Challenges In Pharmacovigilance Dr Vishwas, by Dr. Vishwas Sovani MD ,VP Pharma Delivery TCSPresentation Transcript
Challenges in Pharmacovigilance - Different sponsors, same drug Dr. Vishwas Sovani MD , VP Pharma Delivery TCS
Different Sponsors same drug
Drug used as comparator in trial
Drug sold under license by another company
Generics marketed by various companies
Orphan drugs marketed by more than one company
Biosimilars marketed by more than one company
Same drug, different indications, different companies
Same drug different formulations different companies
Australian Guidelines for PV responsibilities of sponsors
When 2 or more separately registered medicinal products which are identical in all respects except their name are marketed in Australia by separate sponsors, each sponsor is obliged to meet the usual PV obligations.
Where co marketing arrangements exist, the sponsors may enter into practical arrangements for joint data collation & analysis but each is individually responsible for the legal responsibility.
One more such arrangement that is allowed, is appointment of a common Qualified PV person for that product
Different Sponsors: Best practices
Licensee partner agreements
Timely reporting becomes a challenge
Different safety reporting software - Repeat work
Data shared between sponsors (electronic via E2B)
Limitations of gateway capacity
Standardizing Terminology using MedDRA
Integrating Electronic Document Management repositories to manage workflow & correspondence
PV operations for generic manufacturers
Data entry and reporting for own products
Reporting of same molecule of other manufacturer whenever the information is received on call??
Data submission to country authorities where company markets the product
Aggregate safety reporting / Signal detection
Assessment of safety across all cases reported for the active moiety from all manufacturers
Difficult to obtain data from other manufacturers
Alternative is to do data mining from the official regulatory databases:
Netherlands Pharmacovigilance Foundation
UK Yellow Card database
WHO Uppsala Monitoring Centre
Literature case processing
Products from all manufacturers for an active moiety
Great value in signal detection in the generic scenario
Need appropriate time cut-offs during searches
Finally… Companies can enter into Safety Data Exchange Agreements
Bioequivalence difficult to prove
If manufacturing method is different, it may lead to a little different
effect & also side effects
EMEA stipulates that biosimilars manufacturers must have a plan
for continuous post-marketing monitoring and pharmacovigilance
The current systems for naming of generic synthetic pharmaceutical products cannot be applied to biosimilars, as they are not identical to the originator product.
Distinct International Non-proprietary Names (INNs) and trade names should be given to each biosimilar product, to optimise adverse events recording and product tractability.
Reactive evolution of Pharmacovigilance
Lack of standardization of processes and data within organization
- Across product lines
- Across geographic locations
Lack of harmonization
Delay in making better decisions
- Multiple applications
- Multiple guidelines
Industry Challenges What do we need? Paradigm shift
Ideal safety monitoring system
PV in the 21st century could also be considered a systems approach to PV, with IT systems enabling.
Pioneers in the drug safety field developed many of those best practices over the past three decades.
Modern computer technology has allowed these individual best practices to be joined in a supportable process
The technical tools now available can identify alerts from random data.
These computer systems can make the human more productive and less likely to miss important public health information hidden in ‘haystacks’ of data.
They also provide the needed tools and work environments to analyze the data so that a full assessment can be conducted in an efficient and effective manner.
One such is “Safety in a Capsule”
Safety in a Capsule
Safety in a Capsule from Tata Consultancy Services (TCS) is a pre-packaged comprehensive solution for the safety requirement of pharmaceutical companies.
It combines TCS’ Drug Development Services with industry‘s leading products to provide cost effective Drug Safety services for pro-active pharmacovigilance.
The products include:
Adverse Events Reporting System
Powerful set of case management features ,a comprehensive suite of data consistency checks online, discrepancy management system & allows users to create and save queries and case lists
Call Center Application - Comprehensive data receipt system
Signal detection solution
It is a workflow-based analytical tool, works seamlessly with the AE Reporting System data as well as data from external sources, such as the U.S. Food & Drug Administration and the WHO. Drug safety teams can monitor and analyze – in a single instance, legacy, clinical, and pre- and post-market adverse event data.
Unified Architecture for Drug Safety & Pharmacovigilance ADR submitted through Safety Manager ADR collected by the Call Centre Call Centre creates new ADR record which is pulled in by AE Rep System Unified Drug Safety and Pharmacovigilance environment AE Rep System and external DB for Signal detection, assessment & management AE Rep System generated reports for regulatory submission
Benefits Safety in a Capsule
Risk mitigation - The solution leverages safety analytics for early insight into the drug’s safety profile; rapidly detect and analyze patterns in adverse events that may indicate emerging drug safety risks pre and post-market.
Flexible analytics - It helps perform analytics and reports in a flexible and timely manner, which would help assure regulators and consumers that the approved drugs are safe and effective.
Modular services - Solution design is modular which work in your existing environment
PV issues could arise if same product marketed by different companies
They are in the areas of aggregate reporting & signal detection, literature searches
Biosimilars are different cup of tea
If companies have to risk manage the molecule optimally, they will need to analyse data from international databases,literature & realtime cases
A platform based IT led approach should enable them to achieve this
Back up slides
Industry Challenges in Pharmacovigilance
Clinical development & Pharmacovigilance work in silos with different objectives
Clinical database & safety database are held by different groups
CR&D is ultimately responsible for finding blockbusters of tomorrow while the safety department is compliance driven & mainly a keeper of timelines & metrics.
What is needed is seamless continuous safety monitoring
Continuous Safety Monitoring
Data input from all sources on realtime basis
Review & analysis of cases on a regular & automatic basis
Not possible for individual companies unless out licenced
Done by regulatory agencies
Better Risk management if companies could do it themselves
Determinants of signal selection
Detection of new adverse drug reactions (Signals) after marketing is often based on a manual review of reports sent to a Spontaneous Reporting System (SRS).
Several factors may help to determine whether or not a particular signal is worth further investigation.
In general, four categories may be identified, which are for instance represented by the acronym `SNIP', used by the Medicines Control Agency.
S trength of a signal,
whether or not the issue is N ew,
the clinical I mportance as judged by the seriousness of the reaction and severity of the cases
potential for P reventive measures by the regulatory authorities
Signal Detection Current Data Mining databases
Spontaneous reporting is a passive system,
inconsistent reporting is a limitation with more frequent reporting for unusual reactions, reactions for new drugs and serious reactions
. Data could be inaccurate.
FDA database has >2mln reports over 35 years
Prescription event monitoring (PEM)
Used to detect ADEs by collecting high-quality data from family doctors, on a select group of patients exposed to a specific (new) drug, for a limited period of time.
Lacks adequate control group as it has clusters of patients. Eg Tolterodine & hallucinations
Large linked health administrative databases ,
Medicaid in the USA and the Ontario provincial databases, contain data on millions of subjects.
May apply to elderly or low income & not whole population
Electronic medical records (EMRs)
Contain a large number of data fields, including details such smoking , laboratory data and social circumstances, on a smaller number of patients and may also be used for data mining
Other databases Clinical trials databases and specialist databases such as overdose or toxicology databases may also contain valuable information
Data Mining - statistical techniques
Clustering or database segmentation eg: Fenfluramine Phentermine & heart disease
Link analysis refers to methods that identify associations or links between records or sets of data
Deviation detection looks for outliers or values that deviate from the norm and can be seen either graphically or statistically.
Measures of disproportionality are the only techniques which have been used to identify ADEs. They have been used by the Netherlands Pharmacovigilance Foundation , the UK Yellow Card database , WHO Uppsala Monitoring Centre and PEM database.
e.g. Withdrawal bleeding with OCs while on Itraconazole
It is currently not possible to link all available datasets together and run one of the data mining techniques to identify all possible adverse events
Safety-in-a-Capsule TM - Solution Stack Services Processes Qualification & Validation Safety & Pharmacovogilance Implementation Configuration Administration Customization Production Support Technology Physical Security Data Security Data Privacy Business Continuity Information Security Monitoring Early warning Threshold triggers E-mail Alerts Signal detection Statistical Analysis Informed judgment Analysis Clinical Review, PA, Comparisons, Correlations, Drug-Drug Interaction Reporting SAE reporting PSUR, SUSAR, Periodic Oracle – AERS Oracle – TMS Oracle – Portal Siebel – Call Center DrugLogic – QSCAN Oracle – Business Intelligence Collection & Processing Maintain Database Data Collection (Call Center, Internet, e-Mail, Fax, etc.) Data Entry Medical coding Cleansing & Scrubbing Validation