Regulatory challenges for
combination-ATMP products
Gert Bos
BSI Healthcare




             Drug device Combination Produ...
This presentation
   ATMP defined
   Regulation and implementation
   CAT
   Evaluation procedure
   Certification
  ...
Regulation

• Regulation 1394/2007
        Published on Dec 10 2007, applicable from Dec 30 2008
• Definition Advanced Th...
‘Advanced therapy medicinal product’

• any of the following MPs for human use:
    a gene therapy MP as defined in 2001/...
Tissue engineered products

• cells or tissues of human or animal origin, or both.
• cells or tissues viable or non-viable...
‘engineered’ cells & combination-ATMP

Engineered cells:
• Cells/tissues subject to substantial manipulation, non-
  subst...
Examples of combination-ATMPs

• Artificial skin embedded in wound care product


• Chondrocytes in cartilage scaffold wit...
Highlights regulation

• Pre-market:
    Combination ATMPs: ERs of MDD
    Specific GMP and GCP guidelines
    Specific...
Implementing legislation




• Procedure for evaluation and certification
• Dossier req. module 3, 4
• Site visits
• Guide...
Implementing legislation




• Amending 2001/83, annex I, part IV
    New definitions GTMP and somatic CTMP
    Risk bas...
3 SANCO directives on tissues and cells

• 2004/23/EC: standards of quality & safety for
  donation, procurement, testing,...
Committee for Advanced Therapies (CAT)




CK Schneider, PEI
Evaluation procedure

• PRE authorisation:
    Product compliance to ERs
    Guidelines to GMP (2003/94/EC) and GCP
   ...
CAT

                      Rapporteur &
                      Co-rapporteur
                           +
                 ...
Tasks Committee for Advanced Therapies

• Initial evaluation, re-examination, PMS
     => draft opinion to CHMP
• Classifi...
ATMP evaluation
                    Two phase review




MH Pinheiro, EMEA
ATMP evaluation – combination products

• Agency must recognise results of any assessment
  by a notified body MDD / AIMD
...
ATMP evaluation – re-examination

• 15 days and 60 days without clock stop
• Same concept, new reviewers
• CAT must be con...
State of play 2009

• First meetings CAT
• CAT looking for interested parties
• Discussion CAT/EMEA with NBOG – NBmed
• Te...
Scientific advise




MH Pinheiro, EMEA
Certification quality and non-clinical data
• Only for SMEs
• Quality data, or Quality and non-clinical
• For scientific e...
Certification quality and non-clinical data




EMEA
One slide on risk management




J Petracek, EMEA
CAT monthly report
• http://www.emea.europa.eu/pressoffice/presshome.htm
CAT monthly report
Borderlines

• TEP may contain viable and non-viable cells
• No viable cells & no principal metabolic action
  => no ATMP
...
ATMP containing devices

• Devices as referred to in art. 7 of ATMP
    Not a med.dev. (scaffolds, biomaterials, matrices...
Further NoBo involvement

• Several Notified Bodies volunteer knowledge to CAT


• Discussion EMEA / NB-med / NBOG on coop...
ISO/TC194/SC1 – Tissue product safety

• CEN TC 316
• Secretariat: DIN
• Chair: Sabine Kloth
• Work on ISO/CD 13022 standa...
RGM/1

• Technical Committee to mirror the work of ISO/TC
  150/SC7 "Tissue-engineered medical products"


• Work on stand...
Additional items and further reading……..
• 2001/20/EC – clinical trials
• 2002/98/EC – blood derivatives
• Regulation 1234...
32

Contact Us

     Name:      Gert Bos
       Title:   Head of Regulatory and Clinical Affairs

   Address:     BSI
    ...
Upcoming SlideShare
Loading in …5
×

Informa Atmp Gert Bos Nov 2009 Final

1,304 views

Published on

ATMP - medical device combination products

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
1,304
On SlideShare
0
From Embeds
0
Number of Embeds
6
Actions
Shares
0
Downloads
27
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Informa Atmp Gert Bos Nov 2009 Final

  1. 1. Regulatory challenges for combination-ATMP products Gert Bos BSI Healthcare Drug device Combination Products Informa, Prague, CZ 17 November 2009
  2. 2. This presentation  ATMP defined  Regulation and implementation  CAT  Evaluation procedure  Certification  State of play today  Scientific recommendation  Dossier Requirements  NoBo involvement SME
  3. 3. Regulation • Regulation 1394/2007  Published on Dec 10 2007, applicable from Dec 30 2008 • Definition Advanced Therapy MP • Definition Tissue Engineered product (MP) • Principles of medicines legislation to apply • Mandatory centralised procedure • Gene therapy and somatic cell therapy MP  to be brought under annex I of 2001/83 • Committee for Advanced Therapies (CAT) http://ec.europa.eu/enterprise/pharmaceuticals/advtherapies/index.htm
  4. 4. ‘Advanced therapy medicinal product’ • any of the following MPs for human use:  a gene therapy MP as defined in 2001/83/EC,  a somatic cell therapy MP as defined in 2001/83/EC,  a tissue engineered product. • ‘Tissue engineered product’ means a product that:  contains or consists of engineered cells or tissues, and  is presented as having properties for, or is used in or administered to human beings with a view to regenerating, repairing or replacing a human tissue.
  5. 5. Tissue engineered products • cells or tissues of human or animal origin, or both. • cells or tissues viable or non-viable • additional substances, such as  cellular products & bio-molecules,  Biomaterials & chemical substances,  scaffolds or matrices. • non-viable human or animal cells and/or tissues in products that do not act principally by pharmacological, immunological or metabolic action, excluded.
  6. 6. ‘engineered’ cells & combination-ATMP Engineered cells: • Cells/tissues subject to substantial manipulation, non- substantial manipulations listed, and/or • cells or tissues not intended to be used for same essential function(s) in recipient as in donor. Combination-ATMP: • MDD or AIMD, and • cellular or tissue part contain viable cells or tissues, or • Non-viable cellular/tissue part acting pharmaceutically
  7. 7. Examples of combination-ATMPs • Artificial skin embedded in wound care product • Chondrocytes in cartilage scaffold with cell sorting and seeding device • bone void fillers with human bone morphogenic proteins • Wound dressings with human growth hormones
  8. 8. Highlights regulation • Pre-market:  Combination ATMPs: ERs of MDD  Specific GMP and GCP guidelines  Specific rules for labeling and packaging • Post-market:  Follow-up efficacy and adverse reactions  Risk management  traceability
  9. 9. Implementing legislation • Procedure for evaluation and certification • Dossier req. module 3, 4 • Site visits • Guide on minimum quality and non-clinical data
  10. 10. Implementing legislation • Amending 2001/83, annex I, part IV  New definitions GTMP and somatic CTMP  Risk based approach  Updated req. modules 3, 4, 5
  11. 11. 3 SANCO directives on tissues and cells • 2004/23/EC: standards of quality & safety for donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells • 2006/17/EC: technical requirements for donation, procurement and testing of human tissues and cells • 2006/86/EC: traceability requirement, notification serious adverse events, requirements for coding, processing, preservation, storage and distribution of human tissues and cells
  12. 12. Committee for Advanced Therapies (CAT) CK Schneider, PEI
  13. 13. Evaluation procedure • PRE authorisation:  Product compliance to ERs  Guidelines to GMP (2003/94/EC) and GCP  Rules for packaging and labelling • POST authorisation:  Follow up efficacy and adverse reactions, and risk management  Traceability
  14. 14. CAT Rapporteur & Co-rapporteur + CHMP co- ordinator + ATMP experts Lucia D’Apota, EMEA
  15. 15. Tasks Committee for Advanced Therapies • Initial evaluation, re-examination, PMS => draft opinion to CHMP • Classification: product = ATMP? => scientific recommendation from CAT • Certification => CAT opinion => EMEA certification • Scientific advices for ATMP => CAT involved • Other => consultation by CHMP, advice to Commission
  16. 16. ATMP evaluation Two phase review MH Pinheiro, EMEA
  17. 17. ATMP evaluation – combination products • Agency must recognise results of any assessment by a notified body MDD / AIMD • May request NoBo further information on assessment • If not included  Agency to seek scientific opinion from NoBo  CAT may decide no NoBo involvement needed
  18. 18. ATMP evaluation – re-examination • 15 days and 60 days without clock stop • Same concept, new reviewers • CAT must be consulted by CHMP • CAT to provide draft opinion • Withdrawals publicly accessible
  19. 19. State of play 2009 • First meetings CAT • CAT looking for interested parties • Discussion CAT/EMEA with NBOG – NBmed • Templates and SOPs • Guideline on traceability • Guideline GMP for ATMPs • Integration work GTWP and CPWP into CAT
  20. 20. Scientific advise MH Pinheiro, EMEA
  21. 21. Certification quality and non-clinical data • Only for SMEs • Quality data, or Quality and non-clinical • For scientific evaluation and certification • Evaluated by CAT • 90 days with clock stops • Possibility for site visit • STAND ALONE evaluation procedure • Not directly binding for clinical trial / market approval • Certificate does not replace data for later submission • No benefit/risk, no guarantees
  22. 22. Certification quality and non-clinical data EMEA
  23. 23. One slide on risk management J Petracek, EMEA
  24. 24. CAT monthly report • http://www.emea.europa.eu/pressoffice/presshome.htm
  25. 25. CAT monthly report
  26. 26. Borderlines • TEP may contain viable and non-viable cells • No viable cells & no principal metabolic action => no ATMP • Cell/device not by default engineered: substantial manipulation to be considered • ATMP with autologous and allogenic cells => allegenic use • TEP and sCT => TEP • GT and TEP or sCt, then GT > TEP > sCT • Hospital exemptions under national laws
  27. 27. ATMP containing devices • Devices as referred to in art. 7 of ATMP  Not a med.dev. (scaffolds, biomaterials, matrices)  Description physical characteristics, performance  Description interaction genes, cells, tissues • Combined ATMP:  Cellular / tissue part as above  Info on choice / intended function MDD/AIMD  Evidence conformity to Essential Requirements  Evidence compliance with BSE/TSE requirements  If available: results NoBo assessment
  28. 28. Further NoBo involvement • Several Notified Bodies volunteer knowledge to CAT • Discussion EMEA / NB-med / NBOG on cooperation planned in 2 weeks • NoBo to chair ISO/CD 13022 on standard for Risk- Management of cell-based products • NoBo participates in RGM/1 in UK, Gert Bos participates as member elect
  29. 29. ISO/TC194/SC1 – Tissue product safety • CEN TC 316 • Secretariat: DIN • Chair: Sabine Kloth • Work on ISO/CD 13022 standard for Risk-Management of cell-based products • Input into this from EMEA / CAT Example: equipment used for the manufacture of ATMPs
  30. 30. RGM/1 • Technical Committee to mirror the work of ISO/TC 150/SC7 "Tissue-engineered medical products" • Work on standardization to support regulation in regenerative medicine • Chair: Ben Sheridan – BSi • NB proposed seat: Gert Bos
  31. 31. Additional items and further reading…….. • 2001/20/EC – clinical trials • 2002/98/EC – blood derivatives • Regulation 1234/2008 – new variations • EMEA/CHMP/96268/2005 – EMEA guideline on risk management systems for medicinal products for human use • EMEA/149995/2008 – guideline of safety and efficacy follow up – risk management on ATMPs • #@! Obtaining re-imbursement ! • www.emea.europa.eu/htms/human/advanced_therapies/intro.htm • ec.europa.eu/enterprise/pharmaceuticals/pharmacos/new_en.htm • www.emea.europa.eu/htms/human/advanced_therapies/interested_parties.htm
  32. 32. 32 Contact Us Name: Gert Bos Title: Head of Regulatory and Clinical Affairs Address: BSI Kitemark House, Maylands Avenue Hemel Hempstead, HP2 4SQ, UK Telephone: +44 (0)1442 278664 Fax: +44 (0)8450 765601 Email: Gert.Bos@bsigroup.com Links: www.bsigroup.com/healthcare

×