Overview of Comments Received On

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European Medicines AgencyEvaluation of Medicines for Human Use

London, 23 July 2007

Doc. Ref. EMEA/333892/2007

OVERVIEW OF COMMENTS RECEIVED ON

DRAFT GUIDELINE

Table 1: Organisations that commented on the draft Guideline as released for consultation

Name of Organisation or individual Country

1 European Cancer Patient Coalitions(ECPC) 03.07.06 EU

2 European Federation of Pharmaceutical Industries and Associations

(EFPIA) 30.06.06

EU

3 EURORDIS 28/06/06 EU

4 Raoul CM Hennekam MD PhD

Professor of Clinical Genetics and Dysmorphology, Institute of Child HealthGreat Ormond Street Hospital for Children, University College London

Professor of Pediatrics and Clinical Genetics, Dept of Pediatrics

Academic Medical Center, University of Amsterdam

UK

5 BioIndustry Association(BIA) 03.07.06

Trade association for innovative enterprises in the UK bioscience sector. It

represents over 300 members, the majority of which are involved in realising

the human health benefits that bioscience promises.

UK

6 Merck Sharp & Dohme(MSD) 23/06/06 EU7 IDIS pharma 30/06/06

Specialist in the provision of named patient and compassionate use services.

IDIS on average make 1600 notifications to the MHRA a week with regard to

named patient supply in the UK; IDIS supply to over 300 customers in

Europe (3800 products).

UK

8 E Bi 30/06/06 W ld id


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3.1. Centres opening the programme only if they could enrolpatients in regulatory trials (as a gift to investigators), lettingcentres that decided not to participate to the productdevelopment out of the scope of the compassionate use, and

thus discriminating patients.3.2. Companies opening a programme only in MSs where they can

charge for the product even for a compassionate use.3.3. Programmes recruiting on a first come first served basis if the

product supply is limited. This may not correspond to theobjectives needs of those patients with the most severe medical

condition and in the greatest need of a new product under acompassionate use, who can not rush to the hospital to become

the first served.

3.4. Programmes recruiting at the sole discretion of the physicians,and selecting himself the patients to receive the product on acompassionate use, which is not satisfying when the productsupply is limited.

3.5. Companies asking patient organisations to decide on the

selection criteria if the demand exceeds the product availability.3.6. Or Ethics committees advising to organise a lottery or a random

process to select the eligible patients under such limited supplyconditions.

3.7. Companies monitoring the shortage of product with a waitinglist, transferring product from MSs where demand is lower to

MSs where the demand is higher.3.8. Programmes stopping enrolling new patients at the time of

marketing authorisation but continuing providing the drug forfree to those already in the programme, until pricing andreimbursement negotiations are completed. On the contrary, inother MSs, the same company continued enrolment, with no

restrictions, or stopped delivering the product for free before the

reimbursement decision was made, thus preventing the poorestpatients to continue treatment.

4. That the procedures for the announcement of the programme should

be similar in all MSs.

The details of this announcement is the responsibility of the MS.However some possible measures exist in all MSs: letter to

doctors, public section on the web site on the NCA, informationto patient organisations. There is a balance between promotingthe product and neutrally informing on the compassionate useprogramme. As for the announcement that a new clinical trial is


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enrolling, fairness in the announcement that a compassionate useprogramme is open is equally important.

The current situation is that usually, the applicant and MSs negotiate all

these points in a separate manner. This creates inequality anddiscrimination among patients depending on where they live. As

drugs eligible for compassionate use are to treat life-threatening or severediseases, such disparities are not acceptable.

Inequity in accessing a compassionate use programme also exists when

the disease is so rare that only a few member states develop the necessaryefforts to open the programme. For example, a compassionate use

programme for Carbaglu started in France in August 2001. Marketing

authorisation was granted on January 24th, 2003. During that period, halfof the patients who benefited from the product as compassionate use wereall living in France, reflecting the difficulties to open access in all MS.Other examples2with delayed access to orphan drugs due to absence of acompassionate use programme in some of the member states can be

documented about Fabrazyme (ATU started 80 days before EUmarketing authorisation, whereas sales could be detected in Spain only377 days after marketing authorisation), Glivec (compassionate usestarted 90 days before EU marketing authorisation in France and

Germany, whereas sales were detected 373 days after EU marketingauthorisation in Belgium, 189 in Greece, 100 days in Ireland), or

Tracleer. Another example is the compassionate use programme forHIV protease inhibitors started in April 1996 in France, and one to twoyears later in some other EU MSs: hospitalisation rates declined duringthe weeks that immediately followed the initiation of ritonavir andindinavir compassionate use programmes in France (ATU) in April 1996,that was six months prior to marketing authorisation.

On the contrary, the Agency could certainly help developing the

Regulation (EC) No 726/2004 common approach by incorporating allthese aspects in the discussion with the applicant at the time ofassessment of the compassionate use programme. Even if not allconditions are finally the same in all MSs, it is more transparent toannounce these differences early and prior to the initiation of theprogramme.

The Agency should not renounce to this important role it can play in

public health in Europe by over-restricting the definition of condition

of distribution.


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consultation withthe applicant, asnecessary, theeligibility of the

medicinal productto the centralised

procedure.

5. CHMP OPINION

35 BIA: There are some issues as to how this procedure will work inpractice. Clarity is required as to who will be responsible for assessing thedata package. Will there be a rapporteur/co-rapporteur as for the

centralised marketing authorisation procedure? If that is the case, will

they be involved in the assessment of a future (or pending) marketingauthorisation application for the product in question? The timeline forissuing the CHMP opinion should be stated in the guideline to ensure

timely access of the medicinal product to patients. Moreover, the adoptionof the opinion for compassionate use should not delay the assessment of

the MAA, which may be carried out in parallel.

Procedural aspects will be developed in a separate paper. This guideline sets the

general principles.

36 MSD / EuropaBio: The guideline is silent as to any timeframes underwhich a CHMP must review and issue its opinion.

Procedural aspects will be developed in a separate paper. This guideline sets thegeneral principles.

37 IDIS: The Guidance could be enhanced via the inclusion of a clearprocess flow diagram including time frames.

Procedural aspects will be developed in a separate paper. This guideline sets the

general principles.38 - Detailedjustification shouldbe provided tosupport the claim

that the productmeets the criterialisted in Art 83(2),in accordance with

the definitionsprovided in this

guideline.

MSD: It is not clear if this justification has to be provided by the MS(s)requesting a CHMP opinion, or if this will be requested from the sponsorof the compassionate use program.

Justification will be provided by the applicant and validated by the EMEA/CHMP.Procedural aspects will be developed in a separate paper. This guideline sets thegeneral principles.

39 EFPIA / EuropaBio: As currently written, the section does not giveany indication on the delay for issuing a CHMP opinion. This isconsidered unsatisfactory for the reasons detailed below.Throughout this section there is a notable lack of timelines associatedwith the opinion process. This is not considered acceptable, as this would

potentially delay compassionate access whilst Member States await the

Procedural aspects will be developed in a separate paper. This guideline sets thegeneral principles.


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products that are ()Proposed to change last sentence to:() aiming at treating a group of patients suffering from a life threateningdiseaseor a chronically or seriously debilitating disease.

or possibly:() a chronic or seriously handicapping disease...

Question 4 EFPIA: Lacks in clarity. Change to:

If appropriate, your doctor may contact the health authority thatsupervises compassionate use programmes in your country.

The Q&A has been reviewed in line with the comments received and the revised

guideline.

Question 5 EFPIA: It is unclear whom this Q&A is addressed to. In any event, wedoubt that it can as written be understood by the majority of patients. If theintention is to redirect the patient/physician to the national health authority,the Q&A must be clearer on this point.

Reword title:Are compassionate use programmes available in all the European

Member States?Replace the two sentences by:No, compassionate use programmes are currently not available in allMember States and the recommendations made by the EMEA are no legalobligations for the Member States. Your doctor can verify with your

national health authority if a compassionate use program is possible.

The Q&A has been reviewed in line with the comments received and the revisedguideline.

Question 6 EFPIA: Avoid any possible confusion with CHMP opinions. Change 1st

sentence to:The name of the product which has undergone an EMEA compassionateuse review will be published on the EMEA website.

The Q&A has been reviewed in line with the comments received and the revised

guideline.

Documents

Overview of Comments Received On