Industry Day SymposiumSESSION 2:

“The Regulatory Imperative: International Perspective”

World CongressTissue Engineering and Regenerative

Medicine International SocietyVienna, Austria

September 5-8, 2012

Organized byTERMIS-AM and TERMIS-EUIndustry Committees

Concept/Discovery Researchto Successful Product

2

SCIENCETalent/People

SCIENCETalent/People

Public/Private Funding

Public/Private Funding

DiscoveryResearch

Clinical Trials MarketMarket Successful Product

Regulatory Evaluation & Product Approval

Public(s) Perception& Market Acceptance

Intellectual Property& Patent Protection

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

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

4

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:

1. “Hurdles in Tissue Engineering/Regenerative Medicine Commercialization: A Survey of North American Academe and Industry,” Tissue Engineering, January 2011.

2. “Challenges in Tissue Engineering and Regenerative Medicine Product Commercialization: Building an Industry,” Tissue Engineering, January 2011.

5

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

6

---

Publication:“Hurdles in Tissue Engineering/Regenerative Medicine Commercialization: A Survey of the Financial Industry,” Tissue Engineering, November 2012 (in press).

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

7

The Regulatory Imperative: International Perspective

Regulatory FrameworkPrinciples and requirements governing assessment of regenerative

products, i.e., review and marketing approval

GlobalizationChallenges for regulatory authorities due to the global R&D effort in

TE/RM outside their purview, i.e., outside US and EU

Regulatory HarmonizationDevelopment 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

8

Symposium ParticipantsPresentations

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

PanelTim Bertram, DVM, PhD; Tengion, Inc., USA

Maria Pascual-Martinez, PhD; TiGenix

Alison Wilson; Cell Data Services

Leslie Wolfe, PhD; Genzyme

ChairKiki B. Hellman, PhD; The Hellman Group, LLC, USA

SummaryTim Bertram, DVM, PhD; Tengion, Inc., USA

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An agency of the European UnionPresented by: Lucia D’Apote, PhDEuropean Medicines Agency

European Regulatory environment of regenerative medicine

TERMIS Industry Symposium7 September 2012, Vienna (Austria)

Overview

11 Lucia D’Apote - EMA

The EMA CAT and the RegMed pipeline in Europe

Regulatory path and regulatory requirements

Specificities and Challenges

International Cooperation (EMA-FDA)

12 Lucia D’Apote - EMA

The EMA CAT and the RegMed pipeline in Europe

Lucia D'Apote - EMA13

7 Westferry Circus Canary Wharf London E14 4HB United Kingdom

Tel: +44 (0) 20 7418 8400Fax: +44 (0) 20 7418 8416

www.ema.europa.eu

Established in 1993, operational since 1995

14

The ATMP Regulation

New Scientific Arena

Expertise

Beyond Traditional

Research

Lucia D'Apote - EMA

Lucia D'Apote - EMA15

ATMP Pipeline – what we see

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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

http://www.ema.europa.eu/docs/en_GB/document_library/Work_programme/2010/11/WC500099029.pdf

Lucia D'Apote - EMA17

► 318 clinical trials from EudraCT (1 May 2004 - 31 December 2010)

►244 national = more than 70%►74 multinational = less than 30%

ATMP Pipeline – what we will see

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Products

► phase I and II or I/II: 81%► phase III/IV:19% ► phase IV, as assigned in the database: 7 CT

Based on self-classification:►GTMPs + sCTMPs + TEPs: 250►GTMPs =54 = 22%►sCTMP/TEPs= 196 = 78%

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 pharma24% SMEs72% other (non registered SMEs)

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

Lucia D'Apote - EMA21

majority of CT in solid tumours (67 products), followed by the cardiovascular area (48 products), and haematology including haematological malignancies (33 products)

Therapeutic areas

Orphan ATMPs

26 CT with Orphan ATMPs

Mainly commercial sponsors

Majority with cell-based products

75 ODD so far are ATMPs !!!

Lucia D'Apote - EMA22

23 Lucia D’Apote - EMA

Regulatory path and regulatory requirements

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A medicinal product may only be placed on the marketin 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)

EU Marketing Authorisation (MA) for EU Marketing Authorisation (MA) for ATMPsATMPs

2424 EMA - Lucia D'APOTE

Lucia D'Apote - EMA25

Risk based approach

Lucia D'Apote - EMA26

Risk-management plan and follow-up safety/efficacy

Lucia D'Apote - EMA27

Same evaluation, different MA?

Lucia D'Apote - EMA28

• Conditional approval vs Exceptional circumstances- to meet unmet medical needs of patients and in the interest of

public health

Accellerated assessment 150 days

Lucia D'Apote - EMA29

- 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

30 Lucia D’Apote - EMA

Specificities and Challenges

ATMP Translation: perceived challenges

31 Lucia D’Apote - EMA

Gene and Cell based products are complex Market (specific and small)Lack of funds and costly investments

Regulatory barriers

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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!

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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

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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

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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

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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’

Prospective product development

Lucia D'Apote - EMA37 Courtesy of dr. Paula Salmikangas, 2012

Retrospective product development

Lucia D'Apote - EMA38

Courtesy of dr. Paula Salmikangas, 2012

The way forward

39 Lucia D’Apote - EMA

Raise awareness – strengthen dialogue

Learn from experience

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Nature Reviews Drug Discovery, vol 9, March 2010, 185-201

Regulatory Rapporteur, vol 8, July-August 2011, 4-7

Lucia D'Apote - EMA41

Advice during development

Lucia D'Apote - EMA42

Regulatory strategy: save time Scientific advice: Complying with SA/PA is significantly associated with positive outcome

97%

38/39

30%

6/20

72%

93/129

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Compliant with SA Non-compliant with SAreceived

No SA received

Positive MAA outcome related to compliance with SA/PA received

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

43 Lucia D’Apote - EMA

44 Lucia D’Apote - EMA

International Cooperation (EMA-FDA)

45 Lucia D’Apote - EMA

FDA-EMA-HC ATMP ClusterICH Regulators Forum Cell Therapy Group

Parallel Scientific advice

http://www.ema.europa.eu/docs/en_GB/document_library/Other/2009/11/WC500014868.pdf

46

Parallel Advice FDA

Confidentiality Agreement FDA

Applicant to address request to both Agencies

Agreement principles since 2004 pilot

Applicant initiative- exceptionally Agency initiative

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

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Outcome

No applicant involvement in draft reports

Parallel separate advice given not ‘joint’ advice

Confidentiality maintained

Standard fee applies

Lucia D'Apote - EMA49

Thank you for your attention!Thank you for your attention!

Lucia D’APOTE European Medicines Agency (EMA)

lucia.dapote@ema.europa.eu

Regulatory and Scientific Experience in Regenerative Medicine in OCTGT

Celia M. Witten, PhD, MDOffice Director

Office of Cellular, Tissue, and Gene TherapiesCenter for Biologics Evaluation and ResearchUnited States Food and Drug Administration

Termis Industry SymposiumVienna, Austria

September 7, 2012

51

Outline

• FDA Mission & Organization

• OCTGT Activities

• Special Programs

2

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.

52 3

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

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

New IND and IDEs Submitted to OCTGT: Commercial or Research Sponsors

0

20

40

60

80

100

120

140

2003 2004 2005 2006 2007 2008 2009 2010 2011

commercial

research

6

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

Regulatory Review

8

FDA Medical Product Regulatory Paradigms are Tiered

• Risks Inherent to the Product

• Manufacturing Complexity

• Clinical Uses

• Other Differences

Leads to Tiered Review Requirements

9

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

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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

Policy & Regulatory Guidance

Development

12

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)

Recent CBER Guidances

13

FY 2012 Program Priorities

Guidance for Industry:

Draft – Preclinical Safety Assessmentof Investigational Cellular and GeneTherapy Products

14

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

International Activities and Standards

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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

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

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

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

Regulations vs. Standards

• Regulations– 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

Use of Consensus Standards by Federal Agencies

• Mandated by PL 104-113 National Technology

Transfer and Advancement Act of 1995

• Interpreted by OMB Circular No. A119

http://www.whitehouse.gov/omb/circulars_a119_a119fr

• Standards and Global Harmonization

22

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

Use of Standards in CBER

• Use in Review of Applications– Sponsor cites standard in meeting or application

• ISO 10993.xx (Biocompatibility)• ATCC VR-1516 (Adenovirus Type 5 Reference Material)

– Use as Information Resource• ASTM 2451-05 – 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

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

21CFR312.120, which addresses good clinical practice issues, ability to validate data from onsite inspection if necessary, supporting information, etc.

25

International Clinical Trials

• Acceptance of foreign data as sole basis for marketing approval is governed by 21CFR312.120– 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

Special Programs

27

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.

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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

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

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: http://www.fda.gov/BiologicsBloodVaccines/NewsEvents/ucm232821.htm

• Regulatory Questions: CBEROCTGTRMS@fda.hhs.gov

Patrick Riggins, Ph.D. – (301)827-6536

32

Public Access to CBERCBER website:http://www.fda.gov/BiologicsBloodVaccines/default.htm

Phone: 1-800-835-4709 or 301-827-1800

Consumer Affairs Branch (CAB) Email: ocod@fda.hhs.govPhone: 301-827-3821

Manufacturers Assistance and Technical Training Branch (MATTB)Email: industry.biologics@fda.govPhone: 301-827-4081

Follow us on Twitter https://www.twitter.com/fdacber

33

Contact Information

Celia Witten, Ph.D., M.D.

Office Director, OCTGT

CBER/FDA

1401 Rockville Pike (HFM-700)

Rockville, MD 20852-1448

301-827-4163

celia.witten@fda.hhs.gov

34

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?

84

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?

85

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?

86

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

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

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

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A copy of the slides for Session 2 will be available

online via the TERMIS website,

www.termis.org.