The role and tasks of the National Medicines Agencies

The role and tasks of the National Medicines AgenciesEU legislation for VMPsInstanbul, 18 – 19 April 2011

Jiří BurešInstitute for State Control of Veterinary Biologicals and Medicines

The views presented here are my personal views and they are not to be intepreted as the views of the Czech NCA

EU and its legislation (1)

EU a body of treaties, law and court judgements which operates

alongside the legal systems of the European Union´s member states. It has direct effect within the EU's member states and, where conflict occurs, takes precedence over national law

Supremacy Direct effect

Horizontal (Treaties, Regulations, Decisions) Vertical (Directives)

„Four freedoms“

EU and its legislation (2)

EU legislation Primary Secondary ECJ Decisions Soft law

Recommendations

Notice to Applicants, Guide, Guidelines, Notes for Guidance, Points to Consider

Communications

Opinions National legislation

?? Medicinal product (MP)

Definition – Dir.2001/82/EC as amended by Dir. 2004/28/EC any substance or combination of substances

presented as having properties for treating or preventing disease in animals; OR

any substance or combination of substances which may be used in, or administered to, animals with a view either to making a medicinal diagnosis, or to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis

Medicinal product „by presentation“ (1) a substance presented as having properties either

for treating disease in animals or for preventing disease in animals.

The nature of a medicinal product considered by the European Court of Justice on a number of occasions.

There are policy reasons for not having too broad or too narrow an interpretation of medicinal products. It is recognised that there may be some overlap between a medicinal product by presentation and a medicinal product by function.

Medicinal product „by presentation“ (2) A medicinal product by presentation may arise

Where the product is “indicated or recommended” for treating or preventing disease

Where the average well informed consumer gains the impression, which, provided it is definite, may even result from implication, that the product in question should, regard being had to its presentation, have the properties of treating or preventing disease

In particular the external form of the product (eg tablet, pill or capsule) may serve as strong evidence of the intention to market the product as a medicinal product (but cannot be the sole or conclusive evidence)

Not only the form of product but the form of packaging may be strong evidence of intention to market the product as a medicinal product, which may for reasons of marketing policy tend to make it resemble a medicinal product

Particular regard may be had to the form of packaging and product information which makes reference to medical endorsement of the product.

A statement that a product is NOT a medicinal product is persuasive evidence which may be taken into consideration but it is not in itself conclusive.

Medicinal product „by presentation“ (3) Examples of ECJ rulings:

Leentert van Bennekom - ECJ 30 Nov 1983 Vitamines in the form of tablets, pills and capsules Legislation – seeks to preserve consumers not only from harmful oe toxic MPs

but also from a variety of products used instead of the proper medicines Concept of presentation – „has to be broadly construed“

Jean Marie Delattre - ECJ 21 March 1991 Products bearing a claim they are NOT MP ECJ – form and manner of packaging similar to that of MP, then product may be

regarded a MP Commission of the European Communities v Federal Republic of Germany

ECJ 15 Nov 2007 German authorities regarded a garlic preparation in capsules as a MP ECJ – capsule form as a sinlge indicator, is not ecxlusive to MPs

Johann Stephanis Wilhelmus Tervoort - ECJ 28 Oct 1992 Herbal teas marketed without any indication of any therapeutic property Product recommended or indicated as having prophylactic or therapeutic

properties shall be regarded as MP, even if it is generally regarded a foodstuff and even if it has no known therapeutic effect according to the current knowledge

Medicinal product „by function“ (1)

Case C-140/07, Hecht-Pharma GmbH v Staatliches Gewerbeaufsichtsamt Lüneburg of 15 January 2009 In its answer to the first question the ECJ considered that Directive 2001/83/EC is

limited to industrially-produced medicinal products and excludes products not covered by the definitions of medicinal product as laid down in Article 1(2) of said Directive. The ‘rule of doubt’ provided for in Article 2(2) of Directive 2001/83/EC applies only to products which satisfy the conditions for classification as a medicinal product.

The ECJ also observed that the definition of medicinal product by function seeks to cover products with scientifically observable pharmacological properties which are ‘genuinely designed to (…) restore, correct or modify physiological functions’. Hence, a product of which it cannot be scientifically established that it can restore, correct or modify physiological functions by means of pharmacological, immunological or metabolic action cannot be considered a medicinal product by function.

Nevertheless the ECJ considered that this does not rule out the possibility of differences of interpretation and classification of products between the different Member States. Consequently, it is possible that a product is classified as a food supplement in one Member State, whereas it is considered a medicinal product in another.

Medicinal product „by function“ (2)

But if all characteristics of a product should be taken into account for the classification of medicinal product by function, how should the ‘physiological effect’ of a product then be evaluated? Should a product be classified as a medicinal product by function even if it is incapable of restoring, correcting or modifying physiological functions on the basis of its composition and use according to indicated dose, or are the requirements more stringent? According to the ECJ: “(…) products containing a substance having a physiological effect cannot automatically be classified as medicinal products by function (…)”. Every product should be carefully examined on an individual basis by the competent authority. This authority should particularly assess the precise pharmacological, immunological or metabolic characteristics of the product in so far as these can be established by current scientific knowledge. But even if such effects are acknowledged for a substance, this does not necessarily lead to the conclusion that a product containing that substance is medicinal by function. The mere fact that pharmacological, immunological or metabolic characteristics can be established should in the words of the ECJ: ‘not lead to the classification as medicinal products by function of products which, while having an effect on the human body, do not significantly affect the metabolism and thus do not strictly modify the way in which it functions’.

Therefore, a product used in line with the prescribed dose is not a medicinal product by function, if according to its composition, it is unable to appreciably restore, correct or modify the physiological functions

Medicinal product – example of a national court judgement Recent example of the national court

judgment for a veterinary medicinal product Teat sealant http://www.courtsni.gov.uk/NR/rdonlyres/

53C4194D-58BC-44D6-9AE3-7E7369F22609/0/j_j_WEA7789Final.htm

Medicinal products for veterinary use

Biocidal products

Bordeline products Feedingstuffs / feed additives

Medicated feedingstuffs

„New therapies“Blood,

blood products

Veterinary devices

Veterinary autogeneous vaccines

Other „out of scope“

products

In vitro diagnostics

Role of NCAs

RegulationRegulation

ScienceScience

Contribution to the socio-economic

development

Acquis Communautaire

National legislation

National policies

International agreements

National institutions

EU institutions

Bilateral 3rd countriesagreements

Role of NCAs

Animal health / welfare – Public heath –Environment

Compliance with Acquis Communautaire Single market EU activities Equal conditions International harmonisation Availability of VMPs National policies

Main tasks NCAs

Marketing Authorisation / Post-authorisation Management of Veterinary Medicinal Products

Inspection activities Pharmacovigilance Advertisement of VMPs Activities at the EU level Use of VMPs (incl. „cascade“ and records) Supervision / sanctions Improving availability of VMPs National policies / activities

Marketing authorisation – general requirements Benefit : risk assessment

Scientific capacity (! qualified staff) Legislation

„hard law“ „soft law“

Co-operation at the EU level Common understanding Mutual trust Training

Regulatory / administrative efficiency Legislation Co-operation / Co-ordination at the EU level Specific national requirements Timelines E-submissions

Compliance with the Acquis Communautaire

Marketing authorisation of VMPs National procedure Mutual recognition procedure / Decentralised

procedure Centralised procedure Bordeline products „MAY“ provisions

National procedure (1) Limited number of products in the EU

environment Same requirements as for the other types of

procedures while market limited to a single MS Directive 2001/82/EC as amended

„Old products“ Compliance with Acquis New applications vs. Old products Accession experience:

Pre-accession update Legal basis Updated dossier

National procedure (2)

Currently the way for MU/MS – limited market products Products „tailored“ to specific needs of respective

Member States Fish, bees, game, small ruminants



Mutual recognition / Decentralised

procedure (1) Accession experience – MRP (DCP) means a true EU perspective in the licensing system Legislation / guidelines / best practice guides Formal Co-ordination group – CMDv (Dir.

2001/82/EC) Organisation / Co-operation / Communication

NCAs Industry (applicants)

Timelines IT tools (CTS) Language

Mutual recognition / Decentralised procedure (2)

Resources Scietific capacity of the NCAs – Benefit : risk justification –

challeging the RMS AR „potential serious risk“

http://ec.europa.eu/health/files/eudralex/vol-6/newdoc/2006_c_132_08_en.pdf

Mutual trust Agreement / referrals Harmonised SPCs Availability of medicines General contribution to an EU harmonised views in the

area of VMP regulation Identification of outstanding issues


NCA acting as Concerned Member State (CMS) AR from the RMS Product literature in the dossier (applicant) Critique of the RMA AR with reference to the

information submitted in the dossier LoQ Agreement x Referral procedure

Mutual trust - Priorisation of assessment


NCA acting as Reference Member State (RMS) Leading authority

Scientific assessment Procedure Co-ordination

Assessment report Quality – clear with respect to benefit : risk conclusions / LoQ

Conclusions Post-authorisation management

Variations Renewals


Currently – MRP/DCP used mainly for authorisation of generics to the well established products E.g. tiamulin, doxycycline, amoxycilin / clavulanic acid,

enrofloxacin, flunixin Pre-accession experience

Observeship to VMRFG Elaboration of a procedure for applicants and candidate

Member States (C-CMS) Authorisation of VMPs under this procedure before the

accession Administrative repeat use after the accession for full

integration of the products under MRP



Centralised procedure (1) Applications submitted to the European Medicines

Agency (EMA – formerly EMEA) EMA

http://www.ema.europa.eu/ema/index.jsp?curl=/pages/home/Home_Page.jsp&jsenabled=true)

Secretariat Scientific committee

Committe for Veterinary Medicinal products (CVMP) Scientific opinion

European Commission (DG SANCO) http://ec.europa.eu/health/index_en.htm Decision

Centralised procedure (2)

Products liable to the CP Obligatory

Products specified in the Annex to the Reg. 726/2004 Optional

VMP containing new APIs not authorised in the Community on the date of entry into force of the Regulation

Product constituting significant therapeutic, scientific or technical innovation

Immunological VMP for the treatment of animal diseases subject to Community prophylactic measures

Centralised procedure (3)

Role and tasks of the NCAs in the CP Usually – nomination of a member of the Scientific

Committee Member of a scientific committee

Time needed for preparation of the committee meetings (monthly)

3 – 5 working days needed Sufficient expertise / network of experts available to the

CVMP member Rapporteur / Co-rapporteur / peer-reviewer

Centralised procedure (4) !! Rules for experts apply – under revision

Expertise Conflict of interests

Comments from Member States Check of product literature for CP QRD group Standing Committee membership (European

Commission) Consultion procedure Meetings if needed (approx. 1 / year)

Supervison and sanctions



Bordeline products (1)

Definition of a medicinal product (vide supra) Article 2, par. 2 of Dir. 2001/82/EC

In cases of doubt, where taking into account all its characteristics, a product may fall within the definition of a "veterinary medicinal product" and within the definition of a product covered by other Community legislation, the provisions of this Directive shall apply

Number of products – clear categorisation difficult Presentation, claims, intended use, dosage form, packaging ......


Czech Republic – non-harmonised category of veterinary non-medicinal products under the veteinary act In-vitro diagnostics

Diagnosis of infectious agents Food-borne diseases

Disinfectans External treatment of intact skin or externally accesible

mucosae Minor skin injuries, operation field, disinfection of udder

Dietetics Vitamin / mineral products Cosmetic products


Still different approach in different Member States formation of a „bordeline products“ subgroup

under the CMDv



„MAY“ provisions (1)

„MAY“ provisions – may be implemented if deemed necessary by the Member States for implementation of the national policies – examples Possibility to exclude life autogenous vaccinnes from the

scope of directive (Art. 4) Possibility to exempt certain products for aquarium fish,

cage birds, homing pigeons, terrarium animals, small rodents, and ferrets and rabbits kept exclusively as pets from the authorisation (Art. 4)

Authorisation of marketing of products for which a MA has been granted by another Member States, where health situation so requires (Art. 7)


Provisional use of immunological products without MA in case of serious epizootic diseases (Art. 8)

Use of immunological VMPs authorised in the 3rd country for animals imported/exported to/from the 3rd country (Art. 8)

Specific rules for safety and pre-clinical and clinical trials of homeopathic VMPs

„Blue box“ information to be indicated at the outer packagings of veterinary medicinal products authorised under 726/2004 (Art. 58)

Exemption of labels / package leaflets for specific VMPs to be in the official language of a Member State (Art. 61)


Prohibition of the manufacture, import, possession, sale, supply and/or use of immunological veterinary medicinal products on the whole or part of its territory under specific circumstances (Art. 71)

Pharmacovigilance reporting – specific requirements on veterinary practitioners and other health professionals (Art.72)

Susension of product due to pharmacovigilance (Art. 78)

OCABR / OBPR for veterinary immunologicals (Art. 81, 82)

Activities at the EU level EC

Veterinary Pharmaceutical Committee Standing Committee for Veterinary Medicinal Products Notice to Applicants Legislation Other (WHO / Codex, AMR ....)

EMA CVMP Working parties

Guidelines Advisory groups Contribution to international activities

VICH Codex

3Rs

Activities at the EU level

HMA http://www.hma.eu/ Policies / strategies Optimisation of the regulatory network function Co-ordination of activities / co-operation

PSUR worksharing Antiicrobial resistance issues (AMR) Availability of veterinary medicinal products

Contribution to the development of the EU regulatory environment Task force – veterinary legislation

National policies / activities (1)

Areas conferred on the Member State in accordance with the EU law subsidiarity principle

„May“ provisions Use of VMPs Prescription habits

National policies / activities (2) Immunologicals

Veterinary autogenous vaccines Availability – MU/MS Clinical trials Antimicrobial resistance Novel therapies

Cells, tissues

National policies / activities (3) Legal categories of VMPs Distribution / retail channels Fees Other scientific activities

Thank you for your attention !

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Documents

The role and tasks of the National Medicines Agencies