European Union: EU Pharmaceutical Review - Life Sciences

Last Updated: 1 July 2004
Article by Stephen Bennett


In February we reported that agreement had been reached on the likely final form of the revision to the medicinal products Directive. Directive 2004/27/EC (the "New Directive") amends Directive 2001/83/EC (the unamended text is referred to here as the "Old Directive"). The New Directive was published in the Official Journal of the European Union on 30 April 2004 and Member States have to amend their national laws to ensure compliance by 30 October 2005.1

Uncertainties about the effect of the Old Directive in relation to applications under the abridged procedure to obtain authorisation for generic products spawned the Generics2 and recent Cyclosporin3 cases. This article considers whether the New Directive has clarified how these and similar difficulties will now be addressed.


The New Directive provides an "abridged procedure" which is very similar to that in the Old Directive. Under the Old Directive, a generic competitor could obtain marketing authorisation for his product where:

  1. the data exclusivity period in relation to the reference product had expired; and
  2. he could show that his generic product was "essentially similar" to the reference product.

This is one form of the so-called "abridged procedure". In broad terms this type of arrangement remains under the New Directive. However, instead of having to show his product is essentially similar, the generic producer will now need to demonstrate that his product is a "generic medicinal product" which is defined for the first time. The application of the definition of "generic medicinal product", as with the test of essential similarity, is likely to be a contentious area. Further, it is not clear that the new "generic medicinal product" test deals effectively with the ambiguities which led to the disputes in the Generics and Cyclosporin cases.


The Generics case enunciated a definition for "essential similarity" as follows: "…a medicinal product is essentially similar to an original medicinal product when it satisfies the criteria of having the same qualitative and quantitative composition in terms of active principles, of having the same pharmaceutical form, and of being bioequivalent unless it is apparent in the light of scientific knowledge that it differs from the original product as regards safety or efficacy". On the basis of this definition, the European Court of Justice ("ECJ") held that data submitted by the innovator to obtain marketing authorisation for new indications could be relied upon by a generic applicant without having to wait for the expiry of any period of data exclusivity in respect of the data relating to the new indication.


The definition of "essentially similar" as set out in the Generics case has been incorporated, with additions, into the definition of a "generic medicinal product" in the New Directive. A product is defined in the New Directive as a generic medicinal product when it has "the same qualitative and quantitative composition in active substances and the same pharmaceutical form as the reference medicinal product, and whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability studies." As with the definition of essential similarity, there is no mention of the indication for which the product is authorised. The absence of a reference to the indication authorised is the textual basis for the ECJ's decision in Generics. Accordingly, it seems the answer to the question posed in Generics will not change under the New Directive - there will be no automatic data exclusivity for data submitted to obtain marketing authorisation for additional indications. However, the New Directive does offer something additional for new indications: a further year of data exclusivity will be available for new indications which offer "significant clinical benefit ".


The Cyclosporin case is reviewed in detail in the article, ECJ Decides on Protection for Drug Dose and Formulation Types (see "Next Page" link provided at the bottom of this article). In brief, the ECJ considered whether a separate period of data exclusivity existed in relation to the data required to obtain authorisation for new formulations or doses of existing drugs under the Old Directive. The ECJ decided in the Cyclosporin case that data required to be submitted by an innovator company to obtain marketing authorisation for its new formulation could be relied upon by a competitor even where the data for that new formulation was less than 6/10 years old4. The ECJ ruled that this would be the case even where the later authorised product had a different formulation or dose to that originally authorised and so could not be said to be essentially similar5 to the originally authorised product.


The New Directive's definition of generic medicinal product states: "The various immediate-release oral pharmaceutical forms shall be considered to be one and the same pharmaceutical form." The three formulation types in the Cyclosporin case were immediate release oral formulations. Under this new definition, all three of the Cyclosporin forms would be considered as the same "pharmaceutical form". No period of data exclusivity should therefore result from the fact of a change of pharmaceutical form alone, which is one ambiguity from the essential similarity test which has been dealt with by the New Directive.

What the New Directive does not address is the position in relation to other formulation variants outside the scope of immediate-release oral pharmaceutical forms. For instance, will variations in formulations for administration by other routes or controlled release oral formulations be outside the definition of generic medicinal products and will the data in relation to them attract data exclusivity? There seems little doubt that such changes in formulation are outside the definition of generic medicinal product. However, for the ECJ that may make little difference. In the Cyclosporin case, the ECJ decided that differences in pharmaceutical form, whilst an express requirement of the essential similarity test, could be ignored for the purposes of authorising generic products.


The definition of generic medicinal product retains the requirement that the generic product should have the same quantitative composition to be considered a "generic medicinal product". A different dose means that the product would not have the same quantitative composition and so could not be a "generic medicinal product". For a different dose of an authorised product to be considered a generic medicinal product, the requirement in relation to quantitative composition would have to be ignored. In the Cyclosporin case, however, the ECJ held that it was appropriate to ignore a difference in quantitative composition when considering authorisation of a generic product. Whilst it may be predictable that the ECJ would do as it did in the Cyclosporin case and ignore the "quantitative composition" requirement when considering authorisation of generic products under the New Directive, the New Directive does not deal with the point expressly.


The New Directive deals expressly with variations to the active ingredient itself. The definition of generic medicinal product provides that "different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance shall be considered to be the same active substance, unless they differ significantly in properties with regard to safety and/or efficacy". The suggestion from this wording is that where a variation to the active ingredient has a significant effect on safety or efficacy further data will be required to obtain approval and such variations will be outside the scope of the generic medicinal product definition. Whether a further period of data exclusivity will apply to such data is unclear. If the ECJ's policy, as applied in the Cyclosporin case, continues to prevail, it may be that the Court could consider that even data in relation to changes in the active ingredient which have the required significant effect on efficacy or safety should be freely available for the purposes of authorising generic products.


The final form of the New Directive confirms that the data exclusivity regime has, as expected, been harmonized across the EU and EEA (European Economic Area) as the "8+2+1" rule. That is, the data can be used by an applicant to apply for marketing authorisation for a generic medicinal product eight years after the date the reference product was authorised but cannot market the product until a further two years have elapsed. A further year of exclusivity is granted to new therapeutic indications which are of "significant clinical benefit".


The New Directive appears to offer some improvements for innovators by harmonising the data exclusivity period at the longer end of the unharmonised range and by offering additional protection for further indications. However, in some areas, such as new formulations and doses, ambiguity remains in the New Directive. On the ECJ's current form, these ambiguities could be resolved in favour of generic manufacturers.


1. Directive 2004/27 applies only to the mutual recognition procedure. Regulation 726/2004 sets out the EU's centralised procedure for the authorisation of medicinal products. 2. ECJ - C368/96 3. ECJ - C106/01 4. The data exclusivity period was 6 or 10 years under the Old Directive depending on the Member State. 5. According to the Generics case, products are only essentially similar where they have the same pharmaceutical form, quantitative composition (ie same dose) and are bioequivalent.

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

To print this article, all you need is to be registered on

Click to Login as an existing user or Register so you can print this article.

This article is part of a series: Click ECJ Decides on Protection for Drug Dose and Formulation Types for the next article.
In association with
Related Video
Up-coming Events Search
Font Size:
Mondaq on Twitter
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
Email Address
Company Name
Confirm Password
Mondaq Topics -- Select your Interests
 Law Performance
 Law Practice
 Media & IT
 Real Estate
 Wealth Mgt
Asia Pacific
European Union
Latin America
Middle East
United States
Worldwide Updates
Check to state you have read and
agree to our Terms and Conditions

Terms & Conditions and Privacy Statement (the Website) is owned and managed by Mondaq Ltd and as a user you are granted a non-exclusive, revocable license to access the Website under its terms and conditions of use. Your use of the Website constitutes your agreement to the following terms and conditions of use. Mondaq Ltd may terminate your use of the Website if you are in breach of these terms and conditions or if Mondaq Ltd decides to terminate your license of use for whatever reason.

Use of

You may use the Website but are required to register as a user if you wish to read the full text of the content and articles available (the Content). You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these terms & conditions or with the prior written consent of Mondaq Ltd. You may not use electronic or other means to extract details or information about’s content, users or contributors in order to offer them any services or products which compete directly or indirectly with Mondaq Ltd’s services and products.


Mondaq Ltd and/or its respective suppliers make no representations about the suitability of the information contained in the documents and related graphics published on this server for any purpose. All such documents and related graphics are provided "as is" without warranty of any kind. Mondaq Ltd and/or its respective suppliers hereby disclaim all warranties and conditions with regard to this information, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. In no event shall Mondaq Ltd and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use or performance of information available from this server.

The documents and related graphics published on this server could include technical inaccuracies or typographical errors. Changes are periodically added to the information herein. Mondaq Ltd and/or its respective suppliers may make improvements and/or changes in the product(s) and/or the program(s) described herein at any time.


Mondaq Ltd requires you to register and provide information that personally identifies you, including what sort of information you are interested in, for three primary purposes:

  • To allow you to personalize the Mondaq websites you are visiting.
  • To enable features such as password reminder, newsletter alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our information providers who provide information free for your use.

Mondaq (and its affiliate sites) do not sell or provide your details to third parties other than information providers. The reason we provide our information providers with this information is so that they can measure the response their articles are receiving and provide you with information about their products and services.

If you do not want us to provide your name and email address you may opt out by clicking here .

If you do not wish to receive any future announcements of products and services offered by Mondaq by clicking here .

Information Collection and Use

We require site users to register with Mondaq (and its affiliate sites) to view the free information on the site. We also collect information from our users at several different points on the websites: this is so that we can customise the sites according to individual usage, provide 'session-aware' functionality, and ensure that content is acquired and developed appropriately. This gives us an overall picture of our user profiles, which in turn shows to our Editorial Contributors the type of person they are reaching by posting articles on Mondaq (and its affiliate sites) – meaning more free content for registered users.

We are only able to provide the material on the Mondaq (and its affiliate sites) site free to site visitors because we can pass on information about the pages that users are viewing and the personal information users provide to us (e.g. email addresses) to reputable contributing firms such as law firms who author those pages. We do not sell or rent information to anyone else other than the authors of those pages, who may change from time to time. Should you wish us not to disclose your details to any of these parties, please tick the box above or tick the box marked "Opt out of Registration Information Disclosure" on the Your Profile page. We and our author organisations may only contact you via email or other means if you allow us to do so. Users can opt out of contact when they register on the site, or send an email to with “no disclosure” in the subject heading

Mondaq News Alerts

In order to receive Mondaq News Alerts, users have to complete a separate registration form. This is a personalised service where users choose regions and topics of interest and we send it only to those users who have requested it. Users can stop receiving these Alerts by going to the Mondaq News Alerts page and deselecting all interest areas. In the same way users can amend their personal preferences to add or remove subject areas.


A cookie is a small text file written to a user’s hard drive that contains an identifying user number. The cookies do not contain any personal information about users. We use the cookie so users do not have to log in every time they use the service and the cookie will automatically expire if you do not visit the Mondaq website (or its affiliate sites) for 12 months. We also use the cookie to personalise a user's experience of the site (for example to show information specific to a user's region). As the Mondaq sites are fully personalised and cookies are essential to its core technology the site will function unpredictably with browsers that do not support cookies - or where cookies are disabled (in these circumstances we advise you to attempt to locate the information you require elsewhere on the web). However if you are concerned about the presence of a Mondaq cookie on your machine you can also choose to expire the cookie immediately (remove it) by selecting the 'Log Off' menu option as the last thing you do when you use the site.

Some of our business partners may use cookies on our site (for example, advertisers). However, we have no access to or control over these cookies and we are not aware of any at present that do so.

Log Files

We use IP addresses to analyse trends, administer the site, track movement, and gather broad demographic information for aggregate use. IP addresses are not linked to personally identifiable information.


This web site contains links to other sites. Please be aware that Mondaq (or its affiliate sites) are not responsible for the privacy practices of such other sites. We encourage our users to be aware when they leave our site and to read the privacy statements of these third party sites. This privacy statement applies solely to information collected by this Web site.

Surveys & Contests

From time-to-time our site requests information from users via surveys or contests. Participation in these surveys or contests is completely voluntary and the user therefore has a choice whether or not to disclose any information requested. Information requested may include contact information (such as name and delivery address), and demographic information (such as postcode, age level). Contact information will be used to notify the winners and award prizes. Survey information will be used for purposes of monitoring or improving the functionality of the site.


If a user elects to use our referral service for informing a friend about our site, we ask them for the friend’s name and email address. Mondaq stores this information and may contact the friend to invite them to register with Mondaq, but they will not be contacted more than once. The friend may contact Mondaq to request the removal of this information from our database.


This website takes every reasonable precaution to protect our users’ information. When users submit sensitive information via the website, your information is protected using firewalls and other security technology. If you have any questions about the security at our website, you can send an email to

Correcting/Updating Personal Information

If a user’s personally identifiable information changes (such as postcode), or if a user no longer desires our service, we will endeavour to provide a way to correct, update or remove that user’s personal data provided to us. This can usually be done at the “Your Profile” page or by sending an email to

Notification of Changes

If we decide to change our Terms & Conditions or Privacy Policy, we will post those changes on our site so our users are always aware of what information we collect, how we use it, and under what circumstances, if any, we disclose it. If at any point we decide to use personally identifiable information in a manner different from that stated at the time it was collected, we will notify users by way of an email. Users will have a choice as to whether or not we use their information in this different manner. We will use information in accordance with the privacy policy under which the information was collected.

How to contact Mondaq

You can contact us with comments or queries at

If for some reason you believe Mondaq Ltd. has not adhered to these principles, please notify us by e-mail at and we will use commercially reasonable efforts to determine and correct the problem promptly.