Suspension and Recall of Medicinal Products in Russia

 

March 23, 2023

BRACE Law Firm ©

 

Ensuring the safety of medicinal products is a priority task of the state in the sphere of healthcare. To implement it, authorized executive bodies and participants in the pharmaceutical market are charged with duties to exercise quality control and safety monitoring at all stages of the circulation of medicinal products. The result of such activities may be the suspension of application (sale), cancellation of state registration, or recall of series of medicinal products released into circulation.

Federal Law No. 61-FZ dated April 12, 2010, On the Circulation of Medicinal Products (the "Law on Circulation of Medicinal Products") does not fully disclose the indicated concepts. At the same time, letters from controlling bodies regarding the suspension of application (sale), cancellation of state registration, or recall of series of medicinal products released into circulation often raise questions among circulation entities.

In this article, we will analyze what the current legislation implies by these terms, the grounds and procedures for their application regarding medicinal products for medical use, and examine possible legal consequences using examples from judicial practice.

Suspension of Application (Sale) of a Medicinal Product

Suspension of the application of a medicinal product means a temporary ban on its sale and use. It is carried out in the event of the detection of violations of requirements for its safety during the implementation of pharmacovigilance.

The procedure for suspending application is regulated by Article 65 of the Law on Circulation of Medicinal Products and Order of the Ministry of Health of Russia No. 777n dated November 14, 2018, On Approval of the Procedure for Suspending the Application of a Medicinal Product for Medical Use (the "Order No. 777n").

The decision to suspend the application of medicinal products for medical use is made by the Ministry of Health of Russia based on information received from Roszdravnadzor or the Ministry of Industry and Trade of Russia.

Grounds for suspending the application of a medicinal product:

• receipt from Roszdravnadzor of information on adverse reactions during the use of the medicinal product, specifics of its interaction with other medicinal products that may pose a threat to life or health, or non-compliance of data on efficacy and safety with the data contained in the instructions for use (the "adverse reactions");
• failure by Marketing Authorization Holders (MAH) / legal entities that received permits to conduct clinical studies to report information on the detection of adverse reactions;
• submission by Roszdravnadzor of a conclusion on the unreliability of the results of a clinical study of the medicinal product;
• failure to comply with an order issued by Roszdravnadzor based on the results of carrying out selective quality control of the medicinal product;
• the composition and (or) production technology of the medicinal product differ from those declared in the registration dossier;
• the medicinal product is produced at a manufacturing site not indicated in the registration dossier;
• the manufacturer lacks documents confirming the compliance of the quality of the medicinal product with the requirements established during its state registration;
• the manufacturer of medicinal agents has not eliminated violations of the requirements of the Rules of Good Manufacturing Practice (GMP) or license requirements that may lead to the production of medicinal products dangerous to life and health within the period agreed with the Ministry of Industry and Trade of Russia.

From January 1, 2026, another ground is introduced: failure by the Marketing Authorization Holder or owner to submit information and documents for conducting an examination of the medicinal product for interchangeability or failure to submit an application for amendments to the registration dossier for the medicinal product in the event that data on interchangeability with another product is published.

The initiator of the procedure has the right to be FSBI "Scientific Centre for Expert Evaluation of Medicinal Products" (FSBI "SCEMP") of the Ministry of Health of Russia. The suspension period will be 6 months.

Upon receipt of this information, the Ministry of Health of Russia:

• posts a notification for the Marketing Authorization Holder or owner of the medicinal product regarding the consideration of the issue of suspending the application of the medicinal product on its official website and in the State Register of Medicinal Products (SRMP);
• within 3 business days, conducts a verification of the received information and makes a decision on the suspension of application or refusal. If information on the detection of adverse reactions is being considered, then prior to making a decision, an examination of the ratio of expected benefit to the possible risk of application is appointed (the decision-making period in such a case is extended for the duration of the examination);
• sends the decision to the Marketing Authorization Holder or owner of the medicinal product, and also notifies the state authorities of the constituent entities of the Russian Federation in the sphere of health protection, Roszdravnadzor, and the Ministry of Industry and Trade of Russia about the adoption of the decision to suspend the application of the medicinal product. Information on the adopted decision is also posted on the official website and in the SRMP.

The Marketing Authorization Holder (owner) of the medicinal product in respect of which a decision on the suspension of its application has been made has the right to file a complaint against this decision with the Ministry of Health of Russia. The period for consideration of the complaint is 15 business days from the date of its registration. The decision is sent within 1 business day from the date of its adoption on paper or in the form of an electronic document.

Furthermore, interested parties are not deprived of the right to challenge the adopted decision on the suspension of the application of a medicinal product in court in accordance with Chapter 24 of the Arbitration Procedure Code of the Russian Federation (APC RF) "Challenging non-normative legal acts, decisions and actions (inaction) of state bodies." For the court to satisfy the application, it will be necessary to prove the following circumstances in aggregate:

• non-compliance of the challenged decision, action (inaction) with the law or other legal act;
• violation of the rights and legitimate interests of the applicant in the sphere of entrepreneurial and other economic activity or illegal imposition of any duties on them, creation of other obstacles to carrying out entrepreneurial and other economic activity.

Let us cite the following example from judicial practice. A manufacturer applied to the arbitration court with a statement challenging the decision of the authority on the temporary ban on the circulation of a medicinal product manufactured by it. The court of the first instance examined the inspection report, which revealed violations during the production of the product, as well as documents confirming the facts of the occurrence of severe consequences during its use. It refused to satisfy the application. The appellate instance, at the request of the manufacturer, appointed a forensic examination regarding the compliance of the product with the requirements of the normative documentation with selective sampling of ampoules for examination in a random manner. The examination established that the ampoules submitted for examination did not contain any other medicinal agent or unknown composition and complied with the requirements of the normative documentation. The decision of the court of the first instance was overturned, and the challenged non-normative act of the state body was recognized as non-compliant with the requirements of the legislation. The cassation instance indicated that a selective check of a part of the product does not refute gross violations of the organization of production and quality control, which is the basis for suspending the circulation of the medicinal product [1].

Other methods of protection, for example, a claim for damages, have, in our opinion, much less chance of success. Thus, in one case, a Company applied to the arbitration court with a statement of claim for the recovery of damages in the amount of 528 million rubles from the authority. As established during the court session, the Company concluded a contract for the supply of a medicinal product. During its execution, the state body suspended the circulation of the product in connection with the need to verify information about the non-compliance of the product with the requirements of technical regulations. The Company tried to challenge the suspension of the circulation of medicinal products in court. After the refusal to satisfy the application, they filed a lawsuit for damages. They referred to the fact that Roszdravnadzor does not take any actions to check the quality of the product and does not resume the circulation of the medicinal product. The shelf life of the medicinal products expired, which entailed the infliction of damages in the amount of the cost of the goods. The court indicated that to satisfy the requirements for the recovery of damages, the presence of harm, the unlawfulness of the defendant's behavior, and a causal link between such behavior and the ensuing harm are necessary. In the case under consideration, the actions of Roszdravnadzor were recognized as lawful by a judicial act that entered into legal force. The claim was refused [2].

Cancellation of Registration of a Medicinal Product

As a general rule, medicinal products are released into civil circulation on the territory of the Russian Federation if they have passed state registration and are entered in the State Register of Medicinal Products (Articles 13 and 27 of the Law on Circulation of Medicinal Products). In turn, the law provides for the possibility of canceling the state registration of a medicinal product, which will effectively mean a ban on its further circulation in the country.

The decision to cancel the state registration of a medicinal product is made by Roszdravnadzor.

The exhaustive list of grounds for making such a decision is provided by Article 32 of the Law on Circulation of Medicinal Products. Let us consider them in more detail using examples from judicial practice.

1. Receipt, based on the results of safety monitoring, of a conclusion on the risk or threat to life or health when using a medicinal product that exceeds its efficacy.

This ground is directly related to the detection of inadequate quality of goods and may entail a claim for damages for both the manufacturer and the MAH, as well as for wholesale trade organizations and pharmacy organizations. Thus, in one case, the customer filed a lawsuit against a pharmacy to oblige it to remove 297 packages of a medicinal product from the warehouse, the registration of which was canceled, and to recover 416 thousand rubles in damages. The pharmacy objected, believing that the responsibility for the transfer of goods of inadequate quality lies with the manufacturer, not the supplier of medicines. The court established that the state registration of the medicinal product was canceled due to the detection of substandard quality. Since this excludes the possibility of their use, and the replacement of goods with similar ones is not possible, the court recognized the plaintiff's claim for recovery of damages amounting to the cost of the low-quality goods as lawful [3].

In another similar case, the Ministry of Health filed a lawsuit against a supplier to oblige it to replace a product, the registration of which was canceled, with goods freely circulating on the market, and to recover a fine under the contract in the amount of 218 thousand rubles. The supplier objected to the satisfaction of the claim, citing that at the time of delivery of the goods, the medicinal product was not among the rejected, falsified, substandard, counterfeit, or withdrawn from circulation medicinal agents, and accordingly, quality goods were delivered. The requirements of the Ministry of Health were satisfied in full for the above reasons [4].

2. Submission by the holder or owner of the Registration Certificate for the medicinal product of an application for the cancellation of state registration.

In this case, we are talking about a voluntary refusal by the indicated persons, the reasons for which do not have legal significance. In practice, an interesting question arises: if the cancellation of state registration is not actually related to any violations of quality characteristics and occurred upon the manufacturer's application, can the supplier be responsible for the actions of a third party and bear adverse consequences?

Thus, in one case that reached the Supreme Court of the RF, the customer applied to the arbitration court with a statement of claim against the supplier to oblige it to accept the medicinal product delivered under the state contract in the amount of 4,212 packages and to recover funds in the amount of 3.9 million rubles paid for the goods. The reason for applying to the court was the fact of cancellation by the Ministry of Health of Russia of the state registration and exclusion of the delivered product from the SRMP upon the manufacturer's application. The court of the first instance satisfied the claim in full, indicating that the delivered medicinal product, due to the cancellation of state registration, cannot be used by the plaintiff for medical purposes, which is a significant violation of the requirements for the quality of the delivered goods and gives the right to refuse to perform the contract and demand the return of the sum of money paid for the goods. The court of appellate instance did not agree with these conclusions. It indicated that at the time of delivery of the goods, the supplier could not assume that the Registration Certificate would be revoked. It took into account that the cancellation of state registration is not related to a threat to human life or health, as well as the long period of storage of the product by the customer without use. Based on the indicated circumstances, it saw an abuse of right in the customer's actions with the aim of compensating for its losses related to inefficient procurement planning. It refused to satisfy the stated requirements. The cassation instance upheld the decision of the court of the first instance. The Supreme Court of the RF supported the supplier's arguments, noting that if the defects of the goods arose as a result of the actions of third parties and after the transfer of the goods to the buyer, the supplier cannot be responsible for their defects [5].

At the same time, a year earlier in a similar case, the Supreme Court of the RF supported a different position: cancellation of the state registration of a product indicates its poor quality and allows presenting requirements to the supplier for the return of funds [6].

Obviously, it can be said that the point in the question of whether the availability of state registration is included in the criteria for the quality of a medicine has not been set, and court disputes will be resolved based on the specific circumstances of the case.

3. Non-confirmation of the state registration of a medicinal product upon expiration of the validity period of the Registration Certificate issued for 5 years.

In accordance with Article 28 of the Law on Circulation of Medicinal Products, a Registration Certificate is issued for medicinal products registered in Russia for the first time for 5 years. Upon expiration of the specified period, the medicinal product must undergo the procedure for confirmation of state registration, after which an indefinite Registration Certificate is issued for the product. Confirmation of state registration is of a declarative nature and is carried out by the manufacturer of the medicinal product or its authorized person submitting a package of documents to the Ministry of Health of Russia.

4. Failure to submit information on changes for inclusion in the registration dossier for a registered medicinal product within 30 business days from the date of their occurrence.

The registration dossier for a medicinal product represents a set of documents and materials of an administrative nature, chemical, pharmaceutical, biological, pharmacological, toxicological documentation, and clinical documentation. The amount of information contained in the registration dossier is determined by Order of the Ministry of Health of Russia No. 409n dated July 12, 2017 [7]. Any change in the instructions for use, layouts of primary and secondary packaging, normative documentation according to which the product is produced, information about the product itself and the active pharmaceutical ingredient (API) used, etc., requires appropriate changes to the documents included in the registration dossier of the medicinal product. In turn, failure to enter such information within a 30-day period entails the cancellation of the registration of the medicinal product.

5. Implementation of state registration of a medicinal product in the presence of a previously registered product with the same trade name differing in the qualitative composition of active substances.

6. Implementation of state registration of the same medicinal product of the same holder (owner) of the Registration Certificate under different trade names.

This and the previous ground for cancellation of registration are consequences of the violation of prohibitions established by Part 6 of Article 13 of the Law on Circulation of Medicinal Products on the registration of different medicinal products under the same trade name and, conversely, one medicinal product manufactured by one manufacturer under different trade names.

7. Issuance by a court of a decision on the violation of rights of a copyright holder of intellectual property objects during the circulation of medicinal agents.

An independent ground not related to quality is the violation of the rights of copyright holders. Thus, in one case, the Ministry of Health of Russia registered a medicinal product under the trade name "Gefitinib." According to the instructions for use, this medicinal product contains a chemical compound protected by a patent of another legal entity. The copyright holder applied to the court with a lawsuit against the Company that submitted the application for registration and the Ministry of Health for the protection of rights to the invention. Since the fact of using the invention was confirmed, the court obliged the applicant to submit to the Ministry of Health an application for the cancellation of the state registration of the medicinal product "Gefitinib" [8].

8. Absence of the medicinal product in circulation in the Russian Federation for 3 or more years.

The Ministry of Health of Russia, in order to identify medicinal products absent in civil circulation, in Letter No. 20-3/328 dated March 4, 2019, indicated to holders of Registration Certificates the necessity of submitting an application for the cancellation of state registration of medicinal products absent in circulation on the territory of the Russian Federation for three or more years [9].

9. Failure by the holder or owner of the Registration Certificate to perform measures to ensure the safety of medicinal products within the framework of carrying out pharmacovigilance.

Parts 3 and 4 of Article 64 of the Law on Circulation of Medicinal Products impose on the indicated persons the duties to report to Roszdravnadzor about side effects, adverse reactions, individual intolerance, lack of efficacy of medicinal products, as well as other facts and circumstances posing a threat to life or health when using medicinal products at all stages of circulation of medicinal products, as well as to carry out the reception, recording, processing, analysis, and storage of similar information received by them from state authorities and medicinal product circulation entities.

Thus, in one case, a manufacturer submitted an application for confirmation of state registration of a medicinal product to obtain an indefinite Registration Certificate. Based on the results of the procedure, the Ministry of Health of Russia made a decision to cancel the state registration of the medicinal product due to the non-confirmation of the ratio of expected benefit to possible risk. These circumstances served as the basis for applying to the court. During the court session, it was established that the sale of this product and monitoring of the efficacy and safety of the medicinal product had not been carried out for 5 years due to the validity of the patent for the reference product. The court concluded that the cancellation of the state registration of the medicinal product due to the failure by the owner of the Registration Certificate to perform measures to ensure the safety of medicinal products is lawful and justified [10].

Recall of a Series or Batch of a Medicinal Product

The Law on Circulation of Medicinal Products does not contain the concept and procedure for the recall of a medicinal product. In fact, a recall represents the withdrawal from circulation of a specific or all series of a specific product, which is carried out on the initiative of the manufacturer and brought to the attention of market participants by information letters from Roszdravnadzor. The reason for the recall in the letters is often indicated as non-compliance of the quality of the product with the requirements of normative documentation.

The Rules of Good Distribution Practice within the Eurasian Economic Union [11] provide for the following requirements for the recall procedure:

• the effectiveness of actions to recall medicinal agents from circulation must be regularly evaluated (at least once a year);
• it must be possible to initiate actions to recall medicinal agents from circulation in the shortest possible time at any moment;
• the distributor must follow the instructions of the information letter on the recall from circulation;
• actions for recall and withdrawal from circulation must be documented at the time of their implementation in accordance with established procedures;
• the sequence of actions taken during the recall and withdrawal of a series and (or) batch of a medicinal agent from circulation must be documented and reflected in the final report;
• records related to distribution must be available to the person responsible for the recall of medicinal agents from circulation during working and non-working hours, contain sufficient information about distributors and direct recipients (address, phone number, and fax number), data regarding exported medicinal agents and their samples (series and (or) batch number, name, dosage form, dosage, as well as the quantity supplied).

Liability for Violation of Prohibitions and Restrictions on the Circulation of Medicines

Whichever of the above methods of prohibition or restriction on the circulation of a medicinal product is applied, the sale of such a product is prohibited. Violation may result in administrative or criminal liability.

Administrative liability is provided for by Part 2 of Article 6.33 of the Code of Administrative Offenses of the Russian Federation (CAO RF) "Sale or import into the territory of the Russian Federation of substandard medicinal agents, or illegal production, sale or import into the territory of the Russian Federation of unregistered medicinal agents" and entails the imposition of a fine:

• on officials – from 100,000 to 600,000 rubles;
• on individual entrepreneurs – from 100,000 to 600,000 rubles or administrative suspension of activity for up to 90 days;
• on legal entities – from 1,000,000 to 5,000,000 rubles or administrative suspension of activity for up to 90 days.

Thus, in one of the cases considered, Roszdravnadzor drew up a protocol on an administrative offense under Part 2 of Article 6.33 of the CAO RF against a pharmacy institution and sent it to court. The basis was the materials of the inspection by the Ministry of Internal Affairs (UMVD), which revealed the fact of sale in the pharmacy institution of an unregistered medicinal product in the amount of 1 package. During the consideration of the case by the arbitration court, it was established that the disputed product was excluded from the SRMP in connection with the cancellation of its state registration based on the manufacturer's application. The fact of the sale of the product was revealed a month after the exclusion from the SRMP. By the court's decision, the pharmacy institution was found guilty of committing an administrative offense, and a penalty was imposed in the form of a fine in the amount of 750,000 rubles [12].

For the circulation of substandard or unregistered medicinal agents on a large scale, one may be held criminally liable under Article 238 of the Criminal Code of the Russian Federation. At the same time, a large scale is recognized as the cost of medicinal agents in an amount exceeding 100,000 rubles.

In the absence of aggravating circumstances, the maximum punishment under Part 1 of Article 238 of the Criminal Code of the RF is imprisonment for a term of up to 5 years; additional punishment may also be imposed in the form of a fine in the amount of up to 2,000,000 rubles or in the amount of wages or other income for a period of up to 2 years, deprivation of the right to hold certain positions or engage in certain activities for a term of up to 3 years. Note that this norm was introduced into the Criminal Code relatively recently, at the end of 2014. However, the practice of holding criminally liable for the indicated crimes, although not yet regarding the topic under consideration, already exists [13].

In conclusion, we note that the life and health of citizens depend on the quality of medicinal agents. In this regard, the work carried out by control bodies and medicinal agent circulation entities on the timely detection, suspension of application, termination of state registration, and recall of products from circulation is of utmost importance. Attention is drawn to the fact of insufficient legal regulation of procedures and the consequences of their application, which entails errors in law enforcement and court disputes.

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References

[1] Resolution of the Federal Antimonopoly Service of the Moscow District dated February 12, 2013, in case No. A40-8733/12-149-80.

[2] Decision of the Arbitration Court of the Kurgan Region dated September 2, 2019, in case No. A34-5333/2019.

[3] Resolution of the Arbitration Court of the Ural District dated July 6, 2021, No. F09-3976/21 in case No. A34-3880/2020.

[4] Resolution of the Arbitration Court of the West Siberian District dated February 16, 2021, No. F04-6948/2020 in case No. A27-11171/2020.

[5] Ruling of the Judicial Chamber for Economic Disputes of the Supreme Court of the Russian Federation dated May 31, 2022, No. 310-ES21-28870 in case No. A83-1189/2020.

[6] Ruling of the Supreme Court of the RF dated March 10, 2021, No. 303-ES21-62 in case No. A73-23863/2019.

[7] Order of the Ministry of Health of Russia No. 409n dated July 12, 2017, On Approval of the Procedure for Formation of the Registration Dossier on a Medicinal Product and Requirements for Documents in its Composition, Requirements for the Amount of Information Provided in the Composition of the Registration Dossier for Specific Types of Medicinal Products for Medical Use and the Procedure for Submitting Documents from which the Registration Dossier on a Medicinal Product for Medical Use is Formed for the Purpose of its State Registration.

[8] Resolution of the Ninth Arbitration Appeal Court dated October 18, 2018, No. 09AP-51493/2018 in case No. A40-106405/18.

[9] Letter of the Ministry of Health of Russia No. 20-3/328 dated March 4, 2019, On the Necessity of Submitting to the Ministry of Health of Russia an Application for Cancellation of State Registration of Medicinal Products Absent in Circulation for Three or More Years.

[10] Resolution of the Ninth Arbitration Appeal Court dated May 17, 2021, No. 09AP-12090/2021 in case No. A40-181996/2020.

[11] Approved by Decision of the Council of the Eurasian Economic Commission No. 80 dated November 3, 2016.

[12] Resolution of the Arbitration Court of the North Caucasus District dated June 11, 2020, No. F08-3881/2020 in case No. A53-33503/2019.

[13] Verdict of the Shakhty City Court of the Rostov Region dated August 3, 2020, No. 1-199/2020.