Many German pharmaceutical companies seek to enter the Russian market, but have little or 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?
We talked about this with Mr Alexander Podarewski, the founder of AP Fachübersetzungen from Nuremberg, who specializes in interpreting at inspections and audits.
- My interpreting and translation agency was established in 2010 and covers a wide range of languages. We have translated many pharmaceutical texts into Russian and German, among other languages. However, we have only been interpreting at Russian GMP inspections since 2017, i.e. shortly after the establishment of the Russian inspectorate GILS i NP. The English name is "State Institute of Drugs and Good Practices", which is subordinate to the Ministry of Industry and Trade (Minpromtorg) of the Russian Federation. The GILS i NP institute is responsible for conducting GMP inspections. The application for the issuance of the Russian GMP certificate is submitted to Minpromtorg.
About 30 percent of Russian inspections are not passed - a rather poor result.
- At large pharmaceutical companies, the rate is only about half as high. Nevertheless, Russian inspectors quite often find considerable irregularities at large pharmaceutical companies that have the European and American GMP certificates, as a result of which Minpromtorg refuses to issue the Russian certificate. These irregularities are usually related to the production of sterile drugs if the company doesn't carry out investigations to find the root cause of the irregularity (non-sterility).
We have also seen small pharmaceutical manufacturers with fewer than 100 employees pass the inspection without any issues.
- Yes and no. It should be mentioned that 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. 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 Russia is not yet carrying out inspections according to these new guidelines. However, I believe that implementation will be delayed by a further 6-12 months due to the coronavirus epidemic.
- An inspection starts with the manufacturer submitting an application for inspection and a list of documents to the Minpromtorg. Within 10 days, the Ministry examines 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 manufacturer to prepare for the inspection, obtain the necessary documents 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, but the pharmaceutical company can still deduce the approximate classification from these non-conformities. The inspection report will be prepared within 30 calendar days after the inspection at the site has been completed. Upon 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 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.
- That would be deviations from the approval dossier, non-compliance with aseptic requirements, sterility and insufficient sampling of incoming raw materials. Sometimes companies are not fully familiar with GMP guidelines, according to statements by several inspectors.
- I think it is less important what country the inspectors come from. GMP guidelines are a set of rules and regulations with requirements for the organization of production and quality control. Russian inspectors must therefore 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 the violations as critical/major/minor in the same way. There is a lot of room for interpretation if there is no precise classification. Everything significantly depends on the interpretation of the individual inspector and their qualification and experience.
- Yes, I can. The production processes are inspected according to the manufacturer's application for each individual preparation. You have to be very careful here and only specify the products that are relevant for the target country and therefore should be part of the inspection when you submit your application. I usually would not have pointed this out in particular, but there was a major misunderstanding in one case. All the products that are produced on the site had been registered for this Russian inspection. And that only came to light during the inspection. You can imagine the reaction of the employees of the pharmaceutical manufacturer when they suddenly heard my translation during the inspection: "All [about 30] products are being inspected, whether they would potentially go to Russia or not." Even though only two products were intended for Russia. The mistake lay with the Russian consulting firm that submitted the application to Minpromtorg. It 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' reaction was: "We understand that this is a big misunderstanding. However, we have to do our job according to your application. Your representative listed all [about 30] products in the application and we are obliged to include everything in the report. If you pass this inspection, you will get a GMP certificate for all preparations, which opens up great opportunities for you on the Russian market". This shows how important correct and accurate specialist translations are.
- 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 that at the beginning of the inspection, right after the introductory meeting: "In addition to complying with GMP standards, we will check that you are actually manufacturing what you have stated in your application." They have a reputation for being very strict, but also competent and fair. All the inspectors of the Russian authority have a background in the industry. Although many of them are quite young, they sometimes surprise even "veterans" of the very experienced pharmaceutical league with their professionalism and experience in the whole production.
It does not leave a good impression if the Russian inspectors get the feeling that something is being concealed. Consequently, trust is created when cooperation is open and honest.
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.