EU/3/02/107

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Orphan designation

On 30 July 2002, orphan designation (EU/3/02/107) was granted by the European Commission to Professor Keith Judkins, United Kingdom, for purified bromelain for the treatment of partial deep dermal and full-thickness burns.

The sponsorship was transferred to Teva Pharma GmbH, Germany, in June 2010 and subsequently to MediWound Germany GmbH, Germany, in July 2013.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

What are 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.

What is the estimated number of patients affected by the condition?

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).

What treatments are available?

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.

How is this medicine expected to work?

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.

What is the stage of development of this medicine?

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.

Opinions on orphan medicinal product designations are based on the following three criteria:
  • 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.

Key facts

Product details for <p>Purified bromelain</p>
Active substancePurified bromelain
Medicine Name
Disease/conditionTreatment of partial deep dermal and full-thickness burns
Date of decision30/07/2002
OutcomePositive
Orphan decision numberEU/3/02/107

Review of designation

During its meeting of 3-4 October 2012, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/02/107 for NexoBrid (concentrate of proteolytic enzymes enriched in bromelain, previously known as purified bromelain) as an orphan medicinal product for the treatment of partial deep dermal and full-thickness burns. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other satisfactory methods of treatment. As other satisfactory methods of treatment for patients with this condition are authorised in the European Union (EU), the COMP also looked at the significant benefit of the product over existing treatments. The COMP recommended that the orphan designation of the medicine be maintained*.


*The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with a comparable therapeutic indication cannot be placed on the market.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of NexoBrid for ‘removal of eschar in adults with deep partial- and full-thickness thermal burns’. This falls within the scope of the product’s designated orphan indication, which is ‘treatment of partial deep dermal and full-thickness burns’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2002. Partial deep dermal and full-thickness burns remain a condition that is debilitating in the long term and life-threatening, particularly due to infection and sepsis (when bacteria and their toxins circulate in the blood and damage the organs), acute respiratory-distress syndrome (failure of the lungs causing severe difficulty breathing), hypovolaemia (loss of blood volume) and extensive scarring that might prevent normal mobility.

Prevalence of the condition

The sponsor provided updated data on annual numbers of patients hospitalised for burn wounds from available databases and the scientific literature. On the basis of the information provided by the sponsor and the knowledge of the COMP, the Committee concluded that the prevalence of partial deep dermal and full-thickness burns remained below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was still estimated to be approximately 1 person in 10,000. This is equivalent to a total of around 51,000 people in the EU.

Existence of other satisfactory methods of treatment

At the time of the review of the orphan designation, other methods were authorised in the EU for the treatment of partial deep dermal and full-thickness burns. Surgery was still the most direct method of debridement, which involves the removal of eschar (dead tissue) from the wound before further treatment. Some antibiotic medicines, as well as medicines containing enzymes to clean dead tissue and infected burns, were also authorised for use in burns patients.

Significant benefit over existing treatments

The COMP concluded that the claim of a significant benefit of NexoBrid in the treatment of partial deep dermal and full-thickness burns was justified because, when compared with standard debridement treatment in a study involving 156 hospitalised burns patients, it was shown to reduce the need for surgery as well as the extent of skin grafting required (decreasing trauma, pain and scarring for the patient).

Therefore, although other satisfactory methods for the treatment of this condition had been authorised in the EU, the COMP concluded that NexoBrid is of significant benefit for patients affected by partial deep dermal and full-thickness burns.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that NexoBrid still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community register of orphan medicinal products.

Sponsor’s contact details

Teva Pharma GmbH
Graf-Arco-Str. 3
89079 Ulm
Germany
Tel. +49 6105 97 676 17
Fax +49 6105 97 767 60
E-mail: ekkehard.baader@teva.de

Patients' organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.