Litigation Related to the State Registration of Medicinal Products

 

February 10, 2022

BRACE ©

State registration of medicinal products is one of the most important priorities of pharmaceutical activity. However, disputes often arise during the registration of medicines, the resolution of which moves to the courts. Within the framework of this article, we will consider the main types of legal disputes arising during the registration of medicines.

Challenging the Refusal of State Registration of a Medicinal Product

In accordance with Cl. 2 Part 1 Art. 27 of Federal Law No. 61-FZ dated April 12, 2010, "On the Circulation of Medicines" (hereinafter – "Law No. 61-FZ", "The Law on Circulation of Medicines"), based on the results of the expertise of the quality of the medicine and the expertise of the ratio of expected benefit to the possible risk of using the medicinal product, the Ministry of Health of Russia makes a decision on the state registration of the medicinal product or on the refusal of state registration of the medicinal product. The ground for refusal of state registration of a medicinal product for medical use is a conclusion that the quality and (or) efficacy of the medicinal product being registered for medical use are not confirmed by the data obtained or that the risk of harm to human health due to taking the medicinal product for medical use exceeds the efficacy of its use [1].

It is not uncommon for an applicant – a pharmaceutical company – to disagree with the decision made by the state body, especially when this decision is a refusal of state registration of a medicinal product. As a general rule, a decision of the Ministry of Health of Russia on the refusal of state registration of a medicinal product can be appealed in the manner established by the legislation of the Russian Federation. Such procedure is regulated by Chapter 24 of the Arbitration Procedure Code of the Russian Federation.

Case No. A40-62100/21-93-444. Sorbent LLC vs Ministry of Health of Russia.

As an example, we can cite a court case challenging the decision of the Ministry of Health of Russia to refuse to conduct an expertise of a medicine for medical use regarding the expertise of the quality of the medicine and the expertise of the ratio of expected benefit to the possible risk of using the medicinal product for medical use. The applicant challenged the refusal of state registration of the medicinal product Nisilid (INN "Nimesulide") granules for the preparation of suspension for oral administration, 100 mg. In this case, the court found the application not subject to satisfaction on the grounds that the medicinal product was a generic medicinal product.

In its application, the applicant explained that when using the medicinal product declared for state registration in the dosage form "granules for the preparation of suspension for oral administration", the final dosage form used by the patient is a liquid dosage form for oral administration, and for such a dosage form, submission of a bioequivalence study report is impossible. However, according to the submitted application and other documents of the registration dossier, the medicinal product being registered, with the indicated method of use, is a "suspension" [2].

Recall that according to the Order of the Ministry of Health of Russia No. 538n dated July 27, 2016, "On Approval of the List of Names of Dosage Forms of Medicinal Products for Medical Use", applicable to the names of dosage forms of medicinal products for medical use, applications for state registration of which are submitted to the Ministry of Health, the dosage forms "solution" (a liquid dosage form obtained by dissolving solid, liquid, or gaseous substances in an appropriate solvent or a mixture of miscible solvents) and "suspension" (a liquid dosage form representing a heterogeneous dispersed system containing one or several solid active substances distributed in a liquid dispersion medium) are classified as different dosage forms [3].

In this regard, the court supported the position of the Ministry of Health that classifying the registered medicinal product as medicinal products that "are solutions for oral administration" or "are produced in the form of powders or lyophilisates for the preparation of solutions" is not possible. The company could declare as a reference product only a product in the same dosage form as its own or one assessed as equivalent. Thus, in the court's opinion, the decision of the Ministry of Health of Russia to refuse to conduct an expertise of the medicine for medical use regarding the expertise of the quality of the medicine and the expertise of the ratio of expected benefit to the possible risk of using the medicinal product for medical use was lawful and complies with civil legislation and cannot violate the rights and legitimate interests of the applicant.

Challenging the Cancellation of Medicine Registration

The decision to cancel the state registration of a medicinal product is made by the Ministry of Health of Russia. After such a decision is made, the medicinal product is excluded from the state register of medicines and is not subject to use. The grounds for canceling state registration are:

• Submission of a conclusion on risk or threat to human health and life;
• Submission of an application for cancellation of state registration of the medicinal product;
• Non-confirmation of state registration upon expiration of the registration certificate issued for 5 years;
• Failure to provide information necessary to be included in the registration dossier within 30 working days from the date of changes;
• Implementation of state registration under a trade name of a medicinal product differing in the qualitative composition of active substances from the previously registered one;
• Implementation of state registration of the same medicinal product in the form of 2 or more medicinal products under different trade names;
• Issuance by a court of a decision on the violation of rights of the rights holder of intellectual property objects during the circulation of medicines;
• Absence of the medicinal product in circulation in the Russian Federation for 3 or more years. In the latter case, the Ministry of Health explains that holders of registration certificates are obliged to submit applications for the cancellation of state registration of medicinal products absent from circulation in the territory of the Russian Federation for 2 or more years [4].

From January 1, 2023, the grounds for canceling state registration will be supplemented by another point. In particular, if the holder or owner of the registration certificate of the medicinal product fails to submit within 6 months from the date of suspension of the use of the medicinal product the documents necessary for the commission of experts of the expert institution to conduct an expertise of the registration dossier for the medicinal product in order to determine the interchangeability of the medicinal product for medical use, as well as if an application is not submitted by the owner or holder of the registration certificate of medicinal products that are interchangeable regarding making changes to the documents contained in the registration dossiers for registered medicinal products for medical use concerning information indicated in the instructions for medical use of medicinal products [5].

Case No. A40-2357/17. B. Braun Melsungen AG vs Ministry of Health of Russia

A pharmaceutical company appealed to the arbitration court with an application to recognize as illegal the inaction of the Ministry of Health of Russia, expressed in improper verification of the completeness and reliability of information contained in the materials submitted by the applicant on confirmation of the state registration of the medicinal product "Povidone-Iodine", ointment for external use, 10%. The arbitration court of the first instance satisfied the stated claims, concluding that the defendant's inaction was proven. However, the Ministry of Health appealed this decision in the appellate instance.

The applicant – a Russian company acting as a representative of the manufacturer – submitted an application for confirmation of state registration for the specified medicine. The Ministry of Health of Russia made a decision to conduct an expertise regarding the specified medicine. Based on the results of the expertise of the quality of the medicine and the expertise of the ratio of expected benefit to the possible risk of using the medicinal product, it was established that it is impossible to assess the ratio of expected benefit to the possible risk of using the medicinal product, according to which it is impossible to conclude on the medical use of the medicinal product, since there is no experience of using the medicinal product in the territory of Russia because the product was not sold in the Russian territory. The applicant based its claims on the fact that the Ministry of Health allowed inaction expressed in improper verification of the completeness and reliability of information contained in the materials submitted by the applicant to the application for confirmation of state registration of the medicinal product, failure to send the applicant a request for clarification of the submitted information on the turnover of the medicinal product in the territory of the Russian Federation, and failure to notify the applicant in writing about the appointment of an expertise of the ratio of expected benefit to the possible risk of using the medicinal product. Based on this conclusion, the Ministry of Health made a decision to cancel the state registration and exclude the applicant's product from the State Register of Medicines.

The court indicated that the basis for refusal to confirm state registration of a medicinal product is a decision of the relevant authorized federal executive body that the quality and (or) efficacy of the medicinal product are not confirmed by the data obtained or that the risk of harm to human or animal health due to taking the medicinal product exceeds the efficacy of its use.

Medicinal products are introduced into civil circulation in the territory of the Russian Federation if they are registered. Upon expiration of 5 years from the date of issuance of the registration certificate for medicines registered in the Russian Federation for the first time, an indefinite registration certificate of the medicinal product is issued subject to confirmation of its state registration. In this regard, the appellate court supported the conclusions of the court of the first instance that in case of detection of unreliability of information contained in the materials submitted by the applicant, the Ministry of Health is obliged to send the applicant a request for clarification of the specified information and conduct a check of the completeness and reliability of information contained in the materials submitted by the applicant and in case of detection of unreliability of information contained in the materials, send the applicant a request for clarification of information. In addition, the Ministry of Health of the Russian Federation was obliged to notify the applicant of the decision taken regarding the conduct of the expertise or refusal to conduct the expertise.

However, no documents confirming the commission of the specified actions were presented by the defendant. In this regard, the court concluded that the Ministry of Health allowed inaction expressed in improper verification of the completeness and reliability of information contained in the materials submitted by the applicant. It is also important to note that in this case, the court of the first instance obliged the Ministry of Health to restore the rights and legitimate interests of the applicant by resuming the procedure for confirmation of state registration of the medicinal product.

Case No. A40-11957/16. Nativa LLC vs Ministry of Health of the Russian Federation, FSBI "SCEMP" of the Ministry of Health of Russia.

Another example of protection of rights when challenging the cancellation of state registration of a medicinal product is the case on challenging the conclusion of the commission of experts on the results of the expertise of the quality of the medicine and the decision of the Ministry of Health on the cancellation of state registration of the medicinal product.

The Ministry of Health made a decision to cancel the state registration of the medicinal product based on the expert conclusion of the FSBI "Scientific Center for Expertise of Medical Application Products". According to the experts' conclusion, the efficacy of the medicine taking into account the introduced changes is confirmed, the safety of the medicine taking into account the introduced changes is not confirmed, the expected benefit of using the medicinal product does not exceed the possible risk of using the medicinal product taking into account the introduced changes, in accordance with which the medical use of the medicinal product INN "Calcitonin", taking into account the changes introduced to the documents contained in the registration dossier, is impossible. The quality and (or) efficacy of the medicinal product are not confirmed by the data obtained or that the risk of harm to human or animal health due to taking the medicinal product exceeds the efficacy of its use. Making such a conclusion, the experts referred to the Information Letter of the Ministry of Health of Russia, which, citing the European Medicines Agency, indicated a significant increase in the risk of developing malignant neoplasms in patients taking calcitonin preparations for a long time in the dosage form of nasal spray, and recommendations to recall all calcitonin medicinal products in the dosage form of nasal spray.

However, in the "Periodic Safety Update Report of the Medicinal Product" submitted by the applicant for the period from October 26, 2013, to October 25, 2014, the applicant informed about the absence of reports of adverse reactions, adverse events, serious adverse reactions associated with the use of the medicinal product from medical specialists, consumers, or other persons not employed in the healthcare sector.

Despite the Information Letter of the Ministry of Health of Russia containing recommendations to recall all calcitonin medicinal products in the dosage form of nasal spray, calcitonin preparations present on the Russian market were not withdrawn from circulation before the applicant applied to the Ministry. In this regard, the court sided with the applicant and recognized the expert conclusion as illegal and the decision to cancel state registration as invalid.

Recognition of State Registration of a Medicine as Invalid

The Law on Circulation of Medicines does not contain grounds for recognizing a decision on state registration of a medicine as invalid. However, this does not imply that special grounds are required to recognize state registration as invalid or that it is impermissible. Most cases where the state registration of a medicinal product is recognized as invalid are related to the violation of rights of rights holders of intellectual property objects during the circulation of medicines.

Case No. A41-67858/2018. FBSI SRC VB "Vector" vs Diapharm LLC.

A federal budgetary institution of science applied to the Arbitration Court of the Moscow Region with a statement of claim against a limited liability company to suppress actions violating and creating a threat of violation of the plaintiff's exclusive rights. The institution did not agree with the court's conclusions and considered that the courts did not take into account that the registration certificate of a medicinal product is a document related to the introduction of this product into civil circulation, while the use of a trademark in documentation related to the introduction of goods into civil circulation is a violation of the exclusive right to such a trademark [6].

An agreement on the sale/purchase of a non-exclusive license for the use of an invention was concluded between the institution and the company, according to which the latter was granted a non-exclusive license for the right to use the invention under the patent and the trademark in the form of a non-exclusive license.

To exercise rights under the license agreement during the validity period of the patent and the license agreement, the institution sent a letter to the Department of State Control of Medicines and Medical Equipment with a request to permit the company to produce the sodium salt of double-stranded ribonucleic acid and the medicinal product based on it "Ridostin".

The institution received a refusal from the Ministry of Health of Russia to exclude the pharmaceutical substance Sodium salt of double-stranded ribonucleic acid and the medicinal product "Ridostin" produced by Diapharm LLC from the State Register of Medicines due to the absence of an established violation of the rights of the rights holder of intellectual property objects during the circulation of medicines.

The plaintiff, believing that the presence of the name of the medicinal product "Ridostin" in the registration certificates violated its exclusive right to the trademark, and also that the transaction between Diapharm LLC and the company is invalid, filed a lawsuit in court.

The court of the first instance refused to satisfy the claims and justified this by the fact that the institution did not present admissible, relevant, and reliable evidence, the totality of which would sufficiently testify to the use of the institution's trademark or a designation confusingly similar to this trademark for labeling products for which this trademark is registered. Since the court concluded that the fact of use by Diapharm LLC and the company of the trademark belonging to the institution was not proven, the institution's claim in this part was left unsatisfied. The court of the first instance stated that the transaction challenged by the institution regarding the transfer of rights of the holder of the registration certificate for the medicinal product "Ridostin" does not violate the exclusive rights of the plaintiff either to the trademark, as it is not the use of the trademark within the meaning of Article 1484 of the Civil Code of the Russian Federation, or to the patent of the Russian Federation, since it ceased to be valid prior to the conclusion of this transaction. In this regard, the court of the first instance concluded that there were no grounds to satisfy the institution's claims.

The appellate court agreed with the conclusions of the court of the first instance. The Intellectual Property Court based its decision on the fact that a citizen or legal entity possessing the exclusive right to a result of intellectual activity or a means of individualization (rights holder) has the right to use such result or such means at its discretion in any manner not contradicting the law. The rights holder may dispose of the exclusive right to the result of intellectual activity unless the Civil Code of the Russian Federation provides otherwise. The rights holder may, at its discretion, permit or prohibit other persons from using the result of intellectual activity or means of individualization. The absence of a prohibition is not considered consent (permission).

The institution stated a claim to suppress the actions of Diapharm LLC and the company violating its exclusive right to the trademark. The institution sees such a violation in the use of the trademark belonging to it in registration certificates and in the sale of a medicinal product labeled with the trademark belonging to the institution.

The requirement to suppress actions violating the exclusive right can be satisfied only if the unlawful behavior of a specific person has not yet been completed or there is a threat of violation of the right [7]. Thus, a requirement to prohibit an offer for sale or to prohibit the sale of counterfeit goods is not subject to satisfaction if such goods belonging to the defendant have already been sold by them.

Requirements for a general prohibition to a specific person for the future to use the result of intellectual activity or means of individualization are also not subject to satisfaction. Such a prohibition is established directly by law (paragraph three of Clause 1 of Article 1229 of the Civil Code of the Russian Federation).

The Intellectual Property Court notes that this method of protecting a right is provided for a continuing or incomplete offense, and such measures are measures to protect a violated intellectual right, therefore they are applied in connection with a specific offense.

The courts of the first and appellate instances concluded that the institution did not present a sufficient set of evidence testifying to the commission by Diapharm LLC and the company of a continuing violation of the institution's exclusive right. The court stated that a license agreement was in effect between the institution and Diapharm LLC for a long time, in accordance with which the company had the right to produce a medicinal product labeled with the trademark "Ridostin".

Moreover, the courts established that after the expiration of the patent of the Russian Federation and the validity period of the license agreement, the defendants took actions aimed at changing the name of the medicinal product in the registration certificate. In particular, the company took measures to make changes to the registration certificate regarding the name of the medicinal product. The courts also took into account that actually neither Diapharm LLC nor the company introduced the medicinal product labeled with the designation "Ridostin" into civil circulation; nothing else followed from the case materials.

The court of cassation instance believed that the totality of circumstances established by the courts in this case allowed the courts to make a reasoned and legally based conclusion about the absence of legal grounds for satisfying the institution's requirement to suppress the violation of its exclusive right to the trademark.

Regarding the institution's arguments that the courts unreasonably refused to recognize the transaction between Diapharm LLC and the company as invalid, the Intellectual Property Court noted that, referring to the invalidity of the transaction by virtue of the specified rule of law, the institution did not cite norms providing for the need to obtain the consent of the trademark rights holder to conclude a transaction for the transfer of rights of the holder of the registration certificate for the medicinal product "Ridostin". The institution should have justified by virtue of which rule of law it applied with the corresponding requirement. Neither the cassation appeal nor other procedural documents of the institution contained such justification.

The Intellectual Property Court also took into account that from the principle of legal certainty it follows that the decision of the court of the first instance was based on a full and comprehensive study of the circumstances of the case and could not be canceled solely on the grounds of disagreement with the assessment of circumstances given by the court of the first instance [8]. The court in this case decided to leave the cassation appeal of the federal budgetary institution of science unsatisfied.

Case No. A40-188378/14. Novartis Pharma AG vs Ministry of Health of Russia, BioIntegrator LLC, IIHR CJSC

Novartis Pharma AG appealed to the Arbitration Court of the City of Moscow with claims against the Ministry of Health of the Russian Federation, BioIntegrator LLC, IIHR CJSC to prohibit the Ministry of Health of Russia from using information on the results of preclinical and clinical studies of the medicinal product "Gilenya®" for the purposes of state registration of the generic medicinal product fingolimod ("Nescler"); to recognize the state registration of the medicinal product fingolimod ("Nescler") as invalid; to prohibit BioIntegrator LLC from introducing the medicinal product fingolimod ("Nescler") into circulation until 17.08.2016; to prohibit IIHR CJSC from introducing the medicinal product fingolimod ("Nescler") into circulation until 17.08.2016.

By the decision of the arbitration court of the first instance, the satisfaction of the lawsuit was refused.

The use of protected information is confirmed by the bioequivalence study report of medicinal products "Gilenya" and "Nescler" contained in the registration dossier of the medicinal product "Nescler", which states: "Since the study of pharmacokinetic parameters and confirmation of bioequivalence to the comparator drug is the goal of this study, and also due to the hypothesis of similarity of pharmacokinetic parameters, this section is based on information obtained in previous studies of the original drug".

However, in the opinion of the appellate instance, the court of the first instance erroneously considered that the requirements of Part 6 of Article 18 of the Law on Circulation of Medicines do not apply to the registration of the medicinal product "Nescler", since the application for state registration was filed before the start of the specified norm. Also, the court of the first instance groundlessly considered that the application for state registration was filed first by one person – IIHR CJSC, and the registration was eventually made to another person – BioIntegrator LLC. Such a conclusion contradicts the applicable rules of law and evidence available in the case materials.

As follows from the explanations of the Ministry of Health of Russia, IIHR CJSC indeed filed an application for state registration of the medicinal product "Nescler". However, a year and a half later, BioIntegrator LLC filed an independent application for state registration of the product Nescler.

The court agrees with the plaintiff's argument that the date of filing the application by IIHR CJSC is irrelevant to the state registration of the product "Nescler", which was carried out based on the application of BioIntegrator LLC, since the decision of the Ministry of Health of Russia on the state registration of the product Nescler indicates only one application – filed by BioIntegrator LLC, there is no reference to the application of IIHR CJSC. The court rejects the defendants' arguments about the filing of applications by two legal entities, the purpose of which was the registration of the product for BioIntegrator LLC.

According to Cl. 2 of the Administrative Regulation of the Ministry of Health of the Russian Federation for the provision of state services for state registration of medicinal products for medical use, approved by Order of the Ministry of Health of Russia No. 428n dated 22.10.2012, applicants for the provision of state services for state registration of medicinal products for medical use are the developer of the medicinal product for medical use or another legal entity authorized by it.

Asserting the representation of interests of BioIntegrator LLC when filing an application on its own behalf, IIHR CJSC referred to an agreement on scientific and technical cooperation and development of medicines. However, in the application submitted to the case materials, the attached documents lack an agreement confirming that BioIntegrator LLC authorized IIHR CJSC to perform registration for it.

The defendants' reference to the presence of a transfer of rights agreement in the list of documents attached to the application does not testify to the existence of such authorization.

At the same time, the reference of the court of the first instance to the fact that persons carrying out the procedure for state registration of the medicinal product "Nescler" could carry out any transactions between themselves not limited by law is groundless. A civil law transaction cannot change the established procedure for state registration of medicinal products.

The Ministry of Health of Russia registered the medicinal product "Nescler" on 20.11.2014, that is, more than 2 years after the start of Part 6 of Art. 18 of the Law on Circulation of Medicines. At the same time, there is no evidence that the plaintiff gave consent to the use of protected information.

In this regard, the decision of the Arbitration Court of the City of Moscow in case No. A40-188378/14 was canceled and the state registration of the medicinal product fingolimod ("Nescler") was recognized as invalid [9]. However, disagreeing with the resolution adopted in the case by the Ninth Arbitration Appeal Court, BioIntegrator LLC, IIHR CJSC, and the Ministry of Health of Russia appealed to the Intellectual Property Court with cassation appeals [10].

The Intellectual Property Court, having studied the case materials, concluded to cancel the resolution of the appellate court and leave the decision of the court of the first instance in force. The Intellectual Property Court considered that "the provisions of Part 6 of Article 18 of Law No. 61-FZ apply to legal relations on state registration of the medicinal product 'Nescler', and the appellate court made an incorrect conclusion that Part 6 of Article 18 of Law No. 61-FZ applies to any information on conducted preclinical and clinical studies of the original medicinal product".

Consequently, the systemic interpretation of the provisions of Articles 18 and 26 of Law No. 61-FZ allows asserting that the prohibition established by Part 6 of Article 18 of the Law "On Circulation of Medicines" does not apply to information published in specialized printed publications. The use of such information is recognized by the legislator as lawful. A different interpretation of this norm would lead to the impossibility of implementing the provisions contained in Article 26 of Law No. 61-FZ.

Not always unambiguous decisions are made when considering controversial cases related to the registration of medicinal products; often, both the executive authority and the pharmaceutical company can be right, which depends on the specific circumstances of the case.

_________________________

References

[1] Federal Law No. 61-FZ dated 12.04.2010 "On the Circulation of Medicines".

[2] Decision of the Arbitration Court of the City of Moscow dated 13.07.2021 No. A40-62100/21-93-444.

[3] Order of the Ministry of Health of Russia No. 538n dated 27.07.2016 "On Approval of the List of Names of Dosage Forms of Medicinal Products for Medical Use".

[4] Letter of the Ministry of Health of Russia No. 20-3/328 dated 04.03.2019 "On the necessity of submitting to the Ministry of Health of Russia an application for cancellation of state registration of medicinal products absent from circulation for three or more years".

[5] Federal Law No. 475-FZ dated 27.12.2019 "On Amendments to the Federal Law 'On the Circulation of Medicines' and the Federal Law 'On Amendments to the Federal Law 'On the Circulation of Medicines'".

[6] Subparagraph 3 of Paragraph 2 of Article 1484 of the Civil Code of the Russian Federation.

[7] Paragraph 57 of the Resolution of the Plenum of the Supreme Court of the Russian Federation No. 10 dated 23.04.2019 "On the Application of Part Four of the Civil Code of the Russian Federation".

[8] Resolution of the Presidium of the Supreme Arbitration Court of the Russian Federation No. 16549/12 dated 23.04.2013.

[9] Resolution of the Ninth Arbitration Appeal Court No. 09AP-53676/2016-GK dated 14.11.2016 in case No. A40-188378/14.

[10] Resolution of the Intellectual Property Court dated 17.12.2015 in case No. A40-188378/2014.