Transcript The Regulatory Imperative: International Perspective

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
Concept/Discovery Research
to Successful Product
Public/Private
Funding
Discovery
Research
Clinical Trials
Intellectual Property
& Patent Protection
Market
Regulatory Evaluation
& Product Approval
Successful Product
Public(s) Perception
& Market Acceptance
SCIENCE
Talent/People
2
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
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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 startup, 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
--Publication:
“Hurdles in Tissue Engineering/Regenerative Medicine Commercialization: A Survey of the
Financial Industry,” Tissue Engineering, November 2012 (in press).
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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
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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
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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
Tim Bertram, DVM, PhD; Tengion, Inc., USA
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European Regulatory environment of
regenerative medicine
TERMIS Industry Symposium
7 September 2012, Vienna (Austria)
Presented by: Lucia D’Apote, PhD
European Medicines Agency
An agency of the European Union
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
The EMA CAT and the RegMed pipeline in Europe
12 Lucia D’Apote - EMA
Established in 1993, operational since 1995

7 Westferry Circus
Canary Wharf
London E14 4HB
United Kingdom
Tel:
+44 (0) 20 7418 8400
Fax: +44 (0) 20 7418 8416
13
Lucia D'Apote - EMA
www.ema.europa.eu
The ATMP Regulation
Committee for Advanced Therapy
New Scientific Arena
Expertise
Beyond Traditional
Research
14
Lucia D'Apote - EMA
ATMP Pipeline – what we see
15
Lucia D'Apote - EMA
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
http://www.ema.europa.eu/doc
s/en_GB/document_library/Wor
k_programme/2010/11/WC500
099029.pdf
ATMP Pipeline – what we will see
318 clinical trials from EudraCT (1 May 2004 - 31 December
2010)
► 244 national = more than 70%
► 74 multinational = less than 30%
►
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Lucia D'Apote - EMA
Products
Based on self-classification:
► GTMPs + sCTMPs + TEPs: 250
► GTMPs =54 = 22%
► sCTMP/TEPs= 196 = 78%
►
►
►
18
phase I and II or I/II: 81%
phase III/IV:19%
phase IV, as assigned in the database: 7 CT
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
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
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
Orphan ATMPs
26 CT with Orphan
ATMPs
Mainly commercial
sponsors
Majority with cellbased products
75 ODD so far are
ATMPs !!!
22
Lucia D'Apote - EMA
Regulatory path and regulatory requirements
23 Lucia D’Apote - EMA
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
25
Lucia D'Apote - EMA
Risk based approach
26
Lucia D'Apote - EMA
Risk-management plan and follow-up
safety/efficacy
27
Lucia D'Apote - EMA
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
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.
29
Lucia D'Apote - EMA
Specificities and Challenges
30 Lucia D’Apote - EMA
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
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)
33
-
Manufacture in GMP environment
*
Potency assay: product specific, at least semi-quantitative, linking product testing with clinical effect
/biological activity
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
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’
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Prospective product development
37
Lucia D'Apote - EMA
Courtesy of dr. Paula Salmikangas, 2012
Retrospective product development
Courtesy of dr. Paula Salmikangas, 2012
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Lucia D'Apote - EMA
The way forward
Raise awareness – strengthen dialogue
Learn from experience
39 Lucia D’Apote - EMA
Nature Reviews Drug
Discovery, vol 9,
March 2010, 185-201
Regulatory Rapporteur,
vol 8, July-August
2011, 4-7
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Advice during development
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Lucia D'Apote - EMA
Regulatory strategy: save time
Scientific advice: Complying with SA/PA is significantly
associated with positive outcome
Positive MAA outcome related to compliance with SA/PA
received
100%
90%
97%
80%
70%
38/39
72%
60%
93/129
50%
40%
30%
30%
20%
6/20
10%
0%
Compliant with SA
Non-compliant with SA
received
No SA 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
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Lucia D'Apote - EMA
43 Lucia D’Apote - EMA
44 Lucia D’Apote - EMA
International Cooperation (EMA-FDA)
FDA-EMA-HC ATMP Cluster
ICH Regulators Forum Cell Therapy Group
Parallel Scientific advice
http://www.ema.europa.eu/docs/en_GB/document_libra
ry/Other/2009/11/WC500014868.pdf
45 Lucia D’Apote - EMA
Parallel Advice FDA
Confidentiality Agreement FDA
Applicant to address request to both Agencies
Agreement principles since 2004 pilot
Applicant initiative- exceptionally Agency initiative
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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
Outcome
No applicant involvement in draft reports
Parallel separate advice given not ‘joint’ advice
Confidentiality maintained
Standard fee applies
48
Thank you for your attention!
Lucia D’APOTE
European Medicines Agency (EMA)
[email protected]
49
Lucia D'Apote - EMA
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
Outline
• FDA Mission & Organization
• OCTGT Activities
• Special Programs
51
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.
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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
140
120
100
80
commercial
research
60
40
20
0
2003 2004 2005 2006 2007 2008 2009 2010 2011
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
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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
10
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
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Policy & Regulatory
Guidance
Development
12
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
FY 2012 Program Priorities
Guidance for Industry:
Draft – Preclinical Safety Assessment
of Investigational Cellular and Gene
Therapy 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
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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.
28
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 lifethreatening 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
OCTGT Regulatory Resources
• OCTGT Learn Webinar Series:
http://www.fda.gov/BiologicsBloodVaccine
s/NewsEvents/ucm232821.htm
• Regulatory Questions:
[email protected]
Patrick Riggins, Ph.D. – (301)827-6536
81
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Public Access to CBER
CBER website:
http://www.fda.gov/BiologicsBloodVaccines/default.htm
Phone: 1-800-835-4709 or 301-827-1800
Consumer Affairs Branch (CAB)
Email: [email protected]
Phone: 301-827-3821
Manufacturers Assistance and Technical Training Branch
(MATTB)
Email: [email protected]
Phone: 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
[email protected]
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?
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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, preclinical testing, and clinical assessment.
• TE/RM product pipeline is broad and deep presenting unique
challenges for regulators such that the EMA CAT and FDA PreSubmission 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
89
A copy of the slides for
Session 2 will be available online
via the TERMIS website,
www.termis.org.
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