Educational Web Seminar Ask the Experts

Transcription

1 Educational Web Seminar Ask the Experts Thursday, November 14, :00 PM - 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 Adrian Gee, MI Biol, l 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 CE Credit and certificates of attendance provided upon request Today s web seminar presentation slides are available publicly at 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 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 1

2 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 processing facilities will speak and answer questions about navigating the clinical research roadmap and draw on their own experiences. Cellular Therapy Clinical Research Roadmap Developed by PACT s cell processing facilities A resource for researchers new to the field of cellular therapy. 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. 2

3 Roadmap Category I - Translational Research Roadmap Category II - Resource Development 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 Seminar November 14, 2013 Catherine Matsumoto City of Hope 3

4 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. NIH Director - Elias Zerhouni, 2003 as N Engl J Med 2005; 353: October 13, 2005 PACT Manual of Procedures, PACT website Discovery to Translational Therapeutic candidate identified during the basic research and discovery phase Mechanism of action in disease model Early ypreclinical therapeutic proof of concept studies Identify unique/novel issues related to your product Identify assays needed to further characterize the therapeutic candidate PACT Website, Resource Center, Clinical Research Roadmap Id tif dditi l li i l t di th t 4

5 T1 Clinical trials design Regulatory affairs Biostatistics Manufacturing Product characterization Pre clinical studies Bench Bdid Bedside The Gap (a.k.a. Valley of Death ) Image: Published online 11 June 2008 Nature 453, (2008) doi: /453840a It s nothing a few stem cells and another 75 years of research can t fix D id H M K J M D David H. McKenna, Jr., M.D. Molecular & Cellular Therapeutics University of Minnesota 5

6 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 From Manual of Procedures, PACT W Principal Investigator Clinical Research Team Project Manager Biostatistician Regulatory Expert(s) QA Expert(s) QC Expert(s) Technology Transfer/Product Development/cGMP Manufacturing Experts From Study Team, Clinical Research Roadmap, Resource Cen 6

7 May be need to overlap expertise/responsibilities due to funds, logistics, institutional set-up, etc.. Project manager may be medical technologist Biostatistician 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 may be from other categories *ODAT Mtgs Development Mtgs cgmp Facility/Cell Therapy Lab Lab/Med Director Technology Transfer Mtgs Operations/Facility Director/Tech Sup QA Director PI Team Mtgs Ad Hoc Mtgs R & D Lead Tech Trial Initiation Mtgs Technical Team Mtgs ODAT = Office of Discovery & Translation, CTSI Diane Kadidlo 7

8 When to involve cgmp facility/ct lab? How to approach technology transfer? How to cover costs of translation/validation/ clinical production? Thank you! Preclinical Studies Adrian Gee Center for Cell & Gene Therapy Baylor College of Medicine 8

9 Collect in vitro & in vivo data to demonstrate: Potential clinical value in treatment of a specific disease Safety 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 Selection of storage and shipment conditions Generation of Standard Operating Procedures Finalization of release tests Training of manufacturing staff 9

10 Work with Investigators to determine product specifications Dose, number of doses, volume, means of administration Develop manufacturing procedure using GMP compliant 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 validation 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 10

11 You can Design and generate a pre-clinical data package for the IND submission Obtain assistance in development of the product 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 11

12 FDA FDA IND 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 Investigator (1572), Manufacturing & Quality Assurance representation 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 12

13 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 Critical Citi lraw Materials (e.g., animal lderived dcomponents), t) inprocess 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 13

14 Format of an IND Application Traditional or Common Technical Document (CTD) format 21 CFR 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 (e.g., time sensitive) i 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 controlssound experimental design, reproducible results, accurate interpretation of results, and use of complimentary assays is often helpful Investigational New Drug (IND)/Preclinical/Quality 1. Formal Meetings Between the FDA and Sponsors or Applicants Preclinical Assessment of Investigational Cellular and Gene Therapy Products Draft Preclinical assessment of cell and gene therapy products, see OCTGT Learn Video Series, at: htm 4. Quality Systems Approach to Pharmaceutical CGMP Regulations Investigational New Drug Applications (INDs) Determining Whether Human Research Studies Can Be Conducted Without an IND Exploratory IND studies Process Validation: General Principles and Practices Draft Target Product Profile A Strategic Development Process Tool Draft

15 Chemistry, Manufacturing, and Controls (CMC) 1. cgmp for Phase 1 Investigational Drugs Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs) Potency Tests for Cellular and Gene Therapy Products ICH Q5D: Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/Biological Products ICH Q5E: Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process Clinical 1. Frequently Asked Questions Statement of Investigator (Form FDA 1572) Draft Guidance for IRBs, Clinical Investigators, and Sponsors MedWatch Form FDA 3500A: Mandatory Reporting of Adverse Reactions Related to Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) Information Program on Clinical Trials for Serious Life- Threatening Diseases and Conditions Draft How to Comply with the Pediatric Research Equity Act Draft ICH E6: Good Clinical Practice: Consolidated Guidance

16 Ask The Experts Myriam Armant Catherine Matsumoto David H. McKenna Adrian Gee John M. Centanni Web seminar presentation slides and presentation slides from previous web seminars are available publicly at Select Education PACT Web Seminars 16

17 Physicians This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of AABB and PACT. AABB is accredited by the ACCME to provide continuing medical education for physicians (Provider number ). AABB designates this educational activity for a maximum of 1 hour(s) of Category 1 credit toward the AMA Physicians Recognition Award. Each physician should claim those credits that he/she actually spent in the activity. California Clinical Laboratory Personnel AABB is an approved, accrediting agency for continuing education for California-licensed clinical laboratory personnel. This event has been approved for a maximum of 1 contact hour(s). AABB s accrediting agency number is California clinical laboratory personnel must provide a personal signature and other required information on the attendance log. Florida Clinical Laboratory Personnel AABB is approved by the Florida Board of Clinical Laboratory Personnel, Provider number , as a provider of continuing education programs for Florida-licensed clinical laboratory personnel. AABB designates this education activity for a maximum of 1.2 contact hour(s). California Nurses AABB is approved by the California Board of Registered Nursing, Provider Number 4341, as a provider of 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 information on the attendance log. General Attendees Administrators, nurses (other than California-licensed nurses), clinical laboratory personnel (other than California- and Florida-licensed personnel), and other health-care professionals may receive a certificate of attendance along with 1 contact hour for participation. Interested in obtaining CE credit for attending this web seminar? Each attendee must: Sign and fax roster to Complete the online survey (Survey link above is embedded in the reminder sent 11/13/13) Note: Please complete within 48 hrs of the web seminar After the web seminar rosters and surveys have been processed, you will receive an from AABB regarding the CE certificates for this event, which will include instructions on how to print your CE certificates for the workshop. To access the Live Learning Center Development>Live Learning Center Please note that attendees signing the sign-in sheet is AABB s method of verifying attendance at the event. 17

18 Thank you for attending! To register for updates on upcoming web seminars, workshops, and PACT attended meetings visit us on the web at: 18