.1. Medical thermal containers:
- duration of cold and heat impact;
- the rate of change in the temperature of the internal volume of the empty and with a full set of ice packs to the normalized values of ambient temperatures;
- maximum useful volume and minimum weight;
- resistance to mechanical influences during transportation (shocks and vibrations);
- Sanitary-epidemiological materials used in their design;
- Carrying convenience.
15.2. Medical devices for temperature monitoring:
- accuracy of recording the temperature of the internal volume (not worse than ± 0.5°C);
- ability to test the performance before use;
- presence of indication of threshold values of controlled temperature range;
- possibility to determine the duration of violations of the controlled temperature range;
- setting the calendar and real time;
- reading information about the registered temperatures without access to the monitored volume;
- availability of the possibility of transferring registered information on the observance of temperature conditions via digital communication channels.
15.3. Stationary refrigeration and refrigerated transport:
- presence of forced circulation of air in the internal volume;
- the possibility of switching on the forced circulation of air in the internal volume when the chamber is opened;
- availability of remote temperature monitoring of internal volume.
16. A set of mandatory accompanying documents for medicinal productsshould contain a copy of the instruction for use, which is a summary description of the chemical, pharmaceutical, pharmacological properties of the medicinal product, as well as information on its clinical application, with obligatory indication of the values of the reference biological characteristics of quality, real biological characteristics of quality, thatare determined during the state acceptance of the quality and their shelf life.
17.A set of documents for the Cold Chain medical products:
- instructions for use in accordance to GOST;
- Sanitary-epidemiological conclusion on the product;
- registration certificate;
- certificate of compliance with performance characteristics.
III. The main criteria for ensuring the quality of medicines in the production and logistics of the Cold Chain.
1. Criteria for assessing the compliance of the organization of pharmaceutical production with the requirements for the production of guaranteed quality medicines:
- availability of an input device control system for the biological characteristics of the substances used in drugs manufacturing;
- compliance with the proper production rules (GMP) during the production process of medicines;
- availability of output production control to determine the real values of the biological characteristics of the quality of manufactured drugs by instrumental methods by comparison with the reference quality characteristics determined in the process of state registration.
2. Criteria for the effectiveness of the introduction of state acceptance by quality:
- evaluation of real biological characteristics of the quality of medications taken in comparison with the reference ones;
- assessment of the suitability of the resource to the requirements of the state contract and the adjustment, if necessary, of the price of medicines;
- elimination of non-certified products from use in the Cold Chain logistics;
- confirmation of the authenticity of the medications taken excluding counterfeiting.
3. Criteria for the effectiveness of the Cold Chain organization:
- exclusion of the possibility of using medicines that have lost their quality;
- maximum reduction in the probability of loss of medicinal products life under the influence of environmental factors during transportation and storage for the entire period preceding their use and obtaining reliable, documented information on compliance with established temperature and time regimes, as well as identification of time spots and specific reasons that led to the violation of the requirements of the Cold Chain.
IV. The list of the main activities in supply logistics and quality control of medicines.
1. Bring the legislative and regulatory framework for the circulation of medicines to the requirements of the current concept of the Cold Chain.
2. Preparation the storage facilities and transport for the delivery and placement of purchased medicines.
3. Calculation the needs for certified medical devices of an express quality control, thermal containers, documentary temperature monitoring devices and the amount of financing for their purchases.
4. Organization of centralized procurement of medicines according to approved criteria for comparative assessment of the values of biological characteristics of quality, efficiency, safety and the optimal price corresponding to these characteristics.
5. Organization of state acceptance by the quality of medicines on the territory of the manufacturer.
6. Packaging of purchased medicines in self-supporting medical reusable thermal containers of the customer.
7. Organization of local and remote, through digital communication channels, documentary temperature monitoring using medical thermal registrators.
8. Shipment of packaged medicines to customers using aviation, road and / or railway refrigerated transport.
9. Acceptance of medicines delivered to the storage facilities with an assessment of their biological characteristics of quality and shelf life.
10. Application of medical thermo-containers with automatic regulation of internal temperature for delivery of medicines to hard-to-reach and remote regions of the country.
V. Areas of responsibility for providing logistics and quality control measures for medicines.
1. The Ministry of Health of the Russian Federation is responsible for:
- drafting documents for the legislative and regulatory framework for logistics and quality control of medicines and medical equipment for use in the Cold Chain;
- centralized planning, competitive bidding and procurement of medicines and medical equipment;
- state acceptance by the quality of substances and medicines manufactured on their basis;
- organization of delivery and storage of medicines and medical equipment.
2. Federal service for surveillance in Healthcare is responsible for monitoring the compliance with the requirements of regulatory documents that determine rules of logistics and quality control in the turnover of medicines and medical equipment.
1. Summary of the "Supply logistics and quality control of thermolabile medicines in the Cold Chain" Concept.
2. The report by Ushakov A.I. at the All-Russian Scientific and Practical Conference "Innovations in Medical, Pharmaceutical, Veterinary and Ecological Microbiology" (St. Petersburg, March 30 - 31, 2017).
3. Resolution of the All-Russian Scientific and Practical Conference "Innovations in Medical, Pharmaceutical, Veterinary and Environmental Microbiology" (St. Petersburg, March 30 - 31, 2017).
4. The response of the First Vice-Rector of the St. Petersburg State Academy of Veterinary Medicine from May 17th, 2017.
5. The response of the First Vice-Rector of the St. Petersburg State Academy of Veterinary Medicine from February 7th, 2018.
6. The FSBUU review at the Kirov Military Medical Academy from 12.02.2018.
7. The report by Ushakov A.I. at the All-Russian scientific-practical conference "Microbiology: from a microscope to a genomic analysis" (St. Petersburg, May 17 - 18, 2018).
8. Commentary on the report of Ushakov A.I. at the All-Russian scientific-practical conference "Microbiology: from a microscope to a genomic analysis" (St. Petersburg, May 17 - 18, 2018).
9. Letter to the Deputy Minister of Health of the Russian Federation from March 20, 2013, No. 23-03 / 18.
10. Response of the Director of the Department of Ministry of Health of the Russian Federation from April 23, 2018 No. 2034052 / 25-4.
11. Letter to the Director of the Department of Ministry of Health of the Russian Federation from 10.05.2018, No. 36-05 / 18.
12. GR-magazines "TET-AT-TET WITH AUTHORITY" May and December 2017.
Founder and supervisor of studies A.I. Ushakov
of a small business company Termo-Kont MK LLC,
Chairman of the BRICS Quality Control Committee
in Cold Chain Supply Logistics of medicines,
a member of the International Association
parenteral drugs (USA),
Honorary Professor of the Modern Humanitarian Academy
(contact phone number +7 (985) 233-46-58)