15 May 2022

Storage of Medicinal Products in Russia: Legal Regulations

May 15, 2022

BRACE Law Firm ©

Storage of medicinal products is an integral part of the circulation of medicinal products, carried out from the moment of receipt until the moment of use. However, the significance of this standard procedure cannot be underestimated. Only compliance with all requirements guarantees the safety of the medicinal product. Furthermore, compliance with storage rules is one of the licensing requirements for manufacturers of medicines and persons engaged in pharmaceutical and medical activities.

Requirements for the storage of medicinal products are regulated simultaneously by several regulatory acts:

Rules of Storage of Medicinal Products approved by Order of the Ministry of Health and Social Development of Russia No. 706n dated August 23, 2010 (the "Storage Rules", "Order No. 706n");
Rules of Good Practice for Storage and Carriage of Medicinal Products for Medical Use approved by Order of the Ministry of Health of Russia No. 646n dated August 31, 2016 (the "GSP Rules");
Pharmacopoeia Monograph OFS.1.1.0010.18 Storage of Medicinal Products (the "Pharmacopoeia Monograph").

In addition, specific storage requirements for such medicinal products as narcotic and psychotropic, radiopharmaceutical, and immunobiological products are contained in other regulatory legal acts.

In this article, we will analyze the rules for the storage of medicinal products (the "MPs") taking into account the requirements of all the above regulatory acts and the prevailing law enforcement practice.

Before reviewing the topic, we note that under Article 4 of Federal Law No. 61-FZ dated April 12, 2010, On Circulation of Medicinal Products (the "Law on Circulation of Medicinal Products"), medicinal products are understood as medicinal preparations (dosage forms used for prevention, diagnosis, treatment of disease, rehabilitation, for preservation, prevention, or termination of pregnancy) and Active Pharmaceutical Ingredients (substances regardless of origin intended for the production or manufacturing of medicinal preparations). We also note that this article will not cover the rules for the storage of medicinal products for veterinary use.

Who Must Comply with Medicine Storage Rules?

According to the meaning of Article 58 of the Law on Circulation of Medicinal Products and the above regulatory acts, storage rules apply to all medicinal product circulation entities (also, the "Pharma Organization"), namely:

manufacturers of medicinal products;
wholesale organizations of medicinal products;
pharmacy organizations;
individual entrepreneurs holding a license for pharmaceutical activity or medical activity;
medical organizations.

General Requirements for Storage Premises

The above regulatory acts contain a set of requirements for premises for storing medicinal products. Let us dwell on them in more detail.

1. The layout, composition, and size of storage areas must ensure the preservation of MPs.

Storage areas for MPs must be divided into zones. For manufacturers and wholesale organizations, the complex of premises must include the following zones:

a) acceptance;

b) main storage;

c) expedition;

d) storage of medicinal products requiring special conditions;

e) storage of identified falsified, substandard, and counterfeit medicinal products;

f) quarantine storage of medicinal products.

The area of premises used by other medicinal product circulation entities must be divided into the following zones:

a) acceptance;

b) storage of medicinal products requiring special conditions;

c) storage of identified falsified, substandard, and counterfeit medicinal products, as well as medicinal products with an expired shelf life;

d) quarantine storage of medicinal products [1].

For manufacturers and wholesale organizations of MPs, additional standards for storage areas are established: at least 150 sq. m. (Clause 13 of the GSP Rules).

Administrative and amenity premises (manager’s office, restroom, etc.) must be separated from storage premises. It is prohibited to store food products, tobacco products, beverages (except for drinking water), and medicinal products intended for personal use in storage premises.

2. The finishing of premises must comply with sanitary and hygienic requirements.

All regulatory acts indicate that the finishing (inner surfaces of walls, ceilings) must be smooth and allow for wet cleaning. The GSP Rules additionally require that inventory and cleaning materials, as well as detergents and disinfectants, be stored in separate zones (cabinets).

3. Premises must be equipped with a sufficient amount of furniture for storing MPs (racks, cabinets, pallets, etc.).

Racks (cabinets) for storage are installed in such a way as to ensure access to medicinal products, loading and unloading operations, free passage of personnel, and accessibility for cleaning.

They must be identified/labeled, have rack cards located in a visible zone, and ensure the identification of medicinal products in accordance with the accounting system used by the medicinal product circulation entity. The use of an electronic data processing system instead of rack cards is permitted.

Separately, specific features of storage in warehouse premises are established. Medicinal products therein must be placed on racks (in cabinets) or on sub-pallets (pallets). Placement of medicinal products on the floor without a pallet is not permitted. Pallets may be placed on the floor in a single row or on racks in several tiers depending on the height of the rack. Placement of pallets with medicinal products in several rows by height without the use of racks is not permitted.

4. Temperature and humidity enabling strict storage conditions for medicinal products must be maintained in the premises.

The required air exchange and temperature are created using air conditioners, supply and exhaust ventilation, or other equipment.

5. Premises must be equipped with the necessary number of measuring instruments to monitor and record temperature and humidity.

Premises are equipped with instruments for recording air parameters (thermometers, hygrometers, or psychrometers). These instruments must be entered into the State Register of Measuring Instruments and are subject to periodic verification and/or calibration in accordance with the requirements of the legislation of the Russian Federation on ensuring the uniformity of measurements. Furthermore, Clause 7 of the Storage Rules establishes requirements for the placement of this equipment:

measuring parts of these instruments must be placed at a distance of at least 3 m from doors, windows, and heating appliances;
parts of the instruments from which visual readings are taken must be located in a place accessible to personnel at a height of 1.5-1.7 m from the floor.

The Pharmacopoeia Monograph also recommends placing them in areas where the greatest probability of temperature and humidity fluctuations exists or where deviations from the required parameters are most frequently observed.

Readings of these instruments must be recorded daily in a special registration log on paper or in electronic form (for electronic hygrometers). A responsible person is appointed to maintain it. The shelf life of the log according to the Storage Rules is 1 year, not counting the current year. It is worth noting that the GSP Rules establish different storage periods for the log: 2 years. These contradictions do not contribute to the stability of law enforcement practice.

Violations of premises requirements are often identified by controlling authorities. For instance, during a scheduled on-site inspection, Roszdravnadzor revealed the absence of identified zones for acceptance of medicinal products, quarantine storage, and storage of falsified, substandard, and counterfeit medicinal products in a pharmacy point. The company was held administratively liable under Part 4 of Article 14.1 of the CAO RF for carrying out activities with a gross violation of licensing requirements and conditions, and a fine of 100,000 rubles was imposed [2].

General Rules for Organization of Medicine Storage

Storage conditions for any medicinal product are established by its manufacturer by including them in the regulatory documentation (included in the registration dossier for the MP), the instructions for medical use, and the information contained on the primary and/or secondary packaging and transport packaging. Pharma Organizations are required to ensure the storage of medicinal products in accordance with the conditions established by the manufacturer.

One of the important conditions for storing medicinal products is compliance with the proper temperature and humidity. In this regard, the Pharmacopoeia Monograph provides a Table of correspondence between the storage mode indicated by the manufacturer on the packaging and the permissible temperature range.

Storage mode established by the manufacturer	Permissible temperature range
Store at a temperature not exceeding 30°C	From 2 to 30°C
Store at a temperature not exceeding 25°C	From 2 to 25°C
Store at a temperature not exceeding 15°C	From 2 to 15°C
Store at a temperature not exceeding 8°C	From 2 to 8°C
Store at a temperature not lower than 8°C	From 8 to 25°C
Store at a temperature from 15 to 25°C	From 15 to 25°C
Store at a temperature from 8 to 15°C	From 8 to 15°C
Store at a temperature from -5 to -18°C	From -5 to -18°C
Store at a temperature below -18°C	From -18°C
Does not require special storage conditions	From 15 to 25°C without requirements for light- and moisture-protective packaging
Do not freeze	Not lower than +2°C, unless otherwise specified in the pharmacopoeia monograph or regulatory documentation

For the majority of products, special conditions are not established, which means they are stored at a temperature from 15 to 25°C.

Regarding humidity, unless otherwise established, storage of medicinal products is carried out at a relative humidity of not more than 65%, depending on the relevant climatic zone (I, II, III, IVA, IVB).

In storage premises, medicinal products are placed in accordance with the requirements of the regulatory documentation indicated on the packaging of the medicinal product, taking into account:

physicochemical properties of the medicinal products;
pharmacological groups (for pharmacy and medical organizations);
method of administration (internal, external);
state of aggregation of Active Pharmaceutical Ingredients (liquid, loose, gaseous).

Stored medicinal products must be identified using a rack card or, when using computer technologies, using codes and electronic devices.

Separately, it is necessary to touch upon such an important aspect of storage as the organization of medicine quality control. During storage, the pharmaceutical organization must conduct daily monitoring of Roszdravnadzor information letters on the suspension or termination of circulation of medicinal products, as well as monitor the expiration dates of stored medicines.

Order No. 706n establishes the obligation of Pharma Organizations to keep records of medicinal products with a limited shelf life on paper or in electronic form with archiving, and to exercise control over their timely sale. The procedure for keeping records of said medicinal products is established by the head of the Pharma Organization.

The question arises: what to do if the shelf life of a medicinal product has expired? Clause 12 of Order No. 706n establishes the obligation, upon identification of such medicines, to store them separately from other groups of medicinal products in a specially designated and marked (quarantine) zone. The order does not establish where and how to store falsified and counterfeit medicines. In the GSP Rules, this issue is regulated differently. Thus, Clause 15 of the GSP Rules indicates the need for a storage zone for identified falsified, substandard, counterfeit products and products with an expired shelf life, and a zone for quarantine storage of medicinal products. At the same time, within the meaning of Clause 30, MPs regarding which circulation has been suspended by Roszdravnadzor or regarding which a decision on further circulation has not been made are stored in the quarantine zone.

Storage Features of Medicines Depending on Environmental Factors

Under the influence of environmental factors, some medicines may change their physicochemical properties and, as a result, become substandard. To prevent such adverse consequences, regulatory acts establish storage features for a number of MPs.

Order No. 706n identifies the following groups of MPs depending on the possible impact of environmental factors on them:

MPs requiring protection from light (photosensitive);
MPs requiring protection from exposure to moisture (moisture-sensitive);
MPs requiring protection from volatilization and drying;
MPs requiring protection from exposure to elevated temperature or low temperature (thermosensitive);
MPs requiring protection from exposure to gases contained in the environment;
odorous, coloring MPs;

For each of the groups, storage features preventing the impact of these factors are established. Let us consider the main ones. The full list of requirements is set out in Section VI of the Storage Rules.

Photosensitive MPs are stored in premises or specially equipped zones ensuring protection from natural and artificial lighting. Active Pharmaceutical Ingredients are stored in containers made of light-protective materials (orange glass containers, metal containers, aluminum foil packaging or materials colored black, brown, or orange, etc.), and medicinal products are stored in cabinets or on racks without exposure to direct sunlight or other bright directional light.

Moisture-sensitive MPs are stored in a cool place at a temperature of up to +15°C, in tightly sealed containers made of materials impermeable to water vapor (glass, metal, aluminum foil, thick-walled plastic containers) or in the primary and secondary (consumer) packaging of the manufacturer. Active Pharmaceutical Ingredients with hygroscopic properties are stored in a glass container with hermetic sealing, poured over with paraffin.

MPs requiring protection from volatilization and drying are stored in a cool place, in hermetically sealed containers made of materials impermeable to volatile substances (glass, metal, aluminum foil) or in the primary and secondary (consumer) packaging of the manufacturer.

Thermosensitive MPs are stored in strict accordance with the temperature mode indicated by the manufacturer. Thermolabile MPs are stored in pharmaceutical refrigerators or refrigerators for blood and its products. For monitoring, all refrigerators must be equipped with temperature measuring instruments (thermometers, thermographs).

MPs requiring protection from exposure to gases are stored in hermetically sealed containers, filled to the top if possible.

Odorous and coloring MPs are stored in hermetically closed containers impermeable to odor.

Coloring MPs are stored in a separate cabinet in tightly sealed containers. Special inventory is allocated for working with them.

Disinfectant MPs are stored in an isolated premise away from plastic, rubber, and metal items and premises for obtaining distilled water.

Storage Features of Flammable and Explosive Medicines

Due to their specifics, additional requirements are imposed on the storage of flammable and explosive medicines.

We note that according to Clauses 51 and 57 of Order No. 706n:

1) Flammable MPs include:

highly flammable MPs (alcohol and alcohol solutions, alcohol and ether tinctures, alcohol and ether extracts, ether, turpentine, lactic acid, ethyl chloride, collodion, cleol, Novikov's solution, organic oils);
combustible MPs (sulfur, glycerin, vegetable oils, bulk medicinal herbal raw materials);

2) Explosive MPs include:

those possessing explosive properties (nitroglycerin);
those possessing explosive hazard properties (potassium permanganate, silver nitrate).

In the Pharmacopoeia Monograph, storage requirements are stated generally: store in specially designed premises equipped with additional safety and security means. During storage, preservation and quality must be ensured, the possibility of manifestation of dangerous properties must be prevented, and safe working conditions must be created for employees working with such medicinal products.

In Order No. 706n, the requirements are detailed much more thoroughly. We list the main ones:

In wholesale trade organizations and at manufacturers of MPs, storage premises are divided into compartments with a fire resistance rating of building structures of at least 1 hour. Floors of warehouse premises and unloading platforms must have a hard, even surface. Warehouse premises are equipped with fireproof racks installed at a distance of 0.25 m from the floor and walls. The width of racks must not exceed 1 m, and longitudinal aisles between racks must be at least 1.35 m.
In pharmacy organizations and at individual entrepreneurs, isolated premises equipped with automatic fire protection means and alarms are allocated for the storage of such MPs.
It is permitted to store no more than 100 kg of MPs with flammable and explosive properties in the premises. If their quantity is greater, they are stored in a separate building.
In pharmacy organizations, it is permitted to store highly flammable and combustible Active Pharmaceutical Ingredients up to 10 kg in built-in fireproof cabinets. Cabinets must be removed from heat-emitting surfaces and aisles, with doors at least 0.7 m wide and at least 1.2 m high.
Storage must be carried out separately from other medicinal products.
At workplaces in production premises of pharmacies, flammable medicinal products may be stored in quantities not exceeding the shift requirement.
Highly flammable liquids are stored in tightly sealed glass or metal containers. The filling degree of the container is no more than 90% of the volume, for alcohols — no more than 75%. Large containers are placed on racks in a single row by height.
Explosive MPs must be protected from dust. Containers must be tightly closed.
It is not permitted to store flammable MPs with mineral acids, compressed and liquefied gases, inorganic salts, and explosive MPs with acids and alkalis.

For violations of requirements for the storage of flammable and explosive medicinal products, liability is also imposed under Part 4 of Article 14.1 of the CAO RF. A significant number of these are identified during inspections of ethyl alcohol circulation. Among the main ones:

premises are not divided into separate premises (compartments) [3];
fireproof pallets are absent, storage is carried out in several rows by height [4];
joint storage with other medicinal products is permitted [5].

Storage of Narcotic and Psychotropic Medicinal Products

Order No. 706n does not regulate the storage of narcotic and psychotropic medicinal products. It contains only a reference rule to the Rules for Storage of Narcotic Drugs and Psychotropic Substances approved by Decree of the Government of the Russian Federation No. 1148 dated December 31, 2009. More details on the storage of narcotic drugs and psychotropic substances can be read in the article "Narcotic and Psychotropic Medicinal Products: Legal Regulation".

Storage of Potent and Poisonous Medicines, Medicines Subject to Subject-Quantitative Accounting

Potent and poisonous medicines include medicinal products containing potent and poisonous substances included in special lists [6] approved by the Government of the Russian Federation.

Storage rules for potent and poisonous MPs differ depending on whether they are under international control or not [7].

If yes, their storage is carried out in technically fortified premises complying with requirements for the storage of narcotic drugs and psychotropic substances. Joint storage of potent, poisonous medicinal products and narcotic, psychotropic medicinal products in one room is permitted. In this case, storage must be carried out on different shelves of a safe (metal cabinet) or in different safes (metal cabinets).

If not, storage is carried out in metal cabinets sealed or lead-sealed at the end of the working day.

The list of medicinal products subject to Subject-Quantitative Accounting (hereinafter – "SQA") is approved by the Ministry of Health of Russia [8]. It includes several groups of products:

MPs containing Narcotic Drugs and Psychotropic Substances and their precursors in combination with pharmacologically inactive and active substances;
MPs containing potent and poisonous substances;
combined MPs containing Narcotic Drugs and Psychotropic Substances in small doses and other pharmacologically active substances;
other MPs indicated in the List.

Medicinal products subject to SQA, except for narcotic, psychotropic, potent, and poisonous medicinal products, are stored in metal or wooden cabinets sealed or lead-sealed at the end of the working day.

Violations of storage of this category of medicines are often identified by bodies of the Ministry of Internal Affairs during operational-search or other verification activities. Materials on identified violations are transferred to the territorial body of Roszdravnadzor. Thus, the Main Directorate of the Ministry of Internal Affairs of Russia for the Rostov Region revealed that medicinal products subject to SQA were stored in a utility room in a cardboard box in a pharmacy organization. By the decision of the arbitration court, the company was held administratively liable under Part 4 of Article 14.1 of the CAO RF with the imposition of an administrative fine in the amount of 150,000 rubles. As an analysis of judicial practice shows, the punishment imposed in the event of such violations is, as a rule, more severe than for violation of other storage rules and starts from 150,000 rubles with a minimum sanction under this article of 100,000 rubles.

Ensuring Quality of Medicine Storage

The GSP Rules, in addition to requirements for the storage of medicines, regulate the obligations of Pharma Organizations to develop and maintain a quality system for their storage.

Thus, Clause 3 of the GSP Rules imposes an obligation on the head of the Pharma Organization to develop a set of measures ensuring the quality of MP storage. Let us consider them in more detail.

First, the medicinal product circulation entity must have approved documents regulating the procedure for employees to perform actions when storing medicinal products, the procedure for servicing and verifying measuring instruments and equipment, keeping records, reports, and their storage (hereinafter – "Standard Operating Procedures", "SOPs") and control over compliance therewith must be exercised.

In fact, an SOP represents a list of step-by-step actions that an employee must perform when carrying out a particular work operation. The development of SOPs is aimed at minimizing possible violations since, thanks to their presence, the employee does not need to study regulatory acts in detail and only strict compliance with developed algorithms is required.

SOPs are developed by Pharma Organizations independently. For methodological assistance, Roszdravnadzor developed a model sample SOP for storage and carriage (transportation) of an immunobiological medicinal product – a vaccine for the prevention of the new coronavirus infection COVID-19 [9].

In the event of a violation of SOPs by employees, an internal audit is conducted and corrective actions are developed to eliminate the identified violations.

Second, documentary registration of all actions and achieved results must be carried out during the performance or immediately after the completion of the relevant actions. This requirement eliminates the possibility of a formal approach to executing documents, including retroactively.

Third, the liability of employees for violation of GSP Rules and SOP requirements must be determined. By order of the head of the Pharma Organization, a person responsible for the implementation and assurance of the quality system is appointed, who monitors the effectiveness of the quality system and updates SOPs. The duties and liability of employees of the medicinal product circulation entity, including the responsible person, are consolidated in job descriptions.

We also note that the head of the Pharma Organization must also approve a schedule plan for initial and subsequent training (briefings) of personnel, and further control its execution and effectiveness. A separate briefing is necessary for the storage of medicines for which special storage conditions are established.

The presence of a quality system in a Pharma Organization is included in the subject of Roszdravnadzor control, and its absence is also qualified by controlling authorities as a violation of licensing requirements and conditions under Part 4 of Article 14.1 of the CAO RF. Thus, during a scheduled licensing control of pharmaceutical activity, Roszdravnadzor revealed that the pharmacy lacked SOPs: procedure for cleaning premises, risk management procedure; verification of the shelf life of medicinal products and pharmacy assortment goods. Employees were not familiarized with the following SOPs: exchange and return of medicinal products and pharmacy assortment goods; acceptance control of goods. The pharmacy was fined 100,000 rubles. It was not possible to challenge this in court. The court pointed out that the mandatory nature of the development, approval, and familiarization of employees with these SOPs is provided for by Clauses 25, 45, 46, 50 of the GSP Rules.

Summing up, we draw attention to the necessity of strict compliance with the rules for the storage of medicinal products. An analysis of judicial practice shows that courts do not recognize these violations as minor, due to the possible risk of harm to the life and health of citizens. At the same time, we note that unification of regulatory acts on this issue is required, since the presence of a significant number of them regulating the same legal relations cannot have a favorable effect on law enforcement practice.

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References

[1] Names of zones are given in accordance with Clauses 14-15 of the GSP Rules and differ from names in OFS.1.1.0010.18 and Order No. 706n.

[2] Resolution of the Arbitration Court of the Moscow District dated March 21, 2022, No. F05-34407/21 in case No. A40-122346/2021.

[3] Resolution of the Seventh Arbitration Appeal Court dated July 28, 2020, No. 07AP-5369/20 in case No. A03-5930/2020.

[4] Resolution of the Arbitration Court of the North Caucasus District dated July 20, 2020, No. F08-5334/20 in case No. A61-6380/2019.

[5] Resolution of the Fifteenth Arbitration Appeal Court dated May 25, 2018, No. 15AP-5696/18.

[6] Decree of the Government of the Russian Federation No. 964 dated December 29, 2007, On Approval of Lists of Potent and Poisonous Substances for the Purposes of Article 234 and Other Articles of the Criminal Code of the Russian Federation, as well as the Large Size of Potent Substances for the Purposes of Article 234 of the Criminal Code of the Russian Federation.

[7] International legal acts:

United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.
Convention on Psychotropic Substances.
Single Convention on Narcotic Drugs of 1961, as amended by the 1972 Protocol Amending the Single Convention on Narcotic Drugs, 1961.

[8] Order of the Ministry of Health of the Russian Federation No. 183n dated April 22, 2014, On Approval of the List of Medicinal Products for Medical Use Subject to Subject-Quantitative Accounting.

[9] Letter of Roszdravnadzor No. 01-67950/20 dated November 18, 2020.