FEDERAL AGENCY FOR MEDICINES AND HEALTH PRODUCTS Federal Agency for Medicines and Health Products (FAMHP) Compassionate Use and Medical Need Program Pharma.be-BeApp,

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

Documents

FEDERAL AGENCY FOR MEDICINES AND HEALTH PRODUCTS Federal Agency for Medicines and Health Products (FAMHP) Compassionate Use and Medical Need Program Pharma.be-BeApp,