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FEDERAL AGENCY FOR MEDICINES AND HEALTH PRODUCTS

Federal Agency for Medicines and Health Products

(FAMHP)

Compassionate Use and Medical Need Program

Pharma.be-BeApp , Brussels

16 November 2007

Greet MUSCHHead of R&D

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Overview

1 : Legal Framework

2 : Review of applications received until now

3 : Points of concern

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1 :Legal Framework

1.1 : Regulation ( EC ) 726/2004

Art. 83 : Compassionate Use

« making a medicinal product available for CU reasons to a group of patients with a chronically or seriously delibilating disease or whose disease is considered to be life threatening and who cannot be treated satisfactorily by an authorised medicinal product . »

-> The medicinal product must be subject of a MA application or must be ondergoing a Clinical Trial

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1 :Legal Framework1.2 : CHMP Guideline on CU of medicinal

products pursuant to (EC) 726/ 2004

Article 83 ( adopted 19 July 2007 ) - Compassionate use implementation remains a MS’s

competence Art.83 is complementary to national legislations and provide an option to MS who wish to receive a CHMP opinion

- The medicinal product is either the subject of an application for a centralised marketing autorisation or is undergoing clinical trials in the EU and/or elsewhere

- Patients should always be considered for inclusion in clinical trials before being offered compassionate use programs

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1.2 : CHMP Guideline on CU of medicinal products pursuant to (EC) 726/ 2004 Article

83

- In this guideline compassionate use does not refer to the use of an authorised medicinal product for

an indication different from the one mentioned in the SPC

- Other Principles and definitions

- Initiation and request of CHMP opinion

- CHMP opinion itself : grounds for assessing a request ; documentation to be supplied ; Pharmacovigilance

- Link with MA

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1.3 : National Law on medicinal products :

1 May 2006

Compassionate Use :

For medicinal products without a MA

Medical Need Program :

For medicinal products with a MA for a certain indication

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3 : National Law on medicinal products :1 May 2006

Compassionate Use :

Art.6 quater point 2 Articles 106 and 107 in the RD executive measures of the Law 1 May 2006


Art.6 quater point 3 Articles 108 and 109 in the RD executive measures of the Law 1 May 2006

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3 : National Law on medicinal products :1 May 2006

Medical Need Program : Art.6 quater point 3 :

• Application for MA for the indication envisaged is ongoingor

• MA for the indication envisaged has been granted but is not yet available on the market for the indication envisagedor

• Clinical trials are still running or clinical trials have been performed prooving the feasability of the MP for the indication envisaged

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1.4: RD executive measures (Law 01.05.06)

Compassionate Use :

Art. 106 : Establishing a general program :

- Positive advice of the EC mandatory - Inclusion criteria for acceptance of patients

- Indication- Timespan in which the program will be running - Distribution ( modalities , costs , accountability )- Informed Consent- data as required by the EU NfG

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Compassionate Use :


- Application to the CA ( DGMP : Department R&D ) - same documentation including the positive advice of EC

- data and formulars according to EU NfG- CA evaluates whether a CHMP opinion is to be requested or not

If yes : CHMP advice to be followed If not : tacit approval after 2 weeks period

- Archiving : copy of documents for a 10 years period

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Compassionate Use :


In case of emergency :

Application to CA and EC justifying the urgency of the case

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Compassionate Use :

Art. 107 : Acceptance of Patiënts

- Treating physician sends a request per patiënt , declaring that :

- he takes the responsability for the use of this MP ( not yet authorised

- chronic , life threatening disease , no alternative MP available on the Belgian market to treat the disease ; he describes the disease

- he will inform the patiënt completely of all the modalities of the program

- he will asap ask the patiënt for informed consent

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Compassionate Use :

Art. 107 : Acceptance of Patiënts - The company verifies the conformity to the program for each request and informs the applicant asap .

- negative outcome : rationale is explained- positive outcome : the MP is provided to the

treating physician according the established modalities and he labels the MP « compassionate use / not for sale )

- documents prooving that the treating physician has respected his duties are to be archived for 10

years.

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Art.108 : Establishing a general program :

- Notification to EC :- Inclusion criteria for acceptance of patients- Indication- Timespan in which the program will be running - Distribution ( modalities , costs , accountability )- Informed Consent

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- Notification to CA ( FAMHP: Department R&D ) : including the name of the EC concerned

- Tacit approval aswell for EC as CA after a period of time of 2 weeks

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- MAH informs the treating physician of the existence of the Medical Need Program and its conditions for application

- Copy of documents to be archived by MAH to proove conformity to the Law/RD for a period of 10 years

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In case of emergency :

Application to CA and EC justifying the urgency of the case

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-Treating physician sends a request per patiënt , declaring that:

- he takes the responsability for the use of this MP ( not yet authorised )- chronic , life threatening disease , no alternative

MP available on the Belgian market to treat the disease ;

he describes the disease - he will inform the patiënt completely of all the

modalities of the program - he will asap ask the patiënt for informed consent

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- The company verifies the conformity to the program for each request and informs the applicant asap .

- negative outcome : rationale is explained- positive outcome : the MP is provided to the treating

physician according the established modalities and he labels the MP « compassionate use / not for sale )- documents prooving that the treating physician has respected his duties are to be archived for 10 years.

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2: Applications received until now

2.1 :Compassionate use :

* Number of applications received :only 8

urgent cases ( one patient )

one program with positive advice of EC ( orphan drug )

* Questions raised :

one patient programs CU programs requested for registered drugs

( incorrect comprehension of the definition ; is improving with time … but still a concern )

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2.2 : Medical Need Program :

* Number of applications received : 17

Only 7 out of 17 with notified EC approval

Data obtained from the “ Literature “ : considered as “invalid“

Questions raised :

patients included in the original clinical trial but not fulfilling the re-imbursement criteria of RIZIV/INAMI

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2.2 : Medical Need Program :

legal framework too limitative ( data from the

literature not retained as “ 4th criterium for MNP “

current position FAMHP : stimulate application

for MA orphan drug / off-label use to be rediscussed with new

government ?

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3 : Other points of concern

* Need for information / communication towards EC’s and health care professionals * Request to EC’s to notify the FAMHP for outcome

decision related to approval CU-MNP via [email protected]

* Enhanced scientific interaction between EC-CA about the justification of existing alternative therapies for instance or in case of negative opinion of EMEA * Notification to CHMP and role of CHMP ( need for

harmonisation for CU programs in patients view perspective )* Publication of register of approved CU ? * Follow-up of inclusion of patients in a CU/MNP program?* Amendments of CU/MNP programs ?* Safety reporting

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4: Measures for improvement..?

* Suggestions :

All applications / advices introduced via EC to be reported to CA via [email protected]

Inventory of practical cases by EC’s

Specific attention for 3th criterium for MNP:feasability of enrigestered drug to be prooved by CT in the new indication envisaged …

Template for CU/MNP to be provided by sponsors ? ( Informed Consent ; MNP ; Commitment of the treating physician )

Prospectives ..?

Inventory of problems as experienced by sponsors …

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Many thanks for your attention

federal agency for medicines and health products federal agency for medicines and health products...

Documents

health products federal

ma slide

medicinal product available

authorised medicinal

guideline compassionate

compassionate use programs

certain indication slide

clinical trial slide