slide1 n.
Skip this Video
Download Presentation
Talking Points

Loading in 2 Seconds...

play fullscreen
1 / 51

Talking Points - PowerPoint PPT Presentation

  • Uploaded on

Post-Market Surveillance & Third-Party Reporting Systems A presentation to the LSRO Panel on Dietary Supplements and Adverse Event Reporting. Rick Kingston PharmD Vice President & Senior Clinical Toxicologist PROSAR International Poison Center & Associate Professor

I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
Download Presentation

PowerPoint Slideshow about 'Talking Points' - howell

Download Now An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.

- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

Post-Market Surveillance&Third-Party Reporting SystemsA presentation to the LSRO Panel on Dietary Supplements and Adverse Event Reporting

Rick Kingston PharmD Vice President & Senior Clinical Toxicologist PROSAR International Poison Center


Associate Professor

Department of Experimental and Clinical Pharmacology

College of Pharmacy, University of Minnesota

talking points
Talking Points
  • Introduction to PROSAR International Poison Center (IPC)
  • Brief overview of Post-Market Surveillance and sources of data relied upon by Companies
  • The EPA FIFRA 6(a)(2) model
  • Product Stewardship and evolution of the PROSAR IPC model
talking points cont
Talking Points (cont.)
  • PROSAR IPC- Data Collection- Severity Assessments- Surveillance, Analysis, and Benchmarking- Responding to a serious event
  • Strengths and limitations of “spontaneous reporting”
  • Implications for the Metabolife project
  • Challenges related to Dietary Supplement Surveillance and Safety
organizational profile service offerings and focus
Organizational Profile,

Service Offerings,

and Focus

  • Health & Safety Information Services
    • Healthcare practice
    • leverage technology extensively
      • Case Manager
      • Case Explorer
  • PROSAR International Poison Center (IPC) serving clients with specialized post-market surveillance needs since 1997
    • >100,000 cases per year
    • private center serving >200 clients
prosar ipc services
  • PROSAR International Poison Center (Health & Safety Call Center focused on consumer product medical support and surveillance)
  • International Animal Poison Center (Industry focused surveillance center for incidents involving animal health)
  • Pet Poison Hotline (Public)
  • Toxicology Consulting
    • Pre & Post Market Product Safety Assessments
    • Risk Assessments
prosar international poison center
PROSAR International Poison Center
  • Markets served:
    • Consumer Products: Personal Care, Food, Household
    • Industrial Chemical
    • Drug/Pharmaceutical
    • Ag-Chem-Pesticide-Herbicide
    • Animal Health
international animal poison center service
International Animal Poison Center Service
  • Director, Lynn Hovda, R. Ph., D.V.M., M.S., CSPI, DACVIM
  • Animal care provided by DVM’s, CVT’s, and Toxicologists
  • Serving corporate clients and the general public
  • EPA and FDA reporting
our staff
Our Staff...
  • Highly credentialed, healthcare professionals with over 150 years experience in clinical, academic, and research environments
    • Specific expertise in Toxicology, Pharmacology, Infectious Disease Epidemiology, and Industrial Hygiene
    • Physicians Board Certified in Internal Medicine, Emergency Medicine, Occupational Medicine, Veterinary Medicine, and Medical Toxicology
    • Academic affiliation with University of Minnesota College of Pharmacy
experienced multi disciplinary staff
Experienced, Multi-Disciplinary Staff

NameYears Experience

Leo Sioris, Pharm. D. 24

Richard Kingston, Pharm. D., CSPI 23

Steve Borron, M.D., M.S., FACEP, ABMT 15

Lynn Hovda, R. Ph., D.V.M., M.S., CSPI, DACVIM 16

Dean Filandrinos, Pharm. D., M.S. 9

John Gualtieri, Pharm. D. 7

John Shevlin, R. Ph., CSPI 21

Joele Richardson, R. Ph., CSPI 9

Ann Thompson, M.S., CIC 15

Lawrence Betts, M.D., Ph.D., CIH 27

Kurt Walstrom, Pharm. D. 6

Fred Oehme, D.V.M. 23

Jeanne Sutich, D.V.M. 3

partial client list
Partial Client List





Dow Corning



Fuji USA

Huntsman Corporation

ICI Americas

Johnson Wax Professional

PRC - DeSoto

Rohm & Haas

Spartan Chemical



Animal Health:

Bayer Animal Health

Fort Dodge Animal Health


Lambert Kay


Pharmacia Animal Health



Household Products:


Church & Dwight



Iron Out Incorporated

WD-40 Company


Reckitt Benckiser

SC Johnson

Personal Care Products:


Bath & Body Works

Church & Dwight



SC Johnson


White Rain



Bayer Advanced

Bayer Crop Protection

Bell Laboratories Inc.

Cargill Dow LLC

Dow Agrosciences



Scott’s (Ortho)


Food Products:

Best Foods

Dole Food Company Inc.

HJ Heinz Company L.P.

International Multifoods

Kellogg Company







LecTec Corp.


Zila Pharmaceutical

consumer product post market in market surveillance
Consumer Product Post-Market/In-Market Surveillance
  • What is it???? The processes whereby manufactures, regulators, health professionals, the public at large, and others monitor the performance and experience related to a given products life-cycle in the open market.
post market in market surveillance
Post-Market/In-Market Surveillance
  • Why is it necessary????“Your market population will likely be much larger than any of your pre-market test populations”
post market in market surveillance1
Post-Market/In-Market Surveillance
  • “The absence of reliable evidence of risk should not be mistaken for reliable evidence of the absence of risk”
regulations and safety
Regulations and Safety

The question to ask:Are there systems or processes in place to identify safety issues through methods other than serendipitous discovery?


How do you acknowledge the varying levels of quality and integrity of typical “spontaneous reports” received regarding any consumer product

post market in market surveillance2
Post-Market/In-Market Surveillance
  • Helps identify intended and unintended use patterns that may potentially contribute to Adverse Events
  • Allows assessment of how the product performs by itself or in the presence of other products or substances
  • Helps insure that “unique” populations are not adversely affected
  • Should also help define a relative “Safety profile”

What should it accomplish??

adverse event reporting systems utilized by industry cpsc monitoring systems
Adverse Event Reporting Systems Utilized by Industry:CPSC Monitoring Systems

National Electronic Injury Surveillance System (NEISS):

  • Surveys 100 ER’s selected as a nationwide probability sample of all 5,300+ U.S. Hospitals with ER’s
  • Designed to provide the Commission with evidence of need for: - a product recall - a public awareness campaign - a product safety standard
adverse event reporting systems utilized by industry cpsc internal monitoring systems
Adverse Event Reporting Systems Utilized by Industry:CPSC Internal Monitoring Systems

Consumer Communications: Individual Reports Involving Death or Injury

  • Results in CPSC investigation into injury allegations
  • May include on-site, face-to-face interviews and analysis of the product involved as well as medical records related to the injury

Manufacturer Communications (CPSC): Individual Reports Involving Death or Injury

adverse event reporting systems utilized by industry fda monitoring systems
Adverse Event Reporting Systems Utilized by Industry: :FDA Monitoring Systems
  • FDA MedWatch - Depends on either the patient or a Healthcare Practitioner to identify an effect, identify a suspected cause, question a relationship and report it to a “governmental” body - reporting is typically a “one-way” street (not designed to engage the caller and provide “clinical advice”)
other external surveillance databases systems or services
Other External Surveillance Databases, Systems or Services

Medical Literature (human & animal)

  • More in-depth reports with medical details on the injury
  • Often lacking on “circumstance” info*** (focused on what was done after the exposure)
  • Often serves as basis or support for “pro-active” regulation (animal or human data)
other external surveillance databases systems or services1
Other External Surveillance Databases, Systems or Services
  • Media Clipping Service
  • Surveys/reports of death or injury in the lay press that involves consumer products
  • Product Liability Claims
american assn poison control centers aapcc toxic exposure surveillance system tess
American Assn. Poison Control Centers (AAPCC) Toxic Exposure Surveillance System“TESS”
  • Designed to allow documenting of all inquiries made to the poison center
  • Basic set of data elements collected
  • Provides a good overall picture of the “marketplace”
  • Very “Sensitive” for certain types of reports but not necessarily “specific”
toxic exposure surveillance system tess
Toxic Exposure Surveillance System“TESS”
  • Telephone based reporting: Phone Calls  Exposures  Injury/Poisonings“Hospitalization”  Injury/Poisonings
minnesota poison prevention findings y2k
Minnesota Poison Prevention FindingsY2K
  • For all pediatric cases, 97.6% result in non-significant outcomes (<=minor effects) and 91.1% of cases result in no reported adverse effects. These outcomes are achieved with fewer than 5 patients receiving specific therapies other than decontamination.
  • Of all pediatric cases, 666(3.0%) received specific decontamination therapy other than simple dilution/irrigation such as syrup of ipecac or activated charcoal. (The lack of need for specific interventions may be the result of previously cited Minnesota data reporting that more than 55% of exposures from all routes including all reasons are “taste/touch” or mucous membrane types of exposures. These types of trivial exposures represent 71% of all “ingestions”.)
adverse event reporting systems utilized by industry epa monitoring systems
Adverse Event Reporting Systems Utilized by Industry: EPA Monitoring Systems
  • Environmental Protection Agency: FIFRA 6(a)(2)
  • Process maximally engages the Manufacturer in the process - Encouraged and supported Product Stewardship Efforts
aer systems epa monitoring systems
AER Systems:EPA Monitoring Systems
  • 6(a)(2) & Product Stewardship Identify, Manage, Evaluate:Adverse incidents reportedly associated with products
  • Previous 6(a)(2) Requirements:Only serious or unexpected effects judged related to a product reported to EPA
aer systems epa monitoring systems1
AER Systems:EPA Monitoring Systems
  • 1998 Revisions- All cases meeting minimum data elements must be reported to the Agency- No cause and effect relationship need be established- 2 types of reports a) Minor/more common effects aggregated b) More serious effects reported individually- New Penalties a) Civil b) Criminal
adverse event reporting systems utilized by industry epa monitoring systems1
Adverse Event Reporting Systems Utilized by Industry: EPA Monitoring Systems
  • Industry’s Response to the 6(a)(2) Challenge- “Industry’s Voluntary Report Forms” (see: Incident DataAddendum’s for specific eventsReport format for single reportable incidentsGuidance document for form completion
adverse event reporting systems utilized by industry epa monitoring systems2
Adverse Event Reporting Systems Utilized by Industry: EPA Monitoring Systems
  • FOCUS AREAS1) General Incident Data Addendum’s for specific events Report format for single reportable incidents Guidance document for form completion2) Aggregate Reporting Form Guidance Document for form completion

6(a)(2) Incident Reporting Process

Reported Event

Administrative Incident Data

Single Incident Report

(Significant Reportable
























Aggregate Incident Report

Minor and/or More Common

Reportable Incidents

classification of incidents involving humans
Classification of Incidents Involving Humans
  • Aggregate Incident Report(Collect 3 months, report in 2)Minor and/or More Common Reportable IncidentsH-D
  • Single Incidents Reports:Significant Reportable Incident H-B, H-C (Collect 1 month report following month) H-A (Human Death: Report within 15 days of notification)
challenges in incident classification
Challenges in Incident Classification
  • Additional Considerations“Duration” vs. “Intensity of clinical effects”
evolution of the prosar model
Evolution of the PROSAR Model
  • Strongly influenced by national Product Stewardship efforts by Industry- Responsible Care- Responsible Distribution- ProductCare
  • Also influenced by evolution of “standard of care” as the model proliferated (consumer expectations)
product stewardship
Product Stewardship
  • CSPA – ProductCare VisionTo promote the production and distribution of safe and effective formulated products that provide desirable benefits for household, commercial, institutional and industrial customers and consumers, and their families, pets and their environment.
product stewardship eg cspa product care
Product Stewardship(eg. CSPA Product Care)
  • In-Market Support, Incident Evaluation and Follow-up
    • Principle 5
      • We will support dissemination of safety related product information regarding routine use of our products that is accurate, complete and in context to the inquiry or concern
      • When product-related incidents occur, we will have systems in place to minimize adverse effects, assist our consumers/customers and provide needed information
product stewardship eg cspa product care1
Product Stewardship(eg. CSPA Product Care)
  • In-Market Support, Incident Evaluation and Follow-up
    • Principle 5 (cont.)
      • We will strive to influence product and label design as well as develop educational messages on safe and responsible product use based on information regarding unintended events and other types of exposures involving our products
prosar ipc incident monitoring systems
PROSAR IPC Incident Monitoring Systems

Data Collection:

  • Information system and data collection tools based on basic subset of information fields
  • Basic subset captures both TESS data elements and EPA data elements.
  • Proprietary “Case Manager” further individualizes data fields depending on the client and the Industry
  • Heavily focused on documenting events surrounding the exposure, product specific details, other conditions affecting product use
prosar ipc incident monitoring systems1
PROSAR IPC Incident Monitoring Systems

Data Collection:

  • Product Specific DetailsMultiple methods of product verificationEvaluating the role of labelingMarketing
prosar ipc incident monitoring systems2
PROSAR IPC Incident Monitoring Systems

Case Analysis and Incident Severity Assessments:

  • Not designed to determine “relatedness”
  • Based on a “consistency” rating (eg. Likelihood that based on all available factors, exposure outcome and severity appears to be either consistent, inconsistent, or indeterminable, with the known toxicologic/safety profile
  • Proprietary “Case Manager” further individualizes data fields depending on the client and the Industry
prosar ipc incident monitoring systems3
PROSAR IPC Incident Monitoring Systems

Surveillance, Analysis, and Benchmarking:

  • Benchmarking is provided through an automated data analysis system: PSI (PROSAR Safety Index)
prosar safety index
PROSAR Safety Index
  • Designed to help identify when to “take a closer look”
  • Analytical tool to aid in identifying products that fall outside of their normal safety profile
  • Based on the total number of “significant outcomes” compared against all symptomatic incidents involving a given product or class of products for a given time period
  • Initially calculated at the following levels:
    • Individual product
    • Company
    • PROSAR (also allows normalizing with product sales data)
future levels of incident evaluation
Future Levels of Incident Evaluation
  • Next level of Incident Assessment:“Registry” approach to follow-up Product Surveillance

The SAS Initiative (Safety Assurance Surveillance)

responding to a serious event
Responding to a “serious” event
  • Action is typically dictated by:- type of incident- supporting documentation- existing regulatory reporting requirements- ability to investigate, verify, and add definition
  • Monitoring for Sentinel Events:
    • Critical Mass increases likelihood of discovery
  • Hypothesis Generation:
    • Background noise vs. emerging issue
    • Aids in Design of Research?
  • Generation of Safety Profile:
    • Sufficient “Penetrance”?
    • Insure representative sample  relative intensity
  • Outcome Severity Classifications
    • Some symptoms not amenable to clear-cut classification
    • Indirect vs. Direct Effects
    • Physiologic vs. Psychologic S/S
  • Assessment of Causation/Relatedness
    • Data does not lead to determination of “cause and effect” relationship
    • At best may suggest an Epidemiological Association
  • Under-reporting/Over-reporting
    • reporting of “real” vs. “perceived” threats
    • Media and promotion
    • Possible “link” not recognized
limitations continued
Limitations continued
  • Accuracy and Report Quality
    • Voluntary vs. Mandatory
    • Spontaneous Reports  Rigorous Prospective Clinical Research
    • Objective vs. Subjective Data
    • Translation of layman’s symptom descriptions into complex medical terminology (i.e. paresthesias, numbness, tingling, peripheral neuropathy)
    • Second hand reporting
    • Hidden agenda’s
implications for the lsro project
Implications for the LSRO Project
  • Metabolife Analysis -- Outstanding Issues:Report quality and integrityAbility to verify individual incidentsAbility to verify exact product(s) involvedLaboratory confirmationHidden Agenda’sCollection of data in a systematic formatNormalizing for product sales(eg. DEET)Independent verification of informationAbility to follow-up at this late date
implications for the lsro dietary supplement aer project
Implications for the LSRO Dietary Supplement AER Project

II. Advising on a appropriate model of Post-Market Surveillance for Dietary Supplements:

  • Must differentiate between “ingredients” vs. “products”
  • For AER/Surveillance…..No one system will suffice: All likely reporting avenues that patients, consumers, and healthcare professionals will use to request or report information must be cultivated for maximum input
  • Mandatory vs. Voluntary Reporting for Manufacturers