1. Sophie Skorupka M2 AREIPS 15 novembre 2016
COMPASSIONATE USE
Sophie Skorupka
M2 AREIPS
15 novembre 2016
Article 83 of regulation (EC) No 726/2004

2. What is compassionate use ?
Compassionate use is a treatment option that allows the use of an unauthorised medicine. Under strict conditions, products in development can be made available to groups of patients who have a disease with no satisfactory authorised therapies and who cannot enter clinical trials
EU legislation
Article 6 of Directive 2001/83/EC
Article 83 of Regulation (EC) N° 726/2004
Cohort ATU (cATU) in France
Directive 2001/83/EC les principes et lignes directrices de bonnes pratiques de fabrication des substances actives des médicaments à usage humain – article 6 on MA
Temporary Authorisation for Use

3. Beginning of compassionate use programmes and expanded access
1962 : After Thalidomide tragedy, FDA implemented a new regulation on clinical trials
From 1962 to the beginning of the 1980s, access to investigational drugs was an informal process governed primarily by telephone
No written policies
The advent of AIDS (1980)
June 1983 : FDA proposed a regulation on the use of investigational drugs for therapeutic purposes, including compassionate use (the final IND regulation was implemented in 1987)
In France : “l’Agence du Médicament” allows in compassionate use, after pressures from AIDS patients (= ATU)
Before 2004 and Article 83 of Regulation (EC) N° 726/2004, only France and Italy had compassionate use programmes
Expanding Access to Investigational Therapies for HIV Infection and AIDS,

4. GUIDELINE ON COMPASSIONATE USE OF MEDICINAL PRODUCTS
Pursuant to article 83 of regulation (EC) No 726/2004

5. Compassionate use programmes are intended to facilitate the availability to patients of new treatment options under development
Recital 33 of Regulation (EC) No 726/20042 states that “In order to meet, in particular, the legitimate expectations of patients (...) a common approach should be followed, whenever possible, regarding the criteria and conditions for the compassionate use of new medicinal products under MS’ legislation”
Guideline on compassionate use of medicinal products, pursuant to article 83 of regulation (EC) No 726/ Doc. Ref: EMEA/27170/2006

6. Guideline Aim This guideline is designed to
Facilitate and improve access to compassionate use programmes by patients in the EU
Favour a common approach regarding
The conditions of use
The conditions for distribution
The patients targeted for the compassionate use of an unauthorised new medicines
Increase transparency between Member States in terms of treatment availability

7. Guideline scope
The use of Article 83 is applicable to unauthorised medicinal products for human use
For patients with a chronically or seriously debilitating disease, or a life threatening disease, and who cannot be treated satisfactorily by an authorised medicinal product
Group of patients
The medicinal product is either “the subject of an application for a centralised marketing authorisation in accordance with Article 6 of Regulation (EC) No 726/2004 or is undergoing clinical trials” in the European Union or elsewhere
Article 83 is not applicable
Medicinal products which are not eligible for the Centralised Procedures
Compassionate use on a named patient basis
A medicinal product, which has already been authorised via the Centralised Procedure
Guideline on compassionate use of medicinal products, pursuant to article 83 of regulation (EC) No 726/ Doc. Ref: EMEA/27170/2006

8. Guideline scope Compassionate use ≠ clinical trials
Compassionate use is not a substitute for properly conducted trials
Compassionate use ≠ off-label use
Compassionate use does not refer to the use of an authorised medicinal product for an indication different from the one mentioned in section 4.1 of the summary of product characteristics (SPC), i.e. off-label use
Patients should always be considered for inclusion in clinical trials before being offered compassionate use programmes
Guideline on compassionate use of medicinal products, pursuant to article 83 of regulation (EC) No 726/ Doc. Ref: EMEA/27170/2006

9. CHMP OPINION
Guideline on compassionate use of medicinal products, pursuant to article 83 of regulation (EC) No 726/2004

10. CHMP opinion for compassionate use
How to request a CHMP opinion ?
MS’ Competent Authority must notify to the EMA
Only for medicinal product with an application for a centralized marketing authorization
MS may indicate whether they consider that a CHMP opinion on the conditions for compassionate use would be of interest
Companies should not directly contact the EMA to request a CHMP opinion
Guideline on compassionate use of medicinal products, pursuant to article 83 of regulation (EC) No 726/ Doc. Ref: EMEA/27170/2006

11. CHMP opinion for compassionate use
When does CHMP can provide his opinion ?
CHMP opinion
MS notified EMA and requested CHMP opinion
More than one MS have notified the EMA their use of Art. 83 for the same C.U.
Guideline on compassionate use of medicinal products, pursuant to article 83 of regulation (EC) No 726/ Doc. Ref: EMEA/27170/2006

12. CHMP opinion for compassionate use
CHMP gives his opinion on
Conditions of use
Conditions for distribution
Patients targeted for compassionate use in a given therapeutic indication
MSs shall take account of any available opinions, even if these opinions are not binding
Adopted opinions are applicable to any subsequent notifications from another MS concerning the same programme
Guideline on compassionate use of medicinal products, pursuant to article 83 of regulation (EC) No 726/ Doc. Ref: EMEA/27170/2006

13. CHMP opinion for compassionate use
Only 5 opinions have been provide by CHMP since 2004
Name of Medicine
Member State notifying the Agency
Date of opinion
Tamiflu IV
Finland
01/2010
IV Zanamivir
Sweden
02/2010
Sofosbuvir
10/2013
Daclatasvir
11/2013
Ledipasvir / Sofosbuvir
Ireland
02/2014
In more than 10 years : indication only in virology and only 3 MS

14. To conclude
EMA’s will is to have common approach and centralised procedures in EU
Improvements ?
Very few MSs have requested CHMP opinions
Only MS’ Competent Authority can request CHMP opinions (Industry ? Patient groups ?)
There’s still different approaches on compassionate use by MS

15. THANK YOU FOR YOUR ATTENTION !