Guidance

Orphan medicinal products

The MHRA will review applications for orphan designation at the time of a marketing authorisation (MA) or variation application.

From:
Medicines and Healthcare products Regulatory Agency
Published
31 December 2020
Last updated
22 February 2021 — See all updates

The MHRA offers incentives in the form of market exclusivity and full or partial refunds for marketing authorisation fees to encourage the development of medicines in rare diseases. Waiver from scientific advice fees will also be available for UK based SMEs.

See the UK Rare diseases strategy for other supportive activities.

Application process

The MHRA is responsible for reviewing applications from companies for orphan designation at the time of a marketing authorisation application (MAA).

There is no pre-marketing authorisation orphan designation.

If a medicinal product has been designated orphan in the EU under Regulation (EC) 141/2000 a Great Britain (GB) orphan MAA can be made under regulation 50G of the Human Medicines Regulation 2012 (as amended). A UK-wide orphan MAA can only be considered in the absence of an active EU orphan designation.

If a UK-wide orphan marketing authorisation is granted and the medicinal product subsequently receives EU orphan designation, the market authorisation holder (MAH) would need to submit a variation to change this to a Great Britain orphan MA.

To qualify for orphan designation in an orphan condition, a medicine must meet the following criteria:

  • it must be intended for the treatment, prevention or diagnosis of a disease that is life-threatening or chronically debilitating

  • the prevalence of the condition in Great Britain must not be more than 5 in 10,000, or it must be unlikely that marketing of the medicine would generate sufficient returns to justify the investment needed for its development

  • no satisfactory method of diagnosis, prevention or treatment of the condition concerned exists in Great Britain, or, if such a method exists, the medicine must be of significant benefit to those affected by the condition

    • Satisfactory methods may include authorised medicinal products, medical devices or other methods of diagnosis, prevention or treatment which are used in Great Britain.

How to apply

Marketing Authorisation Applicants should submit the Great Britain Orphan Drug Designation Application Form (MS Word Document, 831 KB) with their MAA in module 1.2 of the eCTD, specifically indicating in the cover letter their intention to seek an orphan designation.

You should use our eAF and cover letter tool to determine what information you need to include in your application. If you do not include the correct information your application will not be validated.

Applications for orphan designation will be examined by the MHRA’s advisory committee, the Commission on Human Medicines (CHM). A decision on fulfilment of the orphan criteria runs in parallel with the assessment of the marketing authorisation procedure.

Following the validation of the MAA, a decision on orphan status will be made at the time of the decision on approval of the marketing authorisation (see guidance on new assessment procedures). Any questions concerning the fulfilment of the orphan designation criteria will be raised with the company during the evaluation of the MAA.

If the MHRA concludes that the criteria for orphan designation are not met, there will be an opportunity to appeal the decision to the CHM before the MA is granted. The applicant should inform the MHRA of the intention to appeal as soon as possible.

Market exclusivity period

On grant of a marketing authorisation with orphan status, the medicinal product will benefit from up to 10 years of market exclusivity from similar products in the approved orphan indication.

The start of this market exclusivity period will be set from the date of first approval of the product in Great Britain.

The remaining market exclusivity periods for centrally authorised orphan medicine marketing authorisations granted prior to 1st January 2021 that have been converted to Great Britain marketing authorisations will continue to apply. It is not necessary to submit orphan maintenance reports to the MHRA, but they can be provided as additional information.

In the UK/Great Britain there is no orphan designation issued separately from the MA. Therefore, if a Change of Ownership application is submitted, the orphan designation will automatically transfer.

Paediatric indications

Orphan medicines authorised in Great Britain with the results of studies from a paediatric investigation plan (PIP) included in the product information are eligible for an additional 2 years of market exclusivity.

Review of market exclusivity period

Regulation 58D of the Human Medicines Regulation 2012 (as amended) establishes the possibility for the UK Licensing Authority to request that the market exclusivity be reduced from 10 to 6 years, under certain circumstances, if the orphan criteria are no longer met in relation to the medicinal product.

Variation applications (section 4.1 of the Summary of Products Characteristics)

Marketing authorisation holders with orphan status are required to submit the Great Britain Orphan Drug Designation Application Form (MS Word Document, 831 KB) with their variation MA application for new or extensions to orphan therapeutic indications. The orphan criteria will be assessed in parallel to the approval of the new indication.

A new period of market exclusivity is only given if the applied for therapeutic indication falls within a new orphan condition.

For non-orphan indications, a new marketing authorisation application is required.

Fees

There are no additional fees to apply for orphan designation. Information on fee waivers and refunds for orphan medicines is provided in the amended MHRA application fees.

SME status

Companies who have, or intend to seek, SME status should ensure that they have the relevant documentation in place if an SME fee refund is to be applied for.

We have published information on payment easements for SMEs. The cover letter should also specify that SME status has been approved.

Orphan register

All medicines that gain an orphan marketing authorisation from the UK Licensing Authority will be listed on its Orphan Register.

When the period of market exclusivity for an indication ends, the orphan designation for that indication expires and is removed from the Orphan Register. The product will remain on the Orphan Register if other authorised orphan indications remain within their period of exclusivity.

Once all of the orphan designations associated with an approved medicine have expired or been withdrawn by the sponsor, the medicine ceases to be classified as an orphan medicine and no longer benefits from the orphan incentives. The product will be removed from the Orphan Register.

Contact

For further information, please email our Customer Services Centre at info@mhra.gov.uk or call 020 3080 6000. Alternatively, contact your Trade Association by emailing:

Published 31 December 2020
Last updated 22 February 2021 + show all updates

  1. Added new information about the application process for products with an orphan designation, on how a review of market exclusivity period would work and on the orphan register.

  2. Added a link to the Orphan register.

  3. First published.

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