Regulatory translations in CEE

Translations required as part of the regulatory approval process for medicinal products are, arguably, one of the most exciting areas in the translation industry today. It’s a growth area, and while it’s heavily regulated — or perhaps because of this fact — it is in a state of constant flux.

Not surprisingly, the majority of the pharmaceutical market across Central and Eastern Europe (CEE), which is estimated to be worth in excess of $63 billion, is occupied by global pharmaceutical companies. This applies to both innovative, patented products, as well as generic products, which constitute over half of the market value.

With the high concentration of organizations that exist in the pharmaceutical industry, leading manufacturers from the United States, the European Union (EU) and Japan have the largest share. However, the CEE pharmaceutical markets are also increasingly targeted by smaller companies. These companies tend to make use of rapid access to these markets as a result of their countries’ membership in the EU.

The Russian pharmaceutical market is a special case. It may constitute some two thirds of the whole CEE pharmaceutical market and has its own specific regulations when it comes to regulatory approval. But here, too, imported drugs have by far the largest share of the market, which is dominated by generic products rather than by the original patented drugs.

The pharmaceutical industry in CEE

There are few national pharmaceutical champions in the region. Many of those formed before 1990 have been acquired by larger companies over the years. For example, in 2002, Sandoz, a Novartis company, acquired Lek Pharmaceuticals, Slovenia’s largest pharmaceutical company, which has a strong footprint in CEE. Zentiva, a major force in the generics market in Central Europe, was acquired by Sanofi in 2009. Still, a few major companies remain independent, such as KRKA from Slovenia (with revenues of $1.39 billion), Richter Gedeon from Hungary ($982 million), Polpharma from Poland ($375 million) and Russia’s Pharmstandard ($1.4 billion). All of these producers of generic goods maintain a strong focus on CEE.

Pharmaceutical companies marketing in CEE typically need to deal with three types of countries: EU member states, EU accession countries, and others, such as Russia. Those which are member states of the EU — the Czech Republic, Bulgaria, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia and Slovenia — are governed by the regulations of the London-based European Medicines Agency (EMA) or other harmonized regulations.

For certain medicines, companies must use EMA’s centralized procedure, which results in a single marketing authorization valid in all EU countries plus Iceland, Liechtenstein and Norway (EEA-EFTA states). As part of this procedure, applicants need to provide product information — a summary of product characteristics and any labeling and package leaflets — translated into all EU languages as well as Icelandic and Norwegian for linguistic review by individual national authorities.

Translations of the same product information materials are also normally required if applicants choose to apply for registration in a single country via the local national authority or to use one of the other two procedures harmonized within the EU:  the decentralized procedure, which results in the simultaneous authorization of a medicine in more than one EU country; or the mutual-recognition procedure, whereby companies apply for the existing authorization of a medicine authorized in one EU member state to be recognized in other EU countries.

The number of languages required by the EMA for centralized marketing authorization in Europe currently stands at 24 — the EU official languages plus Icelandic and Norwegian. This number is now set to grow. Croatia is primed to join the EU in 2013, bringing a new language to the group of official EU languages, as well as those required by the EMA for centralized authorizations.

The EMA has been taking steps to set the stage for the eventual accession by launching the Instrument for Pre-accession Assistance program back in 2009. Its aim is to support the participation of the beneficiary countries from CEE — Albania, Bosnia-Herzegovina, Croatia, the former Yugoslav Republic of Macedonia, Kosovo (under UNSC Resolution 1244/99), Montenegro, Serbia and Turkey — in the activities of the EMA, in preparation for these countries’ future collaboration in the EU regulatory network.

As for the registration processes harmonized by the EMA, it is worth noting that translations of product information are significantly facilitated by the existence of approved local versions of the Quality Review of Documents (QRD) templates, which exist for all the EMA-required languages. These are all available on the EMA’s website, and they need to be used. Similarly, product information translated into all the required languages for already authorized medicines is available online post-approval. These QRD templates contain the standardized structure and phrases used in product information, reviewed by individual national authorities.

The templates for the centralized procedure have been recently updated to Version 8, while those for the decentralized and mutual recognition procedures have been updated to Version 2. The updates contain corrections of a number of inaccurate translations together with some linguistic and typographical errors.

In practice, detailed knowledge of the national templates and how to customize these for the specific substances for which authorization is sought helps determine the quality of individual regulatory translators. While simple in theory, there are always a number of factors that need to be taken into account, such as the specifics of the given manufacturer, previously approved product information, document versions, other comparable substances already approved and so on.

Terminology also plays an important role. Regulatory translators make good use of MedDRA — the Medical Dictionary for Regulatory Activities. MedDRA ( includes clinically validated terminology that applies to all phases of drug development. On the flip side, MedDRA is currently available in only ten languages and only in Czech from the CEE language set.


Linguistic checking

and the fast track

Specifically for Croatia, which has long been mentioned as the most imminent candidate to join after Bulgaria and Romania became EU members in 2007, EMA started a pre-accession linguistic checking process for product information in the Croatian language as early as January 2011. The objective is to prevent regulators and pharmaceutical companies having to scramble to produce required Croatian translations for centrally authorized medicines around the time of Croatia’s actual accession in 2013. This is because the companies that officially own the specific marketing authorization for a given medicinal product, the Marketing Authorization Holders (MAH), are legally obliged to provide translations of the product information in any new official language as of the date of accession.

This voluntary pre-accession checking procedure has been set up in cooperation with the Croatian National Competent Authorities (NCA). The timeline for the checking of translations is 80 days. As part of this procedure, a full set of product information annexes (including the summary of product characteristics, labeling and package leaflet texts for all strengths and pharmaceutical forms), is submitted by MAHs to the EMA in Croatian, along with the English-language versions for reference.

The Croatian agency has 60 days to check the translation against the approved English reference text and provide linguistic comments. The MAH then has ten days to check the revised version, implement the comments and submit the final translation to EMA, who forwards it to the Croatian NCA. They then have ten days to perform the final check and acceptance.

While this pre-accession linguistic check for Croatian is voluntary, MAHs are asked to include a reference in their future cover letters to the status of this process. The current process refers specifically to Croatian, but it may work as the model for any future new EU member states and their official languages.

As many CEE countries have gravitated toward the EU, the EMA has put in place a fast-track procedure for EU products thanks to nCADREAC, the new collaboration agreement between drug regulatory authorities in Central and Eastern European countries, specifically Bulgaria, Croatia and Romania. This has built on the success story of the previous CADREAC agreement, which originally included Bulgaria, Cyprus, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, Slovenia and Turkey.

The (n)CADREAC procedures have offered the possibility of harmonizing the summary of product characteristics, patient information leaflets, labeling and documentation for a product between existing EU member states and candidate countries. In practice, the procedures have enabled country-specific marketing authorization of a medicinal product that has been already authorized in the EU using the centralized procedure or the mutual recognition procedures. As with other national authorizations, summary of product characteristics, patient information leaflets and labeling need to be provided in the national language as part of the application.



While the CEE EU members and those on the path to becoming members are using the EMA procedures or are harmonizing with them, Russia adopted a new pharmaceutical regulation called 為洽 為洽炬活牴泵炫洩洩 洎泵洵活炬炯炭派泵炫炫狠炤 炯炬泵洛炯炭派 (On the Circulation of Medicines) in 2010, which has caused a little confusion and led to subsequent updates.

One of the new regulation objectives was to help expand the local pharmaceutical industry, which requires foreign pharmaceutical companies to share their expertise and technologies with local businesses or face trade restrictions. This has been set against the efforts to support local companies in line with the $4 billion Pharma 2020 Strategy, Russia’s health reform plan developed in 2010, which aims to increase the share of the domestic industry on the total pharmaceutical expenditure from the current 20% to a minimum of 50%.

In practice, there have been a few flaws. The new regulation, for instance, introduces the requirement to conduct clinical trials of new drugs in Russia prior to registration. International clinical trials would be accepted so long as Russian patients were among trial participants. In the EU, on the other hand, there is no requirement for the exact location of clinical trials. Instead, the EU places a heavy emphasis on how well the clinical trials are conducted from an ethical perspective, especially for trials conducted outside of EU/EEE-EFTA countries, and the compliance with good clinical practice. A statement to the effect that clinical trials carried out outside the EU meet the ethical requirements of Directive 2001/20/EC is required. Not surprisingly, Russia’s requirement to conduct clinical trials on Russian patients has led to a general slowdown in the number of new drug registrations in Russia.

However, if a company applying for authorization in Russia has an existing EU registration file, a separate document for Russian approval is not required, since the data will be comparable with that set by the EMA. The entire dossier as such will need to be translated into Russian, though.

Sourcing medical translators

There are some challenges associated with building good teams of translators for CEE regulatory agencies. One is the sheer number of available translators, given the size of these markets and the need for a relatively narrow specialization in individual therapeutic areas; these are mid-size or smaller countries, except for Russia and Poland.

With all the existing templates from regulatory agencies and the medical terminology in place, excellent understanding of the subject matter and the medical practice in a given locale is a major advantage, preferred over linguistic or stylistic excellence.

On the positive side, it may be easier to find medical practitioners in the CEE countries than is perhaps the case in many other regions. This is due to the fact that more often than not, the average basic wages of the medical staff in these countries, while higher than the region’s typical wages, are still relatively low in comparison with other regions. For instance, in the Czech Republic, the current agreement between the government and the association of doctors is for the starting wages of doctors to be 1.5 times the average Czech salary. In comparison, starting doctors in Germany make more than two times the average salary there. Of course, how these wages are calculated and their international comparison is not so straightforward, but this is the general situation.

While doctors within CEE may enjoy high status, their average wages don’t adequately reflect the amount of education, practice required, or the sheer number of hours worked relative to other professions. This is certainly true compared to many Western European countries, for instance. This has many medical practitioners having to augment their basic salaries with extra assignments, and involvement in medical translations is one of their options.

One thing to remember about regulatory translations in CEE is that these are not just about the potential of the market available to pharmaceutical companies. Translations of medicinal product information into CEE languages are actually required for any EMA centralized applications for marketing authorization across the entire EU. This adds to their importance and the need to get them right the first time.