EU/3/02/107: Orphan designation for the treatment of partial deep dermal and full-thickness burns

Burns are classified in three degrees of severity. These depend on how deep the burn is. First-degree burns are limited to the thin outermost layer of the skin. This layer is called epidermis. One example is sunburn. Second-degree burns affect the thick layer of skin or connective tissue beneath the epidermis. This layer contains blood, lymph vessels, sweat glands, and nerve endings. Second-degree burns are divided into two groups. These are called superficial and deep partial-thickness burns. The superficial ones result in blistering and are painful. Healing occurs naturally in one to three weeks.

Deep partial-thickness burns have blisters, a pale white or yellow colour and absence of pain sensation. Regrowth of the skin takes between three weeks and two months. Disabling scars can develop in the long term. Third-degree burns involve all skin layers (full thickness). This includes a layer of fat under the connective tissue. There is usually little pain at the beginning. The skin appears dry, leathery and is no longer elastic. Deep partial or full-thickness burns can be life-threatening.

At the time of designation, partial deep dermal and full-thickness burns affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 38,000 people*, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union. At the time of designation, this represented a population of 380,600,000 (Eurostat 2002).

Most deep partial-thickness and full-thickness burns larger than three centimetres in diameter are best treated with early removal of dead tissue. The removal is done by surgery. Healthy skin is taken from other parts of the body to replace the removed tissue. The use of purified bromelain might reduce the need for surgery. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that purified bromelain could be of potential significant benefit for the treatment of burns.

Purified bromelain is extracted from plants. It consists of a mixture of enzymes. Enzymes are proteins that control specific functions and chemical reactions. These enzymes might be useful in dissolving dead tissues at the site of the burn.

The effects of purified bromelain have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical evaluation in patients with deep partial-thickness and full-thickness burns had not been completed.

This medicinal product had not been marketed anywhere worldwide for this condition. Also, it had not been designated as orphan medicinal product for this condition at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 27 June 2002 recommending the granting of this designation.

Update: Purified bromelain (NexoBrid) was authorised in the EU on 18 December 2012 for removal of eschar in adults with deep partial- and full-thickness thermal burns.

• the seriousness of the condition,
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the European Union) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.