department of health center for biologics and human servicesevaluation and research and human...
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DEPARTMENT OF HEALTHDEPARTMENT OF HEALTH CENTER FOR BIOLOGICS CENTER FOR BIOLOGICS AND HUMAN SERVICESAND HUMAN SERVICES EVALUATION and RESEARCHEVALUATION and RESEARCH
Update on OCTGT Guidance Development
Program
Cellular, Tissue, and Gene Therapies Advisory Committee Meeting
April 11, 2008
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FDA Good Guidance Practices(GGP)
Ensures proper development, formatting, processing, Ensures proper development, formatting, processing, routing, and use of FDA guidance documents routing, and use of FDA guidance documents Mandated by “Food and Drug Administration
Modernization Act of 1997" (FDAMA) Administrative Practices and Procedures; Good Guidance
Practices,” 21 CFR 10.115 CBER SOPP 8002 Annual Guidance Agenda published in Federal Register
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Guidance Documents
Documents prepared for FDA staff, Documents prepared for FDA staff, applicants/sponsors, and the public that: applicants/sponsors, and the public that: Describe the agency’s interpretation of or policy
on a regulatory issue; Relate to the processing, content, and
evaluation/approval of submissions; Relate to the design, production, manufacturing,
testing, labeling, and promotion of regulated products;
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Other Documents Guidance documents do NOT include documents Guidance documents do NOT include documents
related to:related to:
Internal FDA procedures; Agency reports; General information provided to consumers or health
professionals; Speeches; Journal articles and editorials; Media interviews and press materials; Warning letters; Memoranda of understanding; Other communications or actions taken by individuals at FDA or
directed to individual persons or firms; Documents directed at public health emergencies
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Guidance Documents
Guidance documents are intended to Guidance documents are intended to represent our current thinking on matters represent our current thinking on matters discussed in the documents.discussed in the documents. CBER staff may depart from guidance documents
only with appropriate justification and supervisory concurrence (21 CFR 10.115(d)(3)).
Any consistent deviation from a guidance document indicates that we should revise it
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Level 1 Guidance Documents Federal Register announcing the availability of the Federal Register announcing the availability of the draftdraft
guidance for public commentguidance for public comment Placed on CBER web sitePlaced on CBER web site FDA offers a comment period (usually 60 to 90 days) FDA offers a comment period (usually 60 to 90 days) After reviewing the public comments, CBER will revise the After reviewing the public comments, CBER will revise the
guidanceguidance Federal Register, announcing the availability of the final Federal Register, announcing the availability of the final
guidance. guidance. The public may submit comments on the final guidance at any The public may submit comments on the final guidance at any
time. time. CBER may issue a level 1 guidance for immediate CBER may issue a level 1 guidance for immediate
implementationimplementation
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Level 2 Guidance Documents All guidance documents not considered to be All guidance documents not considered to be
Level 1Level 1 Level 2 documents set forth existing practices Level 2 documents set forth existing practices
or minor changes in interpretation or policyor minor changes in interpretation or policy
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Communication with the Public During Guidance Development
When When consideringconsidering the development of guidance the development of guidance CBER may freely discuss issues with the public.
If the issues to be addressed are particularly complex or controversialIf the issues to be addressed are particularly complex or controversial Holding a public meeting Holding advisory committee meeting on the issues Before drafting the guidance
Once preparation of a draft guidance document has been initiated Once preparation of a draft guidance document has been initiated Specifics of the guidance are not discussed with the public.
When the guidance has been issued in draftWhen the guidance has been issued in draft Issues related to the draft guidance may be discussed Issues related to specific intentions regarding the finalization of the guidance
are not discussed 21 CFR 10.80
FDA may solicit information from the public at any time during the FDA may solicit information from the public at any time during the guidance development process. guidance development process.
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Published Guidances in Current FDA Annual Guidance Agenda (71 FR
51225, September 1, 2006)
Umbilical Cord Blood Intended For Hematopoietic Reconstitution in Patients With Hematological Malignancies Draft, 1/2007 CTGTAC Discussions- 2/2003, 3/2007
Preparation of Investigational Device Exemptions and Investigational New Drugs for Products Intended to Repair or Replace Knee Articular Cartilage Draft 7/2007 CTGTAC Discussions- 3/2005
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Published Guidances in Current FDA Annual Guidance Agenda (71 FR
51225, September 1, 2006)
Validation of Rapid Microbiological Methods for Assessing Sterility of Cellular and Gene Therapy Products Draft 2/2008
Certain Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Recovered From Donors Who Were Tested For Communicable Diseases Using Pooled Specimens or Diagnostic Tests Final, 1/2007
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Additional Published Guidances 2006-2007
Regulation of Human Cells, Tissues and Cellular and Tissue-Based Products (HCT/Ps)- Small Entity Compliance Guidance Immediate Implementation, 8/2007
Eligibility Determination for Donors of Human Cells, Tissues and Cellular and Tissue-Based Products Final 8/2007
Cell Selection Devices for Point of Care Production of Minimally Manipulated Autologous Peripheral Blood Stem Cells (PBSCs) Draft 7/2007
Class II Special Controls Guidance Document: Cord Blood Processing System and Storage Immediate Implementation, 1/2007
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Additional Published Guidances 2006-2007
Gene Therapy Clinical Trails – Observing Subjects for Delayed Adverse Events Final 11/2006 CTGTAC Discussions- 3/1999, 11/2000, 4/2001, 10/2001
Supplemental Guidance on Testing for Replication Competent Retrovirus in Retroviral Vector Based Gene Therapy Products and During Follow-up of Patients in Clinical Trials Using Retroviral Vectors Immediate Implementation, 11/2006 CTGTAC Discussions- 3/1999, 11/2000, 4/2001, 10/2001
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Recently Finalized Guidances
Content And Review Of Chemistry, Manufacturing, And Control (CMC) Information For Human Somatic Cell Therapy Investigational New Drug Applications (INDs) Final 4/2008 CTGTAC Discussions- Topics included in discussion at
numerous meetings Content And Review Of Chemistry, Manufacturing,
And Control (CMC) Information For Human Gene Therapy Investigational New Drug Applications (INDs) Final 4/2008 CTGTAC Discussions- Topics included in discussion at
numerous meetings
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Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee
Cartilage
Written by Cross-Center TeamWritten by Cross-Center Team CDRH CBER Reflects CTGTAC input
CDRH participated in meetingCDRH participated in meeting March 2005March 2005
Leverages ASTM document Leverages ASTM document Written by ASTM subcommittee FDA staff participation according to FDA policies and
ASTM process
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Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee
CartilageScopeScope IND/IDE products to repair or replace articular IND/IDE products to repair or replace articular
cartilage of the kneecartilage of the knee Devices Biologics Combinations Products
ExcludesExcludes Unicondylar and total knee implants Meniscus replacement products “361” HCT/P products
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Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee
Cartilage
Manufacturing and CMC InformationManufacturing and CMC Information Brief explanation of requirements forBrief explanation of requirements for
Devices Biologics Combination Products
Tailored for specifics of product Tailored for specifics of product compositioncomposition
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Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee
CartilageNonclinical Data and TestingNonclinical Data and Testing Purposes of Animal StudiesPurposes of Animal Studies
Biological response to products Durability of response (1 year) Toxicology Dose response
Mechanical Testing Mechanical Testing Compare to normal cartilage Justify why not possible
BiocompatibilityBiocompatibility ISO 10993 and/or ASTM F748-04
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Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee
Cartilage
Nonclinical Data and TestingNonclinical Data and Testing ASTM document- F2451-05, “Standard Guide
for in vivo Assessment of Implantable Devices Intended to Repair or Regenerate Articular Cartilage,”
cartilage defect locations; cartilage defect locations; discussion of articular cartilage defect preparation;discussion of articular cartilage defect preparation; description of gross and histological assessments;description of gross and histological assessments; description of various mechanical evaluations and description of various mechanical evaluations and
their applicability. their applicability.
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Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee
Cartilage
Clinical Study ProtocolsClinical Study Protocols Exploratory Trials-design featuresExploratory Trials-design features Exploratory Trials-knowledge learnedExploratory Trials-knowledge learned
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Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee
Cartilage
Clinical Study ProtocolsClinical Study Protocols Confirmatory TrialsConfirmatory Trials
Recommend randomized, controlled trial Double blind Blinded evaluators of major endpoints
Alternative design may be consideredAlternative design may be considered
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Preparation of IDEs and INDs for Products Intended to Repair or Replace
Knee Cartilage
Study EndpointsStudy Endpoints Clinically meaningful endpoints as primary Clinically meaningful endpoints as primary
in confirmatory studiesin confirmatory studies Improvement in pain Improvement in physical function
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Preparation of IDEs and INDs for Products Intended to Repair or Replace
Knee Cartilage
Study EndpointsStudy Endpoints Examples of secondary endpointsExamples of secondary endpoints
Arthroscopic examination Physical examination Histologic examination at short and long term Serological assessment for antibody and
evidence of inflammation Synovial fluid examination
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Preparation of IDEs and INDs for Products Intended to Repair or Replace
Knee Cartilage
Investigational Product AdministrationInvestigational Product Administration Detailed description of procedures
Surgical techniqueSurgical technique Plans for post-operativePlans for post-operative
Follow-upFollow-up Length of follow-up to be based on in vivo and
in vitro studies Two-year follow-up for subset of subjects
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Preparation of IDEs and INDs for Products Intended to Repair or Replace
Knee Cartilage
Adverse event (AE) reportingAdverse event (AE) reporting AE reporting per regulations (IND or IDE)AE reporting per regulations (IND or IDE) Subsequent surgical interventionsSubsequent surgical interventions
Revision Removal Reoperation
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Resources on the Web
Consolidation of OCTGT guidancesConsolidation of OCTGT guidances Cellular and Gene Therapies
http://www.fda.gov/cber/genetherapy/gtpubs.htm
Tissues http://www.fda.gov/cber/tissue/docs.htm
References for the Regulatory Process for References for the Regulatory Process for the Office of Cellular, Tissue and Gene the Office of Cellular, Tissue and Gene Therapies (OCTGT)Therapies (OCTGT) www.fda.gov/cber/genadmin/octgtprocess.htm
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Summary FDA guidance process to communicate with FDA guidance process to communicate with
stakeholdersstakeholders Good Guidance Practices (GGP) Governed by regulations 21 CFR 10.115
OCTGT Recent GuidancesOCTGT Recent Guidances Current Annual Guidance Agenda Additional Guidances to meet needs arising between Annual
Guidance Agendas FDA Guidance on Cartilage Repair ProductsFDA Guidance on Cartilage Repair Products
CBER and CDRH Joint Guidance CTGTAC Meeting provided input for guidance development Leveraged FDA participation in Standards Development
Organization (ASTM)
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Conclusions OCTGT has an active guidance development OCTGT has an active guidance development
program that includesprogram that includes Strategic Guidance Planning (Annual Agenda) Responds to changing needs
OCTGT Guidance Program leveragesOCTGT Guidance Program leverages Input from CTGTAC meetings Other public meetings (NIH RAC, Workshops,
Scientific Meetings, Industry Liaison Meetings) Cross-center efforts within FDA Participation with Standards Development
Organizations