PharmacoVigilance SIG 21 st October to 22 nd October 2003 - PowerPoint PPT Presentation

PharmacoVigilance SIG 21 st October to 22 nd October 2003

Pharmacovigilance: • What is it? • Why should we care? • How do we do it? • The Pharmacovigilance Landscape • A Pharmacovigilance Roadmap • References

PhV S IG Delegat es • Howard Bilofsky, GSK howard.s.bilofsky@gsk.com • Ron Behling, BMS ronald.behling@bms.com • Rowan Gardner, Biolauncher rowan@biolauncher.com • Rajesh Ghosh, Novartis rajesh.ghosh@pharma.novartis.com • Craig Funt, BMS craig.funt@bms.com • Franck Hémont, Ipsen franck.hemont@ipsen.com • Chris Jones, CERN chris.jones@cern.ch • Mike O'Connor, Wyeth oconnorm@wyeth.com • John Paugh, Wyeth paughj@wyeth.com • Uwe Trinks, Sentrx uwe.trinks@sentrx.com • John Wise, Tavistock Europe Ltd. john.wise@tavistockeurope.com

It is not. It concerns every person in a The Big Myths company from the CEO downwards. If such a misconception exists in a company, it is crucial it is tackled head-on • Responsibility for Pharmacovigilance is confined only to those in the company’s Pharmacovigilance department Those in Pharmacovigilance are anti-product • and Pharmacovigilance is negative activity for a product’s success

PhV What is it?

What is Pharmacovigilance? • Pharmacovigilance is the name given to the process of detection, assessment and prevention of adverse drug reactions in humans. • What is the difference between Risk Management & Pharmacovigilance?

Whatever it is – it has to be done in Europe! “The marketing authorisation holder must ensure that it has an appropriate system of pharmacovigilance in place in order to assure responsibility and liability for its products on the market and to ensure that appropriate action can be taken, when necessary.” The Rules Governing Medicinal Product s in t he European Union, Volume 9 - Pharmacovigilance Medicinal Product s for Human and Vet erinary use, sect ion 1

And in the US A! • Drug sponsors are required to keep FDA informed regarding any developments that may affect the safety and effectiveness of their products, whether under clinical study or following FDA approval for marketing. • The authority to require the necessary records and reports is contained in Sections 505(I), (j) and (k) of the Federal Food, Drug, and Cosmetic Act, and the regulations spelling out the kinds of records and reports required are in 21 CFR 310.303, 310.304, 310.305, 312.32, and 314. • The broad intent of these regulations is to promote the kind of communication needed to ensure safe and effective drugs, and to enable the FDA to take whatever action is needed to accomplish this. • The basic purpose is health protection through improved drugs.

FDA example – S afety Reports From The FDA Web Site * http://www.fda.gov/cder/reports/rtn/2001/rtn2001-3.htm

S uspected Adverse Drug Reactions (S ADR) S ADR S PONTANEOUS CLINICAL* S ERIOUS UNEXPECTED S ERIOUS UNEXPECTED S ERIOUS EXPECTED S ERIOUS EXPECTED NON-SERIOUS UNEXPECTED NON-SERIOUS UNEXPECTED NON-SERIOUS EXPECTED NON-SERIOUS EXPECTED EXPEDITED REPORTING PR/ PSUR ONLY * In the clinical space, events can be related and unrelated

S ADRs and their source • Not Drug related – Disease relat ed – Treatment-related (Hospitalization etc.) – Accidents – S uicide Attempts • User or Physician “ Errors” – Medication Error (Wrong Fulfillment) – Malprescription, Off-label Use – Intended Overdose (Non-compliance, Suicide Attempt) – Accidential Overdose (Non-compliance, Patient Education)

S ADRs and their source • Drug Titration Problems – S low Metabolism – Multi-Drug Regimen (Each Enzyme S ubstrate is also an Inhibitor) – Nutritional Influences (Grapefruit Juice) – Gender/ Racial Gap • Drug/ Drug Interactions – Rare, but usually serious – Can happen to established drugs • Genetic S uscept ibilit y – Rare, but usually serious – Class related (e.g Rhabdomyolysis for S tatins) – Drug related (specific met abolites etc.)

PhV Why do we care?

Public Citizen’ s Website

Sec. 314.80 Post marketing report ing of adverse drug experiences. (c) Report ing requirement s. The applicant shall report t o FDA adverse drug experience informat ion, as described in this sect ion. The applicant shall submit t wo copies of each report described in t his section t o t he Cent ral Document Room, 12229 Wilkins Ave., Rockville, MD 20852. FDA may waive the requirement for t he second copy in appropriat e inst ances. (1)(i) Postmarket ing 15-day ` ` Alert report s` ` . The applicant shall report each adverse drug experience that is bot h serious and unexpected, whet her foreign or domest ic, as soon as possible but in no case lat er than 15 calendar days of initial receipt of t he informat ion by t he applicant .

A Career Limiting Opportunity (CLO)

… and Because Pharmacovigilance is Important • Pre-marketing phase: experience of a drug’ s safety and efficacy is limit ed to its use in clinical t rials wit h limited patient numbers and treatment duration in conditions not necessarily reflecting use in the hospital or in general practice once marketed • Information on rare but serious adverse drug reactions, chronic toxicity, use in special groups (e.g. pregnant women, children, elderly) and drug interactions may be incomplete or not available • Certain adverse drug reactions may only be detected after a very large number of people have received the medicine

How do we do it?

Pharmacovigilance Processes ! Electronic Submission (FDA) ! Electronic Submission (FDA) ! Dictionaries & Code ! CI OMS Form ! Dictionaries & Code ! CI OMS Form Lists Lists ! PSUR (Data) ! PSUR (Data) ! Security, fully ! Security, fully ! Call Center I nterface ! Call Center I nterface ! US Periodic ! US Periodic compliant compliant ! Data entry ! Data entry ! Electronic Submission ! Electronic Submission ! MedDRA ! MedDRA (EMEA) ! Standards -based data (EMEA) ! Standards -based data maintenance maintenance import utility import utility ! Configurable Edits & ! Configurable Edits & ! MedDRAencoding ! MedDRAencoding Alerts Alerts ! Multi-lingual support ! Multi-lingual support Regulatory Case Reporting Administration Acquisition/ Data Entry SCEPTRE Pharmacovigilance System Modules ! Query by example ! Query by example Data Document (not dependent (not dependent ! Scan/ fax source ! Scan/ fax source Repository Management Workflow upon I T) upon I T) documentslink documentslink ! Signal detection images to cases ! Signal detection images to cases ! I nterface to ! View images ! View images ! I nterface to COTS Ad Hoc Query tool Ad Hoc Query tool ! Automatically initiate ! Automatically initiate ! Case Routing ! Case Routing workflow workflow ! Electronic I nbox ! Electronic I nbox ! Management dashboard ! Management dashboard ! Alerts ! Alerts ! Due diligence letters ! Due diligence letters

Pharmacovigilance for Management Risk Management Analysis Data Collection Medical Review Reporting S ystems & Infrastructure Regulatory & S OPs

No Pharmacovigilance Dept. is an Island CCS I LABELING TRAINING MARKETING PH REC CDM MTI + PC S AFETY CS DS S UBMIS S IONS QC CUS TOMER S ERVICE BUS INES S PARTNERS

Business S OP tied t o IT S OPs Quality Module 2.0: Validation of Computer Systems Annex 1: Lexicon Annex 2: CSV Documentation Hierarchy Annex 3: GSS CSV Organization Operational SOPs Validation SOPs Organizations Maintenance of Software Installation and QMC CS Computer Facilities Administration Memberlist GSS/OP 1001 GSS/IT-1001 Physical Access to Software Program QMC Computer Systems Development Memberlist GSS/OP 1002 GSS/IT 1002 Computer Systems Systems and Software Access Control Program Change Control GSS/OP 1003 GSS/IT 1003 Backup and Restore Software Validation Procedures GSS/IT 1004 GSS/OP 1004 Valid. Protocol Template Archiving Critical Data Software Release Control GSS/OP 1005 GSS/IT 1005 Transmission of Customer Installation Qualification Computer Data of Computer Hardware GSS/OP 1006 GSS/IT 1006 Business Recovery Operational Qualification GSS/OP 1007 of Software Business Recovery Plan GSS/IT 1007 BRP Test Log Vendor Quality Audit GSS/IT 1008 Vendor QA Checklist Vendor QA Report Template

Craig’ s S preadsheet 1_Final industry survey results (masked).xls

The Pharmacovigilance “ roadmap”

What are the PhV value propositions? • Maximize risk management – Opt imize possibilit y of Market ing Aut horization – Minimize t ime t o Market ing Aut horization • Minimize Compliance Risk • Drive down the cost of PhV