Source: http://www.europarl.europa.eu/sides/getDoc.do?type=REPORT&reference=A6-2007-0031&language=RO
Timestamp: 2013-05-24 16:46:55+00:00
Document Index: 37679359

Matched Legal Cases: ['Articolul 47', 'articolul 251', 'articolul 95', 'articolul 5', 'Articolul 1', 'ARTICOLUL 2', 'ARTICOLUL 2', 'ARTICOLUL 2', 'ARTICOLUL 2', 'ARTICOLUL 2', 'ARTICOLUL 4', 'articolul 26', 'articolul 26', 'ARTICOLUL 5', 'articolul 26', 'articolul 6', 'articolul 6', 'articolul 26', 'articolul 7', 'articolul 26', 'articolul 7', 'articolul 62', 'articolul 62', 'ARTICOLUL 9', 'ARTICOLUL 9', 'articolul 6', 'articolul 6', 'articolul 9', 'articolul 5', 'articolul 5', 'ARTICOLUL 10', 'articolul 6', 'articolul 11', 'ARTICOLUL 15', 'ARTICOLUL 15', 'articolul 57', 'articolul 57', 'Articolul 19', 'Articolul 19', 'Articolul 19', 'ARTICOLUL 19', 'Articolul 19', 'ARTICOLUL 21', 'ARTICOLUL 21', 'articolul 65', 'articolul 63', 'articolul 63', 'ARTICOLUL 23', 'ARTICOLUL 23', 'articolul 18', 'ARTICOLUL 23', 'articolul 17', 'articolul 57', 'articolul 26', 'articolul 26', 'ARTICOLUL 25', 'ARTICOLUL 25', 'ARTICOLUL 26', 'articolul 5', 'articolul 7', 'ARTICOLUL 27', 'Articolul 13', 'articolul 13', 'ARTICOLUL 27', 'ARTICOLUL 28', 'Articolul 1', 'articolul 1', 'articolul 2', 'ARTICOLUL 28', 'Articolul 3', 'ARTICOLUL 28', 'Articolul 4', 'ARTICOLUL 29', 'articolul 30', 'ARTICOLUL 29', 'articolul 3', 'articolul 26', 'ARTICOLUL 30', 'articolul 178']

RAPORT referitor la propunerea de regulament al Parlamentului European şi al Consiliului privind medicamentele pentru terapie avansată şi de modificare a Directivei 2001/83/CE şi a Regulamentului (CE) nr. 726/2004 - A6-0031/2007
Procedură : 2005/0227(COD)Stadiile documentului în şedinţăStadii ale documentului :
A6-0031/2007Texte depuse :
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7 februarie 2007PE 380.740v02-00 A6-0031/2007
referitor la propunerea de regulament al Parlamentului European şi al Consiliului privind medicamentele pentru terapie avansată şi de modificare a Directivei 2001/83/CE şi a Regulamentului (CE) nr. 726/2004
(COM(2005)0567 – C6-0401/2005 – 2005/0227(COD))
Comisia pentru mediu, sănătate publică şi siguranţă alimentară
Raportor: Miroslav Mikolášik
Raportoare pentru aviz (*): Hiltrud Breyer, Comisia pentru afaceri juridice
(*) Cooperarea consolidată între comisii - Articolul 47 din Regulamentul de procedură
(Procedura de codecizie: prima lectură)
– având în vedere propunerea Comisiei înaintată Parlamentului European şi Consiliului (COM(2005)0567)(1),
– având în vedere articolul 251 alineatul (2) şi articolul 95 din Tratatul CE, în temeiul cărora propunerea a fost prezentată de către Comisie (C6-0401/2005),
– având în vedere raportul Comisiei pentru mediu, sănătate publică şi siguranţă alimentară şi avizele Comisiei pentru industrie, cercetare şi energie şi al Comisiei pentru afaceri juridice (A6-0031/2007),
2. solicită Comisiei să îl sesizeze din nou, în cazul în care intenţionează să modifice în mod substanţial această propunere sau să o înlocuiască cu un alt text;
3. încredinţează Preşedintelui sarcina de a transmite Consiliului şi Comisiei poziţia Parlamentului.
(2) În măsura în care aceste produse pentru terapie avansată sunt prezentate ca având proprietăţi pentru tratarea sau prevenirea bolilor organismului uman sau ca putând fi utilizate sau administrate oamenilor, în vederea refacerii, corectării sau modificării funcţiilor fiziologice, prin exercitarea unei acţiuni farmacologice, imunologice sau metabolice, ele sunt medicamente biologice în sensul articolului 1 alineatul (2) şi al anexei I la Directiva 2001/83/CE a Parlamentului European şi a Consiliului din 6 noiembrie 2001 de instituire a unui cod comunitar cu privire la medicamentele de uz uman. Astfel, obiectivul esenţial al normelor de reglementare a producţiei, distribuţiei şi utilizării acestora trebuie să fie acela de protejare a sănătăţii publice.
(2) În măsura în care aceste produse pentru terapie avansată sunt prezentate ca având proprietăţi pentru tratarea sau prevenirea bolilor organismului uman sau ca putând fi utilizate sau administrate oamenilor, în vederea refacerii, corectării sau modificării funcţiilor fiziologice, prin exercitarea în principal a unei acţiuni farmacologice, imunologice sau metabolice, ele sunt medicamente biologice în sensul articolului 1 alineatul (2) şi al anexei I la Directiva 2001/83/CE a Parlamentului European şi a Consiliului din 6 noiembrie 2001 de instituire a unui cod comunitar cu privire la medicamentele de uz uman. Astfel, obiectivul esenţial al normelor de reglementare a producţiei, distribuţiei şi utilizării acestora trebuie să fie acela de protejare a sănătăţii publice.
The Medical Devices Directives (MDD) provide a regulatory framework which is readily adapted to the control of devices containing or made of tissue engineered products. If a tissue engineered product falls within the definition of ‘medical device’ in Article 1 of the MDD (and therefore does not have a mode of action which is primarily pharmacological, immunological or metabolic), it should be regulated under the MDD although additional specific requirements may be necessary.
(5) Medicamentele pentru terapie avansată ar trebui reglementate în măsura în care se intenţionează introducerea acestora pe piaţă în statele membre şi producerea lor, fie pe cale industrială, fie prin intermediul unei metode care implică un proces industrial în sensul articolului 2 alineatul (1) din Directiva 2001/83/CE. Medicamentele pentru terapie avansată care sunt atât preparate în întregime cât şi utilizate într-un spital, în conformitate cu o prescripţie medicală pentru un pacient individual, ar trebui excluse din domeniul de aplicare a prezentului regulament.
(5) Prezentul regulament reprezintă o „lex specialis”, care introduce dispoziţii suplimentare faţă de cele stipulate în Directiva 2001/83/CE. Domeniul de aplicare a prezentului regulament ar trebui să fie reglementarea medicamentelor pentru terapie avansată destinate introducerii pe piaţă în statele membre şi preparării industriale sau producerii printr-o metodă care implică un proces industrial, în conformitate cu obiectivul general al legislaţiei comunitare în domeniul farmaceutic stipulate în titlul II din Directiva 2001/83/CE. Medicamentele pentru terapie avansată care sunt preparate în întregime într-un spital, în mod gratuit, după metode specifice, nenormalizate şi nepatentate, şi utilizate într-un spital, în conformitate cu o prescripţie medicală pentru un pacient individual aflat sub responsabilitatea profesională exclusivă a unui medic sau în cadrul unui studiu clinic, ar trebui excluse din domeniul de aplicare a prezentului regulament.
It should be clarified that this Regulation is a lex specialis in relation to Dir. 2001/83/EC, as it introduces additional requirements that are specific to ATMP. The scope of this Regulation is the general scope of the pharmaceutical legislation, as laid down in Dir. 2001/83/EC. Where hospitals or other institutions prepare products using an established process to create treatments for patients on a routine basis, they should have to comply with the provisions of this Regulation. However, when hospitals produce ATMP for research purposes or on an exceptional, one-off basis, they should not have to comply with the centralised authorisation procedure.
(6) Reglementarea medicamentelor pentru terapie avansată la nivel comunitar nu trebuie să aducă atingere deciziilor adoptate de statele membre cu privire la autorizarea sau nu a utilizării oricărui tip specific de celule umane, cum ar fi celulele stem embrionare, sau celulele animale. De asemenea, nu ar trebui să aducă atingere aplicării legislaţiei naţionale care interzice sau restricţionează vânzarea, furnizarea sau utilizarea medicamentelor care conţin, sunt alcătuite sau derivate din aceste celule.
(6) Legislaţia în vigoare în statele membre privind utilizarea anumitor tipuri de celule, precum celulele stem embrionare, diferă în mod considerabil. Reglementarea medicamentelor pentru terapie avansată la nivel comunitar nu trebuie să aducă atingere deciziilor adoptate de statele membre cu privire la autorizarea sau nu a utilizării oricărui tip specific de celule. De asemenea, nu ar trebui să aducă atingere aplicării legislaţiei naţionale care interzice sau restricţionează vânzarea, furnizarea sau utilizarea medicamentelor care conţin, sunt alcătuite sau derivate din aceste celule. Mai mult, este imposibil de evaluat când cercetarea privind aceste celule va ajunge la stadiul în care produsele comerciale concepute pe baza acestor celule ar putea fi introduse pe piaţă şi nici dacă acest lucru se va întâmpla. În vederea respectării principiilor de bază şi a funcţionării corespunzătoare a pieţei interne şi pentru a garanta siguranţa juridică, prezentul regulament ar trebui să se aplice numai produselor concepute din celule pentru care comercializarea este posibilă într-un viitor apropiat şi care nu va genera controverse majore. Justification
JURI amendment, which was incorporated in the report without vote following Rule 47. The legal base of this regulation (Article 95 TEC) is a single market harmonisation measure. It is not designed to cover situations in which significant national legislative differences are intended to remain (c.f. ECJ Case C-376/98). It is therefore necessary to exclude from the scope of this regulation products using materials which are controversial and for which differing Member States legislative provisions are intended to remain. In any case, products using these materials are unlikely to be ready to be placed on the market in the foreseeable future.
(9) Evaluarea medicamentelor pentru terapie avansată necesită adesea cunoştinţe foarte specializate, care depăşesc sectorul farmaceutic tradiţional şi acoperă arii care se află la graniţa cu alte sectoare, precum biotehnologia şi dispozitivele medicale. Din această cauză, se cuvine crearea, în cadrul Agenţiei, a unui Comitet pentru terapii avansate, pe care Comitetul pentru medicamente de uz uman al Agenţiei ar trebui să îl consulte, în scopul evaluării datelor privitoare la medicamentele pentru terapie avansată, înainte ca acesta să emită un aviz ştiinţific definitiv. Mai mult, Comitetul pentru terapii avansate poate fi consultat pentru evaluarea oricărui alt medicament care necesită cunoştinţe specializate, care ţin de domeniul său de competenţă.
(9) Evaluarea medicamentelor pentru terapie avansată necesită adesea cunoştinţe foarte specializate, care depăşesc sectorul farmaceutic tradiţional şi acoperă arii care se află la graniţa cu alte sectoare, precum biotehnologia şi dispozitivele medicale. Din această cauză, se cuvine crearea, în cadrul Agenţiei, a unui Comitet pentru terapii avansate, care ar trebui să fie responsabil cu elaborarea unui proiect de aviz privind calitatea, siguranţa şi eficienţa fiecărui medicament pentru terapie avansată în vederea aprobării finale a Comitetului pentru medicamente de uz uman al Agenţiei. Mai mult, Comitetul pentru terapii avansate ar trebui consultat pentru evaluarea oricărui alt medicament care necesită cunoştinţe specializate, care ţin de domeniul său de competenţă.
Due to a highly specific and unique character of the advanced therapy medicinal products, a new Committee for Advanced Therapies is established within EMEA and composed of experts having specific qualifications or experience in this highly innovative and quickly developing field. Therefore, the new structure should be responsible for drafting an opinion on the quality, safety, and efficacy of products for the final approval by the CHMP. Furthermore, the committee should be consulted for the evaluation of other products under its competence. Amendamentul 5
(10) Comitetul pentru terapii avansate trebuie să reunească cea mai buni experţi în domeniul medicamentelor pentru terapie avansată care există la nivel comunitar. Structura Comitetului pentru terapii avansate trebuie să asigure o acoperire adecvată a sectoarelor ştiinţifice corespunzătoare terapiilor avansate, inclusiv terapia genică, terapia celulară, ingineria tisulară, dispozitivele medicale, farmacovigilenţa şi etica. Asociaţiile de pacienţi şi medicii cu experienţă ştiinţifică în domeniul medicamentelor pentru terapie avansată trebuie, de asemenea, să fie reprezentate.
(10) Comitetul pentru terapii avansate trebuie să reunească cea mai buni experţi în domeniul medicamentelor pentru terapie avansată care există la nivel comunitar. Structura Comitetului pentru terapii avansate trebuie să asigure o acoperire adecvată a sectoarelor ştiinţifice corespunzătoare terapiilor avansate, inclusiv terapia genică, terapia celulară, ingineria tisulară, dispozitivele medicale, farmacovigilenţa şi etica. Asociaţiile de pacienţi şi medicii cu experienţă ştiinţifică în domeniul medicamentelor pentru terapie avansată trebuie, de asemenea, să fie reprezentate. Justification
In order to cover all other medical fields which the advanced therapies may relate to, the Committee for Advanced Therapies should be represented by a more general medical expertise.
(14) În principiu, celulele sau ţesuturile umane conţinute de medicamentele pentru terapie avansată ar trebui obţinute prin donare voluntară şi gratuită. Donările voluntare şi gratuite de ţesut şi celule constituie un factor care poate contribui la standarde de securitate înalte pentru ţesuturi şi celule şi astfel la protecţia sănătăţii umane.
(14) În ceea ce priveşte donările de celule sau ţesuturi umane, principiile europene precum anonimatul atât al donatorului cât şi al primitorului, şi solidaritatea dintre donator şi primitor ar trebui respectate. În principiu, celulele sau ţesuturile umane conţinute de medicamentele pentru terapie avansată ar trebui obţinute prin donaţie voluntară şi gratuită. Statele membre sunt îndemnate să ia toate măsurile necesare pentru încurajarea unei implicări puternice a sectorului public şi non-profit în obţinerea de celule sau ţesuturi umane, deoarece donările voluntare şi gratuite de ţesut şi celule pot contribui la standarde de securitate înalte pentru ţesuturi şi celule, şi astfel la protecţia sănătăţii umane.
(15) Studiile clinice asupra medicamentelor pentru terapie avansată ar trebui efectuate în conformitate cu principiile şi cerinţele etice stabilite în Directiva 2001/20/CE a Parlamentului European şi a Consiliului din 4 aprilie 2001 de apropiere a actelor cu putere de lege şi a actelor administrative ale statelor membre privind aplicarea bunelor practici clinice în cazul efectuării de studii clinice pentru evaluarea produselor medicamentoase de uz uman. Cu toate acestea, ar trebui stabilite norme specifice, care să adapteze Directiva 2005/28/CE din 8 aprilie 2005 de stabilire a principiilor şi a orientărilor detaliate privind aplicarea bunelor practici clinice în ceea ce priveşte medicamentele experimentale de uz uman, precum şi a cerinţelor pentru acordarea autorizaţiei de fabricaţie sau de import pentru astfel de produse, astfel încât să se ia în considerare, în totalitate, caracteristicile tehnice specifice ale medicamentelor pentru terapie avansată.
(15) Studiile clinice asupra medicamentelor pentru terapie avansată ar trebui efectuate în conformitate cu principiile şi cerinţele etice stabilite în Directiva 2001/20/CE a Parlamentului European şi a Consiliului din 4 aprilie 2001 de apropiere a actelor cu putere de lege şi a actelor administrative ale statelor membre privind aplicarea bunelor practici clinice în cazul efectuării de studii clinice pentru evaluarea produselor medicamentoase de uz uman. Cu toate acestea, ar trebui stabilite norme specifice, care să adapteze Directiva 2005/28/CE din 8 aprilie 2005 de stabilire a principiilor şi a orientărilor detaliate privind aplicarea bunelor practici clinice în ceea ce priveşte medicamentele experimentale de uz uman, precum şi a cerinţelor pentru acordarea autorizaţiei de fabricaţie sau de import pentru astfel de produse, astfel încât să se ia în considerare, în totalitate, caracteristicile tehnice specifice ale medicamentelor pentru terapie avansată. Ar trebui prevăzute cerinţe specifice de fabricare pentru medicamentele experimentale aplicabile producţiei de medicamente pentru terapie avansată destinate studiilor clinice efectuate în acelaşi spital în care a avut loc producţia. Aceste norme ar trebui să garanteze un interval de timp adecvat între studiile clinice unice (inclusiv studiile clinice din mai multe centre), precum şi supravegherea coordonată şi schimbul de informaţii.
No specific provision is foreseen in the regulation as far as the production of advanced therapy medicinal products to be used in clinical trials performed in the same hospital where the production took place is concerned. Moreover, clinical trials should be conducted in the safest possible manner (adequate time interval, etc). Amendamentul 8
(16) Fabricarea medicamentelor pentru terapie avansată trebuie să se efectueze în conformitate cu principiile de bună practică de fabricaţie, astfel cum au fost stabilite în Directiva 2003/94/CE a Comisiei din 8 octombrie 2003 de stabilire a principiilor şi orientărilor privind buna practică de fabricaţie cu privire la produsele medicamentoase de uz uman şi medicamentele experimentale de uz uman. În plus, ar trebui stabilite orientări specifice pentru medicamentele pentru terapie avansată, astfel încât natura specifică a acestui proces de fabricaţie să fie reflectată în mod adecvat.
(16) Fabricarea medicamentelor pentru terapie avansată trebuie să se efectueze în conformitate cu principiile de bună practică de fabricaţie, astfel cum au fost stabilite în Directiva 2003/94/CE a Comisiei din 8 octombrie 2003 de stabilire a principiilor şi orientărilor privind buna practică de fabricaţie cu privire la produsele medicamentoase de uz uman, şi medicamentele experimentale de uz uman, şi adaptate, unde este cazul, pentru a reflecta natura specifică a produselor. În plus, ar trebui stabilite orientări specifice pentru medicamentele pentru terapie avansată, astfel încât natura specifică a acestui proces de fabricaţie să fie reflectată în mod adecvat.
Advanced Therapy medicinal products have specific characteristics that differ greatly from traditional medicinal products. That leads to important differences in their manufacturing process (e.g. in Article 11.4. the GMP Directive requires that sample batches of finished products should be kept for 1 year after expiry date. It is, however, difficult to consider expiry dates for certain classes of ATMPs).
(17) Medicamentele pentru terapie avansată pot încorpora dispozitive medicale sau dispozitive medicale active implantabile. Aceste dispozitive trebuie să satisfacă cerinţele esenţiale prevăzute în Directiva 93/42/CEE a Consiliului din 14 iunie 1993 privind dispozitivele medicale şi, respectiv, Directiva 90/385/CEE a Consiliului din 20 iunie 1999 privind apropierea legislaţiilor statelor membre referitoare la dispozitivele medicale active implantabile, în vederea asigurării unui nivel adecvat de calitate şi siguranţă.
(17) Medicamentele pentru terapie avansată pot încorpora dispozitive medicale sau dispozitive medicale active implantabile. Aceste dispozitive trebuie să satisfacă cerinţele esenţiale prevăzute în Directiva 93/42/CEE a Consiliului din 14 iunie 1993 privind dispozitivele medicale şi, respectiv, Directiva 90/385/CEE a Consiliului din 20 iunie 1999 privind apropierea legislaţiilor statelor membre referitoare la dispozitivele medicale active implantabile, în vederea asigurării unui nivel adecvat de calitate şi siguranţă. La evaluarea unui produs combinat, realizată în conformitate cu prezentul regulament, Agenţia ar trebui să ia în calcul, dacă sunt disponibile, rezultatele evaluării dispozitivului medical sau a dispozitivului medical activ implantabil, efectuată de către un organ autorizat în conformitate cu directivele respective. Justification
In order to ensure the continuous utilisation of the vast experience and expertise of the notified bodies on the evaluation of medical devices or active implantable medical devices, the notified bodies may assess the medical device or the active implantable medical device part of the combined advanced therapy medicinal product. In that case, the Agency should take into account the results of these assessments in its final evaluation of the combined product.
(18) Ar trebui stabilite norme specifice, care să adapteze cerinţele Directivei 2001/83/CE privind rezumatul caracteristicilor produsului, etichetarea şi prospectul însoţitor la specificaţiile tehnice ale medicamentelor pentru terapie avansată.
(18) Ar trebui stabilite norme specifice, care să adapteze cerinţele Directivei 2001/83/CE privind rezumatul caracteristicilor produsului, etichetarea şi prospectul însoţitor la specificaţiile tehnice ale medicamentelor pentru terapie avansată. Aceste norme ar trebui să respecte pe deplin dreptul pacientului de a cunoaşte originea tututor celulelor sau ţesuturilor utilizate în prepararea medicamentelor pentru terapie avansată, respectându-se, în acelaşi timp, anonimatul donatorului.
(19) Urmărirea stării pacientului pe termen lung şi farmacovigilenţa sunt aspecte de o deosebită importanţă ale medicamentelor pentru terapie avansată. Prin urmare, atunci când acest lucru este justificat de motive de sănătate publică, trebuie să i se solicite titularului autorizaţiei de introducere pe piaţă crearea unui sistem adecvat de gestionare a riscului, în vederea abordării acestor aspecte.
(19) Urmărirea eficacităţii şi a efectelor secundare sunt aspecte de o deosebită importanţă ale medicamentelor pentru terapie avansată. Prin urmare, în cererea de autorizaţie de introducere pe piaţă, solicitantul ar trebui să prezinte în detaliu posibilele măsuri avute în vedere pentru garantarea acestei urmăriri. Atunci când acest lucru este justificat de motive de sănătate publică, trebuie să i se solicite titularului autorizaţiei de introducere pe piaţă şi crearea unui sistem adecvat de gestionare a riscului, în vederea abordării riscurilor legate de medicamentele pentru terapie avansată.
This amendment would ensure a better coherence with existing pharmaceutical legislation and a high standard of pharmacovigilance.
CONSIDERENTUL 19A (nou)
(19a) Funcţionarea prezentului regulament necesită elaborarea de orientări, fie de către Agenţie fie de către Comisie. În ambele cazuri, trebuie iniţiată o consultare deschisă cu toate părţile interesate, în special cu industria, în vederea punerii în comun a competenţelor limitate în acest domeniu şi a garantării proporţionalităţii. Justification
When drawing up guidelines for the implementation of this Regulation, principles of open consultation with all interested parties, in particular the industry should be enacted in order to allow a pooling of the limited expertise in this area and ensure proportionality.
(21) Având în vedere că ştiinţa evoluează rapid în acest domeniu, companiile care dezvoltă medicamente pentru terapie avansată ar trebui să poată solicita avizul ştiinţific al Agenţiei, inclusiv avize privind activităţile ulterioare obţinerii autorizaţiei. Pentru a stimula acest lucru, taxa pentru avize ştiinţifice ar trebui menţinută la un nivel minim.
(21) Având în vedere că ştiinţa evoluează rapid în acest domeniu, companiile care dezvoltă medicamente pentru terapie avansată ar trebui să poată solicita avizul ştiinţific al Agenţiei, inclusiv avize privind activităţile ulterioare obţinerii autorizaţiei. Pentru a stimula acest lucru, taxa pentru avize ştiinţifice ar trebui menţinută la un nivel minim pentru întreprinderile mici şi mijlocii şi, de asemenea, ar trebui redusă pentru alţi solicitanţi.
This Regulation seeks to encourage and support SMEs in the development of ATMPs. Therefore, it is necessary to introduce special fee-waivers applicable to SMEs on scientific advice.
(22) Ar trebui să fie de competenţa Agenţiei să facă recomandări ştiinţifice privind compatibilitatea sau incompatibilitatea unui anumit produs, care are la bază celule sau ţesuturi, cu criteriile ştiinţifice care definesc medicamentele pentru terapie avansată, în vederea abordării, cât mai curând posibil, a problemelor de intersectare cu alte domenii de activitate, precum dispozitivele medicale sau produsele cosmetice, care pot apărea odată cu evoluţia ştiinţei. (22) Ar trebui să fie de competenţa Agenţiei să facă recomandări ştiinţifice privind compatibilitatea sau incompatibilitatea unui anumit produs, care are la bază gene, celule sau ţesuturi, cu criteriile ştiinţifice care definesc medicamentele pentru terapie avansată, în vederea abordării, cât mai curând posibil, a problemelor de intersectare cu alte domenii de activitate, precum dispozitivele medicale sau produsele cosmetice, care pot apărea odată cu evoluţia ştiinţei. Comitetul pentru terapii avansate cu competenţele sale unice, ar trebui să joace un rol important în furnizarea acestor avize. Justification
Due to its specific expertise in advanced therapy medicinal products, the Committee for Advanced Therapies should be instrumental in providing advice to operators on whether a product is or is not an advanced therapy medicinal product.
(24) Pentru a lua în considerare progresele ştiinţifice şi tehnice, ar trebui să-i fie conferită Comisiei competenţa de a adopta orice schimbări necesare cu privire la cerinţele tehnice pentru cererile de autorizaţie de introducere pe piaţă a medicamentelor pentru terapie avansată, rezumatul caracteristicilor produsului, etichetarea sau prospectul însoţitor al acestuia.
(24) Pentru a lua în considerare progresele ştiinţifice şi tehnice, ar trebui să-i fie conferită Comisiei competenţa de a adopta orice schimbări necesare cu privire la cerinţele tehnice pentru cererile de autorizaţie de introducere pe piaţă a medicamentelor pentru terapie avansată, rezumatul caracteristicilor produsului, etichetarea sau prospectul însoţitor al acestuia. Comisia ar trebui să se asigure că informaţiile relevante privind măsurile planificate sunt puse, în cel mai scurt timp, la dispoziţia părţilor interesate.
Better predictability of future regulations is of the greatest importance for industry in order to make well-planned and cost-effective investments in R&D and production. Therefore, relevant information about envisaged measures should be made known as quickly as possible.
(27) Măsurile necesare pentru punerea în aplicare a prezentului regulament ar trebui adoptate în conformitate cu Decizia 1999/468/CE a Consiliului din 28 iunie 1999 de stabilire a normelor privind exercitarea competenţelor de executare conferite Comisiei.
(27) Măsurile necesare pentru punerea în aplicare a prezentului regulament ar trebui adoptate în conformitate cu Decizia 1999/468/CE a Consiliului din 28 iunie 1999 de stabilire a normelor privind exercitarea competenţelor de executare conferite Comisiei. Procedura de reglementare cu control prevăzută la articolul 5a din decizia respectivă ar trebui să se aplice pentru adoptarea amendamentelor la anexele II-IV la prezentul regulament şi la anexa I la Directiva 2001/83/CE. Întrucât aceste măsuri sunt esenţiale pentru funcţionarea adecvată a întregului cadru de reglementare, ele ar trebui adoptate rapid, în termen de 9 luni de la intrarea în vigoare a prezentului regulament.
Manufacturers will not be in a position to design development protocols until the technical requirements are published and the adaptations of the Good Clinical Practice Directive and the Good Manufacturing Practice Directive are finalised. Therefore, we propose 9 months time limit for the Commission to adopt the necessary measures.
Articolul 1a
Prezentul regulamennt nu se aplică medicamentelor pentru terapie avansată care conţin sau sunt derivate din celulele embrionare sau fetale umane, celulele germinale primordiale sau de la celulele derivate din aceste celule.
JURI amendment, which was incorporated in the report without vote following Rule 47. The legal base of this regulation (Article 95 TEC) is a single market harmonisation measure. It is not designed to cover situations in which significant national legislative differences are intended to remain (c.f. ECJ Case C-376/98). Amendamentul 18
ARTICOLUL 2 ALINEATUL (1) LITERA (B) PARTEA INTRODUCTIVĂ
(b) „produs care provine din ingineria tisulară” înseamnă un produs care: (b) „produs care provine din ingineria tisulară” înseamnă un produs medicinal care: Justification
ARTICOLUL 2 ALINEATUL (1) LITERA (B) PARAGRAFUL 2A (nou)
Produsele care conţin sau sunt concepute exclusiv din celule şi/sau ţesuturi umane sau animale neviabile, care nu conţin celule sau ţesuturi viabile şi a căror acţiune principală nu este una farmacologică, imunologică sau metabolică, nu sunt incluse în această definiţie. Justification
ARTICOLUL 2 ALINEATUL (1) LITERA (D) LINIUŢA 2A (nouă)
- partea sa celulară sau tisulară conţine celule sau ţesuturi viabile; sau
For the purposes of this Regulation, the most important criterion when defining a combined advanced therapy medicinal product should be the viability of its cellular or tissue part. For the patient's safety and the high standards of the evaluation of a product, a combined product should be always classified as an advanced therapy medicinal product when it contains viable tissues or cells.
ARTICOLUL 2 ALINEATUL (1) LITERA (D) A DOUA LINIUŢĂ
- partea sa celulară sau tisulară trebuie să poată exercita asupra organismului uman o acţiune care nu poate fi considerată ca auxiliară celei a dispozitivelor menţionate.
- partea sa celulară sau tisulară care conţine celule sau ţesuturi neviabile trebuie să poată exercita asupra organismului uman o acţiune care poate fi considerată ca esenţială faţă de cea a dispozitivelor menţionate.
A combined product should always be considered as advanced therapy medicinal product when it contains non-viable cells or tissues which act upon human body in a manner that is considered as primary to the action of the device part of the product concerned.
ARTICOLUL 2 ALINEATUL (1) PARAGRAFUL 1A (nou)
În cazul în care un produs conţine celule sau ţesuturi viabile, acţiunea farmacologică, imunologică sau metabolică a acestor celule sau ţesuturi este considerată principalul mod de acţiune a produsului.
This new provision clarifies the rule concerning products which contain viable cells or tissues, whilst maintaining in principle the criterion of “primary mode of action” for borderline classification. For the patient's safety and the high standards of the evaluation of a combined product, the most important criterion should be the viability of the cellular or tissue part of such a product. Amendamentul 23
ARTICOLUL 4 ALINEATELE (2) ŞI (3)
(2) Comisia modifică, în conformitate cu procedura stabilită la articolul 26 alineatul (2), Directiva 2005/28/CE, pentru a lua în considerare caracteristicile specifice ale medicamentelor pentru terapie avansată.
(2) Comisia modifică, în urma consultării cu Agenţia şi în conformitate cu procedura stabilită la articolul 26 alineatul (2), Directiva 2005/28/CE, pentru a lua în considerare caracteristicile specifice ale medicamentelor pentru terapie avansată.
(3) Comisia stabileşte orientări detaliate pentru bunele practici clinice specifice medicamentelor pentru terapie avansată.
(3) Comisia stabileşte, în urma consultării cu Agenţia, orientări detaliate pentru bunele practici clinice specifice medicamentelor pentru terapie avansată.
The Regulation should set out very clearly that the Commission must involve the EMEA, through the Committee for Advanced Therapies, whenever good clinical practice requirements need to be amended or guidelines related to advanced therapy medicinal products need to be drawn up.
ARTICOLUL 5 ALINEATUL (-1) (nou)
Comisia modifică, în conformitate cu procedura stabilită la articolul 26 alineatul (2), Directiva 2003/94/CE, pentru a lua în considerare caracteristicile specifice ale medicamentelor pentru terapie avansată şi, în special, produsele care provin din ingineria tisulară.
Advanced therapy medicinal products have specific characteristics that differ greatly from traditional medicinal products. That leads to important differences in their manufacturing process (e.g. Article 11.4. of the GMP Directive requires that sample batches of finished products should be kept for 1 year after the expiry date. It is, however, difficult to consider expiry dates for certain classes of ATMPs).
Comisia publică orientări detaliate, în conformitate cu principiile de bune practici de fabricaţie şi specifice medicamentelor pentru terapie avansată.
Comisia elaborează orientări detaliate, în conformitate cu principiile de bune practici de fabricaţie şi specifice medicamentelor pentru terapie avansată
For the sake of consistency, the wording should be put in line with the equivalent provision in Article 4(3).
Cerinţe specifice pentru produsele care provin din ingineria tisulară
Cerinţe specifice pentru medicamentele pentru terapie avansată care conţin dispozitive
Pe lângă cerinţele stabilite la articolul 6 alineatul (1) din Regulamentul (CE) nr. 726/2004, cererile de autorizare pentru un produs care provine din ingineria tisulară trebuie să includă o descriere a caracteristicilor fizice şi a performanţei produsului şi o descriere a metodelor de concepere a produsului, în conformitate cu anexa I la Directiva 2001/83/CE.
Pe lângă cerinţele stabilite la articolul 6 alineatul (1) din Regulamentul (CE) nr. 726/2004, cererile de autorizare pentru un medicament pentru terapie avansată care conţine dispozitive medicale, biomateriale, substanţe chimice sau matrice trebuie să includă o descriere a caracteristicilor fizice şi a performanţei produsului şi o descriere a metodelor de concepere a produsului, în conformitate cu anexa I la Directiva 2001/83/CE.
The scope of this article should be clarified and amended to encompass all those products in need of these specific requirements. Restricting the requirements to tissue engineered products would exclude those advanced therapy medicinal products that also have special physical characteristics possibly affecting the performance of the product. However, extending these requirements to all advanced therapy products would create unnecessary work for enterprises; all advanced therapy products do not have special physical characteristics that could affect their performance.
Comisia modifică, în conformitate cu procedura stabilită la articolul 26 alineatul (2) din prezentul regulament, anexa I la Directiva 2001/83/CE, în vederea stabilirii cerinţelor tehnice specifice produselor care provin din ingineria tisulară, în special cele prevăzute la articolul 7, cu scopul de a lua în considerare evoluţia ştiinţei şi tehnicii.
Comisia modifică, în urma consultării Agenţiei şi în conformitate cu procedura stabilită la articolul 26 alineatul (2a) din prezentul regulament, anexa I la Directiva 2001/83/CE, în vederea stabilirii cerinţelor tehnice specifice produselor care provin din ingineria tisulară, în special cele prevăzute la articolul 7, cu scopul de a lua în considerare evoluţia ştiinţei şi tehnicii.
The Regulation should set out very clearly that the Commission must involve the EMEA, through the Committee for Advanced Therapies, whenever the technical requirements laid down in Annex I to Directive 2001/83/EC need to be amended.
(2) Raportorul sau coraportorul numit de Comitetul pentru medicamente de uz uman, în conformitate cu articolul 62 din Regulamentul (CE) nr. 726/2004 este membru al Comitetului pentru terapii avansate. Acest membru este, de asemenea, raportor sau coraportor al Comitetului pentru terapii avansate.
Raportorul sau coraportorul numit de Comitetul pentru medicamente de uz uman, în conformitate cu articolul 62 din Regulamentul (CE) nr. 726/2004 este membru al Comitetului pentru terapii avansate, propus de Comitetul pentru terapii avansate şi având competenţe specifice pentru produs.. Acest membru este, de asemenea, raportor sau coraportor al Comitetului pentru terapii avansate.
In order to ensure the highest level of expertise, the rapporteur and co-rapporteur appointed by the CHMP should be proposed by the Committee for Advanced Therapies and should have specific expertise for the relevant product. Amendamentul 29
ARTICOLUL 9 ALINEATUL (2A) (nou)
(2a) La elaborarea proiectului de aviz pentru aprobarea finală de către Comitetul pentru medicamente de uz uman, Comitetul pentru terapii avansate depune toate eforturile pentru a ajunge la un consens ştiinţific. Dacă nu se poate ajunge la niciun consens, Comitetul pentru terapii avansate adoptă poziţia majorităţii membrilor săi. Proiectul de aviz menţionează poziţiile divergente, precum şi motivele care stau la baza acestora.
In order to guarantee transparency in the process of preparation of a draft opinion, a clear decision procedure should be defined within Committee for Advanced Therapies. Consequently, we suggest that a scientific consensus should be reached by its members. Amendamentul 30
ARTICOLUL 9 ALINEATUL 2B (nou)
(2b) Raportorul sau coraportorul are dreptul de a se adresa direct solicitantului. De asemenea, solicitantul se poate oferi să fie întrebat. Raportorul sau coraportorul informează Comitetele implicate în scris, în cel mai scurt timp, cu privire la datele de contact ale solicitantului.
În cazul în care nu este de acord cu proiectul de aviz al Comitetului pentru terapii avansate, solicitantul poate prezenta, în termen de 15 zile de la primirea proiectului de aviz, observaţii scrise Comitetului pentru medicamente de uz uman. Înainte de emiterea avizului, solicitantul este audiat de Comitetul pentru medicamente de uz uman, în cazul în care solicitantul cere acest lucru în observaţiile sale scrise. Justification
The amendment aims at enhancing a more transparent procedure. Due to Article 9 (2) of Regulation (EC) No 726/2004 where the applicant is given the opportunity to request a re-examination of the opinion of the Committee for Medicinal Products for Human Use in giving written notice to the agency, an applicant receiving an opinion from the Committee of Advanced Therapies shall also receive the opportunity of appeal in order to ensure consistency within the Agency.
(3) Avizul oferit de Comitetul pentru terapii avansate, în conformitate cu alineatul (1), este transmis preşedintelui Comitetului pentru medicamente de uz uman, în timp util, astfel încât termenul limită prevăzut la articolul 6 alineatul (3) din Regulamentul (CE) nr. 726/2004 să poată fi respectat.
(3) Proiectul de aviz oferit de Comitetul pentru terapii avansate, în conformitate cu alineatul (1), este transmis preşedintelui Comitetului pentru medicamente de uz uman, în timp util, astfel încât termenul limită prevăzut la articolul 6 alineatul (3) sau la articolul 9 alineatul (2) din Regulamentul (CE) nr. 726/2004 să poată fi respectat.
Due to the highly specific and unique character of the advanced therapy medicinal products, a new Committee for Advanced Therapies is established within EMEA, composed of experts having specific qualifications or experience in this highly innovative and quickly developing field. Therefore, this new structure should be responsible for drafting an opinion on the quality, safety, and efficacy of products for the final approval by the CHMP. The draft opinion should be given in a timely manner so the deadline laid down in Article 9(2) of Regulation (EC) No 726/2004 can also be met. Amendamentul 32
(4) În cazul în care avizul ştiinţific cu privire la medicamentele pentru terapie avansată, întocmit de Comitetul pentru medicamente de uz uman, în conformitate cu articolul 5 alineatele (2) şi (3) din Regulamentul (CE) nr. 726/2004, nu este conform avizului Comitetului pentru terapii avansate, Comitetul pentru medicamente de uz uman anexează avizului său o explicaţie detaliată a argumentelor ştiinţifice pe care se bazează aceste diferenţe.
În cazul în care avizul ştiinţific cu privire la medicamentele pentru terapie avansată, întocmit de Comitetul pentru medicamente de uz uman, în conformitate cu articolul 5 alineatele (2) şi (3) din Regulamentul (CE) nr. 726/2004, nu este conform proiectului de aviz al Comitetului pentru terapii avansate, Comitetul pentru medicamente de uz uman anexează avizului său o explicaţie detaliată a argumentelor ştiinţifice pe care se bazează aceste diferenţe.
See the justification for the amendment of the Article 9, paragraph 3.
(1) În cazul în care este vorba despre un medicament combinat pentru terapie avansată, întreg produsul, inclusiv toate dispozitivele medicale sau dispozitivele medicale active implantabile încorporate în produs, este evaluat de Agenţie.
(1) În cazul în care este vorba despre un medicament combinat pentru terapie avansată, întreg produsul, inclusiv toate dispozitivele medicale sau dispozitivele medicale active implantabile încorporate în produs, este supus unei evaluări finale de Agenţie.
According to paragraph 2, a medical device or the active implantable medical device part of a combined advanced therapy medicinal product have to be assessed by a notified body in order to benefit from its extensive specific experience. The final evaluation should be carried out by the Agency who should incorporate the assessment of a notified body in its final opinion.
ARTICOLUL 10 ALINEATUL (1A) (nou)
(1a) Cererea de autorizaţie de introducere pe piaţă a medicamentelor combinate pentru terapie avansată include dovada de conformitate cu condiţiile esenţiale menţionate la articolul 6.
In accordance with Article 6 of the proposed Regulation, the device part of a combined advanced therapy medicinal product must meet the relevant device essential requirements. Evidence of conformity with these requirements should be provided in the marketing authorisation application.
(2) În cazul în care dispozitivul medical sau dispozitivul medical activ implantabil care face parte din medicamentul combinat pentru terapie avansată a fost deja evaluat de către un organ autorizat, în conformitate cu Directiva 93/42/CEE sau Directiva 90/385/CEE, Agenţia ia în considerare rezultatele acestei evaluări în propria evaluare a medicamentului respectiv.
(2) Cererea de autorizaţie de introducere pe piaţă a medicamentului combinat pentru terapie avansată include, dacă sunt disponibile, rezultatele evaluării de către un organ autorizat în conformitate cu Directiva 93/42/CEE sau Directiva 90/385/CEE a dispozitivului medical sau a dispozitivului medical activ implantabil. Agenţia ia în considerare rezultatele acestei evaluări în propria evaluare a medicamentului respectiv. Agenţia poate solicita organului autorizat respectiv să transmită orice informaţie referitoare la rezultatele evaluării efectuate de aceasta. Organul autorizat transmite informaţiile respective în termen de o lună. Agenţia poate solicita organului autorizat respectiv să transmită orice informaţie referitoare la rezultatele evaluării efectuate de aceasta. Organul autorizat transmite informaţiile respective în termen de o lună. În cazul în care cererea nu include rezultatele evaluării, Agenţia poate solicita avizul unui organ autorizat, identificat împreună cu solicitantul, privind conformitatea dispozitivului medical cu dispoziţiile din anexa I la Directiva 93/42/CEE sau din Directiva 90/385/CEE.
(2) Prospectul însoţitor trebuie să reflecte rezultatele consultărilor cu grupurile-ţintă de pacienţi, pentru a garanta că acesta este lizibil, clar şi uşor de folosit.
(2) În cazul în care produsele sunt administrate pacienţilor exclusiv de către medici, rezumatul caracteristicilor produsului în conformitate cu articolul 11 din Directiva 2001/83/CE poate fi utilizat ca prospect însoţitor.
Since the predominant majority of Advanced Therapy Medicinal Products will not come into the hands of patients but will be applied by medical practitioners directly, information about the therapy, especially in cases of autologous products, must be given to patients even before the starting material is removed. Therefore the possibility should be introduced to use the summary of product characteristics as package leaflet. Because the package will not come into the hand of patients the necessity for consultations with target patient groups could be deleted.
ARTICOLUL 15 TITLU
Gestionarea riscului după obţinerea autorizaţiei Urmărirea eficacităţii şi a efectelor secundare şi gestionarea riscului după obţinerea autorizaţiei Justification
This is a consequential amendment to amendment 38 (Article 15, paragraph 1).
(1) Pe lângă condiţiile de farmacovigilenţă prevăzute la articolele 21-29 din Regulamentul (CE) nr. 726/2004, solicitantul detaliază, în cererea de autorizaţie de introducere pe piaţă, măsurile care trebuie luate pentru a asigura urmărirea eficacităţii medicamentelor pentru terapie avansată.
(1) Pe lângă condiţiile de farmacovigilenţă prevăzute la articolele 21-29 din Regulamentul (CE) nr. 726/2004, solicitantul detaliază, în cererea de autorizaţie de introducere pe piaţă, măsurile care trebuie luate pentru a asigura urmărirea eficacităţii medicamentelor pentru terapie avansată şi a efectelor secundare.
ARTICOLUL 15 ALINEATUL (2) PRIMUL PARAGRAF
(2) În cazul în care există anumite motive de îngrijorare, Comisia poate, în urma avizului Agenţiei, să solicite, în vederea acordării autorizaţiei de introducere pe piaţă, stabilirea unui sistem de gestionare a riscului menit să identifice, să prevină şi să minimizeze riscurile legate de medicamentele pentru terapie avansată, inclusiv o evaluare a eficacităţii acestui sistem sau efectuarea, de către titularul autorizaţiei, a unor studii specifice după introducerea pe piaţă a produsului, care apoi să fie supuse reevaluării de către Agenţie. (2) În cazul în care există anumite motive de îngrijorare, Comisia solicită, în urma avizului Agenţiei, în vederea acordării autorizaţiei de introducere pe piaţă, stabilirea unui sistem de gestionare a riscului menit să identifice, să caracterizeze, să prevină şi să minimizeze riscurile legate de medicamentele pentru terapie avansată, inclusiv o evaluare a eficacităţii acestui sistem sau efectuarea, de către titularul autorizaţiei, a unor studii specifice după introducerea pe piaţă a produsului, care apoi să fie supuse reevaluării de către Agenţie. Justification
In order to ensure the effectiveness of the risk management system, the Commission should have an obligation to require necessary measures to be carried out when there is a cause for concern.
(1) Titularul unei autorizaţii de introducere pe piaţă a unui medicament pentru terapie avansată stabileşte şi menţine un sistem prin care se asigură că produsul individual, materiile prime şi materiile de bază, inclusiv toate substanţele care au intrat în contact cu eventualele ţesuturi sau celule pe care le conţine medicamentul, pot fi urmărite de la sursă până la spitalul, institutul sau cabinetul medical în care produsul este utilizat, trecând prin etapele de fabricaţie, ambalare, transport şi livrare.
(1) Titularul unei autorizaţii de introducere pe piaţă a unui medicament pentru terapie avansată stabileşte şi menţine un sistem prin care se asigură că produsul individual, materiile prime şi materiile de bază, inclusiv toate substanţele care au intrat în contact cu eventualele ţesuturi sau celule pe care le conţine medicamentul, pot fi urmărite de la sursă până la spitalul, institutul sau cabinetul medical în care produsul este utilizat, trecând prin etapele de fabricaţie, ambalare, depozitare, transport şi livrare.
Traceability during storing steps should also be ensured. Adding ‘storing’ establishes a coherent system of product traceability, and is in line with Directive 2004/23/EC. Amendamentul 41
(4) Titularul autorizaţiei de introducere pe piaţă trebuie să păstreze informaţiile menţionate la alineatul (1) pe o perioadă de minimum 30 de ani de la introducerea produsului pe piaţă sau mai mult dacă acest lucru este impus de Comisie, ca şi condiţie pentru obţinerea autorizaţiei de introducere pe piaţă. (4) Titularul autorizaţiei de introducere pe piaţă trebuie să păstreze informaţiile menţionate la alineatul (1) pe o perioadă de minimum 30 de ani de la expirarea datei de valabilitate a produsului sau mai mult dacă acest lucru este impus de Comisie, ca şi condiţie pentru obţinerea autorizaţiei de introducere pe piaţă. Justification
The proposed wording is unambiguous, whereas “placing on the market” might create difficulties in interpretation. The proposed wording provides a pragmatic solution for the marketing authorisation holder to know exactly from when traceability data must be kept.
(2) Prin derogare de la dispoziţiile articolului 8 alineatul (1) din Regulamentul (CE) nr. 297/95, se aplică o reducere de 90% la taxa care trebuie plătită Agenţiei pentru orice aviz menţionat la alineatul (1) şi la articolul 57 alineatul (1) litera (n) din Regulamentul (CE) nr. 726/2004, în cazul medicamentelor pentru terapie avansată.
(2) Prin derogare de la dispoziţiile articolului 8 alineatul (1) din Regulamentul (CE) nr. 297/95, întreprinderilor mici şi mijlocii li se aplică o reducere de 90% iar altor solicitanţi li se aplică o reducere de 65% la taxa care trebuie plătită Agenţiei pentru orice aviz menţionat la alineatul (1) şi la articolul 57 alineatul (1) litera (n) din Regulamentul (CE) nr. 726/2004, în cazul medicamentelor pentru terapie avansată.
This Regulation seeks to encourage and support SME's in the development of ATMPs. Therefore, it is necessary to introduce special fee-waivers applicable to SME's on scientific advice. The 10% of the basic fee which the SME's should cover themselves is a symbolic amount, in order to prevent any abuse of the totally gratis system. Moreover, to support the applicants which do not fall under the SME criteria and to ensure the competitiveness of the whole sector, a reduction of 65% should be applied to all companies irrespective of their size.
(1) Orice solicitant care dezvoltă un produs pe bază de celule sau ţesuturi poate solicita Agenţiei o recomandare ştiinţifică pentru a determina dacă produsul respectiv cade, din punct de vedere ştiinţific, sub incidenţa definiţiei medicamentelor pentru terapie avansată. Agenţia emite această recomandare în urma consultării cu Comisia.
(1) Orice solicitant care dezvoltă un produs pe bază de gene, celule sau ţesuturi poate solicita Agenţiei o recomandare ştiinţifică pentru a determina dacă produsul respectiv cade, din punct de vedere ştiinţific, sub incidenţa definiţiei medicamentelor pentru terapie avansată. Agenţia emite această recomandare, în urma consultării cu Comisia şi în termen de 60 de zile de la primirea cererii.
It should be clarified that the procedure foreseen in this Article may apply to all types of advanced therapy medicinal products, including products based on genes. The proposed amendment also foresees that an applicant will get clarity on the classification of the concerned product in a timely manner, thus facilitating business planning and further development of the product.
Articolul 19a
Stimulente pentru întreprinderile mici şi mijlocii de biotehnologie
Producătorii de medicamente pentru terapie avansată cu mai puţin de 500 de angajaţi şi cu o cifră de afaceri mai mică de 100 milioane de euro, sau al căror total al bilanţului nu depăşeşte 70 milioane de euro, sunt eligibile pentru toate stimulentele care sunt acordate întreprinderilor mici şi mijlocii, astfel cum au fost definite în Recomandarea 2003/361/CE1 a Comisiei.
1 JO L 124, 20.5.2003, p. 36.
For many young biotech enterprises it is difficult to meet the criteria for an SME. One of the reasons is that a purchase or sale of a patent or platform technology may generate a big oneoff turnover which exceeds the current limitations. These companies should nevertheless enjoy more favourable financial terms.
Articolul 19b (nou)
Articolul 19b
Reducerea taxei pentru autorizaţia de introducere pe piaţă
(1) Taxa pentru autorizaţia de introducere pe piaţă este redusă cu 50%, în cazul în care solicitantul poate demonstra că medicamentul pentru terapie avansată prezintă, în cadrul Comunităţii, un interes public special sau în cazul în care randamentul investiţiei aşteptat, ca urmare a introducerii pe piaţă a produsului respectiv este redus.
(2) Alineatul (1) se aplică, de asemenea, taxelor solicitate de Agenţie pentru activităţile desfăşurate după obţinerea autorizaţiei în primul an, ulterior acordării autorizaţiei de introducere pe piaţă a medicamentului.
3. În cazul întreprinderilor mici şi mijlocii sau al întreprinderilor cu mai puţin de 500 de angajaţi şi o cifră de afaceri mai mică de 100 milioane de euro, sau al căror total al bilanţului nu depăşeşte 70 milioane de euro, se aplică dispoziţiile alineatului (1), fără nicio limită de timp, pentru taxele solicitate de Agenţie pentru activităţile desfăşurate după obţinerea autorizaţiei. Justification
Reductions of the fee for marketing authorisations is necessary in cases of ATMPs serving public interest like orphan drugs or where the applicant is an SME. For those products and enterprises the centralised procedure is a big administrative burden which should be eased by minimised fees. The stipulated cost reductions are also necessary in case of autologous ATMPs and those for intended use because these products can only be introduced into the market to a limited extent.
ARTICOLUL 19C (nou)
Articolul 19c
În ceea ce priveşte aplicarea prezentului regulament, statele membre acordă asistenţă tehnică specifică solicitanţilor şi titularilor autorizaţiilor de introducere pe piaţă. Această asistenţă este disponibilă prin intermediul autorităţilor naţionale competente şi se axează, în special, pe sprijinul acordat spitalelor individuale sau altor instituţii la scară redusă, de exemplu departamente de universităţi, care nu îndeplinesc condiţiile articolului 3 alineatul (7) din Directiva 2001/83/CE. Asistenţa este acordată cu condiţia ca medicamentele pentru terapie avansată să fie preparate şi utilizate sub răspunderea tehnică a medicului specialist şi în conformitate cu prescripţia medicală pentru pacienţii individuali. Justification
Exemptions from the scope of the Directive shall be as limited as possible in order to bring the benefit of new medicines quickly to all patients in Europe. However, special support shall be given to groups of possible applicants with regard to the particularities of this highly innovative sector. This can be best achieved at the national level.
ARTICOLUL 21 ALINEATUL (1) LITERA (C) (c) patru membri numiţi de Comisie, pe baza unei invitaţii publice pentru manifestarea interesului, dintre care doi ca reprezentaţi ai medicilor şi doi ca reprezentanţi ai asociaţiilor de pacienţi.
(c) doi membri şi doi membri supleanţi numiţi de Comisie, pe baza unei invitaţii publice pentru manifestarea interesului, şi în urma consultării cu Parlamentul European, să reprezinte medicii;
(ca) doi membri şi doi membri supleanţi numiţi de Comisie, pe baza unei invitaţii publice pentru manifestarea interesului, şi în urma consultării cu Parlamentul European, să reprezinte asociaţiile de pacienţi;
In order to cover all medical fields which the advanced therapies may relate to, more general medical expertise, i.e. physicians with clinical expertise, should be represented in the Committee for Advanced Therapies. In addition, by introducing alternate members, we would like to ensure a permanent representation of the groups involved. The appointment of these members and their alternates should take place in consultation with the European Parliament. Amendamentul 48
(2) Toţi membrii Comitetului pentru terapii avansate sunt aleşi pentru competenţelor lor ştiinţifice sau experienţa lor cu privire la medicamentele pentru terapie avansată. În scopul alineatului 1 litera (b), statele membre trebuie să coopereze, sub coordonarea directorului executiv al Agenţiei, pentru a se asigura că domeniile ştiinţifice relevante pentru terapiile avansate, inclusiv dispozitivele medicale, ingineria tisulară, terapia genică, terapia celulară, biotehnologia, farmacovigilenţa, gestionarea riscului şi etica se reflectă, în mod adecvat şi echilibrat, în componenţa definitivă a Comitetului pentru terapii avansate.
(2) Toţi membrii şi membrii supleanţi ai Comitetului pentru terapii avansate sunt aleşi pentru competenţelor lor ştiinţifice sau experienţa lor cu privire la medicamentele pentru terapie avansată. În scopul alineatului 1 litera (b), statele membre trebuie să coopereze, sub coordonarea directorului executiv al Agenţiei, pentru a se asigura că domeniile ştiinţifice relevante pentru terapiile avansate, inclusiv dispozitivele medicale, ingineria tisulară, terapia genică, terapia celulară, biotehnologia, farmacovigilenţa, gestionarea riscului şi etica se reflectă, în mod adecvat şi echilibrat, în componenţa definitivă a Comitetului pentru terapii avansate. Cel puţin doi membri şi doi membri supleanţi ai Comitetului pentru terapii avansate au experienţă ştiinţifică în dispozitive medicale.
The alternate members of the Committee for Advanced therapies introduced in paragraph 1 shall comply with the same criteria of scientific qualification or experience in the field of advanced therapy medicinal products as its members. In order to ensure an appropriate level of expertise, it would be important to include experts as members that have a background in the evaluation of medical devices, as many of the products concerned share many characteristics of medical devices.
ARTICOLUL 21 ALINEATUL (5)
(5) Numele şi competenţele ştiinţifice ale membrilor sunt făcute publice de către Agenţie.
(5) Numele şi competenţele ştiinţifice ale membrilor sunt publicate pe site-ul Agenţiei, imediat ce este posibil.
It seems essential for the information on the members of the Committee to be made public and disseminated via the Agency’s website.
(1) Membrii Comitetului pentru terapii avansate şi experţii acestuia se angajează să acţioneze în interesul public şi în mod independent. Aceştia nu au interese financiare sau de altă natură în sectorul farmaceutic, al dispozitivelor medicale sau al biotehnologiei, care le-ar putea afecta imparţialitatea.
Pe lângă cerinţele prevăzute la articolul 65 din Regulamentul (CE) nr. 726/2004, membrii şi membrii supleanţi ai Comitetului nu au interese financiare sau de altă natură în sectorul biotehnologiei şi al dispozitivelor medicale, care le-ar putea afecta imparţialitatea. Toate interesele indirecte care pot fi legate de aceste sectoare sunt înscrise în registrul menţionat la articolul 63 alineatul (2) din Regulamentul (CE) nr. 726/2004. (2) Toate interesele indirecte care pot fi legate de sectorul farmaceutic, al dispozitivelor medicale sau al biotehnologiei sunt înscrise în registrul menţionat la articolul 63 alineatul (2) din Regulamentul (CE) nr. 726/2004.
It should be clarified that an identical level of transparency as for existing Committees within the EMEA (pursuant to Article 63 of Regulation (EC) No 726/2004) applies for the new Committee for Advanced Therapies. It should also be clarified that interests in the biotechnology or medical device sector are forbidden.
ARTICOLUL 23 LITERA (A)
(a) oferă consiliere Comitetului pentru medicamente de uz uman cu privire la datele obţinute în dezvoltarea medicamentului pentru terapie avansată, în vederea elaborării unui aviz cu privire la calitatea, siguranţa şi eficacitatea produsului respectiv;
(a) în vederea elaborării unui proiect de aviz privind calitatea, siguranţa şi eficacitatea unui produs de terapie avansată supus spre aprobarea finală a Comitetului pentru medicamente de uz uman şi în vederea consilierii acestuia cu privire la datele obţinute în dezvoltarea unui astfel de medicament; Justification
Due to the highly specific and unique character of the advanced therapy medicinal products, a new Committee for Advanced Therapies is established within EMEA, composed of experts having specific qualification or experience in this highly innovative and quickly developing field. Therefore, the new structure should be responsible for drafting an opinion on the quality, safety, and efficacy of products for the final approval by the CHMP. Furthermore, the committee should be consulted for the evaluation of other products under its competence.
ARTICOLUL 23 LITERA (AA) (nouă)
(aa) oferă consiliere, în conformitate cu articolul 18, pentru a determina dacă un produs cade sub incidenţa definiţiei medicamentelor pentru terapie avansată;
Having specific expertise in advanced therapy medicinal products, the Committee for Advanced Therapies should have a prominent role in the classification task of whether a product is or is not an advanced therapy medicinal product.
ARTICOLUL 23 LITERA (EA) (nouă)
(ea) contribuie la procedurile de aviz ştiinţific menţionate la articolul 17 din prezentul regulament şi la articolul 57 alineatul (1) litera (n) din Regulamentul (CE) nr. 726/2004;
The Committee on Advanced Therapies should consist of the best possible experts from Member States. Their expertise should therefore be drawn upon for any advice issued regarding an advanced therapy medicinal product.
Comisia, în conformitate cu procedura prevăzută la articolul 26 alineatul (2), modifică anexele I-IV, în vederea adaptării acestora la progresul ştiinţific şi tehnic.
Comisia, în urma consultării cu Agenţia şi în conformitate cu procedura prevăzută la articolul 26 alineatul (2a), modifică anexele II-IV, în vederea adaptării acestora la progresul ştiinţific şi tehnic.
Annex I contains a fundamental and substantial definition. We therefore consider that it should not be subject to any changes through comitology. Should any changes be necessary due to scientific progress, they should be adopted in co-decision, fully involving the European Parliament. The regulation should set out very clearly that the Commission must involve the EMEA, through the Committee for Advanced Therapies, whenever adaptation of the Annexes to technical progress is required. The adaptation of Annexes II to IV should fall under the new regulatory procedure with scrutiny.
ARTICOLUL 25 TITLU
Informarea şi revizuirea
Scientific advances may make additional novel therapies possible which are neither gene therapy, nor cell therapy nor tissue engineering. It would be in the interests of patients for these to be included at some future date in order to allow European authorisation of the resulting products. Amendamentul 56
ARTICOLUL 25 ALINEATUL (1A) (nou)
În acest raport, Comisia evaluează impactul progresului tehnic asupra aplicării prezentului regulament. De asemenea, dacă este necesar, aceasta face o propunere legislativă în vederea includerii noilor terapii care nu implică nici terapia genetică, nici terapia celulară şi nici ingineria tisulară. Justification
Scientific advances may make additional novel therapies possible which are neither gene therapy, cell therapy nor tissue engineering. It would be in the interests of patients for these to be included at some future date, in order to allow European authorisation of the resulting products.
ARTICOLUL 26 ALINEATUL (2A) (nou)
(2a) Atunci când se face referire la prezentul alineat, se aplică articolul 5a alineatele (1)-(4) şi articolul 7 din Decizia 1999/468/CE, având în vedere dispoziţiile articolului 8. Justificare
This amendment is in line with the new comitology provisions (regulatory procedure with scrutiny).
ARTICOLUL 27 PUNCTUL (-1) (nou)
Articolul 13 alineatul (1) [Regulamentul (CE) nr. 726/2004]
(-1) La articolul 13, prima teză a alineatului (1) se înlocuieşte cu următorul text:
„Fără a aduce atingere articolului 4 alineatele (4) şi (5) din Directiva 2001/83/CE, o autorizaţie de introducere pe piaţă care a fost acordată în conformitate cu prezentul regulament este valabilă pe întreg teritoriul Comunităţii.”
This is a consequential amendment to Article 28(2) to ensure legal coherence.
ARTICOLUL 27 ALINEATUL (2A) (nou)
Anexa punctul 3 al doilea paragraf [Regulamentul (CE) nr. 726/2004]
(2a) În anexă, al doilea paragraf al punctului 3 se înlocuieşte cu următorul text:
„După 20 mai 2008, Comisia poate prezenta, în urma consultării cu Agenţia, orice propuneri de modificare a prezentului punct, iar Parlamentul European şi Consiliul iau o decizie cu privire la acest lucru, în conformitate cu tratatul.” Justification
This part of Regulation 726/2004 determines when a Community authorisation must be obtained. Under the present proposal, it may be that certain AT products will not require Community authorisation either because they do not involve one of the processes referred to in point 1 of the Annex to Reg. 726/2004, or because they are not used for the treatment of any of the diseases referred to in point 3 of that Annex. Currently, the list of diseases in point 3 can be extended by the Council on a Commission proposal, without recourse to the EP. Decisions determining the scope of legislative acts must be dealt with by co-decision.
ARTICOLUL 28 PUNCTUL (-1) (nou)
Articolul 1 punctul 4a (nou) (Directiva 2001/83/CE)
(-1) La articolul 1 se adaugă punctul 4a:
„(4a) Produs care provine din ingineria tisulară.
Produs, astfel cum este definit în articolul 2 din Regulamentul (CE) nr. **/** privind medicamentele pentru terapie avansată.”
For the sake of legal coherence and clarity, it is necessary to include a cross reference to the definition of a tissue engineered product in Directive 2001/83/EC on medicinal products, which already contains the definitions of a gene therapy medicinal product and a somatic cell therapy medicinal product.
ARTICOLUL 28 PUNCTUL 1
Articolul 3 punctul 7 (Directiva 2001/83/CE)
(7) Orice medicament pentru terapie avansată, astfel cum este definit în Regulamentul (CE) nr. […/al Parlamentului European şi al Consiliului (Regulamentul privind medicamentele pentru terapie avansată)*], care este atât preparat în întregime, cât şi utilizat în cadrul unui spital, în conformitate cu prescripţia medicală a unui pacient individual.
Orice medicament pentru terapie avansată, astfel cum este definit în Regulamentul (CE) nr. […/al Parlamentului European şi al Consiliului (Regulamentul privind medicamentele pentru terapie avansată)*], care este preparat în întregime într-un spital în mod gratuit, după metode specifice, nenormalizate şi nepatentate, şi utilizate într-un spital, pentru a respecta o prescripţie medicală pentru un pacient individual aflat sub responsabilitatea profesională exclusivă a unui medic sau în cadrul unui studiu clinic. Punctele 1 şi 2 nu se aplică medicamentelor pentru terapie avansată. Justification
For the justification concerning hospitals, see amendment to Recital 5.Exceptions given in Directive 2001/83/EC (Article 3, points 1 and 2) allow pharmacies to prepare medicinal products in accordance with a medical prescription without complying with medicinal product legislation. This exception would also give the in-house pharmacies of hospitals the possibility of producing TEP using standardized methods and on a routine basis. Therefore this amendment is crucial to ensure that only one-off basis products are excluded from the scope of this Regulation.
ARTICOLUL 28 PUNCTUL 2Articolul 4 alineatul (5) (Directiva 2001/83/CE)
(5) Prezenta directivă şi toate regulamentele la care aceasta face referire nu aduc atingere aplicării legislaţiei naţionale care interzice sau restricţionează folosirea oricărui tip specific de celule animale sau umane sau vânzarea, furnizarea sau folosirea medicamentelor care conţin, sunt alcătuite sau derivate din aceste celule. Statele membre transmit Comisiei legislaţia naţională în cauză.
(5) Prezenta directivă şi toate regulamentele la care aceasta face referire nu aduc atingere aplicării legislaţiei naţionale nediscriminatorii care interzice sau restricţionează folosirea oricărui tip specific de celule animale sau umane sau vânzarea, furnizarea sau folosirea medicamentelor care conţin, sunt alcătuite sau derivate din aceste celule, din motive netratate în legislaţia comunitară menţionată mai sus.. Statele membre transmit Comisiei legislaţia naţională în cauză. Comisia va publica aceste informaţii într-un registru. Justification
The Commission’s proposal poses serious problems of compatibility with the legal base (Art. 95 ECT). The reason is that the current wording of Article 28(5) gives a too wide opportunity to restrict the free movement of certain advanced therapy products. Legislative acts based on Art. 95 are intended to improve the conditions of the establishment and functioning of the internal market. The Commission’s proposal does not and should certainly not cover or harmonise aspects of public morality and public policy aspects of advanced therapy. However, the current wording allows restrictions not only related to these subsidiary aspects and should, therefore, be amended in line with suggestions of Parliament’s legal service.
(1) Medicamentele pentru terapie avansată care există pe piaţa Comunităţii, în mod legal, în conformitate cu legislaţia naţională sau comunitară, la momentul intrării în vigoare a prezentului regulament, trebuie să respecte prezentul regulament în cel mult 2 ani de la data intrării în vigoare a acestuia.
(1) Medicamentele pentru terapie avansată, altele decât produsele care provin din ingineria tisulară, care există pe piaţa Comunităţii, în mod legal, în conformitate cu legislaţia naţională sau comunitară, la momentul intrării în vigoare a prezentului regulament, trebuie să respecte prezentul regulament în cel mult 4 ani de la data intrării în vigoare a acestuia.
Today companies are already producing and marketing TEP at national level through national authorisation systems. In order for a company to obtain a centralised marketing authorisation (e.g. design the new trials together with the EMEA, to conduct the trials, to develop the dossier and to submit it to the EMEA for evaluation) the proposed timeframe of 2 years is too short. Taking into account the time required for the above-mentioned steps and in order to avoid products that have been safely treating patients up to now being removed from those patients during the transitional period, we suggest a period of 4 years.
ARTICOLUL 29 ALINEATUL (1A) (nou)
(1a) Produsele provenite din ingineria tisulară care au fost introduse în mod legal pe piaţa comunitară, în conformitate cu legislaţia naţională sau cu cea comunitară la data punerii în aplicare menţionată în articolul 30 alineatul (2) trebuie să respecte prezentul regulament, în termen de maxim 4 ani de la această dată.
Manufacturers will not be in a position to design development protocols until all the requirements specific to tissue engineering products are published. The transitional period for these products must therefore take into account the time to publish all these necessary requirements.
(2) Prin derogare de la dispoziţiile articolului 3 alineatul (1) din Regulamentul (CE) nr. 297/95, nu se plăteşte nici o taxă Agenţiei pentru cererile de autorizare a medicamentelor pentru terapie avansată menţionate la alineatul (1).
(2) Prin derogare de la dispoziţiile articolului 3 alineatul (1) din Regulamentul (CE) nr. 297/95, nu se plăteşte nici o taxă Agenţiei pentru cererile de autorizare a medicamentelor pentru terapie avansată menţionate la alineatele (1) şi (1a).
See the amendment for Article 29, paragraph 1a (new).
ARTICOLUL 29 ALINEATUL (2A) (nou)
(2a) În ceea ce priveşte produsele pentru uz autolog, pe baza solicitării motivate a unui stat membru şi prin derogare de la articolul 3 din Regulamentul (CE) nr. 726/2004, Comisia poate, în conformitate cu procedura prevăzută la articolul 26 alineatul (2) şi în urma consultării cu Comitetul pentru terapii avansate, să aprobe pentru o perioadă de cinci ani o autorizaţie naţională, în conformitate cu principiile din prezentul Regulament. Comisia poate lua o astfel de decizie numai în cazul în care consideră că:
- autoritatea de reglementare a statului membru interesat are o experienţă suficientă în domeniul medicamentelor pentru terapie avansată; şi
- introducerea pe piaţă a medicamentului specific în afara unui anumit stat membru nu este posibilă.
Pentru aplicarea prezentului articol Comisia prevede şi publică în Jurnalul Oficial al Uniunii Europene norme detaliate de procedură.
ARTICOLUL 30 ALINEATELE (3A) ŞI (2B) (noi)
Pentru produsele care provin din ingineria tisulară, prezentul regulament se aplică de la intrarea în vigoare a tuturor condiţiilor prevăzute la articolele 4, 5 şi 8.
Măsurile de punere în aplicare avute în vedere la articolele 4, 5 şi 8 sunt adoptate imediat ce este posibil şi, în orice caz, nu mai târziu de 9 luni de la intrarea în vigoare a prezentului regulament.
ANEXA II PUNCTUL 2.2
2.2. compoziţia calitativă şi cantitativă în substanţe active şi alţi constituenţi ai produsului, a căror cunoaştere este esenţială pentru utilizarea adecvată, administrarea sau implantarea produsului. În cazul în care produsul conţine celule sau ţesuturi, acestea trebuie descrise în detaliu, iar originea lor specifică indicată.
2.2. compoziţia calitativă şi cantitativă în substanţe active şi alţi constituenţi ai produsului, a căror cunoaştere este esenţială pentru utilizarea adecvată, administrarea sau implantarea produsului. În cazul în care produsul conţine celule sau ţesuturi, acestea trebuie descrise în detaliu, iar originea lor specifică indicată, inclusiv specia animală, în cazul în care celulele sau ţesuturile nu sunt de origine umană.
This amendment aims at ensuring that potential recipients having various cultural considerations are duly informed before taking their decision.
ANEXA III LITERA (B)
(b) o descriere a substanţei (substanţelor) active, calitativă şi cantitativă, incluzând, în cazul în care produsul conţine celule sau ţesuturi, menţiunea „Acest produs conţine celule de origine umană/animală [după cum este cazul]” împreună cu o scurtă descriere a acestor celule sau ţesuturi şi a originii lor specifice;
(b) o descriere a substanţei (substanţelor) active, calitativă şi cantitativă, incluzând, în cazul în care produsul conţine celule sau ţesuturi, menţiunea „Acest produs conţine celule de origine umană/animală [după cum este cazul]” împreună cu o scurtă descriere a acestor celule sau ţesuturi şi a originii lor specifice, inclusiv specia animală, în cazul în care celulele sau ţesuturile nu sunt de origine umană;
ANEXA IV LITERA (A) PUNCTUL (III)
(iii) în cazul în care produsul conţine celule sau ţesuturi, o descriere a acestora şi a originii lor specifice;
(iii) în cazul în care produsul conţine celule sau ţesuturi, o descriere a acestora şi a originii lor specifice, inclusiv specia animală, în cazul în care celulele sau ţesuturile nu sunt de origine umană.
Rapid development in the fields of biology, biotechnology and medicine and attempts to achieve sustainable growth of health protection within the European Union lead to the development of new treatments and highly innovative medicinal products.
In this context, products which involve intervention in gene therapy, cell therapy and tissue engineering are of great importance, having a high potential in the treatment of diseases such as cancer, cartilage or bone diseases or injuries, repair of genetic disorders, repair of post heart attack damage as well as skin replacement in burn victims.
Nowadays, the legal framework at the Community level related to these advanced therapies remains fragmented, as only gene therapy and somatic cell therapy medicinal products benefit from a legal definition. Tissue engineered products remain unregulated, which leads to the fragmentation of the market and which does not allow patients to have easy access to the necessary treatments.
The current proposal introduces a single harmonising regulatory framework for the evaluation, authorisation and supervision of advanced therapy medicinal products: marketing authorisation requirements and procedure, post-authorisation vigilance and traceability. The proposed Regulation should be seen within the wider perspective of the existing legislation in this field, such as Directive 2001/83/EC on medicinal products, Regulation (EC) No 726/2004 on the European Medicines Agency (EMEA) or Directive 2004/23/EC laying down quality and safety standards of human tissues and cells. The proposal introduces a European centralised marketing authorisation procedure and creates a new Committee for Advanced Therapies within EMEA, composed of highly qualified and experienced experts in all fields related to these products. In addition, the proposed Regulation sets up a strengthened requirement for the post-authorisation monitoring system and for traceability of the patient and foresees specific technical requirements for tissue engineered products. Moreover, additional specific incentives for the applicants and especially for SMEs are introduced, in order to promote competitiveness within the EU. The rapporteur welcomes this proposal for a Regulation and the introduction of a new coherent legal framework for these innovative, specific and complex medicinal products. He agrees on the necessity of a centralised authorisation procedure in order to facilitate the market access and to ensure the free movement of advanced therapy medicinal products within the Community. Priority should be given to the demonstration of quality, safety and efficacy of these products in order to ensure a high level of health protection within the EU. The highest possible level of legal certainty should be guaranteed while allowing sufficient flexibility at the technical level. Nevertheless, the rapporteur would like to underline the importance of clear definitions in order to avoid a legal uncertainty or grey zones, particularly as regards the definition of combined advanced therapy medicinal products and their evaluation. It should also be made crystal clear that products prepared in a hospital, on a one-off basis for an individual patient, should not comply with the centralised authorisation procedure. Moreover, products applied in the production of advance therapy medicinal products for clinical trials and products for clinical research should not be forgotten.
In addition, the rapporteur would like to stress the important role of the Committee for Advanced Therapies within EMEA. This highly qualified body should play a vital role in the process of scientific evaluation of advanced therapy medicinal products and its internal decision procedure should be clearly defined. Moreover, advanced therapy medicinal products could raise serious ethical concerns, as they are likely to contain human cells or tissues. The Commission's proposal should not have an impact on the national legislation prohibiting or restricting the use of certain type of human or animal cells (such as embryonic stem cells) or the sale, supply or use of medicinal products derived from these cells. According to Parliament's legal service, the original drafting of this provision raises serious concerns in the light of the legal basis of the proposal. The development in biotechnology and biomedicine should be carried out while fully respecting fundamental rights. Rights such as the right to human dignity or to the integrity of the person laid down in the Oviedo Convention as well as in the Charter of fundamental rights should be entirely respected. Therefore, in his first draft report the rapporteur underlined that authorisation procedure should be carried out in accordance with the principle of non commercialisation of the human body or its parts as such. Moreover, the rapporteur proposed amendments in order to exclude the European marketing authorization under this regulation for products modifying the germ line genetic identity of human beings and for products derived from human-animal hybrids or chimeras (but allowing the transplantation of somatic animal cells or tissues to the human body for therapeutic purposes, i.e. Xenotransplantation). These amendments were adopted by the Committee on Legal Affairs. Even though these amendments were adopted by the majority in ENVI committee, the first draft report as amended was rejected in the final vote. The rapporteur is still convinced that the approach chosen by the JURI Committee is the most appropriate. Nevertheless, his intention is to find the broadest possible consensus in this area. Therefore, he does not propose any of these amendments in his new report. Two amendments, 3 and 17, were incorporated in the report without vote in the Environment Committee, following enhanced cooperation (Rule 47) with the Legal Affairs Committee.
OPINION of the Committee on Industry, Research and Energy (20.6.2006)
on the proposal for a regulation of the European Parliament and of the Council on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004
Draftsman: Giles Chichester
Advanced therapies are highly innovative medical products based on genes (gene therapy), cells (cell therapy) or tissues (tissue engineering). These advanced therapies enable revolutionary treatment of diseases and injuries, such as cancer, Parkinson's disease, skin in burn victims or serious cartilage damage, and are expected to change medical practice significantly. Currently, the development of the field of advanced therapies is hampered by the lack of harmonised EU legislation. Especially tissue-engineered products are at the moment not regulated on Community level, which leads to divergent national legislation and authorisation. This hampers the internal market and negatively affects EU's innovative capacity and competitiveness. This proposed Regulation intends to bridge the existing regulatory gap by addressing all advanced therapy products within a single, integrated legal framework. The Regulation builds on already-existing legislation (in particular Directive 2001/83/EC on medical products and Regulation (EC) No 726/2004 on the European Medicines Agency), and should therefore be seen in their totality.
The main elements of the Commission's proposal are:
· A centralised marketing authorisation procedure, to benefit from the pooling of expertise at European level and direct access to the EU market;
· A new and multidisciplinary expert Committee (Committee for Advanced Therapies), within the European Medicines Agency (EMEA), to assess advanced therapy products and follow scientific developments in the field;
· Tailor-made technical requirements, which are adapted to the particular characteristics of these products;
· Strengthened requirements for risk management and traceability;
· A system of low-cost, top-quality scientific advice provided by EMEA;
· Special incentives for small and medium-sized enterprises (SMEs).
The draftswoman welcomes the Commission's proposal. Tissue engineering is an emerging biotechnology sector at the interface between medicine, cellular and molecular biology, materials science and engineering. By developing products designed to replace, repair or regenerate human tissues, it could mean the end of organ shortage, saving every year thousands of people in Europe. The draftswoman therefore welcomes the creation of a robust and comprehensive regulatory framework, that will give the sector harmonised market access, while at the same time foster the competitiveness and guarantee a high level of health protection.
The draftswoman would like to emphasise the fact that the definitions should be precise enough to provide the necessary legal certainty, but at the same time sufficient flexible in order to keep the pace with the evolution of science and technology. Such a balance should also be sought for the marketing authorisation procedure. The draftswoman supports the creation of a fully centralised authorisation procedure to benefit from the pooling of expertise, but at the same time stresses the need to alleviate the regulatory burden that such a procedure might entail, especially on SMEs.
As certain advanced therapy products may be based on human cells, they can raise important ethical issues. Currently, decisions on the use or prohibition of any type of cells, including embryonic stem cells, are a national responsibility. In this proposal, this principle is kept, meaning that decisions on the development, use and/or sale of products based on any specific type of human or animal cells will remain a national responsibility. This is fully in line with the Directive on the quality and safety of human tissues and cells (Directive 2004/23/EC).
The Committee on Industry, Research and Energy calls on the Committee on the Environment, Public Health and Food Safety, as the committee responsible, to incorporate the following amendments in its report:
(5) Advanced therapy medicinal products should be regulated in so far as they are intended to be placed on the market in Member States and either prepared industrially or manufactured by a method involving an industrial process, within the meaning of Article 2(1) of Directive 2001/83/EC. Advanced therapy medicinal products which are both prepared in full and used in a hospital, in accordance with a medical prescription for an individual patient, should thus be excluded from the scope of the present Regulation.
(5) Advanced therapy medicinal products should be regulated in so far as they are intended to be placed on the market in Member States and either prepared industrially or manufactured by a method involving an industrial process, within the meaning of Article 2(1) of Directive 2001/83/EC. Advanced therapy medicinal products which are prepared in full in a hospital on a one-off basis according to a specific, non-standardised and non-patented process, and used in a hospital, in order to comply with an individual medical prescription for an individual patient, should thus be excluded from the scope of this Regulation.
Where hospitals or other institutions prepare products using an established process to create treatments for patients on a serial and routine basis, they should have to comply with the provisions of this Regulation. However, when hospitals produce advanced therapy products for research purposes or on an exceptional, one-off basis, they should not have to comply with the centralised authorisation procedure.
(7b) Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use1 prohibits gene therapy trials that result in modifications to a subject's germ line genetic identity. Directive 98/44/EC of the European Parliament and of the Council of 6 July 1998 on the legal protection of biotechnological inventions2 considers processes for modifying the human germ line genetic identity non-patentable. To ensure legal coherence, this Regulation should prohibit any authorisation of products that modify the germ line genetic identity of human beings.
_____________ 1 L 121, 1.5.2001, p. 34.
2 L 213, 30.7.1998, p. 13.
As Articles 1 and 13 of the Oviedo Convention make it clear, human dignity is compromised when the inheritance of genetic identity is altered. Products which are neither properly subject to clinical trials under Directive 2001/20/EC nor legally patentable under Directive 98/44/EC should not be eligible for authorisation under this regulation.
(7c) This Regulation should prohibit any authorisation of products derived from human-animal hybrids or chimeras or containing tissues or cells originating or derived from human-animal hybrids or chimeras. This provision should not exclude the transplantation of somatic animal cells or tissues to the human body for therapeutic purposes, in so far as it does not interfere with the germ line.
The physical and mental integrity of the person and human dignity must be respected, as underlined in Articles 1 and 3 of the Charter of fundamental rights of the European Union. The creation of human-animal hybrids or chimeras is a threat to the right to integrity of a person and a violation of human dignity. Therefore, no authorisation for products containing or originating from human-animal hybrids or chimeras should be granted under this regulation. However, the Xenotransplantation for therapeutic purposes should not be excluded, as far as it does not interfere with the germ line.
(9) The evaluation of advanced therapy medicinal products often requires very specific expertise, which goes beyond the traditional pharmaceutical field and covers areas on the borderline to other sectors such as biotechnology and medical devices. For this reason, it is appropriate to create, within the Agency, a Committee for Advanced Therapies, which the Committee for Medicinal Products for Human Use of the Agency should consult on the assessment of data related to advanced therapy medicinal products, before issuing its final scientific opinion. In addition, the Committee for Advanced Therapies may be consulted for the evaluation of any other medicinal product which requires specific expertise falling within its area of competence.
(9) The evaluation of advanced therapy medicinal products often requires very specific expertise, which goes beyond the traditional pharmaceutical field and covers areas on the borderline to other sectors such as biotechnology and medical devices. For this reason, it is appropriate to create, within the Agency, a Committee for Advanced Therapies, which should be responsible for preparing a draft opinion on the quality, safety and efficacy of each advanced therapy medicinal product for final approval by the Committee for Medicinal Products for Human Use of the Agency. In addition, the Committee for Advanced Therapies should be consulted for the evaluation of any other medicinal product which requires specific expertise falling within its area of competence.
Due to a highly specific and unique character of the advanced therapy medicinal products, a new Committee for Advanced Therapies is established within EMEA and composed of experts having specific qualifications or experience in this highly innovative and quickly developing field. Therefore, the new structure should be responsible for drafting an opinion on the quality, safety, and efficacy of products for the final approval by the CHMP. Furthermore, the committee should be consulted for the evaluation of other products under its competence.
(9a) The Committee for Advanced Therapies should provide advice to the Committee for Medicinal Products for Human Use on whether a product falls within the definition of an advanced therapy medicinal product.
Due to its specific expertise in advanced therapy medicinal products, the Committee for Advanced Therapies should assist the CHMP in its classification task of whether a product is or is not an advanced therapy medicinal product.
(14) As a matter of principle, human cells or tissues contained in advanced therapy medicinal products should be procured from voluntary and unpaid donation. Voluntary and unpaid tissue and cell donations are a factor which may contribute to high safety standards for tissues and cells and therefore to the protection of human health.
This recital can be deleted as a consequence to the introduction of a new recital 7a and new articles 3a and 28a.
(16) The manufacture of advanced therapy medicinal products should be in compliance with the principles of good manufacturing practice, as set out in Commission Directive 2003/94/EC of 8 October 2003 laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use. Furthermore, guidelines specific to advanced therapy medicinal products should be drawn up, so as to properly reflect the particular nature of their manufacturing process.
(16) The manufacture of advanced therapy medicinal products should be in compliance with the principles of good manufacturing practice, as set out in Commission Directive 2003/94/EC of 8 October 2003 laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use, adapted where appropriate to take account of specific characteristics of advanced therapy medicinal products, especially tissue engineered products. Furthermore, guidelines specific to advanced therapy medicinal products should be drawn up, so as properly to reflect the particular nature of their manufacturing process.
The existing Good Manufacturing principles established by Directive 2003/94/EC may not be fully appropriate as regards to advanced therapy products. A new GMP Directive, especially focusing on Advanced Therapy products, would be appropriate, not just guidance on existing GMP.
(24) In order to take into account scientific and technical developments, the Commission should be empowered to adopt any necessary changes regarding the technical requirements for applications for marketing authorisation of advanced therapy medicinal products, the summary of product characteristics, labelling, and package leaflet.
(24) In order to take into account scientific and technical developments, the Commission should be empowered to adopt any necessary changes regarding the technical requirements for applications for marketing authorisation of advanced therapy medicinal products, the summary of product characteristics, labelling, and package leaflet. The Commission should ensure that relevant information on envisaged measures is made available to interested parties without delay.
(25) Provisions should be laid down to report on the implementation of this Regulation after experience has been gained, with a particular attention to the different types of advanced therapy medicinal products authorised.
(25) Provisions should be laid down to report on the implementation of this Regulation after experience has been gained, with a particular attention to the different types of advanced therapy medicinal products authorised and the measures provided for in Chapter 6 and in Articles 9, 14(9) and 70(2) of Regulation (EC) No 726/2004.
The report on the implementation of this Regulation should cover the whole scope of the present regulation, including the incentive measures for SMEs, the 'fast-track' approvals and the appeal procedure.
Exclusion from the scope
This Regulation shall not apply to any advanced therapy medicinal product which is prepared in full in a hospital on a one-off basis according to a specific, non-standardised and non-patented process, and used in a hospital, in order to comply with an individual medical prescription for an individual patient.
Where hospitals or other institutions prepare products by using an established process to create treatments for patients on a serial and routine basis, they should have to comply with the provisions of this Regulation, ensuring quality, safety and efficacy of products. However, when hospitals produce ATPs for research purposes or on an exceptional, one-off basis, they should not have to comply with the centralised authorisation process. To ensure the coherence with the Article 28, paragraph 1 we introduce the exclusion from the scope in the present Regulation.
ARTICLE 2, PARAGRAPH 1, POINT (D), INDENT 1 A (new)
- its cellular or tissue part contains viable cells or tissues; or
ARTICLE 2, PARAGRAPH 1, POINT (D), INDENT 2
– its cellular or tissue part must be liable to act upon the human body with action that cannot be considered as ancillary to that of the devices referred to.
- its cellular or tissue part containing non-viable cells or tissues must be liable to act upon the human body with action that can be considered as primary to that of the devices referred to.
Ban on commercialisation of the human body
Where an advanced therapy medicinal product contains human tissues or cells, every stage of the authorisation procedure shall be carried out in accordance with the principle of non-commercialisation of the human body or its parts as such. To this end, and for the purposes of this Regulation, Member States shall ensure that:
- the donation of human cells and tissues is voluntary and unpaid and is made of the donor's free will without payment except compensation; and
- the procurement of tissues and cells is carried out on a non-profit basis.
Rapid developments in biotechnology and biomedicine shouldn't compromise the protection of fundamental rights. These rights, including the right to the integrity of the person, are laid down in the Oviedo Convention as well as in the Charter of Fundamental Rights. These standards can only be upheld if they are carefully observed at every stage of the authorisation process. Therefore, EMEA should be subject to this specific obligation. Member States should have an obligation to ensure voluntary and unpaid donation and to guarantee the procurement of tissues or cells on a non-profit basis.
ARTICLE 3 B (new)
Ban on products modifying the human germ line
No authorisation shall be granted to products modifying the germ line genetic identity of human beings.
3. The Commission shall draw up detailed guidelines on good clinical practice specific to advanced therapy medicinal products.
3. The Commission shall draw up detailed guidelines on clinical trial authorization procedures and good clinical practice specific to advanced therapy medicinal and in particular tissue engineered products.
This amendment recognizes that in particular for tissue engineered products for which no legislation and hence no guidelines exist today, these need to be developed, not only with regard to Good Clinical Practice but also related to Clinical trial authorizations.
3. The advice given by the Committee for Advanced Therapies under paragraph 1 shall be sent to the chairman of the Committee for Medicinal Products for Human Use in a timely manner so as to ensure that the deadline laid down in Article 6(3) of Regulation (EC) No 726/2004 can be met.
3. The draft opinion given by the Committee for Advanced Therapies under paragraph 1 shall be sent to the chairman of the Committee for Medicinal Products for Human Use in a timely manner so as to ensure that the deadline laid down in Article 6(3) or 9(2) of Regulation (EC) No 726/2004 can be met.
Due to the highly specific and unique character of the advanced therapy medicinal products, a new Committee for Advanced Therapies is established within EMEA, composed of experts having specific qualifications or experience in this highly innovative and quickly developing field. Therefore, this new structure should be responsible for drafting an opinion on the quality, safety, and efficacy of products for the final approval by the CHMP. The draft opinion should be given in a timely manner so the deadline laid down in Article 9(2) of Regulation (EC) No 726/2004 can also be met. Amendment 17
4. Where the scientific opinion on an advanced therapy medicinal product drawn up by the Committee for Medicinal Products for Human Use under Article 5, paragraphs 2 and 3 of Regulation (EC) No 726/2004 is not in accordance with the advice of the Committee for Advanced Therapies, the Committee for Medicinal Products for Human Use shall annex to its opinion a detailed explanation of the scientific grounds for the differences.
4. Where the scientific opinion on an advanced therapy medicinal product drawn up by the Committee for Medicinal Products for Human Use under Article 5(2) and (3) of Regulation (EC) No 726/2004 is not in accordance with the draft opinion of the Committee for Advanced Therapies, the Committee for Medicinal Products for Human Use shall annex to its opinion a detailed explanation of the scientific grounds for the differences.
See the justification for the amendment of the Article 9, paragraph 3. Amendment 18
1. Where a combined advanced therapy medicinal product is concerned, the whole product, including any medical device or any active implantable medical device incorporated in the medicinal product, shall be evaluated by the Agency.
1. Where a combined advanced therapy medicinal product is concerned, the whole product, including any medical device or any active implantable medical device incorporated in the medicinal product, shall be subject to final evaluation by the Agency.
2. Where the medical device or active implantable medical device which is part of a combined advanced therapy medicinal product has already been assessed by a notified body in accordance with Directive 93/42/EEC or Directive 90/385/EEC, the Agency shall take account of the results of that assessment in its evaluation of the medicinal product concerned.
2. The application for a marketing authorisation for a combined advanced therapy medicinal product shall include an assessment by a notified body identified in conjunction with the applicant in accordance with Directive 93/42/EEC or Directive 90/385/EEC of the medical device or active implantable medical device which forms part of the combined advanced therapy medicinal product. The Agency shall incorporate the results of that assessment in its evaluation of the medicinal product concerned.
In order to ensure the continuous utilisation of the vast experience and expert knowledge of the notified bodies concerning the evaluation of medical devices or active implantable medical devices, the notified bodies should assess the medical device or the active implantable medical device part of the combined advanced therapy medicinal product. The Agency should incorporate these assessments in its final evaluation of the combined product in accordance with paragraph 1.
ARTICLE 14, PARAGRAPH 2
2. The package leaflet shall reflect the results of consultations with target patient groups to ensure that it is legible, clear and easy to use.
2. Where products are exclusively applied to patients by medical practitioners, the summary of product characteristics pursuant to Article 11 of Directive 2001/83/EC can be used as package leaflet.
Since the predominant majority of Advanced Therapy Medicinal Products will not come into the hands of patients but will be applied by medical practitioners directly, information about the therapy, especially in cases of autologous products, must be given to patients even before the starting material is removed. Therefore the possibility should be introduced to use the summary of product characteristics as package leaflet.
Because the package will not come into the hand of patients the necessity for consultations with target patient groups could be deleted.
ARTICLE 15, PARAGRAPH 2, SUBPARAGRAPH 1
2. Where there is particular cause for concern, the Commission may, on the advice of the Agency, require as part of the marketing authorisation that a risk management system designed to identify, prevent or minimise risks related to advanced therapy medicinal products, including an evaluation of the effectiveness of that system, be set up, or that specific post-marketing studies be carried out by the holder of the marketing authorisation and submitted for review to the Agency.
2. Where there is particular cause for concern, the Commission shall, on the advice of the Agency, require as part of the marketing authorisation that a risk management system designed to identify, prevent or minimise risks related to advanced therapy medicinal products, including an evaluation of the effectiveness of that system, be set up, or that specific post-marketing studies be carried out by the holder of the marketing authorisation and submitted for review to the Agency.
4. The Agency shall draw up detailed guidelines relating to the application of paragraphs 1, 2 and 3.
4. The Agency shall draw up detailed guidelines relating to the application of paragraphs 1, 2 and 3. They shall be based on the principles of regulatory cooperation and dialogue with the marketing authorisation holder.
When drawing up post-authorisation risk management guidelines, principles of regulatory cooperation and dialogue with the marketing authorization holder should be enacted in order to allow a pooling of the limited expertise in this area.
ARTICLE 17, PARAGRAPH 2
2. By way of derogation from Article 8(1) of Regulation (EC) No 297/95, a 90% reduction shall apply to the fee payable to the Agency for any advice referred to in paragraph 1 and in Article 57(1)(n) of Regulation (EC) No 726/2004 in respect of advanced therapy medicinal products.
2. By way of derogation from Article 8(1) of Regulation (EC) No 297/95, a 95% reduction for small and medium-sized enterprises and 80% for other applicants shall apply to the fee payable to the Agency for any advice referred to in paragraph 1 and in Article 57(1)(n) of Regulation (EC) No 726/2004 in respect of advanced therapy medicinal products.
This Regulation seeks to encourage and support SME's in the development of ATMPs. Therefore, special fee-waivers should be introduced for SME's on scientific advice. The 5% of the basic fee which the SME's should cover themselves is a symbolic amount, in order to prevent any abuse of the system. To support applicants which are not SMEs and to ensure the competitiveness of the whole sector, a reduction of 70% should be applied to all companies irrespective of their size.
ARTICLE 18, PARAGRAPH 1
1. Any applicant developing a product based on cells or tissues may request a scientific recommendation of the Agency with a view to determining whether the referred product falls, on scientific grounds, within the definition of an advanced therapy medicinal product. The Agency shall deliver this recommendation after consultation with the Commission.
1. Any applicant developing a product based on cells or tissues may request a scientific recommendation of the Agency with a view to determining whether the referred product falls, on scientific grounds, within the definition of an advanced therapy medicinal product. The Agency shall deliver this recommendation, after consultation with the Committee for Advanced Therapies and the Commission, within 60 days of receipt of the request.
The proposed amendment foresees that an applicant will get clarity on the classification of the concerned product in a timely manner, thus facilitating business planning and further development of the product.
Incentives for small and medium-sized biotech enterprises
1. Manufacturers of advanced therapy medicinal products which employ not more than 500 persons and have a turnover not exceeding EUR 100 million, or a balance sheet total not exceeding EUR 70 million, shall be eligible for all incentives granted to small and medium–sized enterprises under Commission Recommendation 2003/361/EC of 6 May 2003 concerning the definition of micro, small and medium-sized enterprises1.
2. The same shall apply to an enterprise in which other enterprises have an interest up to 50 % and which invests more than 15 % of its annual turnover in research and development activities.
_________________ 1 L 124, 20.5.2003, p. 36.
For many young biotech enterprises it is difficult to meet the criteria for an SME. One of the reasons is that a purchase or sale of a patent or platform technology may generate a big one-off turnover which exceeds the current limitations. Another reason is that many enterprises don't comply with the current criteria of independence (interests below 25 %), since they built up alliances with other companies. These problems are likely to have the greatest relevance for biotech enterprises. These companies should nevertheless enjoy more favourable financial terms.
ARTICLE 19 B (new)
Reduction of the fee for marketing authorisation
1. The fee for marketing authorisation shall be reduced to 50 % if the applicant can prove that there is a particular public interest in the Community in the advanced therapy medicinal product or if the return on investment to be expected from the marketing of such a product is small.
2. The first paragraph shall also apply to fees for post-authorisation activities by the Agency in the first year following the granting of the marketing authorisation for the medicinal product. 3. In the case of small and medium-sized enterprises or enterprises which employ not more than 500 persons and have a turnover not exceeding EUR 100 million, or a balance sheet total not exceeding EUR 70 million, the first paragraph shall also apply to the fees for post-authorisation activities by the Agency without a time limit.
4. In the case of an enterprise in which other enterprises have an interest up to 50 % and which invests more than 15 % of its annual turnover in research and development activities, the first paragraph shall also apply to the fees for post-authorisation activities by the Agency without a time limit.
ARTICLE 21, PARAGRAPH 1, POINT (C)
(c) four members appointed by the Commission, on the basis of a public call for expressions of interest, two of them to represent surgeons and two of them to represent patients associations.
(c) two members and two alternates appointed by the Commission, on the basis of a public call for expressions of interest and after consultation of the European Parliament, to represent medical doctors;
In order to cover all medical fields which the advanced therapies may relate to, more general medical expertise, i.e. medical doctors, should be represented in the Committee for Advanced Therapies . In addition, by introducing alternate members, we would like to ensure a permanent representation of the groups involved. The appointment of these members and their alternates should take place in consultation with the European Parliament.
ARTICLE 21, PARAGRAPH 1, POINT (C A) (new)
(ca) two members and two alternates appointed by the Commission, on the basis of a public call for expressions of interest and after consultation of the European Parliament, to represent patients associations.
By introducing alternate members, we would like to ensure a permanent representation of the groups involved. The appointment of these members and their alternates should take place in consultation with the European Parliament.
ARTICLE 21, PARAGRAPH 2
2. All members of the Committee for Advanced Therapies shall be chosen for their scientific qualification or experience in respect of advanced therapy medicinal products. For the purposes of point (b) of paragraph 1, the Member States shall cooperate, under the coordination of the Executive Director of the Agency, in order to ensure that the final composition of the Committee for Advanced Therapies appropriately and in a balanced way covers the scientific areas relevant to advanced therapies, including medical devices, tissue-engineering, gene therapy, cell therapy, biotechnology, pharmacovigilance, risk management and ethics.
2. All members and alternates of the Committee for Advanced Therapies shall be chosen for their scientific qualification or experience in respect of advanced therapy medicinal products. For the purposes of point (b) of paragraph 1, the Member States shall cooperate, under the coordination of the Executive Director of the Agency, in order to ensure that the final composition of the Committee for Advanced Therapies, appropriately and in a balanced way covers the scientific areas relevant to advanced therapies, including medical devices, tissue-engineering, gene therapy, cell therapy, biotechnology, pharmacovigilance, risk management and ethics.
The alternate members of the Committee for Advanced therapies introduced in paragraph 1 shall comply with the same criteria of scientific qualification or experience in the field of advanced therapy medicinal products as its members.
ARTICLE 23, POINT (A)
(a) to advise the Committee for Medicinal Products for Human Use on any data generated in the development of an advanced therapy medicinal product, for the formulation of an opinion on its quality, safety and efficacy;
(a) to draw up a draft opinion on the quality, safety and efficacy of an advanced therapy medicinal product submitted for review; this draft opinion shall be transmitted to the Committee for Medicinal Products for Human Use for approval. The Committee for Advanced Therapies shall advise the Committee for Medicinal Products for Human Use on any data generated in the product’s development;
The Committee on Advanced Therapies should consist of the best possible experts from Member States. Their expertise should therefore form the basis of any product opinion delivered by the CHMP.
ARTICLE 23, POINT (A A) (new)
(aa) to advise the Committee for Medicinal Products for Human Use on the amendments provided for in Articles 4(2),8, 19 and 24;
The assessment of advanced therapy medicinal products often requires very specific expertise, for which reason the specialised Committee for Advanced Therapies is created. Therefore, it is logical that this specialised committee should have an advisory role in the comitology procedure to amend the Annexes and other technical requirements.
ARTICLE 23, POINT (E A) (new)
(ea) to provide advice on the scientific advice procedures referred to in Article 17;
ARTICLE 23, POINT (E B) (new)
(eb) to provide advice on product classification as referred to in Article 18.
The Committee on Advanced Therapies should consist of the best possible experts from Member States. Their expertise should therefore be drawn upon for any advice issued regarding the classification of an advanced therapy medicinal product.
The Commission shall, in accordance with procedure referred to in Article 26(2), amend Annexes I to IV in order to adapt them to scientific and technical evolution.
The Commission shall, in accordance with procedure referred to in Article 26(2), amend Annexes II to IV in order to adapt them to scientific and technical evolution.
Annex I contains a fundamental and substantial definition. Therefore, it should not be subject to any changes through comitology. Should any changes be necessary due to scientific progress, they should be adopted in codecision, fully involving the European Parliament.
Within 5 years of entry into force of this Regulation, the Commission shall publish a general report on its application, which shall include comprehensive information on the different types of advanced therapy medicinal products authorised pursuant to this Regulation.
Within 5 years of entry into force of this Regulation, the Commission shall publish a general report on its application, which shall include comprehensive information on the different types of advanced therapy medicinal products authorised pursuant to this Regulation and on the use and effect of the measures provided for in Chapter 6 of this Regulation and in Articles 9, 14(9) and 70(2) of Regulation (EC) No 726/2004. On the basis of that report, the Commission may propose amendments to this Regulation and Regulation (EC) No 726/2004.
The report on the implementation of this Regulation should cover the whole scope of the present regulation, including the incentive measures for SMEs, the 'fast-track' approvals and the appeal procedure. On the basis of this report, the Commission should re-evaluate the current provisions and propose amendments to improve them, also with a view of harmonizing the different provisions and procedures currently in use within the EMEA.
ARTICLE 26, PARAGRAPH 2 A (new)
2a. The Commission shall ensure that relevant information about envisaged measures is made available to all interested parties in due time.
This is necessary to ensure that Industry and other stakeholders are involved from the very beginning in the elaboration of secondary legislation as well as of guidance documents. This is a concept already introduced in Community legislation (see art. 15.5 of Directive 2004/22/EC of 21 March 2004 on measuring instruments).
ARTICLE 27, POINT 2
Annex, point 1 a (Regulation (EC) No. 726/2004)
“1a. Advanced therapy medicinal products, as defined in Regulation (EC) No […/of the European Parliament and of the Council (Regulation on Advanced Therapy Medicinal Products)].
“1a. Advanced therapy medicinal products, as defined in Regulation (EC) No […/of the European Parliament and of the Council (Regulation on Advanced Therapy Medicinal Products)], except for advanced therapy medicinal products for autologous or intended use which are exclusively manufactured and distributed in one Member State and for which that Member State has envisaged the national marketing authorisation procedure as an alternative, for a period of five years subsequent to the granting of the marketing authorisation at national level. Afterwards an application for renewal within the centralised procedure is necessary with the effect that after the renewal the national marketing authorisation becomes a centralised marketing authorisation.
In order to facilitate the stage of market entry for many SMEs wanting to market their product only in one member state, a marketing authorisation at national level for products marketed at national level should be rendered possible.
This national marketing authorisation should be limited to a period of five years.
The renewal after this first period of five years can be conducted through a centralised marketing authorisation.
ARTICLE 28, POINT 1
Article 3, paragraph 7 (Directive 2001/83/EC)
"7. Any advanced therapy medicinal product, as defined in Regulation (EC) No […/of the European Parliament and of the Council (Regulation on Advanced Therapy Medicinal Products)], which is both prepared in full and used in a hospital, in accordance with a medical prescription for an individual patient.
"7. Any advanced therapy medicinal product, as defined in Regulation (EC) No […/of the European Parliament and of the Council (Regulation on Advanced Therapy Medicinal Products)], which is prepared in full in a hospital on a one-off basis according to a specific, non-standardised and non-patented process, and used in a hospital, in order to comply with an individual medical prescription for an individual patient.
Paragraphs 1 and 2 do not apply to advanced therapy medicinal products. Justification
Exceptions given in Directive 2001/83/EC allow pharmacies to prepare medicinal products in accordance with a medical prescription without complying with medicinal product legislation. This exception would as well give the in-house pharmacies of hospitals the possibility producing TEP using standardized methods and on routinely basis. Therefore this amendment is crucial to ensure that only one-off basis products are excluded from the scope of this Regulation.
ARTICLE 28, POINT 2
Article 4, paragraph 5 (Directive 2001/83/EC)
“5. This Directive and all Regulations referred to therein shall not affect the application of national legislation prohibiting or restricting the use of any specific type of human or animal cells, or the sale, supply or use of medicinal products containing, consisting of or derived from these cells. The Member States shall communicate the national legislation concerned to the Commission.”
“5. This Directive and all Regulations referred to therein shall not affect the application of national legislation prohibiting or restricting the use of any specific type of human or animal cells, or the sale, supply or use of medicinal products containing, consisting of or derived from these cells, on ethical grounds. The Member States shall communicate the national legislation concerned to the Commission. The Commission shall publish the results in a public register.”
Member States should retain the rights to prohibit or allow products on ethical grounds reflecting the views held by that Member State. The Commission should be informed in a transparent manner by the Member States of which products will be allowed to be placed on the market with a view to allowing manufacturers to consult an authoritative list.
1. Advanced therapy medicinal products which were legally on the Community market in accordance with national or Community legislation at the time of entry into force of this Regulation shall comply with this Regulation no later than 2 years after its entry into force.
1. For advanced therapy medicinal products, other than tissue engineered products, which were legally on the Community market in accordance with national or Community legislation at the time of entry into force of this Regulation, an application for a marketing authorisation shall be filed no later than five years after the entry into force of this Regulation.
2. For tissue engineered products which are legally on the Community market in accordance with national or Community legislation at the time of entry into force of the technical requirements referred to in Article 8, an application for a marketing authorisation shall be filed no later than five years after the entry into force of the technical requirements referred to in Article 8.
2. By way of derogation from Article 3(1) of Regulation (EC) No 297/95, no fee shall be payable to the Agency in respect of applications submitted for the authorisation of the advanced therapy medicinal products mentioned in paragraph 1.
3. By way of derogation from Article 3(1) of Regulation (EC) No 297/95, no fee shall be payable to the Agency in respect of applications submitted for the authorisation of the advanced therapy medicinal products mentioned in paragraph 1.
The envisaged Transitional period of two years is too short, since the duration of the clinical trials alone will in many cases exceed the proposed time period.
Furthermore the applicant should only be responsible for the date of filing the application and not for delays due to the Agency/national competent authorities or problems during the assessment phase. Otherwhise, it could deprive patients from these important new medicinal products.
It shall apply from [3 months after entry into force]
2. It shall apply from *, except in relation to tissue engineered products.
3. In relation to tissue engineered products, this Regulation shall apply from the date on which all the requirements referred to in Articles 4, 5 and 8 have entered into force.
4. This Regulation shall be binding in its entirety and directly applicable in all Member States.
* 3 months after the date of entry into force of this Directive.
This is necessary to take into account the different timeframes necessary for the application of Regulations and Directives. The proposal recognizes that the pharmaceutical regime cannot be applied to TEP as it currently stands. It is therefore important that the regulation is applicable only when all the directives modified by it are also of application.
Proposal for a regulation of the European Parliament and of the Council on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004
COM(2005)0567 – C6-0401/2005 – 2005/0227(COD)
ITRE30.11.2005
Giles Chichester20.6.2006
Šarūnas Birutis, Jan Březina, Renato Brunetta, Jerzy Buzek, Joan Calabuig Rull, Pilar del Castillo Vera, Jorgo Chatzimarkakis, Giles Chichester, Den Dover, Lena Ek, Nicole Fontaine, Adam Gierek, Norbert Glante, Umberto Guidoni, András Gyürk, Rebecca Harms, Erna Hennicot-Schoepges, Ján Hudacký, Romana Jordan Cizelj, Anne Laperrouze, Vincenzo Lavarra, Pia Elda Locatelli, Eugenijus Maldeikis, Eluned Morgan, Angelika Niebler, Umberto Pirilli, Miloslav Ransdorf, Herbert Reul, Teresa Riera Madurell, Mechtild Rothe, Andres Tarand, Britta Thomsen, Patrizia Toia, Catherine Trautmann, Claude Turmes, Nikolaos Vakalis, Alejo Vidal-Quadras Roca, Dominique Vlasto
María del Pilar Ayuso González, Dorette Corbey, Peter Liese, Vittorio Prodi, John Purvis, Esko Seppänen
Prior to taking the final vote, Pia Elda Locatelli stated that given the fact that the amendments adopted had changed her initial position on the subject, she therefore could not continue as draftswoman. The Committee then appointed its chairman, Giles Chichester, draftsman.
Draftswoman (*): Hiltrud Breyer
(*) Enhanced cooperation between committees - Rule 47 of the Rules of Procedure
The Commission’s proposal seeks to regulate placing on the European market of products based on gene therapy, cell therapy and tissue engineering. These products are of growing importance for modern medicine and can potentially help a lot of patients, but some serious health risks might occur in case of improper regulation. Especially in the area of tissue engineering no harmonised European approach exists. In general, the Commission’s proposal is welcome by all stakeholders but the public debate and discussion in Parliament committees has shown that there are some points that urgently need clarification to make the proposal legally consistent, to exclude controversial interpretations, to make the proposal coherent with the current legislation and to safeguard Parliament's rights. This is why the Committee on Legal Affairs proposes a number of amendments.
1. The rights of the Parliament in the comitology procedure.
The Commission’s proposal foresees to delegate almost all important questions to the comitology procedure. In such a highly political issue it is important to safeguard Parliament's rights. The Parliament should have the right to examine and to block such decisions. It is unacceptable that Art. 8 of this proposal refers to the comitology procedure although the Commission has not even submitted to the Parliament a draft of adequate technical requirements. The European institutions have just reached a new agreement on the comitology procedure which is a step forward in balancing their powers. In the meantime, a proposed amendment introduces a procedure strengthening Parliament's role. 2. Legal safety on the issue of subsidiarity.
There is broad agreement that the European Union should not harmonise the legislation on the use of human embryos and human embryonic stem cells. The Commission proposes to safeguard the legislative right of the Member States in Article 28(2). However, this provision is not adequate and may be challenged in the Court of Justice, as it causes serious problems with regard to the legal basis of the proposal. It can not be excluded that the proposed Regulation constitutes a complete harmonisation. Therefore, the proposed Art. 28(2) would be an alien substance and breach of Community law would not be excluded. The Committee therefore proposes to exclude embryonic stem cells from the scope of the Regulation in Article 1. It would make clear that there will be no harmonization in these delicate areas. In addition, the wording of Art. 28(2) of the proposal should be changed to underline that Member States, acting on the basis of Art. 30 TEC can further ban or limit the use, the sale, the placing on the market of human and animal cells as well as the use of medicinal products which contain, consist or are derived from such cells.
3. To make the proposal coherent with the current EU legislation, some technologies that are banned in other European legislation should also not get authorisation under the current Commission’s proposal.
Regardless of the competence of the Member States there should not be any compromises regarding human rights and constitutional law, even if progress in some areas is rapid. The principle of the non-commercialization of the human body has to be respected. The integrity of the person is protected under the Oviedo Convention and the Charter of Fundamental Rights. The production of human-animal hybrids or chimeras constitutes a breach of the principle of the integrity of the person and of the principle of inviolability of human dignity. Interventions in the human germ line are explicitly named in the Oviedo Convention as endangering human dignity. Products which intervene in the human germ line are excluded from clinical trials in Directive 2001/20/EC and are non patentable according to Directive 98/44/EC as are also human-animal hybrids being against ordre public.
4. To insure the voluntary and unpaid donation of human tissues and cells the Directive 2004/23/EC must be amended.
Straight in connection with advanced therapies which are subject to rapid development and for products of which the human tissue and cells are increasingly needed, the principle of the non-commercialization of the human body requires Member States to ensure the voluntary and unpaid donation and procurement of human cells and tissues. Therefore the Directive 2004/23/EC must be amended for the purposes of the suggested Regulation.
The Committee on Legal Affairs calls on the Committee on the Environment, Public Health and Food Safety, as the committee responsible, to incorporate the following amendments in its report:
Proposal for a Regulation of the European Parliament and of the Council on advanced therapy medicinal products and amending Directive 2001/83/EC, Regulation (EC) No 726/2004 and Directive 2004/23/EC
The title of the proposal need to be changed, as Directive 2004/23/EC is also amended (see amendment 45).
(6) The regulation of advanced therapy medicinal products at Community level should not interfere with decisions made by Member States on whether to allow the use of any specific type of human cells, such as embryonic stem cells, or animal cells. It should also not affect the application of national legislation prohibiting or restricting the sale, supply or use of medicinal products containing, consisting of or derived from these cells.
(6) Legislation in force in Member States concerning the use of certain types of cells, such as embryonic stem cells, varies considerably. The regulation of advanced therapy medicinal products at Community level should not interfere with decisions made by Member States on whether to allow the use of any specific type cells. It should also not affect the application of national legislation prohibiting or restricting the sale, supply or use of medicinal products containing, consisting of or derived from these cells. Moreover, it is impossible to assess when, if ever, research on these cells will reach the stage at which commercial products made from these cells could be placed on the market. In order to respect the basic principles and the proper functioning of the internal market and to ensure legal certainty, this Regulation should apply only to products made of cells, for which marketing is feasible in the near future and which do not raise major controversies. Justification
The legal base of this regulation (Article 95 TEC) is a single market harmonisation measure. It is not designed to cover situations in which significant national legislative differences are intended to remain (c.f. ECJ Case C-376/98). It is therefore necessary to exclude from the scope of this regulation products using materials which are controversial and for which differing Member States legislative provisions are intended to remain. In any case, products using these materials are unlikely to be ready to be placed on the market in the foreseeable future.
(7a) This Regulation fully respects the prohibition on making the human body and its parts as such a source of financial gain, as set out as an inalienable minimum safeguard in the Charter of Fundamental Rights of the European Union and further underlined by the European Parliament in its resolutions of 10 March 2005 on the trade in human egg cells1 and of 26 October 2005 on patents for biotechnological inventions2. To that end, it is necessary to ensure that the donation of tissues and cells is voluntary and unpaid and that their procurement is carried out on a non-profit basis. Voluntary and unpaid tissue and cell donations also contribute to high safety standards for tissues and cells and therefore to the protection of human health.
1 OJ C 320 E, 15.12.2005, p. 251.
2 Texts Adopted of that date, P6_TA(2005)0407.
Rapid developments in biotechnology and biomedicine must not be allowed to compromise the protection of fundamental rights. These rights of which one of the most important one is the right to the integrity of the person are laid down in the Oviedo Convention as well as in the Charter of Fundamental Rights. These standards should be met especially for tissue- and cell-based advanced therapy medicinal products as highly innovative new products. In this context, voluntary and unpaid donation as well as procurement on a non-profit basis are the key principles that should be imperatively respected in the Community.
(7b) Directive 2001/20/EC1 prohibits gene therapy trials that result in modifications to a subject's germ line genetic identity. Directive 98/44/EC2 provides that processes for modifying the human germ line genetic identity are to be regarded as unpatentable. To ensure legal consistency, this Regulation should prohibit any authorisation of products that modify the germ line genetic identity of human beings. By way of exception, the prohibition of authorisation should not apply to products intended to treat cancers of the gonads.
1 Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use (OJ L 121, 1.5.2001, p. 34).
2 Directive 98/44/EC of the European Parliament and of the Council of 6 July 1998 on the legal protection of biotechnological inventions (OJ L 213, 30.7.1998, p. 13).
As Articles 1 and 13 of the Oviedo Convention make it clear, human dignity is compromised when the inheritance of genetic identity is altered. Products which are neither properly subject to clinical trials under Directive 2001/20/EC nor legally patentable under Directive 98/44/EC should not be eligible for authorisation under this Regulation. Nevertheless, products for the treatment of cancer of the gonades should be permitted to have European marketing authorisation.
(7c) This Regulation should prohibit any authorisation of products derived from human-animal hybrids or chimeras or containing tissues or cells originating or derived therefrom. This provision should not exclude the transplantation of somatic animal cells or tissues to the human body for therapeutic purposes, in so far as it does not interfere with the germ line.
(10) The Committee for Advanced Therapies should gather the best available Community expertise on advanced therapy medicinal products. The composition of the Committee for Advanced Therapies should ensure appropriate coverage of the scientific areas relevant to advanced therapies, including gene therapy, cell therapy, tissue-engineering, medical devices, pharmacovigilance and ethics. Patient associations and surgeons with scientific experience of advanced therapy medicinal products should also be represented.
(10) The Committee for Advanced Therapies should gather the best available Community expertise on advanced therapy medicinal products. The composition of the Committee for Advanced Therapies should ensure appropriate coverage of the scientific areas relevant to advanced therapies, including gene therapy, cell therapy, tissue-engineering, medical devices, pharmacovigilance and ethics. Patient associations and physicians with scientific experience of advanced therapy medicinal products should also be represented.
For the sake of being more precise it is necessary to apply the technical term.
This recital shall be deleted as a consequence to the introduction of a new recital 7(a) and new Articles 3(a) and 28(a).
(16) The manufacture of advanced therapy medicinal products should be in compliance with the principles of good manufacturing practice, as set out in Commission Directive 2003/94/EC of 8 October 2003 laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use, and adapted, where necessary, to reflect the specific nature of the products. Furthermore, guidelines specific to advanced therapy medicinal products should be drawn up, so as to properly reflect the particular nature of their manufacturing process.
(28) Directive 2001/83/EC and Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing European Medicines Agency should therefore be amended accordingly,
(28) Directive 2001/83/EC, Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing European Medicines Agency and Directive 2004/23/EC should therefore be amended accordingly,
This is a consequential amendment to the introduction of Article 28(a) (new) modifying Directive 2004/23/EC on tissues and cells.
This Regulation shall not apply to any advanced therapy medicinal products that contain or are derived from human embryonic and foetal cells, primordial germ cells and cells derived from those cells.
The legal base of this regulation (Article 95 TEC) is a single market harmonisation measure. It is not designed to cover situations in which significant national legislative differences are intended to remain (c.f. ECJ Case C-376/98). Amendment 13
– its cellular or tissue part containing non-viable cells or tissues must be liable to act upon the human body with action that can be considered as primary to that of the devices referred to.
ARTICLE 2, PARAGRAPH 1, POINT (D A) (new)
(da) chimera means:
- an embryo into which a cell of any non-human life form has been introduced; or
- an embryo of any non-human life form into which a human cell has been introduced; or
- an embryo that consists of cells of more than one embryo, foetus or human being;
This definition is introduced for the purpose of Article 3(c)(new) of the present Regulation. Amendment 16
ARTICLE 2, PARAGRAPH 1, POINT (D B) (new)
(db) hybrid means:
- a human ovum that has been fertilised by a sperm of a non-human life form;
- an ovum of a non-human life form that has been fertilised by a human sperm;
- a human ovum into which the nucleus of a cell of a non-human life form has been introduced;
- an ovum of a non-human life form into which the nucleus of a human cell has been introduced; or
- a human ovum or an ovum of a non-human life form that otherwise contains haploid sets of chromosomes from both a human being and a non-human life form.
This definition is introduced for the purpose of Article 3(c) of the present Regulation. Source: Canadian assisted human reproduction act 2004.
Where an advanced therapy medicinal product contains human cells or tissues, the donation, procurement and testing of those cells or tissues shall be made in accordance with the provisions laid down in Directive 2004/23/EC.
Where an advanced therapy medicinal product contains human cells or tissues, the donation, procurement and testing of those cells or tissues shall be made in accordance with the provisions laid down in Directive 2004/23/EC. The Committee for Medicinal Products for Human Use of the European Medicines Agency, hereinafter “the Agency”, shall verify the assurances (or the documentation) of the holder of the marketing authorisation with regard to the voluntary and unpaid donation of tissues and cells as laid down in Directive 2004/23/EC.
Prohibition of commercialisation of the human body and its parts as such
Where an advanced therapy medicinal product contains human tissues or cells, every stage of the authorisation procedure shall be carried out in accordance with the principle of non-commercialisation of the human body or its parts as such. To that end, and for the purposes of this Regulation, Member States shall ensure that:
- the procurement of tissues and cells as such is carried out on a non-profit basis.
Rapid developments in biotechnology and biomedicine must not undermine the protection of fundamental rights. These rights, of which a very important one is the person's integrity, are laid down in the the patenting directive, the Oviedo Convention and the Charter of Fundamental Rights. Amendment 19
Prohibition of products modifying the human germ line.
No authorisation shall be granted for products which modify the germ line genetic identity of human beings, except for those intended to treat cancers of the gonads.
As Articles 1 and 13 of the Oviedo Convention make it clear, human dignity is compromised when the inheritance of genetic identity is altered. Products which are neither properly subject to clinical trials under Directive 2001/20/EC nor legally patentable under Directive 98/44/EC should not be eligible for authorisation under this Regulation, with the exclusion of cancer treatment.
ARTICLE 3 C (new)
Prohibition of products derived from human-animal hybrids or chimeras
No authorisation shall be granted for products derived from human-animal hybrids or chimeras or containing tissues or cells originating or derived therefrom.
This provision shall not preclude the transplantation of somatic animal cells or tissues to the human body for therapeutic purposes, in so far as it does not interfere with the germ line.
The physical and mental integrity of the person and human dignity must be respected, as underlined by the Charter of fundamental rights of the EU. The creation of human-animal hybrids or chimeras is a breach of the right to integrity of a person and a violation of human dignity. In addition, the Directive 98/44/EC on the legal protection of biotechnological inventions stresses that the production of chimeras from germ cells is excluded from patentability. Therefore, no authorisation under this regulation should be granted to products containing or derived from such tissues and cells.
ARTICLE 5, PARAGRAPH -1 (new)
The Commission shall, in accordance with the procedure referred to in Article 26(2), amend Directive 2003/94/EC to take into account the specific characteristics of advanced therapy medicinal product and, especially, tissue engineered products.
Specific requirements for products containing animal cells
In addition to the requirements laid down in this Regulation and the Annexes hereto, products containing non-human cells or tissues shall be authorised only where it is guaranteed that they will not give rise to problems relating to the identification of endogen retroviruses in the external cells and in the recipients, the possible creation of new viruses, possible immune reactions or the possible development of cancer.
The legal base of this regulation (Article 95 TEC) is a single market harmonisation measure. It is not designed to cover situations in which significant national legislative differences are intended to remain (c.f. ECJ Case C-376/98). It is therefore necessary to exclude from the scope of this regulation products using materials which are ethically controversial and for which differing Member States legislative provisions are intended to remain. In any case, products using these materials are unlikely to be ready to be placed on the market in the foreseeable future.
2. The rapporteur or co-rapporteur appointed by the Committee for Medicinal Products for Human Use pursuant to Article 62 of Regulation (EC) No 726/2004 shall be a member of the Committee for Advanced Therapies. This member shall also act as rapporteur or co-rapporteur for the Committee for Advanced Therapies.
2. The rapporteur or co-rapporteur appointed by the Committee for Medicinal Products for Human Use pursuant to Article 62 of Regulation (EC) No 726/2004 shall be a member of the Committee for Advanced Therapies, shall be proposed by the Committee for Advanced Therapies and shall possess specific expertise in relation to the product concerned. This member shall also act as rapporteur or co-rapporteur for the Committee for Advanced Therapies.
In order to ensure the highest level of expertise, the rapporteur and co-rapporteur appointed by the CHMP should be proposed by the Committee for Advanced Therapies and should have specific expertise for the relevant product.
3. The draft opinion given by the Committee for Advanced Therapies under paragraph 1 shall be sent to the chairman of the Committee for Medicinal Products for Human Use in a timely manner so as to ensure that the deadlines laid down in Articles 6(3) or 9(2) of Regulation (EC) No 726/2004 can be met.
Due to the highly specific and unique character of the advanced therapy medicinal products, a new Committee for Advanced Therapies is established within EMEA, composed of experts having specific qualifications or experience in this highly innovative and quickly developing field. Therefore, this new structure should be responsible for drafting an opinion on the quality, safety, and efficacy of products for the final approval by the CHMP. The draft opinion should be given in a timely manner so the deadline laid down in Article 9(2) of Regulation (EC) No 726/2004 can also be met.
2. Where products are exclusively applied to patients by medical practitioners, the summary of product characteristics pursuant to Article 11 of Directive 2001/83/EC may be used as the package leaflet.
2. By way of derogation from Article 8(1) of Regulation (EC) No 297/95, a 95% reduction for SMEs and 70% for other applicants shall apply to the fee payable to the Agency for any advice referred to in paragraph 1 and in Article 57(1)(n) of Regulation (EC) No 726/2004 in respect of advanced therapy medicinal products.
This Regulation seeks to encourage and support SME's in the development of ATMPs. Therefore, it is necessary to introduce special fee-waivers applicable to SME's on scientific advice. The 5% of the basic fee which the SME's should cover themselves is a symbolic amount, in order to prevent any abuse of the totally gratis system. Moreover, to support the applicants which do not fall under the SME criteria and to ensure the competitiveness of the whole sector, a reduction of 70% should be applied to all companies irrespective of their size.
1. Any applicant developing a product based on cells or tissues may request a scientific recommendation of the Agency with a view to determining whether the referred product falls, on scientific grounds, within the definition of an advanced therapy medicinal product. The Agency shall deliver this recommendation, after consultation with the Committee for Advanced Therapies and the Commission, within 60 days after receipt of the request.
1. Manufacturers of advanced therapy medicinal products which employ not more than 500 persons and have a turnover not exceeding EUR 100 million, or a balance-sheet total not exceeding EUR 70 million, shall be eligible for all incentives which are granted to small and medium–sized enterprises as defined in Commission Recommendation 2003/361/EC1.
2. The same shall apply to enterprises in which other enterprises have an interest up to 50%, if those enterprises invest more than 15% of their annual turnover in research and development activities.
1 OJ L 124, 20.5.2003, p. 36.
For many young biotech enterprises it is difficult to meet the criteria for an SME. One of the reasons is that a purchase or sale of a patent or platform technology may generate a big oneoff turnover which exceeds the current limitations. Another reason is that many enterprises don't comply with the current criteria of independence (interests below 25 %), since they built up alliances with other companies. These problems are likely to have the greatest relevance for biotech enterprises. These companies should nevertheless enjoy more favourable financial terms.
1. The fee for marketing authorisation shall be reduced by 50% if the applicant can prove that there is a particular public interest in the Community in the advanced therapy medicinal product or if the return on investment to be expected from the marketing of that product is small.
2. Paragraph 1 shall also apply to fees charged by the Agency for post-authorisation activities in the first year following the granting of the marketing authorisation for the medicinal product.
3. In the case of small and medium-sized enterprises or enterprises which employ not more than 500 persons and have a turnover not exceeding EUR 100 million, or a balance-sheet total not exceeding EUR 70 million, paragraph 1 shall also apply, without any time limit, to the fees charged by the Agency for post-authorisation activities.
4. In the case of an enterprise in which other enterprises have an interest up to 50% and which invests more than 15% of its annual turnover in research and development activities, paragraph 1 shall also apply, without any time limit, to the fees charged by the Agency for post-authorisation activities.
(c) four members appointed by the Commission, on the basis of a public call for expressions of interest, two of them to represent physicians and two of them to represent patients associations.
ARTICLE 21, PARAGRAPH 1, POINT (C) AND POINT (C A) (new)
(c) two members and two alternates appointed by the Commission, on the basis of a public call for expressions of interest and after consultation of the European Parliament, to represent physicians;
(a) to formulate a draft opinion on the quality, safety and efficacy of an advanced therapy medicinal product for final approval by the Committee for Medicinal Products for Human Use and to advise it on any data generated in the development of such a product; Justification
(aa) to provide advice, pursuant to Article 18, to the Committee for Medicinal Products for Human Use on whether a product falls within the definition of an advanced therapy medicinal product;
Having specific expertise in advanced therapy medicinal products, the Committee for Advanced Therapies should assist the CHMP in its classification task of whether a product is or is not an advanced therapy medicinal product.
ARTICLE 23, PARAGRAPH 1 A (new)
When preparing a draft opinion for final approval by the Committee for Medicinal Products for Human Use, the Committee for Advanced Therapies shall endeavour to reach a scientific consensus. If such consensus cannot be reached, the Committee for Advanced Therapies shall adopt the position of the majority of its members. The draft opinion shall mention the divergent positions and the grounds on which they are based.
In order to guarantee transparency in the process of preparation of a draft opinion, a clear decision procedure should be defined within Committee for Advanced Therapies. Consequently, we suggest that a scientific consensus should be reached by its members.
Annex I contains a fundamental and substantial definition. We therefore consider that it should not be subject to any changes through comitology. Should any changes be necessary due to scientific progress, they should be adopted in codecision, fully involving the European Parliament.
In that report, the Commission shall also assess the impact of technical progress on the application of this Regulation and, if necessary, submit a legislative proposal for a review of its scope to include novel therapies which are neither gene therapy, nor cell therapy nor tissue engineering.
Scientific advances may make additional novel therapies possible which are neither gene therapy, nor cell therapy nor tissue engineering. It would be in the interest of patients for these to be included at some future date in order to allow European authorisation of the resulting products.
The Commission shall by no later than the end of 2007 submit a legislative proposal in order to ensure that products used for cosmetic purposes which contain human or animal cells or tissues are also covered by adequate Community legislation.
Until now products used for cosmetic purposes containing human or animal cells or tissues, although already being placed on the market, are not regulated under Community law. This regulation gap needs to be closed.
ARTICLE 26, PARAGRAPH 2, SUBPARAGRAPH 1
2. Where reference is made to this paragraph, and without prejudice to Article 26a, Articles 5 and 7 of Decision 1999/468/EC shall apply, having regard to the provisions of Article 8 thereof.
This is a consequential amendment to the introduction of the new Article 26(a) below.
Without prejudice to the implementing measures already adopted, on 1 April 2008 at the latest, the application of the provisions of this Regulation requiring the adoption of technical rules, amendments and decisions shall be suspended. Acting on a proposal from the Commission, the European Parliament and the Council may renew the provisions concerned in accordance with the procedure laid down in Article 251 of the Treaty and, to that end, they shall review them prior to the expiry of the date referred to above.
The first paragraph shall apply until such time as it is superseded by a new agreement on comitology.
This amendment is preliminary tabled until the new comitology procedure is adopted which ensures more control by the Parliament.
Annex, point 1 a (Regulation (EC) No 726/2004)
“1a. Advanced therapy medicinal products, as defined in Regulation (EC) No […/of the European Parliament and of the Council (Regulation on Advanced Therapy Medicinal Products)*].
“1a. Advanced therapy medicinal products, as defined in Regulation (EC) No […/of the European Parliament and of the Council (Regulation on Advanced Therapy Medicinal Products)*], except for advanced therapy medicinal products for autologous or intended use which are exclusively manufactured and distributed in one Member State and for which that Member State has envisaged the national marketing authorisation procedure in accordance with the criteria of this Regulation as an alternative, for a period of five years subsequent to the granting of the marketing authorisation at national level. Afterwards an application for a single renewal within the centralised procedure shall be necessary, with the effect that, after the renewal, the national marketing authorisation will become a centralised marketing authorisation.
In order to facilitate the stage of market entry for many SMEs wanting to market their product only in one member state, a marketing authorisation at national level for products marketed at national level should be rendered possible. This national marketing authorisation should be limited to a period of five years. The renewal after this first period of five years can be conducted through a centralised marketing authorisation.
“5. This Directive and all Regulations referred to therein shall not affect the application of national legislation prohibiting or restricting the use of any specific type of human or animal cells, or the sale, supply or use of medicinal products containing, consisting of or derived from these cells, by virtue of the Article 30 of the Treaty establishing the European Community.”
As this regulation is a partially harmonizing measure, it should be made clear that Member States has the right to refer to the Article 30 of the TEC when it comes to the access of certain medicinal products to their market. With regard to the Article 95, paragraph 4 of the TEC, the obligation to communicate the national legislation concerned to the Commission is only appropriate if the community measure is a fully harmonizing one.
ARTICLE 28 A (new)
Article 2, paragraph 1 (Directive 2004/23/EC)
Amendment to Directive 2004/23/EC
In Article 2(1) of Directive 2004/23/EC, the second subparagraph shall be replaced by the following:
"Where such manufactured products are covered by other Community legislation, this Directive shall apply only to donation, procurement and testing. However, the donation, procurement and testing provisions of this Directive shall be without prejudice to more specific provisions contained in other Community legislation."
According to the existing legislation, the donation, procurement and testing of human tissues and cells should comply with high standards of quality and safety in order to ensure a high level of health protection in the Community. Moreover, it also has to be ensured that the human body or its parts as such are not commercialised. Therefore, for the purposes of this Regulation, Member States shall have an imperative obligation to ensure voluntary and unpaid donation and to guarantee that the procurement of tissues or cells is carried out on a non-profit basis.
ARTICLE 29, PARAGRAPH 1
The envisaged Transitional period of two years is too short, since the duration of the clinical trials alone will in many cases exceed the proposed time period. Furthermore the applicant should only be responsible for the date of filing the application and not for delays due to the Agency/national competent authorities or problems during the assessment phase. Otherwise, it could deprive patients from these important new medicinal products.
ARTICLE 29, PARAGRAPH 1 A (new)
1a. For tissue engineered products which are legally on the Community market in accordance with national or Community legislation at the time of entry into force of the technical requirements referred to in Article 8, an application for a marketing authorisation shall be filed no later than five years after the entry into force of the technical requirements referred to in Article 8.
ANNEX II, POINT 2.2.
2.2. qualitative and quantitative composition in terms of the active substances and other constituents of the product, knowledge of which is essential for proper use, administration or implantation of the product. Where the product contains cells or tissues, a detailed description of these cells or tissues and of their specific origin shall be provided.
2.2. qualitative and quantitative composition in terms of the active substances and other constituents of the product, knowledge of which is essential for proper use, administration or implantation of the product. Where the product contains cells or tissues, a detailed description of these cells or tissues and of their specific origin, including the species of animal in cases of non-human origin, shall be provided.
ANNEX III, POINT (B)
(b) A description of the active substance(s) expressed qualitatively and quantitatively, including, where the product contains cells or tissues, the statement “This product contains cells of human/animal [as appropriate] origin” together with a short description of these cells or tissues and of their specific origin;
(b) A description of the active substance(s) expressed qualitatively and quantitatively, including, where the product contains cells or tissues, the statement “This product contains cells of human/animal [as appropriate] origin” together with a short description of these cells or tissues and of their specific origin, including the species of animal in cases of non-human origin;
ANNEX IV, POINT (A), POINT (III)
(iii) where the product contains cells or tissues, a description of those cells or tissues and of their specific origin;
(iii) where the product contains cells or tissues, a description of those cells or tissues and of their specific origin, including the species of animal in cases of non-human origin;
JURI23.3.2006
Hiltrud Breyer19.4.2006
Maria Berger, Carlo Casini, Monica Frassoni, Giuseppe Gargani, Piia-Noora Kauppi, Katalin Lévai, Hans-Peter Mayer, Aloyzas Sakalas, Daniel Strož, Diana Wallis, Rainer Wieland, Tadeusz Zwiefka
Hiltrud Breyer, Manuel Medina Ortega, Marie Panayotopoulos-Cassiotou, Michel Rocard
Sharon Bowles, Esther Herranz García, Mieczysław Edmund Janowski, Peter Liese, Maria Martens, Miroslav Mikolášik
Propunerea de regulament al Parlamentului European şi al Consiliului privind medicamentele pentru terapie avansată şi de modificare a Directivei 2001/83/CE şi a Regulamentului (CE) nr. 726/2004
COM(2005)0567 – C6 0401/2005 – 2005/0227(COD)
Comisia competentă în fond Data anunţului în plen
ENVI30.11.2005
Comisia (comisiile) sesizată(e) pentru avizare Data anunţului în plen
ITRE30.11.2006
IMCO30.11.2006
Avize care nu au fost emise Data deciziei
IMCO30.1.2006
Cooperare consolidată Data anunţului în plen
JURI18.5.2006
Raportor(i) Data numirii
Miroslav Mikolášik14.12.2005
Contestarea temeiului juridic Data avizului JURI
Modificarea resurselor financiare Data avizului BUDG
14.9.2006 20.11.2006
Adamos Adamou, Georgs Andrejevs, Liam Aylward, Tiberiu Barbuletiu, Irena Belohorská, Johannes Blokland, John Bowis, Frieda Brepoels, Hiltrud Breyer, Martin Callanan, Dorette Corbey, Chris Davies, Avril Doyle, Edite Estrela, Anne Ferreira, Matthias Groote, Françoise Grossetête, Cristina Gutiérrez-Cortines, Satu Hassi, Gyula Hegyi, Mary Honeyball, Caroline Jackson, Dan Jørgensen, Christa Klaß, Eija-Riitta Korhola, Urszula Krupa, Marie-Noëlle Lienemann, Peter Liese, Jules Maaten, Linda McAvan, Miroslav Ouzký, Antonyia Parvanova, Vittorio Prodi, Frédérique Ries, Dagmar Roth-Behrendt, Guido Sacconi, Karin Scheele, Carl Schlyter, Horst Schnellhardt, Richard Seeber, Kathy Sinnott, Bogusław Sonik, Evangelia Tzampazi, Thomas Ulmer, Anja Weisgerber, Åsa Westlund, Anders Wijkman
Pilar Ayuso, Niels Busk, Philippe Busquin, Hélène Goudin, Umberto Guidoni, Karin Jöns, Henrik Lax, Caroline Lucas, Jiří Maštálka, Miroslav Mikolášik, Bart Staes
Membri supleanţi (articolul 178 alineatul (2)) prezenţi la votul final
Iles Braghetto, Ioannis Gklavakis, Mieczyslaw Janowski, Maria Petre, Zita Plestinská, Konrad Szymanski
Observaţii(date disponibile într-o singură limbă)
Ultima actualizare: 1 martie 2007Notă juridică