Background to data exclusivity

In regulating the pharmaceutical industry, legislators have to balance a number of competing interests.  First, they aim to offer rewards for the research and development that produces innovative new treatments, while also allowing generic competition that will bring down the overall cost of medicines.  Furthermore, they must ensure that sufficient pre-clinical and clinical data are produced by pharmaceutical companies to demonstrate that drugs are safe and effective, while avoiding excessive, repetitive testing in humans beyond what is strictly necessary.

This has led to the development of two layers of exclusivity in the pharmaceutical industry.

• First, the patent system, including supplementary protection certificates and paediatric extensions, which allows the innovator company a monopoly in the market for a defined period.  After that, generic competitors may enter the market, which should mean that prices will fall.
• Second, the innovator company is allowed a period of data and marketing exclusivity.  In order to avoid unnecessary repetitive testing in humans, a generic pharmaceutical company may refer to the pre-clinical and clinical data produced for an earlier reference product when it was authorised, provided it can demonstrate that its product is a "generic" of the reference product.  However, it may only do this after the expiry of the data exclusivity period.  See Data exclusivity for medicinal products in Europe.

This article will focus on the circumstances in which an additional period of data exclusivity is available, either by way of extension to an existing period, or as a stand-alone period.

Old or new regime?

The data exclusivity period depends on when authorisation for the reference product was applied for. For products for which authorisation was applied for prior to November 2005, the data exclusivity period is either six or ten years, depending on the Member State in which it was authorised (with the period being ten years for all medicinal products approved under the centralised procedure).

In the case of reference products for which authorisation was applied for after November 2005, generic companies may refer to the reference product's data after eight years (data exclusivity), but must wait a further two years before actually marketing the generic drug (marketing protection).

New therapeutic indications – extension of one year

Under the new regime, an additional period of marketing protection may be available where new therapeutic indications have been authorised.  Article 10(1) of Directive 2001/83, as amended, provides:

"The ten-year period … shall be extended to a maximum of eleven years if, during the first eight years of those ten years, the marketing authorisation holder obtains an authorisation for one or more new therapeutic indications which, during the scientific evaluation prior to their authorisation, are held to bring a significant clinical benefit in comparison with existing therapies."

Article 14(11) of Regulation 726/2004 (centralised procedure) provides for the same additional year.  The extended period of protection applies to the medicinal product that the authorisation relates to, not just the additional indications.

There are therefore two requirements for extending the exclusivity period on this ground: authorisation of new therapeutic indications and a finding that they bring significant clinical benefit.  An obvious scenario in which a new indication could bring significant clinical benefit is where there is no existing treatment at all for that indication.  Where treatments already exist, it may be necessary to carry out comparative trials to justify benefiting from the additional year of exclusivity.

Well-established substances – stand-alone period of one year

The new regime also rewards the investigation of new therapeutic indications for "well-established substances" (defined according to criteria set out in Directive 2001/83 including having been used for at least ten years).

Where an application is made for a new indication for a well-established substance, a period of one year of data exclusivity is granted, provided significant pre-clinical or clinical studies were carried out in relation to the new indication.  Commission guidance suggests that an applicant that has carried out at least one confirmatory clinical trial versus a suitable comparator will meet the requirement for "significant pre-clinical or clinical studies", though they may still have to submit further data in order to be granted a marketing authorisation for the new indication.

Combinations – independent data exclusivity period

In the case of combination products, significantly more than a short extension or additional period is available.

Before marketing "fixed combinations" of two or more approved drugs not previously approved in combination, it is necessary to submit the results of new pre-clinical tests and clinical trials.  Such a combination product will have an independent period of data and marketing exclusivity – the full 8+2 years of protection.

Change of classification – stand-alone period of one year for limited purposes

Medicinal products are classified according to whether or not they are subject to medical prescription.  The legislation provides that where new facts are brought to their attention, the regulatory authorities must examine and, if necessary, amend the classification of a medicinal product.

In cases where a change in classification has been authorised on the basis of significant pre-clinical tests or clinical trials, the regulatory authority may not refer to those results when assessing an application for a change of classification by another applicant for the same substance, for a period of one year.  In other words, there is a data exclusivity period of one year for the change of classification data.

Orphan products – longer exclusivity periods and extensions

There are also more generous periods of exclusivity available for drugs used for treating rare conditions or conditions for which the likely revenues available do not justify the research required to develop treatments – so called orphan drugs. See our Orphan drugs article for more information.

A drug designated as an orphan drug benefits from a marketing exclusivity of ten years, which may run in parallel with the basic marketing exclusivity if the drug is also authorised (via a separate marketing authorisation) for other indications.

Furthermore, any additional orphan indications for the same product will also benefit from their own ten year period of marketing exclusivity.

Where an application for a marketing authorisation for an orphan product includes the results of studies conducted in accordance with an agreed paediatric investigation plan, the ten year period is extended to a period of twelve years.

Conclusion

Data exclusivity is an effective addition to patent protection.  Under some circumstances, it may apply even when the patent has expired.  It is therefore an important aspect of the strategy to keep in mind when considering investigations into additional uses for new or old drugs and treatments for rare conditions, as well as for planning generic product launches.

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