Particularities of Russian GMP inspections from a specialist interpreter's point of view
Many European pharmaceutical companies seek to enter the Russian market, but have little to no experience with the Russian authorities and their inspectors.
In the first two years after the establishment of the Russian inspection authority GILS i NP on 12 April 2016, Indian pharmaceutical manufacturers were inspected most frequently, but since 2018 German companies have been at the forefront. This will not change for some time to come. What should German pharmaceutical companies know about the challenges of Russian GMP inspections?
"The State Institute of Drugs and Good Practices", which is subordinate to the Ministry of Industry and Trade (Minpromtorg) of the Russian Federation, is the competent authority for GMP inspections. The GILS i NP institute is responsible for conducting the inspections. The application for issuance of the Russian GMP certificate is submitted to Minpromtorg.
Success rate in passing the inspection
About 30 % of Russian inspections are not passed. The rate for large international pharmaceutical companies is only about half as high as for small and medium-sized companies. Even at large pharmaceutical companies that have the European and American GMP certificates, Russian inspectors often find considerable irregularities, as a result of which Minpromtorg refuses to issue the Russian certificate. These irregularities are usually found in the production of sterile drugs. Typical findings are missing or insufficient root cause analyses or deviations in aseptic handling.
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European and Russian GMP guidelines
The GMP guidelines currently in force in Russia are a direct translation of version 4.0 of the 2013 European GMP guidelines. The Russian GMP guidelines have not been changed since the authority was established in 2016. However, it is planned that Russia will carry out inspections according to the new GMP guidelines of the Eurasian Economic Union (EAEU) from June 2020. These new GMP guidelines of the EAEU are a translation of the European GMP guidelines as amended in 2015. They are already finished and approved by the EAEU, but Russian inspections are currently still based on Russian GMP guidelines. The implementation will probably be delayed by another 6-12 months due to the coronavirus epidemic.
Course of a Russian inspection
An inspection starts with the manufacturer submitting an application for inspection and a list of documents to the Minpromtorg. Within 10 days, the Ministry reviews the submitted documents. If there are no questions regarding the documents, an order is prepared to carry out the inspection and forwarded to the GILS i NP institute. The institute prepares a schedule, coordinates it with the Minpromtorg of the Russian Federation, notifies the manufacturer and draws up an inspection plan, taking into account the elements of the production process to be inspected. The inspection plan is then sent to the manufacturer. This enables the company to prepare for the inspection, have the necessary documents ready and make them available to the inspectors. An inspection team of at least two inspectors - depending on the production volume to be inspected - visits the site. The average duration of an inspection is 3 to 5 days. If there are several pharmaceutical companies in the same region, GILS i NP tries to organize everything so that the inspections can be carried out as quickly as possible.
An opening meeting is held at the beginning of an inspection; a summary of the results and observations of the day is given at the end of each working day and a final meeting is held at the end of the inspection.
If violations are found, these will be communicated to the site representatives at the final meeting during the inspection. The violations are not classified. The inspection report will be prepared within 30 calendar days after the inspection at the site has been completed. Upon its completion, one copy remains with GILS i NP, a second copy is sent to the manufacturer's Russian representative, and a third is sent to Minpromtorg for decision-making. The inspection report can only list non-conformities that were mentioned in the final meeting. However, there may be fewer non-conformities if the relevant issues have been clarified and the relevant documents have been submitted subsequently. As soon as the report is completed, the regulatory authority of the manufacturer's respective country is informed. Deviations are frequently found in connection with the approval dossier, aseptic production and sampling of incoming raw materials.
Russian inspections are therefore not fundamentally different from those by other countries. Russian inspectors ensure that the production at the inspected site complies with Russia's current GMP guidelines.
If the product intended for Russia is manufactured, filled, packaged etc. on different lines or plants, the Russian inspectors want to see all these lines and plants.
Naturally, all foreign inspections have certain national particularities, e.g. interpretations and approach of the experts. Not all inspectors classify violations as critical/major/minor in the same way. Everything depends on the interpretation of the individual inspector and their qualification and experience.
Misunderstandings with major implications
The production processes are inspected according to the manufacturer's application for each individual preparation. You have to be very careful here and should only specify the products that are relevant for the target country and therefore should be part of the inspection when you submit your application. In one specific case, a misunderstanding led to all products produced at the site being registered for the Russian inspection. This only came to light during the inspection. Originally only two preparations were to be listed for Russia. The mistake lay with the Russian consulting firm that submitted the application to Minpromtorg. The reason for the misunderstanding was a translation error in the communication: All the products at the site were listed by mistake instead of just two which were relevant for Russia. The inspectors expressed understanding for the error. Nevertheless, the inspectors had to inspect all products according to the application.
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The task of the inspectors is to check that the medicines delivered to Russia are safe for the citizens of their country. They often say at the beginning of the inspection, right after the start: "We will not only check compliance with GMP standards, but also that you are actually manufacturing what you have stated in your application." They have a reputation for being very diligent about compliance with regulations, for being very strict, but also competent and fair. All inspectors of the Russian authority have a background in the industry. Besides some experienced inspectors, many of them are quite young, but some of them surprise even "veterans" of the pharmaceutical industry with their professionalism and experience in the whole production. As a rule, the inspection is carried out competently, objectively and exactly according to the formal specifications. It is very important that the inspectors always feel that the answers are open and honest and that nothing is concealed.
As with other international GMP inspections, each pharmaceutical company inspected should task experienced staff with answering the inspectors' questions wherever possible. And of course it is essential to commission reliable interpreters who are up to the task.
Author:
Alexander Podarewski
... is the Managing Director of the specialist translation agency AP Fachübersetzungen in Nuremberg.
