Advanced Therapies

1
Advanced Therapies

• The proposed EU regulation from the viewpoint of
  a Pharmaceutical company with experience in the
  field of Tissue Engineering
• Priv.Doz.Dr,med.Detlef Niese
• Novartis Pharma AG, Basel CH
• European Biopharmaceutical Enterprises (EBE)
• Member of EuropaBio Advanced Therapies Working
  Group

2
About EBE

• EBE European Biopharmaceutical Enterprises is a
  specialised group of EFPIA created in 2000
• EBE has 65 corporate members engaged in research
  in Europe involving the application of emerging
  bioscience technologies with the aim of launching
  new healthcare products

3
Advanced Therapy Products and Pharmaceutical
Companies

• Academic institutions, small biotech companies
  and some large pharmaceutical companies have been
  involved and are still involved in research and
  development of cell therapy, tissue engineering
  and gene therapy products.
• Regulatory uncertainty and development risks
  associated with these products prove to be
  significant hurdles
• As a pharmaceutical company, Novartis has
  gathered development experience in all sectors of
  advanced therapies

4
A Real Life Case Apligraf

What it looks like
Histology Apligraf
Normal Skin
5
Apligraf A Long Clinical Regulatory Path
VSU-001
Organogenesis formed
DUS-001
1979
1985
1995
1998
2000
2003
2004
1992
1996
E. Bell M.I.T.
FDA Approval Diabetic Foot Ulcers
FDA Designated as device class III interactive
wound dressing
FDA Approval Venous Leg Ulcers
I.D.E. submitted
6
A Diverse Regulatory Environment
EventualRegulatory Classification
Initial Regulatory Classifications
Apligraf
Regulatory
Apligraf
Other
Reg
Device
Medicinal
Unregulated
Device
Medicinal
Unregulated
Germany
Germany
France (Cell
UK
Canada
France (Cell
UK
Canada
Therapy)
Therapy)
Sweden
Italy
Sweden
Italy
USA
USA
Belgium(Tissue
Belgium(Tissue
Denmark
Ireland
Denmark
Ireland
Finland
Finland
Bank)
Bank)
Norway
Austria
Norway
Austria
Greece
Greece
Spain
Spain
Netherlands
Netherlands
Portugal
Switzerland
Portugal
Switzerland
(Transplant)
(Transplant)
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Lessons Learned

• A harmonized regulatory framework for all cell
  based products in Europe is urgently needed to
  address
• Quality assurance
• Development and Marketing authorisation
• Address unique safety efficacy issues
• Include efficacy assessments based on trial
  designs that address ethical and practical
  aspects of surgical research
• Benefits of harmonised regulations
• Protection of patient safety
• Encourage investment by industry and successful
  global commercialisation through level playing
  field
• Provide patients access to innovative valuable
  therapies

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How We See the Proposed Regulation What We
Welcome

• A single, harmonised regulatory framework for all
  advanced therapy products
• Use of the Centralised Procedure through EMEA
  ensuring harmonised efficacy, quality and safety
  requirements for all products
• The creation of a Committee for Advanced
  Therapies consisting of experts in the field
• The use of subsidiarity for ethical aspects such
  as embryonic stem cells

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How We See the Proposed Regulation Our Concerns

• To ensure safety and effectiveness of AT products
  the regulation should apply to all products
  produced following a standardised process (no
  exemptions)
• Instead of exemptions from the regulation,
  consider providing administrative support or
  regulatory expertise as an additional incentive
  for all manufacturers who may require it

10
How We See the Proposed Regulation Our Concerns

• The formation of a specialised committee (CAT) at
  EMEA is welcomed but
• Expertise of members should reflect the broad
  spectrum of products and technologies
• Expertise of members should prevail over national
  representation (which is provided by CHMP)
• Existing legislation needs adaptation to (e.g.
  2001/20, GMP)

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Conclusion

• The new regulation is principally welcome
• Assurance of safety and efficacy through review
  by regulatory authorities supported by an
  expertise based CAT should drive development of
  high quality products and support access for
  patients
• Instead of excluding specific products from the
  regulation, administrative hurdles for hospital
  based products or SMEs should be minimised and
  may require additional incentives
• Careful adaptation of all affected existing
  legislation (like Directive 2001/20 EC) is a
  crucial success factor