According to the World Health Organization, pharmacovigilance (also known as ‘drug safety’) is defined as being “the science and activity related to detecting, assessing, understanding and preventing adverse events and other medicine-related problems.”
Pharmacovigilance was established in Australia in 1963 with the formation of the Australian Drug Evaluation Committee, after reports of thalidomide embryopathy (birth defects in babies after utero exposure to thalidomide).
The Therapeutic Goods Administration (TGA) monitors the safety of medication in Australia by collecting and analysing information related to the benefit-risk balance. The pharmacovigilance responsibilities of sponsors are included in the Australian Register of Therapeutic Goods (ARTG) guidelines and are regulated by the TGA.
Pharmacovigilance Responsibilities of Australian Clinical Trial Sponsors
Sponsors are legally responsible for meeting all pharmacovigilance reporting requirements during a clinical trial. Their duties include:
- Informing the TGA about who their pharmacovigilance contact person is.
- Submitting all serious adverse reaction reports to TGA.
- Notifying TGA of any significant safety issues.
- Keeping the necessary records needed to meet the reporting requirements.
- Responding to any requests for additional information.
The Difference between Serious Adverse Events and Serious Adverse Reactions
Pharmacovigilance distinguishes between serious adverse events and serious adverse reactions.
Serious Adverse Events
Any negative reaction including abnormal lab findings, symptoms, or sickness which is temporarily associated with the use of the treatment/medication in a clinical trial, whether or not it is considered directly related to the investigational product.
Serious Adverse Reactions
A noxious and unintended response to an investigational product which is usually directly caused by the medication. Also includes adverse drug reaction (ADR), adverse effect and undesirable effect. Can be life threatening and result in death in the most serious of cases.
The difference between an ‘event’ and a ‘reaction’ is that a serious adverse reaction is seen as having a casual relationship between medicine and occurrence, in contrast to a serious adverse event.
Significant Safety Issues
Any safety issue that may have a major impact on participants and the benefit-risk balance of the investigational product which could result in regulatory action. Can include:
- The withdrawal/suspension of the medication’s availability.
- Changes in the severity of known serious adverse reactions.
- A significant lack of efficacy for investigational products.
- Safety issues due to misinformation in the product information.
Why Does There Need to be an Effective Pharmacovigilance System?
- Monitor and take responsibility for the safety of the investigational product.
- Meet regulatory requirements for the reporting of serious adverse reactions and significant safety issues.
- Take action in a timely manner.
- Update product information with new safety information that comes to light.
Regulatory Reporting Requirements
Pharmacovigilance Contact Person
A pharmacovigilance contact person is responsible for the reporting requirements for all the medication being sponsored in Australia. They are the primary contact for all correspondence relating to pharmacovigilance between sponsors and the TGA.
- Let the TGA know who their Australian pharmacovigilance contact person is and provide them with their contact details within 15 days of the first medication being entered into the ARTG database.
- Update any contact details of the pharmacovigilance contact person within 15 days.
Serious Adverse Reactions
Sponsors must report:
- Expected and unexpected serious adverse reactions associated with the investigational product.
- Expected and unexpected serious adverse reactions associated with the investigational product and which was published in scientific and medical literature.
- Relevant follow-up information related to serious adverse reaction reports in Australia.
All serious adverse reaction reports should be submitted as soon as possible and no later than 15 calendar days.
Serious adverse events don’t need to be reported when:
- It has been determined that there is no link to the investigational product.
Significant Safety Issues
Report any points of concern and whether any regulatory action is planned (modifications to risk management plan or changes to the package label or product information document).
Significant safety issues must be reported as soon as possible and no later than 72 hours after becoming aware of them.
Essential Data Needed for Adverse Reaction Reports
- Mailing or email address
- Phone number
- Reporter type
- Medical and family history
Investigational product details
- Brand name,
- The AUS R or AUS L number on label
- Active ingredient batch
- Dosage form and strength
- Daily dose in units
- Administration route and site
- Starting date and time,
- Stopping date and time
- Changes to administration
- Any additional relevant information
Details of adverse reactions
- A full description of the reaction(s)
- The primary source’s description of the reaction
- Why it’s considered serious
- A description of the symptoms
- A specific diagnosis of the reaction
- The date and time the reaction began
- The duration of the reaction
- Interval between when the investigational product was administered and the reaction
- Results from relevant tests
- Outcome of the reaction when last observed
- Date of death (if relevant)
- Cause of death
- Relation of investigational product to reaction
- Assessment of reaction
- Clinical trial sponsor’s comments
- Whether the case was medically confirmed
Administrative and sponsor details
- Source of report
- Date the report was received by the sponsor
- Country in which the event occurred
- Name and address of the sponsor
- Name, address, email address and phone number of the pharmacovigilance contact person
- Company/manufacturer’s identification number
- The ADR (adverse drug reaction) identification number
How to Report Significant Safety Issues
- A description of the safety issue
- Sources of information
- An assessment of the risk and potential impact of the issue
- Any actions taken/justification for no further action
- Any relevant documentation
Other Pharmacovigilance Operational Documents and Activities
Pharmacovigilance requires clear, detailed standard operating procedures (SOPs) to ensure all roles, responsibilities, requirements and timelines are well-defined and understood by everyone involved.
Safety contracts and agreements
Sponsors are responsible for following all the Australian reporting requirements which means that they must always meet their pharmacovigilance obligations
A pharmacovigilance contract outlines what safety information has to be collected and how it should be organised.
All staff members involved in pharmacovigilance should have a thorough knowledge of the relevant legislation, guidelines, the reporting process and evaluation. Staff who are responsible for processing safety reports need to be trained for collecting and reporting adverse reactions.
Training for pharmacovigilance should begin straight after employment and there should be documentation to show that training has taken place.
Monitoring and collecting information
The pharmacovigilance system should meet all the record-keeping and reporting requirements. It should:
- Identify and collect all information related to safety of the medication from all possible sources, including:
- Internet and social media reports
- Reports from non-medical sources
- Reports in literature
- Spontaneous reporting of adverse reactions
- Adverse drug reaction reports in the TGA’s Database of Adverse Event Notifications (DAEN)
- Gather enough information to scientifically evaluate reports of adverse reactions.
- Ensure all reports are authentic, accurate, legible, and complete.
- Validate suspected adverse reactions and report them within the required time frame.
Internet and digital media reports
Regularly keep an eye out for suspected adverse event reports which can be found on the internet, on social media, forums, chat rooms and health portals.
Reports of adverse reactions found on the internet and in the digital media are considered as being spontaneous and should be evaluated and followed up on to determine whether they meet the requirements for reporting.
Critically analyse and evaluate all reports to determine the ongoing benefit-risk profile of the investigational product.
The pharmacovigilance data should be readily available from a single access point.
Data transfer and validation
Have methods put in place to ensure that all data that is transferred is received and that there are no reports missing.
All reports can be stored either digitally or in paper form. The storage chosen should be suitable for the required period of retention.
Pharmacovigilance inspection program
TGA conducts inspections, through the Pharmacovigilance Inspection Program (PVIP) to ensure that Australian sponsors are meeting all their Australian pharmacovigilance regulatory requirements.
All sponsors should manage a pharmacovigilance system to ensure that they meet all pharmacovigilance responsibilities including:
- Meeting all pharmacovigilance requirements described in the guidelines.
- Investigating and reporting product quality issues associated with serious adverse reactions and significant safety issues.
- Analysing adverse events and other safety information.
- Taking any action necessary to mitigate safety issues.
Qualified Person Responsible for Pharmacovigilance in Australia
A qualified person responsible for all pharmacovigilance activities in Australia. Ideally, they should be the same person as the Australian pharmacovigilance contact person responsible for reporting to the TGA. They should ensure that the sponsor has an effective pharmacovigilance system in place and abides by the legal requirements.
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