Pharmacovigilance responsibilities of medicine sponsors

Version 2.0, September 2017

Book pagination

1 September 2017

Your regulatory reporting requirements

Your pharmacovigilance reporting requirements (i.e. what, how and when you MUST report) are summarised in the table below.

Report type How to report Reporting timeframe
Australian pharmacovigilance contact person Submitted via TGA Business Services ≤ 15 calendar days of first ARTG entry or of any detail updates
Significant safety issues In writing to the PSAB Signal Investigation Coordinator, via email to: si.coordinator@health.gov.au ≤ 72 hours of sponsor notification
Serious adverse reaction reports that occurred in Australia

Blue card/CIOMS form/E2B reports

Email:

Online: TGA Business Services

≤ 15 calendar days of receipt of minimum information
Quality defect issues, adulterated products, counterfeit products

For notifications of significant safety issues associated with medicine quality defect issues, email: si.coordinator@health.gov.au

For reports of serious adverse reactions associated with medicine quality issues or confirmed medicine quality issues unlikely to warrant a recall, email: adr.reports@health.gov.au

For notifications of medicine quality defect issues that is likely to warrant a recall, email: recalls@health.gov.au

For notifications of GMP compliance issues, email: GMPCompliance@health.gov.au

In accordance with the timeframe for serious adverse reactions or a significant safety issue as applicable
Non-serious adverse reaction reports and overseas adverse reaction reports These are not required to be routinely reported. However, they must be presented as a cumulative table in a Periodic Safety Update Report (PSUR) where one is required, or supplied to the TGA upon request in the requested format. As specified by the TGA PSUR reporting requirements or specific request

Note: Timeframes are in relation to Day 0.

What you must report

Australian pharmacovigilance contact person

Nominate a person in Australia to be responsible for fulfilling your reporting requirements for all medicines you sponsor in Australia. We prefer that you have only one Australian Pharmacovigilance contact person, however, you may have more. This person will be the primary direct contact for all pharmacovigilance correspondence between you and the TGA.

You MUST:

  • provide us with the name and contact details of the Australian pharmacovigilance contact person within 15 calendar days of your first medicine's entry on the ARTG.
  • notify us of the updated name and contact details within 15 calendar days of any changes to the Australian pharmacovigilance contact person or their details.

The Australian pharmacovigilance contact person can be nominated, and/or their details updated, through the TGA Business Services electronic portal. For further assistance, please contact the TBS helpdesk.

You should regularly check your TBS profile to ensure the Australian pharmacovigilance contact person's details remain correct.

The Australian pharmacovigilance contact person MUST reside in Australia and should have a sound understanding of the Australian pharmacovigilance reporting requirements. Please note that the Australian Pharmacovigilance contact person may be different to the qualified person responsible for pharmacovigilance in Australia (QPPVA), although ideally, they are the same person.

Serious adverse reactions

You MUST report any of the following of which you are aware:

  • expected and unexpected serious adverse reactions associated with the use of your medicine, that occurred in Australia
  • expected and unexpected serious adverse reactions associated with the use of your medicine, that occurred in Australia and were reported in the published international or local scientific and medical literature
  • all clinical and medically relevant follow-up information related to serious adverse reaction reports occurring in Australia

All serious adverse reaction reports should be validated (see Validating AR reports), followed up as necessary (see Following up AR reports), and MUST be submitted to us within the 15 calendar day time frame.

The seriousness of the report is linked to the seriousness of the reported adverse reaction. It is important that seriousness assessments are an independent process to medical evaluation, causality and validity of the case and are based on the adverse reaction alone. Where outcomes or treatment information (e.g. hospitalisation) is not available, a conservative approach should always be taken.

You do not need to be report serious adverse events, including from spontaneous reports, where:

  • there is no plausible temporal or causal association with the medicine.
  • the reporter specifically states they believe the events to be unrelated or that a causal relationship can be excluded, and you agree with this assessment.

For the individual adverse reaction reports not required to be reported to us (such as non-serious adverse reaction reports, serious adverse reaction reports from overseas, and invalid adverse reaction reports), you:

  • MUST keep records of these adverse reactions and provide these to us if we request them in the specified format and timeframe
  • MUST include these adverse reactions as a summary tabulation in a PSUR, if one is required
  • MUST report adverse reactions that impact on the benefit-risk balance or overall safety profile of the medicine as a significant safety issue
  • should consider these adverse reactions in any global analysis of a medicine's safety and benefit-risk balance

Significant safety issues

You MUST report all significant safety issues related to your medicine within 72 hours of awareness.

When you report significant safety issues to us, indicate the points of concern and whether you plan to take any regulatory action in Australia for the medicine. This may include changes to the risk management plan, amendments to the package label or product information document, or distribution of a 'Dear Healthcare Professional' Letter. If no regulatory action is planned in response to the significant safety issue, you should provide justification for why this is the case in the Australian context.

You MUST provide us with any additional information we ask for within a specified timeframe to assist us to evaluate the benefits and risks of the medicine. This may include:

  • the volume of sales or prescriptions of the medicine
  • details of the frequency assessment
  • copies of any relevant foreign adverse reaction reports you hold.

When to report

Day 0

We refer to the day the 'clock' starts for reporting as Day 0.

Reporting timelines are based on calendar days, including weekends and public holidays, and relate to the Australian sponsor.

You MUST meet the following reporting timeframes:

Report type Timeframe
Significant safety issue ≤ 72 hours
Serious adverse reaction (in Australia) ≤ 15 calendar days

Reporting timeframes for serious adverse reactions

You MUST report all serious adverse reactions that occur in Australia as soon as possible and no later than 15 calendar days from receipt. The clock for serious adverse reactions starts (as Day 0) on the day that the four minimum data elements in relation to the adverse reaction report are received by any of your personnel - including sales representatives and contractors.

Where you have entered into a relationship with a second company for the marketing of, or research on, the suspected medicine, Day 0 is as soon as any personnel of the primary sponsor (i.e. the sponsor who holds the ARTG number for the medicine) receives the minimum information. The timeframe for regulatory submission should be no longer than 15 calendar days from first receipt by the second company and explicit procedures and detailed agreements should exist between you and the second company to facilitate achievement of this objective.

Follow up information

The reporting time clock restarts when you receive additional clinical or medically relevant information for a previously reported serious adverse reaction.

Only significant follow-up information MUST be reported to the TGA, for example, new information about a case initially classified as non-serious indicates the case should be re-classified (i.e. from non-serious to serious).

You MUST report this information as soon as possible and no later than 15 calendar days after you receive the additional information.

Adverse reactions from literature

You MUST report all serious adverse reaction cases occurring in Australia that are identified through screening the worldwide literature as soon as possible and no later than 15 calendar days from receipt. Day 0 is when you become aware of a publication containing the four minimum data elements.

We prefer that you include a copy of the relevant published article (in English or an English summary/translation) to us when you make the initial adverse reaction report. However if the article is not available at this time, you should provide it within 15 calendar days of submitting your report. If you have difficulty meeting this timeframe, notify us in writing prior to the 15 day period ending.

You may use the services of an external party to conduct searches of the published scientific and medical literature; however, you remain responsible for the performance of the search and subsequent reporting. Day 0 is when anyone, either of the sponsor or the contractual partner (whichever is the earliest), becomes aware of a publication containing the minimum information. The transfer of a pharmacovigilance task or function should be detailed in a contract between you and the service provider, in order to ensure that published literature cases are reported as required within the correct time frames. Where a third party provides a review or a collated report from the published scientific and medical literature, Day 0 is the date the search was run (provided the minimum criteria are available in the abstract), and not the date the information was supplied to your company.

Reporting timeframes for significant safety issues

Significant safety issues MUST be reported as soon as possible but no later than 72 hours of you receiving notice of them. Day 0 is when any of your personnel - including any third parties, vendors or partners that have been delegated pharmacovigilance responsibilities of the sponsor - becomes aware of the issue. This is considered to be as soon as:

  • your review and analysis has determined that a significant safety issue exists (which is not necessarily after completion of an investigation), or
  • when you become aware of the safety actions of a comparable overseas regulatory agency.

You should notify us at identification of the significant safety issue, and not wait until after regulatory action, for example update of the core company data sheet, has been implemented.

We recognise that safety information may be received and processed by your global counterparts before it is disseminated to the local affiliates in Australia for reporting to us. We expect you to have clearly documented internal procedures in place that ensure expedited communication of significant safety issues from the global personnel to your relevant Australian personnel for reporting. You MUST keep records of your communications including dates when global and local personnel were notified and reasons for any delays. Substantial or inappropriate delays between the global and Australian notification may be considered non-compliance with regulatory reporting timeframes.

The reporting clock restarts when you receive additional clinical or medically relevant information related to a previously reported significant safety issue.

How to report serious adverse reactions

Validating adverse reaction reports

Only reports of serious adverse reactions that include the minimum four data elements are considered valid and required to be reported.

The minimum four data elements are:

  1. one or more identifiable reporter(s) (the primary source) - such as their qualification, name, initials, address or contact details (for follow-up)
  2. an identifiable patient - such as their initials, gender, patient identification number, date of birth, age or age group
  3. one or more suspected medicine(s)
  4. one or more suspected reaction(s).

Therefore, all reports of suspected serious adverse reactions should be validated before you submit your report to the TGA. If a report cannot be validated it should still be retained and recorded in your pharmacovigilance system.

It is important to identify the patient and the reporter to avoid case duplication and fraudulent reporting, and allow appropriate cases to be followed up. In this context, identifiable means you can verify the existence of a real patient or a reporter.

If you believe that there is a real patient involved (without any identifiers), it is considered sufficient for reporting. If the reporter does not wish to provide contact details, the adverse reaction is still considered valid if you can confirm the case directly with the reporter at the point of the initial report. If the report is second-hand, make every reasonable effort to verify the existence of an identifiable patient and reporter. All parties providing case information or approached for case information should be identifiable, not only the initial reporter.

A serious adverse reaction report that lacks any of the above four items is invalid and does not qualify for reporting. Invalid reports also include those where:

  • the primary source has explicitly stated that a causal relationship between the medicine and event can be excluded and you agree
  • the type of adverse reaction is unspecified
  • only an outcome or consequence, such as hospitalisation or death, has been reported, with no further information provided on clinical circumstance to consider it a suspected adverse reaction.

A report that is determined to be invalid may still provide pertinent safety information.

Assess reports of adverse reactions on a case-by-case basis. Use your clinical judgement to determine whether it is a valid serious adverse reaction or could constitute a significant safety issue and must be reported - for instance, you should report unexpected sudden deaths where the reporter considers it related to the suspect medicine or clusters of drug-event pairs that may indicate a safety signal.

You should exercise due diligence in following up invalid cases to collect missing data elements. Nevertheless, all reports of adverse reactions, regardless of their validity, should be recorded in your pharmacovigilance system for use in ongoing safety analysis activities. If you do not report an event to the TGA, you should document the reason for this.

Following up adverse reaction reports

Initial reports received by the sponsor that do not include the minimum four data elements should be followed-up as necessary to obtain the missing information.

You should also follow up cases to obtain detailed supplementary information significant to the clinical evaluation of the cases. This is particularly important for:

  • monitored events of special interest (for example identified or potential risks and missing information in the Risk Management Plan)
  • prospective reports of pregnancy (see Reports of exposure during pregnancy and breastfeeding)
  • cases notifying the death of a patient
  • cases reporting new risks or changes in the known risks

You should document your attempts to obtain follow-up information.

Tailor your follow-up to optimise the collection of missing information, in a way that encourages the primary source to submit relevant new information.

For consumer reports of serious adverse reactions, if the information is incomplete, you should attempt to obtain the consumer's consent to contact their healthcare professional to confirm the report and add medical information as required. You cannot downgrade a valid report of an adverse reaction from a consumer if their healthcare professional disagrees with their suspicion (in terms of relatedness and seriousness). In this situation, you should include the opinions of both the healthcare professional and the consumer in your report to us.

Key data elements for adverse reaction reports

We recommend that you try to collect and include as many of the below key data elements about the adverse reaction as possible in the report so it can be assessed. Some information might not be relevant, depending on the circumstances.

Reporter details
  • Name
  • Mailing address and/or Electronic mail address
  • Telephone and/or facsimile number
  • Reporter type (consumer, healthcare professional, etc.)
  • Profession (specialty e.g. physician, pharmacist, other healthcare professional; lawyer, consumer or other non-healthcare professional)
Patient details

Do not report the patient's name to us. We record only the information necessary for us to perform our regulatory function.

  • initials
  • any other relevant identifier such as patient number
  • gender
  • age, age category (adolescent, adult or elderly) or date of birth
  • concomitant conditions
  • the patient's medical history including relevant past medicine history
  • relevant family history
  • weight
  • height
  • ethnicity
  • Aboriginal and/or Torres Strait Islander origin
  • for reports about maternal/paternal or foetal exposure (see Reports of exposure during pregnancy and breastfeeding):
    • the gestation period at time of exposure
    • information about the parent such as their identity, age or date of birth, date of last menstrual period, weight, height, sex, relevant medical history and concurrent conditions, relevant past medicine history.
Details of the suspected medicine(s)
  • brand name as reported
  • International Non-Proprietary Name (INN) or Australian Approved Name (AAN)
  • the AUST R or AUST L number on the label
  • active ingredient batch or lot number
  • indication(s) for which suspect medicine was prescribed or tested
  • dosage form and strength
  • daily dose in units e.g. mg, ml, mg/kg and regimen
  • administration route
  • administration site
  • for reports about maternal/paternal or foetal exposure, route of administration to parent (see Reports of exposure during pregnancy and breastfeeding)
  • starting date and time
  • stopping date and time or duration of treatment
  • changes to medicine administration e.g. medicine withdrawn, dose reduced, dose increased, dose not changed, unknown or not applicable
  • any additional relevant information on medicine
  • if the reaction is suspected to be the result of an interaction with alcohol, food or another medicine, the names and active ingredients of the suspected interacting medicines or substances.
Other treatment(s)

Provide the same information as for Suspected Medicines for:

  • concomitant medicines including non-prescription, over-the-counter medicines, herbal remedies, dietary supplements, complementary and alternative therapies et cetera
  • relevant medical devices.
Details of the adverse reaction(s)
  • a full description of the reaction(s), including body site and severity
  • the primary source's description of the reaction
  • a description of the reaction using the Lowest Level Terms in the MedDRA terminology
  • why the report is considered serious
  • a description of the signs and symptoms
  • a specific diagnosis of the reaction
  • the date and time of the reaction's onset
  • when the reaction ceased, or its duration
  • interval between when the suspect medicine was administered and the reaction
  • dechallenge and rechallenge information
  • results and laboratory data from relevant tests
  • location, e.g. hospital, outpatient clinic, home or nursing home
  • the outcome of the reaction when last observed eg recovered/resolved, recovering/resolving, not recovered/ unresolved or recovered/resolved with sequelae (describe the sequelae)
  • if relevant, date of death
  • whether an autopsy was performed and, if so, any relevant autopsy or post-mortem findings, including coroner's report
  • cause of death for a fatal outcome
  • relatedness of medicine to reaction(s)/event(s)
  • assessment of reaction: source of assessment (e.g., initial reporter, investigator, regulatory agency, company), method of assessment (e.g. global introspection, algorithm, Bayesian calculation) and result
  • case narrative including clinical course, therapeutic measures, outcome and additional relevant information
  • sponsor's comments (e.g., diagnosis/syndrome and/or reclassification of reaction/event)
  • whether the case was medically confirmed, including medical documentations e.g. laboratory or other test data provided by either a consumer confirming the AR occurred, or an identifiable healthcare professional
  • document the whole report as a medically confirmed spontaneous report if:
    • a consumer initially reports more than one reaction and at least one reaction was medically confirmed.
    • if a medically qualified patient, friend, relative of the patient or carer submits a report.
Administrative and sponsor details
  • Source of report (spontaneous, epidemiological study, patient survey, literature, etc.)
  • Date the event report was first received by sponsor
  • Country in which the event occurred
  • Type (initial or follow-up) and sequence (first, second, etc.) of case information reported to authorities
  • Name and address of sponsor
  • Name, address, electronic mail address, telephone number, and facsimile number of pharmacovigilance contact person at the sponsor's Australian address
  • Company/manufacturer's identification number for the case (the same number should be used for the initial and follow-up reports on the same case)
  • The ADR identification number (if known) of possible duplicate reports initially submitted to the TGA by a consumer, healthcare professional or other primary source

Content of an adverse reaction report

Ensure:

  • your report complies with Part A of the General dossier requirements
  • any computer-generated forms are legible, contain the appropriate content and follow the approved layout
  • you do not reduce or condense the report.

You MUST provide the original words the reporter used to describe the adverse reaction. We prefer that you also include the appropriate lowest level terms from the Medical Dictionary for Regulatory Activities (MedDRA) in your adverse reaction report.

If you have sufficient information from the primary source to prepare a concise clinical summary of the individual case, provide a case narrative consistent with the data in other parts of the report. You should present the information in a logical chronological sequence as the patient experienced it, including:

  • the clinical course
  • any therapeutic measures
  • the outcome
  • relevant follow-up information.

You should summarise any relevant autopsy or post-mortem findings. You may include your opinion on whether there is a causal association between the suspected medicine(s) and reaction(s), and details of the criteria you used to make your assessment.

Where you cannot obtain consent to disclose the personal details of the patient or reporter, or to contact the treating doctor for medical confirmation of consumer reports, indicate this in your report as a sponsor comment.

For follow-up reports, you should clearly highlight what follow-up information has been provided and reference the unique TGA ADR record number designated to the initial report (stated in your acknowledgment letter from the TGA).

If the report is likely to be a duplicate - for instance, if you are aware the reporter has reported the adverse reaction to the TGA or it involves multiple suspected medicines - let us know this in your report. You should provide all available details to help us identify the duplicate including the TGA ADR record number allocated to the initial report, if known.

If the reaction is suspected to be the result of an interaction with alcohol, food or another medicine, you should state this clearly in the report and list the suspected interacting products or substances. For combination medicines that contain more than one active ingredient, list each active ingredient. If the primary source suspects a possible causal role of one of the ingredients in the medicine, provide this information in the report.

Submitting serious adverse reaction reports to the TGA

Prepare your report using one of these options:

You can submit individual reports of serious adverse reactions occurring in Australia for your medicine on the ARTG via the following avenues:

Online (preferred)

TGA Business Services

Electronic Data Interchange (TBA)

Email

adr.reports@health.gov.au (Blue card/CIOMS form/E2B reports)

e2b.reports@tga.gov.au (ICH E2B formatted reports only)

Phone 1800 044 114
Fax 02 6232 8392
Mail Adverse Event and Medicine Defect Section
Pharmacovigilance and Special Product Access Branch
Therapeutic Goods Administration
PO Box 100
Woden ACT 2606
Australia

How to report significant safety issues

Reports of significant safety issues should include:

  • A description of the safety issue
  • Source(s) of information
  • Your assessment of the risk and potential impact of the issue
  • Any actions you propose to take, or justification for no further action
  • Any relevant documentation

To notify us in writing of significant safety issues with your medicine on the ARTG, submit your report to the PSAB Signal Investigation Coordinator via:

Email (preferred)

si.coordinator@health.gov.au

Note: all emails will receive an automated response as an acknowledgement of receipt for your significant safety issue notification.

Phone 1800 044 114
Fax 02 6232 8392
Mail Signal Investigation Coordinator
Pharmacovigilance and Special Product Access Branch
Therapeutic Goods Administration
PO Box 100
Woden ACT 2606

Where significant safety issues will result in urgent changes to the Australian Product Information or you are liaising with a Clinical Delegate surrounding the issue, please copy the Signal Investigation Coordinator in your communications to the applicable TGA Clinical Delegate.

Reporting requirements for special situations

Reports from post-registration studies

You MUST report all serious suspected adverse reactions, of which you are aware, relating to the studied (or supplied) medicine, that occur in post-registration studies undertaken in Australia, in accordance with the reporting time frames for serious adverse reactions.

You MUST report any safety issues identified during post-registration studies which may impact the benefit–risk balance of the medicine as a significant safety issue.

This includes post-registration studies for your medicine which:

  • use multiple or combined medicines in the trial.
  • uses blinding. You are only required to report serious adverse reactions if (or when) the blinding is broken.
  • are conducted by a contracted third party (i.e. company-sponsored study). You should have an agreement in place to ensure you can fulfil your reporting requirements.

The above reporting requirements apply only to post-registration studies where your medicine is being used in line with the product information or label indications; for other situations, follow the clinical trials reporting guidelines.

You should have mechanisms in place to:

  • collect full and comprehensive information on any adverse event(s)
  • follow up reports and seek the primary source's opinion on causality
  • evaluate information and assess individual cases in a timely manner
  • report valid adverse reactions related to the studied (or supplied) medicine in accordance with the reporting requirements.

In instances where the post-registration study is conducted or initiated by an investigator independent of the sponsor of the medicine, the responsibility for reporting adverse reactions to us rests with the investigator. However, if you are aware of the study, you should request to be notified by the investigator of serious adverse reactions that occur in the study. Where you become aware of such adverse reactions, you MUST ensure that the adverse reactions are reported to us as required.

You do not need to routinely submit individual adverse reaction reports for:

  • non-serious adverse reactions
  • adverse events not suspected to be related to the medicine by the investigator
  • adverse reactions that occurred overseas during post-registration studies.

However, you MUST retain records of these non-reportable cases to be considered in ongoing global analysis of the benefit–risk balance of the medicine and provide these to us if requested.

Related information and guidance

Reports from other post-marketing initiatives

If you are undertaking other post-marketing initiatives that include collecting information related to your medicine, you may receive reports of adverse events.

Such initiatives might include:

  • patient support, product familiarisation and disease-management programs
  • surveys of patients or healthcare providers
  • collecting information on efficacy or patient compliance
  • market research programs; and
  • voluntary patient registries.

You should have a system in place for collecting and evaluating comprehensive case information so you can determine whether the adverse events are potentially related to the studied (or supplied) medicine.

You MUST report suspected serious adverse reactions received from post-marketing initiative reports in accordance to the reporting requirements for serious adverse reactions.

Reports of exposure during pregnancy and breastfeeding

For reports involving pregnancies where the embryo or foetus could have been exposed to one of your medicines, either through maternal exposure or transmission via semen following paternal exposure, you should:

  • make reasonable attempts to follow up all individual cases and collect information on the outcome of the pregnancy and development of the child after birth. For consumer reports, try to follow up with the patient's healthcare professional.
  • collect as much information as possible so you can assess the causal relationship between any reported adverse event(s) and exposure to the medicine.
  • consider whether a medicine may have been taken prior to conception or during pregnancy; take into account whether an active substance or one of its metabolites has a long half-life.

You MUST:

  • report pregnancies that result in abnormal outcomes suspected to be related to the medicine as serious adverse reactions. Such cases include:
    • congenital anomalies or developmental delay in the foetus or the child
    • foetal death and spontaneous abortion
    • serious adverse reactions in the neonate.
    Note: A premature delivery (i.e. earlier than 37 weeks) is not considered an abnormal outcome unless it resulted in adverse reactions to the neonate or mother.
  • report suspected serious adverse reactions in infants following exposure to a medicine in breastmilk in accordance with the reporting requirements for serious adverse reactions.
  • report any signal of a possible teratogenic effect, such as a cluster of similar abnormal outcomes, as a significant safety issue.

You MUST submit two separate reports to us if both the parent and the child or foetus experienced adverse reactions.

Consumers or healthcare professionals may contact you for information about the teratogenicity of your medicine and/or experience of its use during pregnancy. You should make reasonable attempts to determine whether any possible exposure of an embryo or foetus to the medicine has occurred and follow up to collect information on the outcome of pregnancy and development of the child after birth.

Unless stipulated as a condition of registration, do not routinely report individual cases of:

  • nduced termination of pregnancy where there is no information on congenital malformation
  • exposure during pregnancy where the outcome is normal or there is no data on outcomes.

You MUST include these cases in the next PSUR, if one is required, together with aggregated data on overall pregnancy exposure and details of normal and abnormal outcomes. We may request a report from prospective pregnancy registries to be included in a PSUR for evaluation.

Reports of use in paediatric or elderly populations

It is important to collect safety information in paediatric or elderly populations to help identify potential safety signals specific to particular age groups.

For serious adverse reaction reports, you should make reasonable attempts to obtain and provide to us the patient's date of birth, age or age group.

Lack of efficacy reports

You should record and, if incomplete, follow up, all reports of a lack of therapeutic efficacy. You do not need to routinely report individual cases of suspected lack of efficacy. However, you MUST retain the reports made to you and provide them to us if we request them.

There are certain circumstances when reports of unusual or unexpected lack of efficacy must be treated as serious adverse reactions for reporting purposes - for example, where there is a lack of efficacy of:

  • medicines used for critical conditions or life-threatening diseases
  • vaccines
  • contraceptives
  • anti-infectives.

You should use your clinical judgement when considering if reports of a lack of efficacy qualify for reporting. You should determine whether the reported lack of efficacy is related to the medicine rather than to an inappropriate treatment or the progression of a disease.

For example, do not report lack of efficacy of antibiotics used in life-threatening situations where the medicine was not appropriate for the infective agent. However, you MUST report any cases of life-threatening infection where the lack of efficacy seems to be due to the development of a newly resistant strain of bacterium previously regarded as susceptible, as serious adverse reactions.

Do not report incidences of unexpected lack of efficacy to us if the reporter specifically states the outcome was due to the progression of a disease and not related to the medicine. However, if the reporter believes the outcome was not due to disease progression, this MUST be reported even if you disagree. You should include your opinions in your report to us.

When you report a suspected lack of efficacy, do not code for the indication for which the suspected medicine was administered as an adverse reaction. For example, do not code hypertension as an adverse reaction to an anti-hypertensive medicine. Rather, where the existing condition was altered - that is, it progressed, recurred or was aggravated - by the lack of efficacy, this should be coded as such in the report.

Reports of lack of efficacy may help identify:

  • changes in the manufacturing quality and compliance with good manufacturing practice (see Quality defect reports)
  • differences in how a particular subgroup of patients responds to the medicine
  • in vaccines, reduced immunogenicity in a sub-group of vaccines, waning immunity and strain replacement
  • for anti-infectives, the development of resistance.

If you suspect any of these potential signals, you MUST report them to us as a significant safety issue. Additionally, consider whether further investigation and prompt action is warranted.

Reports of Quality defect issues

You MUST report all serious suspected adverse reactions associated with a suspected or confirmed quality defect in your medicine, including adulterated or counterfeit medicines, in line with the corresponding reporting requirements for serious adverse reactions.

You MUST also report significant safety issues related to a suspected or confirmed quality defect to us, for example a possible batch contamination issue or out-of-specification from a stability program that may have major impact on public health.

You may need to take urgent action in response to a quality defect to protect public health - for example, to recall one or more defective batches of a medicine from the market or issue communications to healthcare professionals. You should have a system in place to ensure that you investigate reports of suspected adverse reactions related to quality defects in a medicine promptly (with the urgency indicated by the nature of the defect) and that you notify us of confirmed quality defects or safety issues warranting recall with the least possible delay, in line with the Uniform Recall Procedure for Therapeutic Goods (URPTG).

Reports of transmission of an infectious agent

The transmission of an infectious agent via a medicine is also considered a serious adverse reaction for reporting purposes.

Transmission of an infectious agent may be suspected based on the temporal relationship, clinical signs or symptoms, or on laboratory findings that indicate an infection in a patient exposed to a medicine. Concentrate on the detection of infections or infectious agents known to be potentially transmissable via a medicine, but also consider the occurrence of unknown agents.

When you evaluate any suspected transmission of an infectious agent via a medicine you should, whenever possible, discriminate between the cause (e.g. an injection or other administration) and source (e.g. contamination) of the infection, and the patient's clinical condition when they were infected (e.g. whether they were immuno-suppressed or recently vaccinated).

Contamination, including inadequate inactivation or the attenuation of infectious agents as active substances, of the medicine concerned is evidence of the transmission of an infectious agent and may suggest a quality defect issue.

Reports of overdose, abuse, off-label use, misuse, medication error or occupational exposure

You MUST report all serious adverse reactions and significant safety issues in accordance with the prescribed reporting requirements that relate to:

  • overdose (accidental and intentional)
  • abuse
  • off-label use
  • misuse
  • medication error
  • occupational exposure.

You should routinely follow up these cases to ensure you have as much information as possible about:

  • early symptoms
  • treatment
  • outcome
  • the context of the adverse reaction - for example, prescription errors, administration, dispensing, dosage, unauthorised indication or population.

If there is no associated adverse event (i.e. the patient is asymptomatic) or the adverse reaction is not serious, you do not need to report these to us. However, these MUST be recorded and should be considered in the ongoing review and analysis of the safety of the medicine, as well as in any applicable PSURs. Additionally, these MUST be provided on request by the TGA within the requested timeframe.

Reports of non-serious adverse reactions and adverse reactions occurring overseas

You do not need to routinely report individual reports of non-serious adverse reactions that occur in Australia and any adverse reactions, whether serious or not, that occur outside Australia.

However, serious adverse reactions occurring overseas in Australian patients using medicines supplied from Australia, for example while the patient is travelling on holiday, should be treated as an Australian case and MUST be reported to us.

Reports related to orphan drugs

Standard reporting requirements, and any other specific requirements that have been applied as a condition of registration, also apply to orphan drugs.

You MUST report all serious adverse reactions and significant safety issues related to orphan drugs in line with reporting requirements.

Reports related to suspended or discontinued products

You MUST continue to collect and report suspected serious adverse reactions and significant safety issues for suspended medicines as per the requirements for any approved medicine in Australia.

If a medicine has been removed from the ARTG, you MUST report serious adverse reactions occurring after a medicine was discontinued until the last batch expiry. After this date, you should report any new significant follow-up information on reported cases and continue to collect (but not report) safety information for review of delayed onset adverse reactions or retrospectively notified cases.

Any medicines that are supplied after they have been removed from the ARTG (and after the date of final batch expiry) will adhere to the reporting requirements for unapproved medicines as appropriate; see Reporting requirements for medicines supplied through an exemption scheme.

Reports related to Australian products marketed overseas

For medicines on the ARTG not currently marketed in Australia but marketed in other countries, ensure there are procedures in place to collect and analyse any information on suspected adverse reactions.

You are not required to report individual adverse reactions that occur overseas to us, but you should include them in your ongoing monitoring activities. If analysis indicates a change in the benefit-risk balance of your medicine, you MUST report this to us as a significant safety issue.

Reports related to overseas products marketed in Australia

Some medicines that are registered or listed on the ARTG and marketed in Australia are manufactured and marketed in different regions by different sponsors overseas. Where there is a commercial agreement in place with an overseas sponsor for such an arrangement, there should be a provision for the timely exchange of safety data in order to monitor the benefit-risk balance of the medicine.

You are not required to report individual adverse events that occur overseas to us, but you should include them in your ongoing monitoring activities. If analysis indicates a change in the benefit-risk balance of the medicine, you MUST report this to us as a significant safety issue.

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