industry day symposium session 2: “the regulatory imperative: international perspective”
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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. - PowerPoint PPT PresentationTRANSCRIPT
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
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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 start-up, development stage, established companies– Funding– Regulatory pathway– IP and technology transfer
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*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
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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
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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
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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%
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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)
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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)
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
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Outline
• FDA Mission & Organization
• OCTGT Activities
• Special Programs
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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
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Policy & Regulatory Guidance
Development
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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
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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
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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
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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
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OCTGT Regulatory Resources
• OCTGT Learn Webinar Series: http://www.fda.gov/BiologicsBloodVaccines/NewsEvents/ucm232821.htm
• Regulatory Questions: [email protected]
Patrick Riggins, Ph.D. – (301)827-6536
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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: [email protected]: 301-827-3821
Manufacturers Assistance and Technical Training Branch (MATTB)Email: [email protected]: 301-827-4081
Follow us on Twitter https://www.twitter.com/fdacber
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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
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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?
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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, 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
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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
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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.