1 Educational Web Seminar Educational Web Seminar Adverse Events and Reactions in Adverse Events and Reactions in Cellular Therapy Cellular Therapy Thursday, February 23, 2012 12:00 Noon 12:00 Noon --1:15 PM ET 1:15 PM ET Objectives • Examine how each type of adverse event should be reported for 361, 351, and licensed cell products • Identify adverse events related to cellular therapy product collection, processing and/or infusion • Illustrate the role of the processing laboratory, the PI, and IRB in reporting adverse events Speakers Karen Snow, BS(ASCP)BB - Quality Manager Massachusetts General Hospital Olive Sturtevant, MT(ASCP)SBB, SLS - Quality Assurance Director Dana Farber Cancer Institute Robert Lindblad, MD - PACT Coordinating Center PI The EMMES Corporation Web seminar presentation slides are available publicly at www.pactgroup.net www.pactgroup.net CME Credit and certificates of attendance provided upon request 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. In accordance with the ACCME Standards for Commercial Supportsm, all faculty for this event have signed a conflict of interest form in which they have disclosed any significant financial interests or other relationships with the industry relative to the topics they will discuss during this program. Faculty Disclosure Nature of Relationship Manufacturer/Provider Robert Lindblad, MD None Speaker, PACT staff N/A Karen Snow None Speaker N/A Olive Sturtevant None Speaker N/A Prali Dave None Planning Committee PACT Staff N/A Lisa Davis None Planning Committee PACT Staff N/A Karin Quinnan None Planning Committee PACT Staff N/A David Styers None Planning Committee PACT Staff N/A Debbie Wood None Planning Committee PACT Staff N/A Sharon Moffett None AABB Staff N/A Tiffany Achane None AABB Staff N/A
30
Embed
Educational Web SeminarEducational Web Seminar Adverse …pactgroup.net/system/files/webinar022312_handouts.pdf · 1 Educational Web SeminarEducational Web Seminar Adverse Events
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
1
Educational Web SeminarEducational Web Seminar
Adverse Events and Reactions in Adverse Events and Reactions in Cellular TherapyCellular Therapy
Thursday, February 23, 201212:00 Noon 12:00 Noon -- 1:15 PM ET1:15 PM ET
Objectives• Examine how each type of adverse event should be reported for 361, 351, and licensed cell products • Identify adverse events related to cellular therapy product collection, processing and/or infusion • Illustrate the role of the processing laboratory, the PI, and IRB in reporting adverse events
SpeakersKaren Snow, BS(ASCP)BB - Quality Manager
Massachusetts General Hospital Olive Sturtevant, MT(ASCP)SBB, SLS - Quality Assurance Director
Dana Farber Cancer InstituteRobert Lindblad, MD - PACT Coordinating Center PI
The EMMES Corporation
Web seminar presentation slides are available publicly at www.pactgroup.netwww.pactgroup.net
CME Credit and certificates of attendance provided upon request
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. In accordance with the ACCME Standards for Commercial
Supportsm, all faculty for this event have signed a conflict of interest form in which they have disclosed any significant financial interests or other relationships with the industry relative to
the topics they will discuss during this program.
Faculty Disclosure Nature of Relationship Manufacturer/Provider
Robert Lindblad, MD None Speaker, PACT staff N/A
Karen Snow None Speaker N/A
Olive Sturtevant None Speaker N/A
Prali Dave NonePlanning Committee
PACT StaffN/A
Lisa Davis NonePlanning Committee
PACT StaffN/A
Karin Quinnan NonePlanning Committee
PACT StaffN/A
David Styers NonePlanning Committee
PACT StaffN/A
Debbie Wood NonePlanning Committee
PACT StaffN/A
Sharon Moffett None AABB Staff N/A
Tiffany Achane None AABB StaffN/A
2
PACT WorkshopOctober 22-23, 2012
Manufacturing Cellular Therapy Products: Practical AspectsHost site: Baylor College of Medicine
Center for Cell & Gene TherapyHouston TX
Putting the Pieces Together
Karen Snow BS(ASCP)BBKaren Snow, BS(ASCP)BBQuality Assurance OfficerBone Marrow Transplant ProgramMassachusetts General HospitalBoston, MA
Define adverse event & adverse reaction
Distinguish reporting requirements indifferent circumstancesd e e t c cu sta ces
Explain different reporting systems
6
3
Any undesirable experience associated with the use of a medical product in a patient. Cellular Therapy Products C ll i Collection Processing Infusion
A noxious and unintended response suspected or demonstrated
to be caused by the collection or infusion
of a cell therapy productof a cell therapy product or by the product itself.
One type of Adverse Event
FACT CT Stds 4th edition8
Must be documented and reported in accordance with the facility’s policies and/or applicable laws and regulations.
At a minimum, any such event must be At a minimum, any such event must be reported to the patient’s physician and the medical director of the facility that issued the product.
Circular of Information for the Use of Cellular Therapy Products November, 2009
7
4
Who needs to know?o
“Reported in accordance with the
facility’s policies ……”
Collections Processing Clinical Clinical BMT, Cardiac, Neurology, Other
Communication helps to put the pieces together!
11
Autologous or Allogeneic
Related (1st or 2nd)or Unrelated
351 or 361 Product
Clinical Trial
Sponsorship (NIH, Industry)
12
5
BMT or Clinical Program Hospital Quality & Safety Committee Outside Facility or Registry (NMDP, CIBMTR) FDA
P i i l I i Principle Investigator Internal Review BoardNational Cancer Institute Clinical Trial Sponsor
13
“…and/or applicable laws and regulations”
ClinicalProgramClinicalProgram
CollectionCollection
Quality & Safety
Quality & Safety
ProcessingProcessing
14
Safety Issue Related to patient, staff or visitor Event outside of the laboratory Repeated Errors P ti t ID Patient ID Sampling Clerical Deviation from standard procedure
15
6
Related to Core GTPs
Facility ✪ Environmental Controls ✪
Form 3486
Equipment✪ Supplies or Reagents Recovery (collection)
1271.150(b)
Processing & Process Controls Labeling Controls Storage Receipt, Pre-distribution, Shipment and
Di t ib tiDistribution Donor Eligibility Screening & testing
17
1271.150(b)
HCT/P Deviation Code Changes:✪ Facilities
Cleaning & sanitation Suitable size, construction
✪ Equipment✪ Equipment Quality control not performed EQ not capable of producing valid results Check FDA website for more details
18
7
Do Not Report as Biological Product Deviation if: No products were distributed Not associated with: Communicable disease transmission Possible product contamination Not Related to core GTP’s Product was released under Urgent Medical Need (Allogeneic)
Was the product infused? Yes = BPD required No = No BPD required
8
“Even if investigation later shows
contamination is a false
A note about product contaminationBPD required when the product is
infused
22
contamination is a false positive”
“A deviation report is required if a positive culture is obtained and the product was distributed, “even if it's later determined to be a false positive result.”
Fatal Life Threatening Requires Medical
21CFR 1271.350(a)
23
Intervention Involves Transmission of
Communicable Disease Must have been Infused
Is a BPD or Medwatch Form Required?
Fatal or Life Threatening? Yes Required Medical Intervention? Yes Communicable Disease Transmission? No Communicable Disease Transmission? No Was the Product Infused? Yes
Not a Biological Product Deviation All four criteria for Medwatch 3500(A) not met
24
9
Investigational New Drug (IND)I ti ti l D i E ti (IDE)Investigational Device Exemption (IDE)
National Cancer Institute (NCI)
The Cancer Adverse Event Reporting System (caAERS) is an open source software tool that is used to collect, process, and report adverse events that occur during clinical trials..that occur during clinical trials..
http://ctep.cancer.gov/reporting/ NCI criteria differ from FDA
requirements
26
Reported by the Principle Investigator when:
SAE (Serious Adverse Event) Adverse event is unexpected Not consistent with investigator brochure No informed consent of possible event Event type has not been observed previously
27
10
Internal Review Board Clinical Trial Sponsor FDA as SAE (Medwatch 3500A) National Cancer Institute National Cancer Institute
28
Adverse Reaction is one type of Adverse Event
Determine Who Needs to Know Define the Type of product Review Reporting Requirements
Safety Reporting In Cell Safety Reporting In Cell Therapy Clinical TrialsTherapy Clinical TrialsTherapy Clinical TrialsTherapy Clinical Trials
Robert Lindblad, MDChief Medical Officer
Principle InvestigatorPACT Coordinating Center
20
Safety ReportingSafety Reporting
Regulatory Agency
58
ManufacturingFacility
Clinical SiteFacility
Product Use
Is this and IND study? Have you met with the clinical team?
Does the clinical team Does the clinical team understand your need to know about infusion reactions?
Do you understand the need to inform the clinical team of manufacturing issues?
For IND StudiesFor IND Studies
Who is the IND Sponsor?Who is the IND Sponsor?◦ Clinical Investigator◦ Manufacturing Investigator◦ Independent Companyp p y
60
21
Clinical Trial Team (Sponsor)Clinical Trial Team (Sponsor) Develop a research question Develop the measurements to answer that
question Develop a protocol
Develop safety reporting strategies
61
Develop safety reporting strategies Develop stopping rules Identify research sites Conduct the trial per protocol Review reported safety events Report the trial results
Clinical SiteClinical Site
Provide medical care Take medical history Conduct physical exam
62
Evaluate medical events Prescribe treatment Report adverse events
Manufacturing FacilityManufacturing Facility
Maintain GMP and GTP procedures Assess for Product Deviations
• Collection, processing and infusion
63
Microbial contamination Suspected disease transmission During or after product administration
22
Regulatory AgencyRegulatory Agency
Identify safety risks Review protocol for safety reporting
parameters Review manufacturing deviations
64
g Review all adverse events in annual
report Review expedited reports when
submitted Evaluate reported adverse events
Safety ReportingSafety ReportingWhere is the Critical Piece?Where is the Critical Piece?
Regulatory
65
g yAgency
ManufacturingFacility
Clinical SiteFacility
Regulatory
Safety ReportingSafety ReportingWhere is the Critical Piece?Where is the Critical Piece?
66
g yAgency
ManufacturingFacility
Clinical SiteFacility
23
Regulatory
Safety ReportingSafety ReportingWhere is the Critical Piece?Where is the Critical Piece?
67
g yAgency
ManufacturingFacility
Clinical SiteFacility
Communication between the Manufacturing Facility and the Clinical Site is critical to maintain the regulatory obligations of the IND
New FDA Regulations for Safety New FDA Regulations for Safety Reporting in INDs Reporting in INDs -- BackgroundBackground March 14, 2003 - FDA issued proposed rule to revise
its regulations governing pre and post marketingsafety reporting for human drugs and biological products.
110 comments received from Manufacturers, Trade R i CRO U i i i
68
Representatives, CROs, Universities, etc. September 29, 2010 - FDA published a final rule
amending safety reporting requirements for INDs and Bioavailability/Bioequivalence (BA/BE) Studies.
September 2010 - Draft Guidance issued to address rule changes
March 28, 2011- Final rule became effective September 28,2011 Final rule enforced
69
24
FDA New Regulation/GuidanceFDA New Regulation/GuidanceClinical Trial Safety ReportingClinical Trial Safety Reporting
Major principles◦ Quit submitting useless individual safety
reports◦ Quit calling things related unless there is
evidence
70
evidence◦ Quit dumping all adverse events into
investigator brochures◦ Sponsors need to think – make decision
regarding expedited reporting◦ Protocol development of creative safety
plans and reporting strategies
DefinitionsDefinitions Adverse event
Adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.
Suspected adverse reaction Suspected adverse reaction means any adverse
71
Suspected adverse reaction means any adverse event for which there is a reasonable possibility that the drug caused the adverse event. For the purposes of IND safety reporting, ‘reasonable possibility’ means there
is evidenceto suggest a causal relationship between the drug and the adverse event.
Adverse Reaction◦ Any adverse event caused by the drug
FDA New Regulation/GuidanceFDA New Regulation/Guidance
New TermsAdverse EventSuspected Adverse ReactionAdverse Reaction
72
Adverse Events
Adverse Reactions
Suspected Adverse Reactions
25
Investigator BrochureInvestigator Brochure
Only include adverse events for which a causal relationship is suspected or confirmed
Update the IB as new information becomes available
Continue to report as unexpected until IB is d t d
73
updated
Previous – Lists any and all AEs reportedNew – List only Suspected Adverse
Reactions
Expedited ReportingExpedited Reporting
The adverse event meets all three of the definitions contained in the requirement: ◦ Suspected adverse reaction
74
◦ Serious ◦ Unexpected
If the adverse event does not meet all three of the definitions, it should not be submittedas an expedited IND safety report.
This has always been a balance for expedited reporting!
75
Related Unexpected
26
Only sponsor can make this determination if it meets the definition of expedited reporting
Sponsor OR Investigator determines SERIOUSNESS
Sponsor decides RELATIONSHIP
Expedited ReportingExpedited Reporting
76
p Sponsor decides EXPECTDEDNESS Sponsor will investigate and document its
decisions Timeline starts when there is adequate
information to determine relationship and expectedness
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
CME CreditCME CreditPhysiciansAABB is an approved, accredited provider (Provider number 0000381) by the Accreditation Council forContinuing Medical Education (ACCME) to provide continuing medical education for physicians. AABBdesignates this education activity for a maximum of 1 credit hour in AMA PRA Category 1 CreditTM
Each physician should claim those credits that he/she actually spends in those activities.
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. 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 PersonnelAABB is approved by the Florida Board of Clinical Laboratory Personnel Provider number 50-4261 asAABB 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 hours.
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 contact hour.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 for participation in those AABB educational activities for which they do notqualify for continuing education credit.
CME CreditCME Credit
Sign and fax roster to 240-306-2527
Interested in obtaining CME credit for attending this web seminar?
Each attendee must:
Complete the online surveyhttp://www.surveymonkey.com/s/pactsurvey_adverseevents
Note: Please complete within 48 hrs of the web seminar
(Survey link above embedded in the reminder email sent 2/22/12)
30
AABB Live Learning Center AABB Live Learning Center
After the rosters and surveys have been processed, you will receive an
email from AABB with instructions on how to print your CME/CE certificates
for this web seminar.www.softconference.com/aabb
Thank you for attending!Thank you for attending!
To register for updates on upcoming web seminars, workshops, and PACT
attended meetings visit us on the web at: www.pactgroup.netwww.pactgroup.net