Date post: | 22-Dec-2015 |
Category: |
Documents |
Upload: | hector-stafford |
View: | 213 times |
Download: | 0 times |
INTERNATIONAL INTERNATIONAL REGULATIONSREGULATIONS
FOR TISSUES & CELLSFOR TISSUES & CELLS
Carolina StylianouCarolina StylianouMinistry of HealthMinistry of Health
CyprusCyprus
14th Training Course BLOOD AND MARROW TRANSPLANTATION
Targu Mures, Romania
Fact: Tissue and Cell therapy is a field in which an intensive worldwide exchange takes place.
Need: Safeguard public health
Goal: worldwide standards
Bone Grafts Distributed/Exported by USABone Grafts Distributed/Exported by USA
0
200,000
400,000
600,000
800,000
1,000,000
1,200,000
1,400,000
1994 2000 2007
Tissue grafts/devices are exported to 45 countries
HHaematopoietic Stem Cellsaematopoietic Stem Cells EUROCET EUROCET data for 2008 data for 2008
Import by EU Member StatesImport by EU Member States - 1122 units of HSC - 1122 units of HSC (Belgium, Bulgaria, Denmark, Germany, Estonia, Ireland, (Belgium, Bulgaria, Denmark, Germany, Estonia, Ireland,
Greece, Spain, France, Italy, Lithuania, the Netherlands, Greece, Spain, France, Italy, Lithuania, the Netherlands, Portugal, Romania, Slovenia, and the United Kingdom). Portugal, Romania, Slovenia, and the United Kingdom).
Export by EU Member StatesExport by EU Member States - 269 units of HSC (Belgium, - 269 units of HSC (Belgium, Bulgaria, Czech Republic, Denmark, Germany, Ireland, Bulgaria, Czech Republic, Denmark, Germany, Ireland, Spain, France, Italy, Cyprus, the Netherlands, Portugal, Spain, France, Italy, Cyprus, the Netherlands, Portugal, Romania and the United Kingdom).Romania and the United Kingdom).
EUROCET (European Registry for Organs, Tissues and Cells, EUROCET (European Registry for Organs, Tissues and Cells,
http://http://www.eurocet.orgwww.eurocet.org//
In many cases data concerning volumes of exports is not In many cases data concerning volumes of exports is not available.available.
To Safeguard Public HealthTo Safeguard Public Health
Common quality standardsCommon quality standards Common glossaries.Common glossaries.
(Harmonisation and comparable (Harmonisation and comparable datadatato disseminate reliable information)to disseminate reliable information)
International RegulationsInternational Regulations
Tissues? Cells?Tissues? Cells?
Bone marrowBone marrow Peripheral Blood Stem cellsPeripheral Blood Stem cells Cord bloodCord blood SkeletalSkeletal SkinSkin VascularVascular OcularOcular Amniotic membraneAmniotic membrane Reproductive cellsReproductive cells
EU directives on Tissues and EU directives on Tissues and CellsCells
2004/23 2004/23 of the European Parliament and of the of the European Parliament and of the Council on setting standards of quality and safety for Council on setting standards of quality and safety for the donation, procurement, testing, processing, the donation, procurement, testing, processing, preservation, storage and distribution of human preservation, storage and distribution of human tissues and cellstissues and cells
2006/172006/17 implementing Directive 2004/23/EC of the implementing Directive 2004/23/EC of the European Parliament and of the Council as regards European Parliament and of the Council as regards certain technical requirements for the donation, certain technical requirements for the donation, procurement and testing of human tissues and cellsprocurement and testing of human tissues and cells
2006/862006/86 implementing Directive 2004/23/EC of the implementing Directive 2004/23/EC of the European Parliament and of the Council as regards European Parliament and of the Council as regards traceability requirements, notification of serious traceability requirements, notification of serious adverse reactions and events and certain technical adverse reactions and events and certain technical requirements for the coding, processing, requirements for the coding, processing, preservation, storage and distribution of preservation, storage and distribution of human human tissues and cellstissues and cells
Stem cells ?Stem cells ?
AdultAdult EmbryonicEmbryonic AllogeneicAllogeneic AutologousAutologous HaematopoieticHaematopoietic SomaticSomatic
Same provisions in regulations
Apply toApply to ProcurementProcurement TestingTesting ProcessingProcessing StorageStorage DistributionDistribution Export/Import Export/Import Clinical use of Clinical use of
tissues & cellstissues & cells
Do not apply toDo not apply to In vitro researchIn vitro research Tissues & cells used Tissues & cells used
as autologous graft as autologous graft within the same within the same surgical proceduresurgical procedure
Hospital exemption Hospital exemption productsproducts
Blood and blood Blood and blood products products (2002/98/EC)(2002/98/EC)
Organs or parts of Organs or parts of organs organs
•AdvancedAdvanced therapy medicinal productstherapy medicinal products
Directive 2004/23 EUDirective 2004/23 EU
• Applies to tissues and cells including Applies to tissues and cells including haematopoietic peripheral blood, haematopoietic peripheral blood, umbilical –cord blood and bone marrow umbilical –cord blood and bone marrow stem cells. stem cells.
• Lays down the standards of quality and Lays down the standards of quality and safety for human tissues and cells safety for human tissues and cells intended for human applications, in intended for human applications, in order to ensure a high level of protection order to ensure a high level of protection of human health.of human health.
The Competent Authorities The Competent Authorities ResponsibilitiesResponsibilities
Supervision of tissue and cell procurement Supervision of tissue and cell procurement and testingand testing
Accreditation, designation, authorisation/Accreditation, designation, authorisation/ licensing of tissue establishmentslicensing of tissue establishments Inspections and control measures to Inspections and control measures to
ensure complianceensure compliance Vigilance and Surveillance of activitiesVigilance and Surveillance of activities Report to the EU Commission on activities Report to the EU Commission on activities
undertaken in relation to the provisions of undertaken in relation to the provisions of the Directivesthe Directives
Report to the EU Commission on Report to the EU Commission on SAEs/SARs and SAEs/SARs and notify other competent notify other competent authorities for tissues/cells that are authorities for tissues/cells that are distributed distributed
Tissue establishment Tissue establishment ResponsibilitiesResponsibilities
Voluntary unpaid donation (donors Voluntary unpaid donation (donors may receive compensation strictly may receive compensation strictly limited to expenses and limited to expenses and inconveniences)inconveniences)
ConsentConsent No unauthorised disclosure of donor No unauthorised disclosure of donor
or patient personal data or patient personal data Donor evaluation and selection is Donor evaluation and selection is
carried out under specified carried out under specified conditionsconditions
But also…But also… Quality system based on the principles of Quality system based on the principles of
good practicegood practice1. Standard operating procedures2. Guidelines3. Training and reference manuals4. Reporting forms5. Donor records6. Information on the final destination of
tissues and cells7. Ensure traceability from donor to recipient8. Validation of processes9. Processing of tissues/cells while exposed to
environment must be in grade A air quality with a background air of at least quality D
As well as…As well as…
Designated responsible personDesignated responsible person Appropriately trained personnelAppropriately trained personnel Written agreements with third parties in Written agreements with third parties in
order to ensure that the quality of order to ensure that the quality of tissues/cells is not compromisedtissues/cells is not compromised
Ensure the quality of tissues/cells during Ensure the quality of tissues/cells during distributiondistribution
Report and/or investigate serious adverse Report and/or investigate serious adverse events to the competent authorityevents to the competent authority
Criteria for SARs reporting to Criteria for SARs reporting to the Competent authoritiesthe Competent authorities
Any unintended response, including a communicable disease, in the donor or recipient associated with the procurement or human application of tissues and cells that is fatal, life threatening, disabling, incapacitating or which results in, or prolongs, hospitalisation or morbidity.
(infection, hypersensitivity, malignancy, toxicity, mismatch, genetic abnormality or other transmission)
Criteria for SAEs reporting to Criteria for SAEs reporting to Competent AuthoritiesCompetent Authorities
Deviations should not be reported as SAEs to CAs Deviations should not be reported as SAEs to CAs unless:unless:
Inappropriate tissues or cells have been released Inappropriate tissues or cells have been released for clinical use, even if not usedfor clinical use, even if not used
The event could have implications for other The event could have implications for other patients or donors because of shared practices, patients or donors because of shared practices, services, supplies or donorsservices, supplies or donors
The event resulted in the loss of any irreplaceable The event resulted in the loss of any irreplaceable autologous tissues or cells or any highly matched autologous tissues or cells or any highly matched (i.e. recipient specific) allogeneic tissues or cells(i.e. recipient specific) allogeneic tissues or cells
The event resulted in the loss of a significant The event resulted in the loss of a significant quantity of unmatched allogeneic tissues or cells.quantity of unmatched allogeneic tissues or cells.
MovementMovement of tissues and cellsof tissues and cells Transport Transport between tissue establishments between tissue establishments
DistributionDistribution between a tissue establishment and a site of between a tissue establishment and a site of human applicationhuman application
Import/ExportImport/Export EU Member State and a Third country. The CA EU Member State and a Third country. The CA can introduce prohibition of or restriction on the importation can introduce prohibition of or restriction on the importation of human tissues and cells to ensure a high level of health of human tissues and cells to ensure a high level of health protection. protection.
Tissue establishments that receive such imports/send such Tissue establishments that receive such imports/send such exports shall ensure that these meet standards of quality and exports shall ensure that these meet standards of quality and safety equivalent to the ones described in this Directive.safety equivalent to the ones described in this Directive. MMovement of tissues and cells between countries within ovement of tissues and cells between countries within European Economic Area actually falls within the definition of European Economic Area actually falls within the definition of transport and distribution and not import and export. If a transport and distribution and not import and export. If a tissue establishment imports tissues and cells and supplies tissue establishment imports tissues and cells and supplies other tissue establishments, the responsibility resides with other tissue establishments, the responsibility resides with this first establishment as the original place of entry.this first establishment as the original place of entry.
Competent Authority
Competent Authority
Tissue Establishment Tissue Establishment
Distribution
QUICK ALERTSAE/SAR
Report
Investigation
Inform
Investigation
COMMISSION
CIRCA
Dissemination of data between TEs and CAs after a SAE/SAR
Advanced Therapy Medicinal Products Advanced Therapy Medicinal Products for human usefor human use
Gene therapy medicinal productGene therapy medicinal product Somatic cell therapy medicinal product Somatic cell therapy medicinal product Tissue engineered medicinal productTissue engineered medicinal product
Cells or tissues have been subjected to substantial Cells or tissues have been subjected to substantial manipulation, so that biological characteristics, physiological manipulation, so that biological characteristics, physiological functions or structural properties relevant for the intended functions or structural properties relevant for the intended regeneration, repair or placement are achieved.regeneration, repair or placement are achieved.
AND/ORAND/OR Cells or tissues that are not intended to be used for the same Cells or tissues that are not intended to be used for the same
essential function /functions in the recipient as in the donor.essential function /functions in the recipient as in the donor.
Substantial manipulation is Substantial manipulation is notnot considered cutting, grinding, considered cutting, grinding, shaping, centrifugation, soaking in antibiotic or antimicrobial shaping, centrifugation, soaking in antibiotic or antimicrobial solutions, sterilisation, irradiation, cell separation, filtering, solutions, sterilisation, irradiation, cell separation, filtering, lyophilisation, freezing, cryopreservation, vitrification.lyophilisation, freezing, cryopreservation, vitrification.
EU Regulation and Directive on EU Regulation and Directive on Advanced Therapy Medicinal productsAdvanced Therapy Medicinal products
Regulation No 1394/2007 of the of European Parliament and of the Council on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004
(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 Directive 2004/23/EC)
2009/120 amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use as regards advanced therapy medicinal products
(The traceability system shall be complementary to, and compatible with, the requirements established in Directive 2004/23/EC of the European Parliament and of the Council , as regards human cells and tissues other than blood cells, and Directive 2002/98/EC, as regards human blood cells)
Committee for Advanced TherapiesCommittee for Advanced Therapies
The Committee for Advanced Therapies (CAT) was The Committee for Advanced Therapies (CAT) was established in accordance with Regulation (EC) No established in accordance with Regulation (EC) No 1394/2007 for ATMPs. It is a multidisciplinary 1394/2007 for ATMPs. It is a multidisciplinary committee, gathering together some of the best committee, gathering together some of the best available experts in Europe to assess the quality, available experts in Europe to assess the quality, safety and efficacy of ATMPs, and to follow scientific safety and efficacy of ATMPs, and to follow scientific developments in the field.developments in the field.
The main responsibility of the CAT is to prepare a The main responsibility of the CAT is to prepare a draft opinion on each ATMP application submitted to draft opinion on each ATMP application submitted to the European Medicines Agency, before the the European Medicines Agency, before the Committee for Medicinal Products for Human Use Committee for Medicinal Products for Human Use (CHMP) adopts a final opinion on the granting, (CHMP) adopts a final opinion on the granting, variation, suspension or revocation of a marketing variation, suspension or revocation of a marketing authorisation for the medicine concerned. At the authorisation for the medicine concerned. At the request of the Agency's Executive Director or of the request of the Agency's Executive Director or of the European Commission, an opinion is also drawn up European Commission, an opinion is also drawn up on any scientific matter relating to ATMPs.on any scientific matter relating to ATMPs.
Hospital Exemption Hospital Exemption ProductsProducts
This is a custom-made cell-containing This is a custom-made cell-containing product that is prepared on a non-routine product that is prepared on a non-routine basis according to specific quality standards. basis according to specific quality standards. It is made available to an individual patient It is made available to an individual patient in a European hospital under the exclusive in a European hospital under the exclusive responsibility of a doctor. responsibility of a doctor.
It is authorised for use by the regulatory It is authorised for use by the regulatory authority of the Member State where the authority of the Member State where the product is made.product is made.
In the USA…..In the USA…..
The Centre for Biologics Evaluation and Research The Centre for Biologics Evaluation and Research ((CBERCBER) at the FDA, regulates HCT/Ps under 21 ) at the FDA, regulates HCT/Ps under 21 CFR, parts 1270 and 1271. CFR, parts 1270 and 1271.
The FDA’s revised regulations are contained in The FDA’s revised regulations are contained in Part 1271 and apply to tissues recovered after Part 1271 and apply to tissues recovered after 2005, which are the current tissue rules. 2005, which are the current tissue rules. Examples of tissues regulated are Examples of tissues regulated are musculoskeletal tissue, skin, corneas, heart musculoskeletal tissue, skin, corneas, heart valves, valves, haematopoietic stem cellshaematopoietic stem cells and and reproductive cells.reproductive cells.
The 3 FDA rules……The 3 FDA rules…… Registration and listing - Requires tissue establishments to
register and list their HCT/Ps with the FDA. This includes the types and uses of the products that will be regulated by these rules. Also, all foreign establishments importing HCT/Ps into the US must register and list such HCT/Ps.
The donor eligibility rule - Requires HCT/P establishments to screen and test tissue and cell donors for relevant communicable disease agents or diseases.
Current good tissue practices - The requirements that govern the methods used in, and the facilities and controls used for, the manufacture of HCT/Ps, including all steps in recovery, donor screening and testing, processing, labelling, packaging and distribution. Also included are the requirements for process validation, labelling, tracking, complaint files and adverse reaction reporting. In general CGTP ensures that HCT/Ps do not contain communicable disease agents, are not contaminated and that they do not become contaminated during manufacturing.
In Australia…….In Australia……. Therapeutic Goods Act 1989 - therapeutic goods
which are imported into Australia, supplied for use in Australia or exported from Australia, conform with a standard applicable to the goods. The Act includes non-cord blood HPCs.
Therapeutic Goods Order 75 - Haematopoietic progenitor cells derived from cord blood must meet the requirements of the document entitled "International Standards for Cord Blood Collection, Processing, Testing, Banking, Selection, and Release" Third edition, dated December 2006, published by the Foundation for the Accreditation of Cellular Therapy and NetCord.
The future…..The future…..
Implementation of European/Global Surveillance and Implementation of European/Global Surveillance and Vigilance systemVigilance system
Role of Regulators, engagement of Clinicians, role of Professional Societies, clarity in reporting requirements, openness, transparency and non-punitive culture, effective communication, patient focus, system standardisation, education of stakeholders
Implementation of a European Coding System