Changes in Russian regulatory environment

Russia, as one of largest and most important pharmaceutical markets in the world underwent significant changes of its pharmaceutical regulatory laws. The new law went into effect in September 2010.

The main question remains: Are these changes going to facilitate registration procedure and at which price?

The regulatory pathway for all type of medicinal products is as follows:

General requirements:

Every pharmaceutical product needs Certificate of Pharmaceutical Product before the product can be manufactured or registered in Russia. Medical devices also need Sanitary Epidemiological Conclusion Certificate. The State Agency that issues Certificate of Pharmaceutical Product is calledRoszdravnadzor. The review of quality, safety and efficacy is performed by National Center of Pharmaceutical Products Expertise (FGU). The Center has has many departments and provides its expertise to the Roszdravnadzor who in turn issues the registration certificate for the product and then the product can enter the national database of registered products. The applicant must submit the registration dossier directly to the National Center and communication between applicants regulatory specialist and experts must be on weekly basis.

Though the regulatory pathway may seem the same both for domestic and foreign manufacturers, documentation and fees differ. GMP certificate is of utmost importance for foreign manufacturers as well as valid manufacturing license. The good thing is that your product doesnt have to be registered elsewhere. It is acceptable to have Russian registration only. As for the dossier the EU file is entirely acceptable but it has to be in Russian. Registration certifiacate is valid for the unlimited period of time. The applicant can be a physical person (i.e. no need to open the company in Russia in order to act as an applicant).

After submission of file, the longest and most compleh phase comes into effect. During this phase different parts of the file are assigned to the different experts at the Institute of Products Quality Control and the Institute of Preclinical and Clinical Expertise. After the review, the expertise is submitted to the Roszdravnadzor who issues the regiatration Certificate. These 3 steps arepractically the same both for generic and innovative products but on the whole, procedure for generic products is somewhat simpler. E.g., bioequivalencestudies dont have to be performed in Russia but clinical trials do have to be performed in Russia.

The average regulatory timeline for the approval takes about 18 months but often it is necessarry to submit additional quality and clinical data which can significantly prolong the timeline itself. Fees are usually split between FGU experts and Roszdravnadzor. The average fees are approx. 50 000$ and more than half of it goes to the FGU experts. Laboratory testing cannot start until the invoice is not paid in full. Laboratory testing relies on manufacturers finished product specifications and Russian and EU pharmacopoeia. Often, the experts refer to the USP.

However, the import procedure of product samples for the laboratory analyses is not simple and can take additional 2-6 months. It takes approx. 2 months to obtain the import license at the Roszdravnadzor and additional delays can be caused by the Custom service itself.

Clinical trials and pharmacovigilance activities

National standards for conducting clinical trials are compatible with ICH guidelines GCP E6. In order to become eligible for the conduct of clinical trials the respective site must prepare submission package which containspresentation of facilities and relevant expertise of personnel. Russia is also member of WHO International Drug Monitoring Program and 50 centers in whole Russia act as a pharmacovigilance units. The applicant must submit the documents to the National Ethics Comittee and Ministry of Health then issues the final approval. The new law favorizes domestic clinical trial in financial terms. If you have foreign clinical trials in your documentation your fees will be higher. The approval of clinical trial in Russia takes approx. 90 days. Most of the clinical trials are sponsored by multinational corporations from USA and Germany.

Variations

Minor variations take up to 3 months for approval and major changes up to 12 months.

New legislation – benefits and deficiencies

The new law introduces fixed timeline for the approval of product which is set at maximally 210 days. Major changes also refer to the fees. Only one type of fees is to be paid – the federal fee and maximal fee cannot be more than 10 000 $. There are also significant changes in the area of clinical trials: There is longer possible to apply for Phase IV study for the same indication if you already finished first clinical trial for it. Also, phase 1 of the product which is intended to be approved in Russia cannot be performed in Russia if the product is manufactured abroad. The new regulations also set the minimal amount of the life insurance for the individual participant in clinical trial. Specialization and experience (at least five years of expereince in clinical trials) of the investigator becomes also very important. Some additional issues are also adressed in the new law such as: new pharmacovigilance rules, labelling of pharmaceutical products, pharmacopoeias etc...

On the other hand, orphan drugs are not mentioned at all despite their extremely high prices in Russian market. Manufacturers of generic products also complains about the restricted access to the clinial trials data of the innovative products.

It is certain that new law shall trigger the necessity for additional regulations which represents a significant challenge for every manufacturer who wants to operate in Russian ever-changing market.