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 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 US$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 which exist in the pharmaceutical industry, the leading manufacturers from the US, EU or Japan have the largest share. However, the CEE pharmaceutical markets are also increasingly targeted by smaller companies, who make use of rapid access to these markets as a result of the membership in the EU of many countries in the region.
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, and it is dominated by generic products rather than the original patented drugs.
The pharmaceutical industry in CEE
There are very few national pharmaceutical champions in the region. Many of those formed before 1990 have been acquired over the years. Sandoz, a Novartis company, acquired Lek Pharmaceuticals, Slovenia’s largest pharmaceutical company with a strong footprint in CEE, in 2002. Zentiva, a major force in the generics market in Central Europe, was acquired by Sanofi in 2009.
Still, a few major companies remain independent, for instance KRKA from Slovenia (with revenues of $1.39B), Richter Gedeon from Hungary ($982M), Polpharma from Poland ($375M) or Russia's Pharmstandard ($1.40B). All of these generics producers maintain a strong focus on CEE.
Pharmaceutical companies marketing into Central and Eastern Europe 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 European Union – Czech Republic, Bulgaria, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, and Slovenia – are governed by the regulations of the Amsterdam-based European Medicines Agency (EMA), or other harmonized regulations.
The role of the EMA
For certain medicines, companies must use the Agency's centralized procedure, which results in a single marketing authorization, which is valid in all EU countries, plus Iceland, Liechtenstein and Norway (EEA-EFTA states). As part of this procedure, applicants need to provide product information – summary of product characteristics (SmPC), labeling and package leaflet (PIL) – translated into all EU languages (including 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 use one of the other two procedures harmonized within the EU: the decentralized procedure (DCP), which results in the simultaneous authorization of a medicine in more than one EU country; or the mutual-recognition procedure (MRP), whereby companies apply for the existing authorization of a medicine authorized in one EU member state to be recognized in other EU countries.
Getting ready for the accession
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 expected 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 (IPA) programme back in 2009. Its aim is to support the participation of the beneficiary countries from Central and Eastern Europe – Albania, Bosnia-Herzegovina, Croatia, former Yugoslav Republic of Macedonia, Kosovo (under UNSC Resolution 1244/99), Montenegro, Serbia and Turkey – in the activities of the European Medicines Agency, in preparation for these countries' future collaboration in the EU regulatory network.
Pre-accession linguistic checking
Specifically for Croatia, which has long been mentioned as the most imminent candidate to join after Bulgaria and Romania became EU members in 2007, the Agency 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 Marketing Authorization Holders (MAHs) 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 (i.e. including all SmPC, 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 EN reference text and provide linguistic comments. The MAH then has 10 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 10 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.
The fast track
As the many CEE countries have gravitated towards 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 harmonization of summary of product characteristics (SmPC), patient information leaflet (PIL), labeling and documentation for a product between existing EU member states and candidate countries. In practice, the procedures have enabled granting a marketing authorization in these countries of a medicinal product which has been already authorized in the EU using the centralized procedure, or the mutual recognition procedures, respectively. As with other national authorizations, SmPC, PIL and labeling need to be provided in the national language as part of the application.
Lex Russia
While the CEE countries that are EU members, (or on the path to becoming one), are using the EMA procedures or are harmonizing with them, Russia has adopted a new pharmaceutical regulation "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 grow 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 the same year, 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. This leads to a general slowdown in the number of new drug registrations in Russia.
If a company applying for authorization in Russia has an existing EU registration file, a separate document for the Russian approval is not required, since the data will be comparable with that set by the EMA. The entire dossier as such will, however, need to be translated into Russian.
Sourcing medical translators
There are some challenges associated with building good teams of translators for CEE regulatory. 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, over linguistic or stylistic excellence.
On the positive side, it is relatively 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 medical staff in these countries, whilst higher, are still relatively low.
While the doctors 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. Certainly less so than in 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 the options.
Look for the nitty-gritty in templates
Returning to 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 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, whilst 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 is one of the aspects which help 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 – specifics of the given manufacturer, previously approved product information, document versions, other comparable substances already approved, etc.
Terminology plays also an important part. Regulatory translators make good use of MedDRA – the Medical Dictionary for Regulatory Activities. MedDRA (www.meddramsso.com) includes the clinically validated terminology that applies to all phases of drug development.
On the flip side, MedDRA is currently available in 10 languages and only in Czech from the CEE language set.
Conclusion
One thing to remember around 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 European Union. This adds to their importance, and the need to get them right fist time.
This article was originally published in MultiLingual magazine, issue #126.