1. World Congress Tissue Engineering and Regenerative Medicine International Society
Vienna, Austria
September 5-8, 2012
Industry Day Symposium
SESSION 2:
“The Regulatory Imperative: International Perspective”
Organized by
TERMIS-AM and TERMIS-EU
Industry Committees

2. Concept/Discovery Research to Successful Product
Public/Private Funding
Discovery Research
Clinical Trials
Market
Successful Product ?
Intellectual Property & Patent Protection
Regulatory Evaluation & Product Approval
Public(s) Perception & Market Acceptance
SCIENCE Talent/People

3. TERMIS-EU Industry Committee
Established 2011
Mission
Motivate translation of academic research into commercial products, in Tissue Engineering/Regenerative Medicine (TE/RM)
Connect the scientific & clinical communities with TE/RM industries
Goals
Give answers to critical questions, paving the road of TE/RM commercial translation, by key stakeholders, from past experiences
Promote academia–industry meetings & partnerships for more effective commercial translation in TE/RM
Members
Yves Bayon, PhD; Covidien – Sofradim Production; Chair
Simon Ellison, MBA; NHS Blood & Transplant
John Barry, PhD; Baxter Innovations
Paul Stroemer, PhD, Reneuron
Chris Mason, PhD; University College of London
Alain Vertes, PhD; London Business School Sloan Fellow 3

4. TERMIS-AM Industry Committee
Established 2009
Mission
Support commercialization in Tissue Engineering/Regenerative Medicine (TE/RM)
Goals
Define and address obstacles/hurdles to product commercialization
Promote collaborations to build a viable TE/RM industry
Members
Kiki B. Hellman, PhD; The Hellman Group. LLC; Chair
Timothy A. Bertram, DVM, PhD; Tengion
Peter C. Johnson, MD; Avery Dennison
Mark Van Dyke, PhD; Wake Forest University Health Sciences
Bill Tawil, PhD; Baxter Biosurgery

5. TERMIS-AM Industry Committee ‘Commercialization Hurdles’
2010 – First Annual Industry Committee Symposium*
Survey of TERMIS-AM membership on perceived hurdles to commercialization of TE/RM products
Most common hurdles identified by academe, and start- up, development stage, established companies
Funding
Regulatory pathway
IP and technology transfer
-----
*Publications:
“Hurdles in Tissue Engineering/Regenerative Medicine Commercialization: A Survey of North American Academe and Industry,” Tissue Engineering, January 2011.
“Challenges in Tissue Engineering and Regenerative Medicine Product Commercialization: Building an Industry,” Tissue Engineering, January 2011.

6. TERMIS-AM Industry Committee ‘Funding’
2011 – Second Annual Symposium*
Survey of financial community (public, private, government)
Key Findings
Investment interest >60%
Perceived challenges for investment
Regulatory pathway clarity
Clinical translation
---
Publication:
“Hurdles in Tissue Engineering/Regenerative Medicine Commercialization: A Survey of the Financial Industry,” Tissue Engineering, November 2012 (in press).

7. The Regulatory Imperative: International Perspective
TERMIS-NA Industry Committee Surveys
Regulatory pathway a major hurdle
Regulatory clarity and predictability – key for commercialization and industrial development

8. The Regulatory Imperative: International Perspective
Regulatory Framework
Principles and requirements governing assessment of regenerative products, i.e., review and marketing approval
Globalization
Challenges for regulatory authorities due to the global R&D effort in TE/RM outside their purview, i.e., outside US and EU
Regulatory Harmonization
Development of a common dialogue and approach among regulatory authorities leading to congruence of national practices and consensus on regulatory requirements, i.e., a unified regulatory strategy

9. Symposium Participants
Presentations
Lucia D’Apote, PhD; European Medicines Agency (EMEA), United Kingdom
Celia Witten, MD, PhD; Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), United States
Panel
Tim Bertram, DVM, PhD; Tengion, Inc., USA
Maria Pascual-Martinez, PhD; TiGenix
Alison Wilson; Cell Data Services
Leslie Wolfe, PhD; Genzyme
Chair
Kiki B. Hellman, PhD; The Hellman Group, LLC, USA
Summary

10. European Regulatory environment of regenerative medicine
TERMIS Industry Symposium
7 September 2012, Vienna (Austria)
Presented by: Lucia D’Apote, PhD
European Medicines Agency

11. Overview The EMA CAT and the RegMed pipeline in Europe
Regulatory path and regulatory requirements
Specificities and Challenges
International Cooperation (EMA-FDA)
11 Lucia D’Apote - EMA

12. The EMA CAT and the RegMed pipeline in Europe
12 Lucia D’Apote - EMA

13. Established in 1993, operational since 1995
7 Westferry Circus
Canary Wharf
London E14 4HB
United Kingdom
Tel: +44 (0)
Fax: +44 (0)
The EMA is the European Union body responsible for coordinating the existing scientific resources put at its disposal by the 27 EU Member States for the evaluation, supervision and pharmacovigilance of medicinal products.
Responsible for the protection and promotion of public and animal health, through the evaluation and supervision of medicines for human and veterinary use.
Mission Statement – “to foster scientific excellence in the evaluation and supervision of medicines, for the benefit of public and animal health.” 13
Lucia D'Apote - EMA 13

14. Committee for Advanced Therapy
The ATMP Regulation
Committee for Advanced Therapy
New Scientific Arena
Expertise
Beyond Traditional
Research 14
Lucia D'Apote - EMA 14

15. ATMP Pipeline – what we see15
Lucia D'Apote - EMA

16. Objective : Facilitate development of ATMPs and access to MA procedure
understand trends in research and development, with a view to planning CAT workload and resources accordingly 16

17. ATMP Pipeline – what we will see
318 clinical trials from EudraCT (1 May December 2010)
244 national = more than 70%
74 multinational = less than 30% 17
Lucia D'Apote - EMA

18. Products Based on self-classification: GTMPs + sCTMPs + TEPs: 250
sCTMP/TEPs= 196 = 78%
phase I and II or I/II: 81%
phase III/IV:19%
phase IV, as assigned in the database: 7 CT 18

19. Sponsors: who
Who is conducting the CT with ATMPs in Europe? 173 sponsors
104=60% Academia/hospitals,
69=40% Industry (including SMEs)
4% big pharma
24% SMEs
72% other (non registered SMEs) 19

20. Sponsors: from where 19 countries in total
15 EU/EFTA Countries (SP, DE, UK, NL, FR, BE)
4 non-EU/ EFTA region (US, Israel, Switzerland, Canada)
almost all academia/charity sponsors situated in Europe
some commercial sponsors (24/69 or 34%) situated outside Europe 20

21. Therapeutic areas
majority of CT in solid tumours (67 products), followed by the cardiovascular area (48 products), and haematology including haematological malignancies (33 products) 21
Lucia D'Apote - EMA

22. Orphan ATMPs
26 CT with Orphan ATMPs Mainly commercial sponsors Majority with cell- based products 75 ODD so far are ATMPs !!!
Clinical trials performed by commercial sponsors: 21 (18%) with OD. 9 by SMEs (n=9) + 12 ‘non-registered SMEs
commercial sponsors investigating orphan ATMPs: 14 based in in Germany, UK, and USA + France, Italy, the Netherlands, Spain, and Israel.
Products: mainly cell-based medicinal products (n=10)
tissue engineered products (n=3), mesenchymal stem cells (n=2), HBSC in homologous use (n=1), HBSC in non-homologous use (n=1), or other cell based medicinal products (n=3). Five clinical studies or 24% of all ATMP trials with orphan drugs were conducted by commercial sponsors with GTMP.
Non-Commercial sponsors performed in total 197 clinical trials, with only five of them conducted in an orphan disease area (3%, Fig. 1a). These five clinical trials were performed by charities and trusts (n=4) and academia (n=1). The total number of non-commercial sponsors conducting clinical trials with orphan drugs was four (one charity conducted two clinical trials ): two based in France, one in Italy, one in Spain). These sponsors were mainly conducting clinical trials with orphan gene therapy medicinal products (n=3); only one clinical trial with an orphan cell-based medicinal product was conducted (mesenchymal stem cells). 22
Lucia D'Apote - EMA 22

23. Regulatory path and regulatory requirements
23 Lucia D’Apote - EMA

24. EU Marketing Authorisation (MA) for ATMPs
A medicinal product may only be placed on the market in the EU,
when a marketing authorisation has been issued by the European Commission (via the Centralised Procedure – EMA) or
it is regulated by the competent authority of a EU Member State
(hospital exemption) 24
EMA - Lucia D'APOTE 24 24 24

25. 25
Lucia D'Apote - EMA 25

26. Risk based approach 26
Lucia D'Apote - EMA

27. Risk-management plan and follow-up safety/efficacy27
Lucia D'Apote - EMA

28. Same evaluation, different MA?
Conditional approval vs Exceptional circumstances
- to meet unmet medical needs of patients and in the interest of public health 28
Lucia D'Apote - EMA 28

29. Accellerated assessment 150 days
in order to meet, in particular the legitimate expectations of patients and to take account of the increasingly rapid progress of science and therapies, for medicinal products of major interest from the point of view of public health and in particular from the view point of therapeutic innovation.
There is no single definition of what constitutes major public health interest. This should be justified by the applicant on a case-by-case basis.
Accellerated assessment 29
Lucia D'Apote - EMA 29

30. Specificities and Challenges
30 Lucia D’Apote - EMA

31. ATMP Translation: perceived challenges
Gene and Cell based products are complex
Market (specific and small)
Lack of funds and costly investments
Regulatory barriers
31 Lucia D’Apote - EMA

32. Challenges with ATMPs: examples
Scientific challenges
Manufacturing constraints & quality issues
Non-clinical challenges
Clinical challenges
Disclaimer: ATMPs are a very diverse group of products, so the challenges listed in the next slides are only examples! 32

33. Quality/manufacturing issues
Control of all starting and raw materials
Human cells/tissues + any human/animal reagents (e.g serum)
Recombinant growth factors
History of cell-lines / vector constructs
Appropriate characterisation and product testing (including potency assay*)
Poor definition and control of a product may directly effect safety & efficacy
Good control of the product is essential for manufacturing changes (e.g. product upscale)
Manufacture in GMP environment
* Potency assay: product specific, at least semi-quantitative, linking product testing with clinical effect /biological activity 33 33

34. Non-clinical challenges
What animal models to be used to test a human cell-based therapy or gene therapy product?
Use of a homologous model? / Disease models?/ Other relevant animal models?
Proof of concept studies / toxicity studies
Dose finding studies?
Bio-distribution studies?
Germ line transmission for GTMP
Environmental risk / Shedding studies for GTMP 34

35. Clinical challenges Dose finding studies
How to find the most effective dose, e.g. for a TEP?
Design of clinical trial
What is a suitable compatitor?
Blinding might be very difficult
Endpoints for TEP (how to measure structure repair?)
Effect of concomitment treatment / surgery on Efficacy & Safety?
Long term efficacy and safety follow-up studies 35

36. Challenges with ATMPs Scientific challenges
Yes!
But not all challenges are scientific!
Regulatory issues
Lack of regulatory expertise
Resources
Reimbursement issues
Competition with ‘hospital exempted ATMPs’ 36

37. Prospective product development
Courtesy of dr. Paula Salmikangas, 2012 37
Lucia D'Apote - EMA

38. Retrospective product development
Courtesy of dr. Paula Salmikangas, 2012 38
Lucia D'Apote - EMA

39. The way forward Raise awareness – strengthen dialogue
Learn from experience
39 Lucia D’Apote - EMA

40. Nature Reviews Drug Discovery, vol 9, March 2010, 185-201
Regulatory Rapporteur, vol 8, July-August 2011, 4-7 40

41. Advice during development41
Lucia D'Apote - EMA

42. Regulatory strategy: save time
Scientific advice: Complying with SA/PA is significantly associated with positive outcome
Regnstrom J, Koenig F, Aronsson B, et al. (2010) Factors associated with success of market authorisation
applications for pharmaceutical drugs submitted to the European Medicines Agency; EJCP 66:39-48 42
Lucia D'Apote - EMA

43. 43 Lucia D’Apote - EMA

44. 44 Lucia D’Apote - EMA

45. International Cooperation (EMA-FDA)
FDA-EMA-HC ATMP Cluster
ICH Regulators Forum Cell Therapy Group
Parallel Scientific advice
45 Lucia D’Apote - EMA

46. Parallel Advice FDA Confidentiality Agreement FDA
Applicant to address request to both Agencies
Agreement principles since 2004 pilot
Applicant initiative- exceptionally Agency initiative 46

47. Procedure Parallel Advice
Initial discussion both Agencies
Prime candidates-breakthrough products – no GL exist or GLs differ between Agencies
Submit request in usual manner
Timetable agreed between Agencies
Tele-video-conference about D60 47

48. Outcome No applicant involvement in draft reports
Parallel separate advice given not ‘joint’ advice
Confidentiality maintained
Standard fee applies 48

49. Thank you for your attention!
Lucia D’APOTE
European Medicines Agency (EMA) 49
Lucia D'Apote - EMA

50. Regulatory and Scientific Experience in Regenerative Medicine in OCTGT
Termis Industry Symposium
Vienna, Austria
September 7, 2012
Celia M. Witten, PhD, MD
Office Director
Office of Cellular, Tissue, and Gene Therapies
Center for Biologics Evaluation and Research
United States Food and Drug Administration

51. Outline
FDA Mission & Organization
OCTGT Activities
Special Programs 2

52. FDA Mission Statement
The FDA is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation.
The FDA is also responsible for advancing the public health by helping to speed innovations that make medicines and foods more effective, safer, and more affordable; and helping the public get the accurate, science-based information they need to use medicines and foods to improve their health. 3 52

53. FDA Organization
CBER (Center for Biologics Evaluation and Research): vaccines, blood and blood products, human tissue/tissue products for transplantation, cells, gene therapy
Office of Cellular, Tissue, and Gene Therapies
Office of Vaccines Research and Review Product Offices
Office of Blood Research and Review
CDER (Center for Drug Evaluation and Research): drugs, some biological products
CDRH (Center for Devices and Radiological Health): devices for treatment, implants, diagnostic devices
CVM
CFSAN
NCTR
CTP
ORA OC 4

54. OCTGT Activities Regulatory review
Policy and regulatory guidance development
International Activities and Standards
Outreach
Advisory Committees
Talks, workshops
Seminars, panel discussions, round table
Publications
Mission-related Research 5

55. New IND and IDEs Submitted to OCTGT: Commercial or Research Sponsors6

56. Examples of OCTGT Products
Stem cell and stem cell-derived products
Hematopoietic, mesenchymal, cord blood, embryonic, iPSc, etc
Somatic cell therapies
Pancreatic islets, chondrocytes, myoblasts, keratinocytes, hepatocytes
Gene therapies
Genetically modified cells
Plasmids, viral vectors, bacterial vectors
Therapeutic vaccines and other antigen-specific active immunotherapies
Cancer vaccines and immunotherapies, such as dendritic cells, lymphocyte-based therapies, cancer cell-based therapies, peptides, proteins
Non-infectious disease therapeutic vaccines, such as peptides, proteins, small molecules 
Devices and combination products
Devices with a cellular component
Selected devices for the manufacture or delivery of cells 7

57. Regulatory
Review 8

58. FDA Medical Product Regulatory Paradigms are Tiered
Risks Inherent to the Product
Manufacturing Complexity
Clinical Uses
Other Differences
Leads to Tiered Review Requirements 9

59. Two General Classes of FDA-Regulated Medical Products
No Premarket Review
Some Human Tissues (361 HCT/Ps)
Some Devices (exempt 510(k))
Some Drugs (monograph)
Premarket Review/notification
510(K) Devices (non-exempt)
PMA Devices
BLA- Biologic Drugs
NDA- Drugs 10

60. Starting Point for FDA Interaction
Guidance in specific investigational areas
Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee Cartilage
Somatic Cell Therapy for Cardiac Disease
General guidances to support specific areas of tissue engineered medical products
CMC guidances for cellular and gene therapy products
General preclinical guidances
Guidances for scaffolds and devices
General clinical guidances
Standards from SDOs (ASTM, ICH, ISO, USP...)
Pre-submission meeting with appropriate FDA Center/office 11

61. Policy & Regulatory Guidance Development12

62. Recent CBER Guidances
Guidance for Industry: Cellular Therapy for Cardiac Disease (Oct 2010)
Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products (Jan 2011)
Guidance for Industry: INDs for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution for Specified Indications (June 2011)
Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines (Oct 2011)
Current Good Tissue Practices (CGTPs) for Manufacturers of Human Cells, Tissue and Cellular and Tissue-Based Products (HCT/Ps)
(Dec 2011)
Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee Cartilage (Dec 2011) 13

63. FY 2012 Program Priorities Guidance for Industry:
Draft – Preclinical Safety Assessment
of Investigational Cellular and Gene
Therapy Products 14

64. Recent CTGTAC Advisory Committee Topics
Testing for Replication Competent Retrovirus (RCR) Lentivirus (RCL) in Retroviral and Lentiviral Vector Based Gene Therapy Trials – November 2010
Cell and Gene Therapy Trials in Retinal Disease – June 2011
New York Blood Center BLA for umbilical cord blood - September 2011
Miltenyi Biotec HDE for CliniMACS CD34 Selection System –September 2011
Organogenesis BLA for the treatment of surgically created gingival and alveolar mucosal surface defects in adults – November 2011 15

65. International Activities and Standards16

66. FDA’s Goals for International Collaborations
To safeguard global public health, 
To assure that consumer protection standards and requirements are met, 
To facilitate the availability of safe and effective products, 
To develop and utilize product standards and other requirements more effectively 
To minimize or eliminate inconsistent standards internationally. 17

67. FDA-European Medicines Agency (EMA)-Health Canada (HC) ATMP Cluster
Regular teleconferences to share thinking on regulatory approaches on both general and specific issues
Share draft documents for comments
Engage reciprocally in workshops advisory committees, and working parties 18

68. Asia Pacific Economic Cooperation-Life Sciences Innovation Forum (APEC/LSIF)
13 countries participated
Goal: To bring together a group of stem cell leaders from corporate, academic, and government sectors to discuss and further develop a regulatory frame work for QA/QC for stem cell products
Information Gathering Opportunities
Regulatory landscape for cell therapies
Guidance documents in place or under development for (stem) cell therapies
(Stem) cell therapy products in clinical trials or already licensed
Outcomes: Regulatory gaps for stem cell products exist among the participating countries 19

69. Regulators Forum Cell Therapy Group
Goal: Identify areas of possible areas for convergence/harmonization
Why convergence/harmonization for cell therapy products?
Cell therapy is an emerging product class posing substantial regulatory challenges
Regulatory frameworks are in different states of maturity internationally
Limited experience in reviewing marketing applications for cell therapy products
ICH & non-ICH product guidelines not directly applicable to CT products
Harmonization of technical requirements useful tool to strengthen the safe and effective use of cell (stem)-based products 20

70. Regulations vs. Standards
Government implementation of statues that have the force of law
Define specific requirements for safety
Provide accurate information to health professionals and consumers
Standards
Voluntary
Frequently developed outside of the government
Written standards describe how manufacturers might meet regulatory requirements
Physical standards provide accepted “benchmark” materials 21

71. Use of Consensus Standards by Federal Agencies
Mandated by PL National Technology Transfer and Advancement Act of 1995
Interpreted by OMB Circular No. A119
Standards and Global Harmonization 22

72. Impact of Guidance and Standards
SDOs can sometimes produce documents or physical standards more quickly than FDA can produce Guidance documents
Effort can be shared with non-FDA experts
SDOs can cover areas that are difficult to put in FDA Guidance
Specific (proprietary) methods for tests or processes
Critical reviews of emerging fields 23

73. Use of Standards in CBER
Use in Review of Applications
Sponsor cites standard in meeting or application
ISO xx (Biocompatibility)
ATCC VR-1516 (Adenovirus Type 5 Reference Material)
Use as Information Resource
ASTM – Standard Guide for in vivo assessment of implantable devices intended to repair or regenerate articular cartilage
ANSI/AAMIISO 7198 Cardiovascular Implants: Vascular Graft Prostheses 24

74. International Clinical Trials
Acceptance of studies in support of an IND or marketing application
If conducted under an IND all requirements must be met unless waived
If not conducted under an IND must meet 21CFR , which addresses good clinical practice issues, ability to validate data from onsite inspection if necessary, supporting information, etc. 25

75. International Clinical Trials
Acceptance of foreign data as sole basis for marketing approval is governed by 21CFR
Applicability of data to u.s. population and medical practice
Studies performed by clinical investigators of recognized competence
Data valid without an onsite inspection or FDA can perform on-site inspection to validate data 26

76. Special Programs 27

77. Fast Track, Accelerated Approval, and Priority Review
These terms apply to licensure or to the licensure process for drugs and biologics
Fast Track: process designed to facilitate the development, and expedite the review of drugs to treat serious diseases and fill an unmet medical need
Accelerated Approval: allows earlier approval of drugs to treat serious diseases, and that fill an unmet medical need based on a surrogate endpoint. A confirmatory trial is needed.
Priority Review: Two tiered system of review times
Standard Review: ten month time frame
Priority Review: six month time frame. Designation is given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. 28

78. Expanding Access to Investigational Drugs
Use of an investigational drug outside of a clinical trial, for the sole purpose of treating a patient or patients with a serious or life-threatening disease who have no acceptable medical options
Levels of expanded access are based on the number of patients to be treated and how much is already known about the drug:
Individual or intermediate size group access
Treatment IND 29

79. Orphan Drug and Humanitarian Device Designation
Orphan Drug Designation: orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S., or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug
This does not alter the standard regulatory requirements and process for obtaining marketing approval
Humanitarian Use Device: designates a device that is intended to benefit patients by treating or diagnosing a disease or condition that affects fewer than 4,000 individuals in the United States per year
HDE exemption 30

80. Food and Drug Administration Safety and Innovation Act (FDASIA)
Signed into law July 9, 2012
Fifth reauthorization of PDUFA
Sec 902- Breakthrough Therapies
Criteria for “Breakthrough Therapy” Designation
Potential agency actions to expedite review of designated drugs
Guidance document on implementation by 18 months 31

81. OCTGT Regulatory Resources
OCTGT Learn Webinar Series:
Regulatory Questions:
Patrick Riggins, Ph.D. – (301) 32

82. Public Access to CBER CBER website:
Phone: or
Consumer Affairs Branch (CAB)
Phone:
Manufacturers Assistance and Technical Training Branch (MATTB)
Phone:
Follow us on Twitter 33

83. Contact Information
Celia Witten, Ph.D., M.D.
Office Director, OCTGT
CBER/FDA
1401 Rockville Pike (HFM-700)
Rockville, MD 34

84. Panel Discussion Question #1
Since product development, including clinical studies in TE/RM is now a global enterprise, what CMC, clinical, and pharmacology/toxicology aspects of international studies may be acceptable to both EMEA and FDA?
What criteria will form the basis for regulatory decision-making in product approval?

85. Panel Discussion Question #2
What priorities do the FDA and EMEA foresee in developing ‘best practices’ for regenerative products, i.e., clinical trial design, manufacturing processes and release criteria, among others?
How can ‘best practices’ from various regulatory agencies be developed and adopted to accommodate reciprocity across national boundaries?
What industrial-regulatory mechanisms are the most effective in establishing a cooperative dialogue with FDA and EMEA regarding such issues?

86. Panel Discussion Question #3
The FDA and EMEA have different legislated product approval pathways permitting accelerated or expedited product approval.
What criteria would form the basis for accelerated or expedited product review of a TE/RM product?
Would any other means of rapid product approval for TE/RM products be considered as long as patient safety is demonstrated?

87. Regulatory Imperative Session Summary
Regulatory barriers are considered as major challenges for TE/RM product commercialization - academics, industrialists, financiers, and regulators.
Both FDA and EMA have recognized the regulatory challenges presented by TE/RM product technologies, raw materials, pre- clinical testing, and clinical assessment.
TE/RM product pipeline is broad and deep presenting unique challenges for regulators such that the EMA CAT and FDA Pre- Submission Meetings allow sponsors to obtain specific guidance on their respective technology (cells, genes, combinations, etc).
TE/RM products are complex presenting unique manufacturing, pre- /non-clinical and clinical challenges for regulation 87

88. Regulatory Imperative Session Summary
Both EMA and FDA:
Take a risk-based/tiered approaches to evaluate the specific risks unique to each TE/RM product submission.
Have identified special pathways (e.g. orphan, accelerated assessments, etc) to encourage TE/RM therapies reaching the market most expeditiously and are safe and effective for the intended patient population.
Promote long-term follow-up on safety, efficacy and durability of TE/RM products
Have entered into agreement for parallel advice and collaborations with industrial organizations on regulation of TE/RM product development
Offer specific guidance to industry in key technological areas of concern: scientific advise being sought by sponsors has focused on non-clinical challenges although clinical trial design have also served as a topic of industrial interest.
Accept international studies for marketing applications if they meet specific requirements for data validity, good clinical practices and supporting information 88

89. Regulatory Imperative Session Summary
The way forward for TE/RM technologies and products includes:
Raise awareness of unique safety challenges and efficacy opportunities
Learn from experience as these new technologies advance to commercialization and become standards of care.
Promoting industrial-regulatory and regulatory-regulatory dialog to promote the commercialization of safe and effective TE/RM technologies for unmet medical needs 89

90. A copy of the slides for Session 2 will be available online via the TERMIS website, 90