1 Educational Web Seminar “Ask the Experts” Thursday, November 14, 2013 12:00 PM 12:00 PM --1:15 PM ET 1:15 PM ET Myriam Armant, PhD Technical Director – CHCT Boston Immune Disease Institute Catherine Matsumoto, BS Director, Office of IND Development and Regulatory Affairs City of Hope David H. McKenna Jr., MD Scientific and Medical Director Molecular and Cellular Therapeutics University of Minnesota Ad i G MI Bi l PhD Adrian Gee, MI Biol, PhD Professor, Departments of Medicine and Pediatrics Center for Cell and Gene Therapy Baylor College of Medicine John M. Centanni, MS Quality Assurance & Regulatory Affairs Manager Medicine/Institute for Clinical and Translational Research University of Wisconsin-Madison Today’s web seminar presentation slides are available publicly at www.pactgroup.net CE Credit and certificates of attendance provided upon request The Accreditation Council for Continuing Medical Education (ACCME) is the governing body that accredits AABB to provide continuing medical education credits for physicians. In accordance with the ACCME Standards for Commercial Support, AABB implemented mechanisms, prior to the planning and implementation of this CME/CEU activity, to identify and resolve conflicts of interest for all individuals in a position to control content of this CME/CEU activity. Faculty Disclosure Nature of Relationship Manufacturer/Provider Myriam Armant, PhD None Speaker N/A Catherine Matsumoto BS None Speaker N/A Catherine Matsumoto, BS None Speaker N/A David H. McKenna Jr., MD None Speaker N/A Adrian Gee, MI Biol, PhD None Speaker N/A John M. Centanni, MS None Speaker N/A Debbie Wood None Planning Committee PACT Staff N/A David Styers None Planning Committee PACT Staff N/A Karin Quinnan None Planning Committee PACT Staff N/A Laarni Ibenana None Planning Committee PACT Staff N/A Holly Baughman None Planning Committee PACT Staff N/A Sharon Moffett None AABB Staff N/A Jared Case None AABB Staff N/A
Transcript
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Educational Web Seminar“Ask the Experts”
Thursday, November 14, 201312:00 PM 12:00 PM -- 1:15 PM ET1:15 PM ET
Myriam Armant, PhDTechnical Director – CHCT Boston
Immune Disease Institute
Catherine Matsumoto, BSDirector, Office of IND Development and Regulatory Affairs
City of Hope
David H. McKenna Jr., MDScientific and Medical Director
Molecular and Cellular TherapeuticsUniversity of Minnesota
Ad i G MI Bi l PhDAdrian Gee, MI Biol, PhDProfessor, Departments of Medicine and Pediatrics
Center for Cell and Gene TherapyBaylor College of Medicine
John M. Centanni, MSQuality Assurance & Regulatory Affairs Manager
Medicine/Institute for Clinical and Translational ResearchUniversity of Wisconsin-Madison
Today’s web seminar presentation slides are available publicly at www.pactgroup.net
CE Credit and certificates of attendance provided upon request
The Accreditation Council for Continuing Medical Education (ACCME) is the governing body thataccredits AABB to provide continuing medical education credits for physicians. In accordance with theACCME Standards for Commercial Support, AABB implemented mechanisms, prior to the planning andimplementation of this CME/CEU activity, to identify and resolve conflicts of interest for all individualsin a position to control content of this CME/CEU activity.
Faculty Disclosure Nature of Relationship Manufacturer/Provider
This interactive webinar will identify critical areas that need to be considered when bringing a cellular therapy to an
Investigational New Drug (IND) application and eventually into the clinic Representatives from the PACT cell processingthe clinic. Representatives from the PACT cell processing
facilities will speak and answer questions about navigating the clinical research roadmap and draw on their own experiences.
Cellular Therapy Clinical Cellular Therapy Clinical Research RoadmapResearch Roadmap
Developed by PACT’s cell processing facilities
A resource for researchers new to the field of cellular therapy.py
To provide a high-level overview that will assist researchers in the identification of the critical areas that need to be considered when developing a cellular therapy intended for evaluation in human clinical studies under an IND.
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Roadmap Category I - Translational Research Roadmap Category II - Resource Developmentp g y p Roadmap Category III - Pre-Clinical Studies Roadmap Category IV - IND Filing
Roadmap Category I - Translational Research Identify steps in determining when a therapeutic candidate is ready to enter
the translational phase. Speaker: Catherine Matsumoto
Roadmap Category II - Resource Development Learn to develop a study team to coordinate the planning and initiation of
preclinical and clinical research studies aimed at bringing the therapeutic candidate to the clinic.
Speaker: Dr. David H. McKenna, Jr.
Roadmap Category III - Pre-Clinical Studies Develop an understanding of implementing translational development and
cell product validation processes to refine and optimize the early preclinical assays and models used during the discovery phase as the therapeutic candidate moves through product lifecycle.
Speaker: Dr. Adrian Gee
Roadmap Category IV - IND Filing Describe the benefits to and identify the elements used in developing a
regulatory plan early on to facilitate the IND development and submission process.
Speaker: John Centanni
Translational Research“Ask the Experts”
PACT Web SeminarN b 14 2013November 14, 2013
Catherine MatsumotoCity of Hope
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“It is the responsibility of those of us involved in today's biomedical research enterprise to translate the remarkable scientific innovations we are witnessing into health gains for the nation. “
N Engl J Med 2005; 353:1621‐1623. October 13, 2005- Elias Zerhouni, 2003 as
NIH Director
PACT Manual of Procedures, PACT website
Therapeutic candidate identified during the basic
research and discovery phase
Mechanism of action in disease model
Early preclinical therapeutic proof of concept
Discovery to Translational
y p p p pstudies
Identify unique/novel issues related to your product
Identify assays needed to further characterize the
therapeutic candidate
Id tif dditi l li i l t di th tPACT Website, Resource Center, Clinical Research Roadmap
Image: Published online 11 June 2008 | Nature 453, 840-842 (2008) | doi:10.1038/453840a
Bench Bedside
“It’s nothing a few stem cells and another 75 years of research can’t fix”
D id H M K J M DDavid H. McKenna, Jr., M.D.Molecular & Cellular Therapeutics
University of Minnesota
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Learn to develop a study team to coordinate the planning and initiation of preclinical andinitiation of preclinical and clinical research studies aimed at bringing the therapeutic candidate to the clinic
From Manual of Procedures, PACT W
Principal Investigator Clinical Research Team Project Manager Biostatistician
R l t E t( ) Regulatory Expert(s) QA Expert(s) QC Expert(s) Technology Transfer/Product
Development/cGMP Manufacturing Experts
From Study Team, Clinical Research Roadmap, Resource Cen
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May be need to overlap expertise/responsibilities due to funds, logistics, institutional set-up, etc..
Project manager may be medical technologist
Biostatistician may be fromBiostatistician may be from institutional core
Regulatory expert may be QA Director
QC expert may be medical technologist independent of production
Tech transfer/product dev/cGMP manufacturing experts maybe from other categories
cGMP Facility/Cell Therapy Lab
• Lab/Med Director
• Operations/Facility Director/Tech Sup
Development Mtgs
*ODAT Mtgs
Technology Transfer Mtgs
p / y / p
• QA Director
• R & D Lead Tech
PI Team Mtgs
Trial Initiation Mtgs
Technical Team Mtgs
Ad Hoc Mtgs
ODAT = Office of Discovery & Translation, CTSI
Diane Kadidlo
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When to involve cGMP facility/CT lab? How to approach technology transfer? How to cover costs of How to cover costs of
translation/validation/ clinical production?
Thank you!
Preclinical Studies
Adrian GeeCenter for Cell & Gene Therapy
Baylor College of Medicine
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Collect in vitro & in vivo data to demonstrate: Potential clinical value in treatment of a specific
disease Safetyy Lack of toxicity Lack of adverse effects
Route and means of administration Likely dose to be used initially in the clinical
trial
Help in the design of the pre-clinical study Review methods for preparing the product Selection of the appropriate animal model Selection of the appropriate in vitro tests Perform experiments to collect the data Help in selection of the product release
criteria
Preparation to manufacture the product under cGMP conditions Coordination with Clinical Protocol Selection of compliant reagents Scale up of manufacturing Scale up of manufacturing Selection of storage and shipment conditions Generation of Standard Operating Procedures Finalization of release tests Training of manufacturing staff
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Work with Investigators to determine product specifications Dose, number of doses, volume, means of
administration Develop manufacturing procedure using GMP
compliant materials to meet thesecompliant materials to meet these specifications
Develop and test methods for storage and shipping
Help with writing Chemistry, Manufacturing & Control (CMC) section of the IND
Demonstrate that the manufacturing procedure reproducibly results in a product that meets release criteria Criteria for acceptance are established before
performing the validationNormally 3 full scale runs are required Normally 3 full scale runs are required
Performed as per SOP All release criteria must be met Contamination & cross-contamination must be
prevented Yields, purities etc must be within expected ranges
Assist in design of validation study Provide information/advice for pre-IND
meetings with FDA Perform validation runs and release testing Perform validation of cell delivery system Provide validation report for CMC section
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You can Design and generate a pre-clinical data package
for the IND submission Obtain assistance in development of the
product manufacturing and testing proceduresproduct manufacturing and testing procedures Generate a validation data section Obtain a data package for the CMC section and
assistance with preparation of the IND CMC
NHLBI, NIH- PACT
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INDFDA
FDA
NHLBI, NIH- PACT Manual of Procedures (MOP)
Develop a plan early in the development process
Identify Regulatory Team Regulatory Liaison, Principle Investigator (1571), Lead Clinical
Become familiar with regulatory resources Code of Federal Regulation (CFR), Guidance for Industry, ICH,
GXPs
Prepare for FDA interactions Understand types of meetings/obligations/time constraints
Develop a Clinical Protocol Schema Clinical indication, patient population, Standard of Care Study design, multicenter/single center, number of subjects,
I/E criteria Route of administration, administration schedule, summary
of subject visits
Generate a Clinical Protocol Consent Form, schedule of study procedures/visits, safety
endpoints/stopping rules, Data Management Plan, Data Monitoring Plan, and Case Report Form
Develop a General Investigational Plan Current clinical need, currently approved products, proposed
future studies
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Manufacturing Process Process flow diagram, manufacturing scale, and summary of
product development activities, storage/stability studies
Quality Assurance/Quality Control Documentation control, review, and approval
C iti l R M t i l ( i l d i d t ) i Critical Raw Materials (e.g., animal derived components), in-process and final product testing, specification setting, and establishing lot release criteria
Quality Systems Documentation system: Test Method (TM), Batch Production
Record (BPR), Standard Operating Procedure (SOP), Certificate of Analysis (COA)
Prospectively design and executed studies Preclinical phase of product development and testing
Product Characterization Process flow diagram, manufacturing scale, and summary of
product development activities Comparability of preclinical material to that intended for
clinical use
Product Safety Testing Critical Raw Materials, in-process and final product testing,
specification setting, and lot release criteria
Pharmacology/Toxicology Studies Proof of concept studies demonstrating efficacy Adequate documentation to include: Protocols, Final Study
Reports, Product Development Reports, TMs, BPRs, and SOPs
Identify Meeting Type Type A, B (pre-IND), or C (pre,pre-IND) Meeting format: Face-to-face or teleconference
Reason for FDA meeting Discuss critical Raw Materials, in-process and/or final
product testing, specification setting, lot release criteria, clinical study design
Scheduling the meeting with FDA Formal meeting request with purpose and anticipated
outcome, draft specific questions, list of meeting participants, pre-meeting materials packet
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Format of an IND Application Traditional or Common Technical Document (CTD) format 21 CFR 312.23 IND Content and Format FDA presentation (see Relevant Guidance Documents)
Content of the IND application Modular, complete yet succinct, provide summary
information with supporting final reports in the Appendix
FDA Project Manager Assign IND number, number of copies to submit, Serial
Submission #
Potential outcomes of an IND submission
1. FDA encourages interactions early in the development process and often throughout development
2. Formal Process - written meeting request, pre-read materials packet, FDA written response, meeting ( i i i )(e.g., time sensitive)
3. FDA embraces good science & peer review (e.g., publications, grants); adherence to these principles is powerful in winning FDA support
4. FDA expects adequate documentation and controls-sound experimental design, reproducible results, accurate interpretation of results, and use of complimentary assays is often helpful
Investigational New Drug (IND)/Preclinical/Quality1. Formal Meetings Between the FDA and Sponsors or Applicants 20092. Preclinical Assessment of Investigational Cellular and Gene Therapy
Products Draft 20123. Preclinical assessment of cell and gene therapy products, see OCTGT
Learn Video Series, at: http://www.fda.gov/BiologicsBloodVaccines/NewsEvents/ucm23282.htmhtm
4. Quality Systems Approach to Pharmaceutical CGMP Regulations 20065. Investigational New Drug Applications (INDs)—Determining Whether
Human Research Studies Can Be Conducted Without an IND 20136. Exploratory IND studies 20067. Process Validation: General Principles and Practices Draft 20088. Target Product Profile—A Strategic Development Process Tool Draft
2007
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Chemistry, Manufacturing, and Controls (CMC)1. cGMP for Phase 1 Investigational Drugs 20082. Content and Review of Chemistry, Manufacturing, and
Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs) 2008
3. Potency Tests for Cellular and Gene Therapy Products 2011
4. ICH Q5D: Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/Biological Products 1997.
5. ICH Q5E: Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process 2004.
Clinical1. Frequently Asked Questions—Statement of Investigator
(Form FDA 1572) Draft 20082. Guidance for IRBs, Clinical Investigators, and Sponsors
20133. MedWatch Form FDA 3500A: Mandatory Reporting of
Adverse Reactions Related to Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) 2005
4. Information Program on Clinical Trials for Serious Life-Threatening Diseases and Conditions Draft 2004
5. How to Comply with the Pediatric Research Equity Act Draft 2005
6. ICH E6: Good Clinical Practice: Consolidated Guidance 1996.
Web seminar presentation slides and presentation slides from previous web
seminars are available publicly atseminars are available publicly at www.pactgroup.net www.pactgroup.net
Select Education PACT Web Seminars
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Physicians
This activity has been planned and implemented in accordance with the Essential Areas and Policies ofthe Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship ofAABB and PACT. AABB is accredited by the ACCME to provide continuing medical education forphysicians (Provider number 0000381). AABB designates this educational activity for a maximum of 1hour(s) of Category 1 credit toward the AMA Physicians Recognition Award. Each physician shouldclaim those credits that he/she actually spent in the activity.
California Clinical Laboratory PersonnelAABB is an approved, accrediting agency for continuing education for California-licensed clinicallaboratory personnel. This event has been approved for a maximum of 1 contact hour(s). AABB’saccrediting agency number is 0011. California clinical laboratory personnel must provide a personalsignature and other required information on the attendance log.
Florida Clinical Laboratory PersonnelC y
AABB is approved by the Florida Board of Clinical Laboratory Personnel, Provider number 50-4261, asa provider of continuing education programs for Florida-licensed clinical laboratory personnel. AABBdesignates this education activity for a maximum of 1.2 contact hour(s).
California NursesAABB is approved by the California Board of Registered Nursing, Provider Number 4341 , as a providerof continuing education programs. AABB designates this event for a maximum of 1.2 contact hour(s).Nurses who want to receive credit must provide a personal signature and other requested informationon the attendance log.
General AttendeesAdministrators, nurses (other than California-licensed nurses), clinical laboratory personnel (otherthan California- and Florida-licensed personnel), and other health-care professionals may receive acertificate of attendance along with 1 contact hour for participation.
Sign and fax roster to 240-306-2527
Interested in obtaining CE credit for attending this web seminar?
Each attendee must:
Complete the online surveyhttps://www.surveymonkey.com/s/PACT_Webinar_Ask_the_Experts
Note: Please complete within 48 hrs of the web seminar
(Survey link above is embedded in the reminder email sent 11/13/13)
After the web seminar rosters and surveys have been processed, you will receive an email from
AABB regarding the CE certificates for this event, which will include instructions on how to print your
CE certificates for the workshop.CE certificates for the workshop.
To access the Live Learning Center www.aabb.org>Professional Development>Live
Learning Center
Please note that attendees signing the sign-in sheet is AABB’s method of verifying attendance at the event.
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Thank you for attending!Thank you for attending!
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