Are regulators up to speed to address the challenges of - - PowerPoint PPT Presentation

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Are regulators up to speed to address the challenges of - - PowerPoint PPT Presentation

Mar 18, 2024 145 likes •387 views

Are regulators up to speed to address the challenges of biotechnological m edicinal products? The CAT W ork program m e 2 0 1 0 -2 0 1 5 Regulatory Science: Are regulators leaders or follow ers? European Medicines Agency 1 5 Decem ber 2 0 1 0

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An agency of the European Union

Are regulators up to speed to address the challenges of biotechnological m edicinal products?

The CAT W ork program m e 2 0 1 0 -2 0 1 5

Regulatory Science: Are regulators leaders or follow ers? European Medicines Agency 1 5 Decem ber 2 0 1 0

Dr Christian K Schneider, MD Committee for Advanced Therapies (CAT), EMA, London Committee for Medicinal Products for Human Use (CHMP), EMA, London Paul-Ehrlich-Institut (PEI), Germany

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Christian Schneider - CAT workprogramme- CHMP December 2010 2

Starting with thanks…

Lucia D‘Apote, PhD (EMA) Patrick Celis, PhD (EMA) Olga Oliver-Diaz (EMA)

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Christian Schneider - CAT workprogramme- CHMP December 2010 3

Complexity of biotechnological products

Insulin 5 700 Daltons Aspirin 180 Daltons Monoclonal antibody 150 000 Daltons Coagulation Factor VIII 280 000 Daltons

www.wikipedia.org www.laborjournal.de

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Christian Schneider - CAT workprogramme- CHMP December 2010 4

Advanced therapies and their challenges

Gene therapy medicinal products Somatic cell therapy medicinal products Genetically modified cells Tissue engineering products

Nat Biotechnol 2005, 23(7) www.heartandmetabolism.org

http://www.cbte.group.shef.ac.uk/

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Christian Schneider - CAT workprogramme- CHMP December 2010 5

Complexity of Advanced Therapies

B cell budding viruses www.aecom.yu.edu/aif/gallery/sem/sem.htm monoclonal antibody

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Christian Schneider - CAT workprogramme- CHMP December 2010 6

Intracellular Intracellular MAPK MAPK signaling signaling pathways pathways

stimuli MAPKKK MAPKK MAPK

Transcription factors

biological response

P

Thr Tyr P

P

Thr

P

Ser

P

Thr

P

Ser

ERK 1 ERK 2

P

Thr Tyr P

MEK 1 MEK 2

P

Thr

P

Ser

Raf-1

P P

Ras

mitogens

Cell adhesion, growth and differentiation factors

nucleus cytoplasm MKK 4 MKK 7 SAPK α / JNK 1 SAPK β / JNK 2 MEKK 1-3

P

Thr

P

Ser

P

Thr Tyr P

G protein

TAK 1 p38

P

Thr Tyr P

MKK 3 MKK 6

P

Thr

P

Ser

stress factors

Enviroment factors, inflammatory cytokines, UV-light,

  • xidative stress, osmolarity shock

responsive cellular genes

  • E. Flory, PEI
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Christian Schneider - CAT workprogramme- CHMP December 2010 7

Complexity of signalling

Overlap and location of positive and negative modulators of NFk-B signalling identified in a cell-based screen within the T-cell receptor signaling pathway

Halsey et al, Genome Biology 2007

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Christian Schneider - CAT workprogramme- CHMP December 2010 8

Challenges with cell-based products

Cells are complex systems

  • Cells are dependent on their (micro-)

environment

  • Cells are reactive to their environment
  • Cell cultures can become heterogeneous
  • Cells might de-differentiate

(e.g. during longer cell culture)

  • Cells might migrate („biodistribution“)
  • Cells are fragile and (sometimes) mortal

=> Regulatory consequences: √ Need for adequate characterization √ but also necessity to accept limitations

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Christian Schneider - CAT workprogramme- CHMP December 2010 9 9

The ATMP Regulation

New Scientific Arena Expertise Beyond Traditional Research

Com m ittee Com m ittee for for Advanced Advanced Therapies Therapies

►Lack of funds and costly investments ►Regulatory barriers ►Market (specific and small)

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Christian Schneider - CAT workprogramme- CHMP December 2010 10

W hy a w ork program m e?

EMA is a key player in the successful im plem entation of ATMP legislation

►A shared vision to address challenges of ATMPs ►Being empowered to take decisions means

taking responsibilities and learn balance

Com m ittee Com m ittee for for Advanced Advanced Therapies Therapies

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Christian Schneider - CAT workprogramme- CHMP December 2010 11

W hy a w ork program m e?

►Understand the environment ►Provide adequate tools to overcome barriers to

translation

►Guidelines in line with scientific progress

Is it the product that has to stretch to the guideline

  • r is it the guideline that has to be realistic for the product?

Com m ittee Com m ittee for for Advanced Advanced Therapies Therapies

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Christian Schneider - CAT workprogramme- CHMP December 2010 12

Challenge: Products legally on the market

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Christian Schneider - CAT workprogramme- CHMP December 2010 13

„I n God w e trust, the rest bring data!“

  • W. Edwards Deming

Pioneer in Quality Philosophy, W. Edwards Deming is widely held to have been one of the leaders who helped create the Total Quality

  • Movement. Deming’s 14 points and his book “Out of the Crisis” are

key documents in the development of Quality Systems for Business

  • management. Dr. Deming is best known for his revolution in the

quality and economic productions in Japan where from 1950 onward he taught top management and engineers, methods for management of quality. These teachings dramatically altered the economy of Japan. In recognition of his contributions the Union of Japanese Science and Engineering (JUSE) instituted the annual Deming prizes for achievement in quality and dependability of product. http://www.resourcesystemsconsulting.com/blog/reference/glossary

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Christian Schneider - CAT workprogramme- CHMP December 2010 14

Efficacy data (Marketing ≠ Efficacy!) („Experience“ ≠ Proof

  • f efficacy!)

Which data can be used? How to deal with claims like „No reports on serious adverse events so far, so a very well tolerated and safe product“?

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Christian Schneider - CAT workprogramme- CHMP December 2010 15

Objective 1

►To successfully respond to im plem entation of the provisions of

Article 2 9 of Regulation ( EC) 1 3 9 4 / 2 0 0 7 : assessm ent of products legally on the EU m arket Developers CAT Know the num ber and kind of products legally on EU m arket Reflect on the criteria for MAA assessm ent Proactive dialogue w ith potential applicants and MSs Report on the experience to EC and MSs in 2 0 1 0 -2 0 1 1

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Christian Schneider - CAT workprogramme- CHMP December 2010 16 16

Objective 2

Developers CAT

►To facilitate developm ent of ATMP and access to registration

procedure

B) Strengthen dialogue w ith stakeholders:

  • Draft a structured work programme tailor-made for the specific needs of

different parties (industry, SMEs, Academia, research groups, patients’ groups).

  • Increase the list of CAT I nterested Parties
  • Engage in dialogue with charity foundations and trusts concerning products

they are developing .

  • Organise a joint conference on ATMPs involving EMA/ CAT, EFPIA, EBE,

EUROPABIO, Learned Societies to share clinical, scientific and regulatory expertise in the field for the benefit of all stakeholders

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Christian Schneider - CAT workprogramme- CHMP December 2010 17

Objective 3

►Prom ote the use of available regulatory procedures and

introduce potential im provem ents Developers CAT Provide regular tutorial training/ w orkshop for all stakeholders ( including assessors, inspectors) Developing an European training and education platform for SMEs and Academ ia Dedicated assistance for ATMP certification subm issions

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Christian Schneider - CAT workprogramme- CHMP December 2010 18

Objective 4

►To explore possibilities offered by the regulatory procedures

to the ATMP field ( by im proving existing procedures and reflecting on alternative procedures) Developers CAT Fast track evaluation? Extend incentives for SMEs to academ ia, hospitals, trusts and sm all research groups? Because the science is evolving fast, on regular basis to screen system to identify potential changes required ( and then engage in dialogue w ith the European Com m ission) Appropriate use of follow -up efficacy system

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Christian Schneider - CAT workprogramme- CHMP December 2010 19

Objective 5

►Foster innovation

Developers CAT Dialogue w ith EC DG Research Prom ote allocation of funds for ATMP research Reinforce contact w ith leaders of EU projects on ATMP

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Christian Schneider - CAT workprogramme- CHMP December 2010 20

Objective 6

►Prom ote access and availability to ATMP for EU patients

Developers CAT Cooperation w ith CTFG Dialogue w ith NCA on ‘hospital exem ption’ Encourage developm ent of ATMPs for unm et m edical needs w ithout alternative treatm ents.

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Christian Schneider - CAT workprogramme- CHMP December 2010 21

The CAT as an open-minded scientific player

Nat Rev Drug Discov 9(3):195-201. Lancet 376(9740):514

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Christian Schneider - CAT workprogramme- CHMP December 2010 22

Holistic view: Step back and look at the entire picture

Francis Bacon Self portrait (1971) Francis Bacon Portrait (1979)

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Christian Schneider - CAT workprogramme- CHMP December 2010 23

…and closing w ith thanks

Developers CAT Yes, w e are up to speed to address the challenges of Advanced therapies m edicinal products – the EMA has created an innovative environm ent!