DEPARTMENT OF HEALTHDEPARTMENT OF HEALTH CENTER FOR BIOLOGICS CENTER FOR BIOLOGICS AND HUMAN SERVICESAND HUMAN SERVICES EVALUATION and RESEARCHEVALUATION and RESEARCH
Update on theUpdate on the Somatic Cell Therapy Letter Somatic Cell Therapy Letter
Cellular, Tissue, and Gene Therapies Advisory Committee Meeting
April 11, 2008
2
Somatic Cell Therapy Letter (SCTL)
Letter issued as of June 2002Letter issued as of June 2002
Requested submission of information onRequested submission of information on product manufacturing quality control procedures product testing clinical trial oversight and monitoring practices
3
Goals of SCTL
Ensure ongoing trials meet current Ensure ongoing trials meet current expectations forexpectations forProduct release testing & characterization
Identify lapses in product testingIdentify lapses in product testingProduct characterization & manufacturing Product characterization & manufacturing
processesprocessesClinical trial oversight & monitoring
Encourage Good Clinical PracticeEncourage Good Clinical Practice
4
Goals of SCTL (cont.)
Gather information on need for additional Gather information on need for additional guidance other regulatory documentsguidance other regulatory documents
Determine need for other forms of Determine need for other forms of outreach to SCT field outreach to SCT field
Enhance the safety of cellular products Facilitate product development
5
Somatic Cell Therapy Letter
Consisted of 8 multi-part Chemistry, Consisted of 8 multi-part Chemistry, Manufacturing, and Control (CMC) Manufacturing, and Control (CMC) questions and 3 multi-part Clinical questions and 3 multi-part Clinical questionsquestions
Requested date for response was 60 days Requested date for response was 60 days from anniversary date of the filefrom anniversary date of the file
Lack of response was not considered a Lack of response was not considered a cause for placing the file on clinical holdcause for placing the file on clinical hold
6
CMC Question Topics
QC/QA program-QC/QA program- description, procedures, personnel, audits
Qualification of starting cells, reagents, Qualification of starting cells, reagents, equipmentequipment
Tracking, segregation, labelingTracking, segregation, labeling Cleaning and sanitizationCleaning and sanitization Control of contamination & cross Control of contamination & cross
contaminationcontamination
7
CMC Question Topics (cont.)
Processing and testing timelineProcessing and testing timeline Product testing methodsProduct testing methods
In-process, final product Sterility validation, aseptic processingSterility validation, aseptic processing Product characterizationProduct characterization Stability programStability program Cross referenced filesCross referenced files
8
Clinical Question Topics
A complete description of the clinical A complete description of the clinical monitoring program including:monitoring program including: A description of the personnel responsible for
monitoring A summary of the procedures for clinical study
conduct monitoring and auditing A request final study reports be submitted A request final study reports be submitted
for all studies for all studies
9
Review Summary
Responses reviewed by IND review team Responses reviewed by IND review team ensure ongoing clinical trials met current expectations identify lapses in product safety testing
Identified safety issues in low number of INDsIdentified safety issues in low number of INDs Safety issues in a specific IND were addressed Safety issues in a specific IND were addressed
between review team and sponsorbetween review team and sponsor Observed broad differences in status of product Observed broad differences in status of product
characterizationcharacterization Identified need for additional CMC guidance Identified need for additional CMC guidance
documents and outreach to SCT fielddocuments and outreach to SCT field
10
CMC- Published Guidance
11
CMC- Published Draft Guidance
12
GMP Guidances with Sections on SCT products
13
Clinical Guidances
Good Clinical Practice Good Clinical Practice is addressed in is addressed in
““ICH E6ICH E6
Good Clinical Good Clinical Practice: Practice: Consolidated Consolidated Guidance”Guidance”
14
CMC Guidance in Development
Potency Measurements for Cell and Gene Potency Measurements for Cell and Gene Therapy ProductsTherapy Products Topic of CTGTAC meeting on February 9, 2006
Guidance document is under developmentGuidance document is under development
15
Outreach
OCTGT gives regulatory presentations at OCTGT gives regulatory presentations at numerous conferences each yearnumerous conferences each year broad audiences across SCT field
Liaison MeetingsLiaison Meetings
CMC talks commonly focus on product CMC talks commonly focus on product characterization and potencycharacterization and potency
CMC talks also address 21 CFR 1271, CMC talks also address 21 CFR 1271, (Tissue Rules)(Tissue Rules)
16
HCT/P Regulations and Guidance
21 CFR 1271, “Tissue 21 CFR 1271, “Tissue Rules”Rules”
In effect in May 2005In effect in May 2005 Focus on the Focus on the
prevention of prevention of transmission of transmission of infectious diseaseinfectious disease
Parts A-D apply to Parts A-D apply to SCT productsSCT products
17
Resources on the Web
Consolidation of relevant information onto Consolidation of relevant information onto CBER websiteCBER website
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.htmwww.fda.gov/cber/genadmin/octgtprocess.htm
18
Summary
CBER experience from SCTL responses CBER experience from SCTL responses contributed to:contributed to: multiple guidance documents
issued and in preparationissued and in preparation
numerous ongoing outreach activities broadly applicable to the field of cell therapies
19
Conclusions Guidances are now available to address our Guidances are now available to address our
expectations for IND submissions and clinical expectations for IND submissions and clinical trial conducttrial conduct
It is not necessary to convey these expectations It is not necessary to convey these expectations and request responses in a separate formatand request responses in a separate format
OCTGT will discontinue issuing the SCTL and OCTGT will discontinue issuing the SCTL and no longer request that sponsors provide updates no longer request that sponsors provide updates in the format of the SCTL questionsin the format of the SCTL questions
IND Sponsors may provide information updates IND Sponsors may provide information updates in amendments and annual reports, as in amendments and annual reports, as appropriateappropriate
20
Thank you
Somatic cell therapy IND sponsorsSomatic cell therapy IND sponsors CTGTAC membersCTGTAC members
