Giovanni Migliaccio Head, Section of Gene and Cell Therapy Istituto Superiore di Sanità

Transcription

1 REGULATION (EC) N 1394/2007 Advanced Therapy Medicinal Prducts Givanni Migliacci Head, Sectin f Gene and Cell Therapy Istitut Superire di Sanità Rme Italy

2 REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL n 1394/2007 n advanced therapy medicinal prducts and amending Directive 2001/83/EC and Regulatin (EC) N 726/2004 Will be in frce in December 2008

3 Scpe f the new Regulatin The inclusin f the Regenerative Medicine Therapies in the medicinal prduct legislatin

4 Definitin f ATMP If advanced therapy prducts are: presented as having prperties fr treating r preventing diseases, r used t restring, crrecting r mdifying physilgical functins (Regenerative Medicine) by exerting principally a pharmaclgical, immunlgical r metablic actin, they are bilgical medicinal prducts.

5 Advanced Therapies Gene Therapy, Smatic Cell Therapy, and Tissue Engineering. This nascent field f bimedicine ffers new pprtunities fr the treatment f diseases and dysfunctins f the human bdy.

6 Tissue Engineering Prducts engineered cells r tissues? regenerating, repairing r replacing a human tissue.

7 Overlapping prducts Organs Transplants Medical Devices Cells / Tissue Engineered Or Nt engineered ATMP Nn viable Cell/tissue Principal mde f actin

8 Viable r nn viable? Prducts cntaining r cnsisting exclusively f nn-viable human r animal cells and/r tissues, which d nt cntain any viable cells r tissues and which d nt act principally by pharmaclgical, immunlgical r metablic actin, shall be excluded frm this definitin.

9 Engineered, when? the cells r tissues have been subject t substantial manipulatin, s that bilgical characteristics, physilgical functins r structural prperties relevant fr the intended regeneratin, repair r replacement are achieved. (The manipulatins listed in Annex I, in particular, shall nt be cnsidered as substantial manipulatins) the cells r tissues are nt intended t be used fr the same essential functin r functins in the recipient as in the dnr.

10 Cmbined advanced therapy medicinal prduct it must incrprate, as an integral part f the prduct, ne r mre medical devices its cellular r tissue part must cntain viable cells r tissues, r its cellular r tissue part cntaining nnviable cells r tissues must be liable t act upn the human bdy with actin that can be cnsidered as primary t that f the devices referred t.

11 Tissue Engineered Prducts A tissue engineered prduct may cntain cells r tissues f human r animal rigin, r bth. The cells r tissues may be viable r nn-viable. It may als cntain additinal substances, such as cellular prducts, bi-mlecules, bimaterials, chemical substances, scafflds r matrices.

12 Transplant, Medical Devices and Advanced Therapy Medicinal Prducts The criteria t classify a cmbinatin f drug and medical devices is the Principal Mde f Actin In the presence f viable cells r tissue the Cmbined Prduct are always a Medicinal Prduct

13 Classificatin Gene Therapy Prduct Mdified by genetic manipulatin Tissue Engineered Prduct Smatic Cell Therapy Prduct

14 Centralized registratin The centralized registratin prcedure is cmpulsry fr ATMP in rder t : vercme the scarcity f expertise in the Cmmunity, ensure a high level f scientific evaluatin f these medicinal prducts in the Cmmunity, preserve the cnfidence f patients and medical prfessins in the evaluatin and facilitate Cmmunity market access fr these innvative technlgies.

15 Restrictin t Marketing The regulatin f advanced therapy medicinal prducts at Cmmunity level shuld nt interfere with decisins made by Member States n whether t allw the use f any specific type f human cells, such as embrynic stem cells, r animal cells. It shuld als nt affect the applicatin f natinal legislatin prhibiting r restricting the sale, supply r use f medicinal prducts cntaining, cnsisting f r derived frm these cells.

16 CAT EMEA t create, within the Agency, a Cmmittee fr Advanced Therapies, which shuld be respnsible fr preparing a draft pinin n the quality, safety and efficacy f each advanced therapy medicinal prduct fr final apprval by the Agency s Cmmittee fr Medicinal Prducts fr Human Use. In additin, the Cmmittee fr Advanced Therapies shuld be cnsulted fr the evaluatin f any ther medicinal prduct which requires specific expertise falling within its area f cmpetence. Patient assciatins and clinicians with scientific experience f advanced therapy medicinal prducts shuld als be represented.

17 Ntified Bdies and cmbined ATMPs Advanced therapy medicinal prducts may incrprate medical devices r active implantable medical devices. Thse devices shuld meet the essential requirements laid dwn in Cuncil Directive 93/42/EEC f 14 June 1993 cncerning medical devices (4) and Cuncil Directive 90/385/EEC f 20 June 1990 n the apprximatin f the laws f the Member States relating t active implantable medical devices (5), respectively, in rder t ensure an apprpriate level f quality and safety. The results f the assessment f the medical device part r the active implantable medical device part by a ntified bdy in accrdance with thse Directives shuld be recgnised by the Agency in the evaluatin f a cmbined advanced therapy medicinal prduct carried ut under this Regulatin.

18 Guidelines and Legislatin Adjustments The peratin f this Regulatin requires the establishment f guidelines t be drawn up either by the Agency r by the Cmmissin. Open cnsultatin with all interested parties, in particular Member State authrities and the industry, shuld be carried ut in rder t allw a pling f the limited expertise in this area and ensure prprtinality. The guidelines n gd clinical practice and gd manufacturing practice shuld be laid dwn as sn as pssible, preferably during the first year after entry int frce and befre the date f applicatin f this Regulatin (December 2008).

19 Supprting activity by EMEA Innvatin Task Frce Scientific Advice New Guidelines by CPWP and GTWP Cell therapy Xengeneic cells Gene therapy Reduced fees fr small and medium enterprises

20 Preclinical data certificatin Studies necessary t demnstrate the quality and nnclinical safety f advanced therapy medicinal prducts are ften carried ut by small and mediumsized enterprises. As an incentive t cnduct thse studies, a system f evaluatin and certificatin f the resulting data by the Agency, independently f any marketing authrizatin applicatin, shuld be intrduced. Even thugh the certificatin wuld nt be legally binding, this system shuld als aim at facilitating the evaluatin f any future applicatin fr clinical trials and marketing authrizatin applicatin based n the same data.

21 Cmmissin Activity fr ATMP Annexes amendment In particular, the Cmmissin shuld be empwered t adpt amendments t Annexes I t IV t this Regulatin (list f the minimal manipulatins) and t Annex I t Directive 2001/83/EC. (It cntains the definitin f smatic cell and gene therapy prducts)

22 Specificity f ATMPs Advanced therapy medicinal prducts shuld be subject t the same regulatry principles as ther types f bitechnlgy medicinal prducts. Hwever, technical requirements, in particular the type and amunt f quality, preclinical and clinical data necessary t demnstrate the quality, safety and efficacy f the prduct, may be highly specific.

23 Clinical trial fr ATMP Clinical trials n advanced therapy medicinal prducts shuld be cnducted in accrdance with the verarching principles and the ethical requirements laid dwn in Directive 2001/20/EC Cmmissin Directive 2005/28/EC f 8 April 2005 laying dwn principles and detailed guidelines fr gd clinical practice as regards investigatinal medicinal prducts fr human use, as well as the requirements fr authrizatin f the manufacturing (GMP) r imprtatin f such prducts (2) shuld be adapted by laying dwn rules tailred t fully take int accunt the specific technical characteristics f advanced therapy medicinal prducts.

24 Specific GMP fr ATMP The manufacture f advanced therapy medicinal prducts shuld be in cmpliance with the principles f gd manufacturing practice, as set ut in Cmmissin Directive 2003/94/EC f 8 Octber 2003 laying dwn the principles and guidelines f gd manufacturing practice in respect f medicinal prducts fr human use and investigatinal medicinal prducts fr human use (3), and adapted, where necessary, t reflect the specific nature f thse prducts. Furthermre, guidelines specific t advanced therapy medicinal prducts shuld be drawn up, s as t prperly reflect the particular nature f their manufacturing prcess.

25 Rle f Directive 2004/23/EC Directive 2004/23/EC f the Eurpean Parliament and f the Cuncil (2) sets standards f quality and safety fr the dnatin, prcurement, testing, prcessing, preservatin, strage and distributin f human tissues and cells. This Regulatin shuld nt dergate frm the basic principles laid dwn in Directive 2004/23/EC, but shuld supplement them with additinal requirements, where apprpriate. Where an advanced therapy medicinal prduct cntains human cells r tissues, Directive 2004/23/EC shuld apply nly as far as dnatin, prcurement and testing are cncerned, since the further aspects are cvered by this Regulatin.

26 Surcing f cell and tissues As a matter f principle, human cells r tissues cntained in advanced therapy medicinal prducts shuld be prcured frm vluntary and unpaid dnatin.

27 Traceability A system allwing cmplete traceability f the patient as well as f the prduct and its starting materials is essential t mnitr the safety f advanced therapy medicinal prducts.

28 Dnr annymity and tracking The rules gverning the labeling shuld cmply fully with the patient s right t knw the rigin f any cells r tissues used in the preparatin f advanced therapy medicinal prducts, while respecting dnr annymity.

29 Overlapping authrizatins Cell and Tissue Bank Dir 2004/23/EC Cell Factry GMP authrized Reg. 2007/1394/EC Pint f use Hspitals Traceability requested

30 Fllw-up Fllw-up f efficacy and adverse reactins is a crucial aspect f the regulatin f advanced therapy medicinal prducts. The applicant shuld therefre detail in its marketing authrizatin applicatin whether measures are envisaged t ensure such fllw-up and, if s, what thse measures are. Where justified n public health grunds, the hlder f the marketing authrizatin shuld als be required t put in place a suitable risk management system t address risks related t advanced therapy medicinal prducts.

31 Prduct already n the market On the Eurpean market are present a grup f prducts falling in the definitin f tissue engineering and smatic cell therapy, previusly authrized by single Member States due t unclear classificatin. These prducts will have 3 t 4 years starting frm Dec t be centrally authrized.

32 Art 28 applicatin Advanced therapy medicinal prducts which are prepared n a nn-rutine basis accrding t specific quality standards, and used within the same Member State in a hspital under the exclusive prfessinal respnsibility f a medical practitiner, in rder t cmply with an individual medical prescriptin fr a custm-made prduct fr an individual patient, shuld be excluded frm the scpe f this Regulatin whilst at the same time ensuring that relevant Cmmunity rules related t quality and safety are nt undermined.