This content is current only at the time of printing. This document was printed on 28 March 2017. A current copy is located at http://apvma.gov.au/node/314
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What happens next
Assessing an adverse experience
The APVMA assesses every adverse experience reported.
- Reports made directly to the APVMA by non-registrants (voluntary reports) are copied to the product registration holder, who is then required to evaluate each report. The registration holder may contact the reporting person or the attending veterinarian to help determine if any follow-up work is required.
- The product registration holder must subsequently report their findings to the APVMA, and the findings are then assessed to determine if further information is required. In some cases, additional expert opinion is sought from other government agencies such as the Office of Chemical Safety and the Department of the Environment, universities, the Australian Veterinary Association, or other appropriate authorities.
- The APVMA also considers any scientific information or information about a registered product that is published or provided by an equivalent international organisation.
- We consider whether the product was used according to label instructions and warnings or whether the use was off-label.
- A standard method of assessment is used to determine whether the adverse experience may have been related to the use of the product (known as the ‘causality assessment’)—Causality assessment algorithm.
- Trend analyses may be performed periodically or if a cluster of reports is submitted involving a particular product. This may result in us either confirming the registration of a product or allowing it to continue with changes to how the product can be used (therefore requiring a change to label instructions and warnings). We may also cancel the registration of a chemical and remove a product from the market. More information on possible actions we may take is provided below.
- We advise everyone who reports an adverse experience of the outcome of its assessment and classification, including any regulatory action or ongoing monitoring activities.
- If an adverse experience is reported directly to a product registration holder, the registration holder must provide a report to the APVMA (known as a registrant report). We assess this report to determine whether any further laboratory, pathology or veterinary work is required before we classify an adverse experience.
Classifying an adverse experience
The APVMA classifies the relationship between exposure to or use of a registered product and a reported adverse experience in terms of ‘probable’, ‘possible’, ‘probable or possible off-label’, ‘unlikely’ and ‘unknown’.
A ‘probable’ classification is given when all the following criteria are met:
- there is a reasonable association between exposure to or the use of a product and the onset and duration of the reported adverse experience
- the description of the presenting signs is consistent with (or at least plausible, given) the known pharmacology and toxicology of the product
- there are no other equally plausible explanations for (or contributing factors to) the adverse experience
- When any of these criteria cannot be satisfied (due to lack of sufficient information or conflicting data) the APVMA cannot classify the relationship as ‘probable’.
A ‘possible’ classification is given when there is a reasonable association between the exposure to the product and the onset of the reported adverse experience. Therefore, it is reasonable to include the adverse reaction as a differential diagnosis, and it is one of the possible explanations for the adverse experience (for example the use of concurrent medication etc), or the association is reasonable but does not meet the criteria for a probable classification.
Probable or possible off-label
This classification is given as per the classifications of ‘probable’ or ‘possible’, but where clear evidence of off-label use also exists (including use in species not listed on the product label, overdosing or underdosing).
An ‘unlikely’ classification is given when sufficient information exists to establish that the adverse experience was not likely to have been associated with how a product was used, or when other more plausible explanations exist for the adverse experience.
An ‘unknown’ classification applies when reliable data are unavailable or are insufficient to make an assessment of an adverse experience.
Feedback and possible corrective action
The APVMA will acknowledge all adverse experience reports within five working days of receiving them.
The conclusions we draw during evaluation of each adverse experience report will be reported back to the reporting person or entity usually within a period of 90 days. For more complex reports, the timeframe may be longer as these often require additional expert assessment and/or the provision of further information. On this basis, the timeframe for a response will vary depending on the nature of the investigation and consultation we undertake. In our response, we will explain the conclusions and what corrective action, if any, will be taken.
The APVMA considers a broad range of issues and options when deciding what, if any, regulatory action is required to ensure registered veterinary medicines and agricultural chemical products sold in Australia are safe and effective. Steps we take in implementing this process include the following:
- for each registered veterinary medicine, we conduct an analysis of all adverse experience reports received. All reports classified as ‘probable’ or ‘possible’ are compared with the total number of doses sold within the relevant financial year and a reporting incidence is calculated (that is, the number of adverse experience reports per number of doses sold). We impose a control limit or ‘warning line’ for reporting incidence figures, which indicates that further action may be required if the reporting incidence is one or more per 10,000 doses sold
- we may take regulatory action if, for a particular product:
- the reporting incidence is greater than one per 10,000 in two out of three consecutive years
- an exceptional incidence of three or more per 10,000 occurs on any one occasion, or
- a consistent rising trend is seen over five years (irrespective of the reporting incidence)
- we consider available scientific literature and information relating to trend analysis and risk assessment when determining if regulatory action is required
- we consider whether the noted presenting signs (adverse experiences) are listed in warning statements on the product label, in which case a higher reporting incidence may be acceptable. We also consider the severity of presenting signs (more severe signs may trigger regulatory action at a lower reporting incidence).
We may take various actions in response to our assessment and classification of an adverse experience report. These actions include, but are not limited to:
- amending the conditions of a product registration, such as requiring changes to the label instructions or warnings
- suspending and/or cancelling the registration of a product
- reviewing the active constituent or product under chemical reconsideration
- referring of the product for action—such as compliance action—or referral to state authorities for action
- educational and promotional activities, such as providing scientific papers or articles on issues identified with a particular product to relevant journals, magazines or newspapers. When required, education about safe and effective use of a product is also provided to the veterinary profession, farming community or the general public.
The APVMA aims to publish an annual report summarising all of the adverse experience reports in a calendar year classified as possible or probable. Information in the annual report is arranged according to the active constituent of the products, so individual products are not identified. A summary of regulatory actions taken by the APVMA in response to particular AERs may also be included.
In accordance with confidentiality and consumer rights and responsibilities, all information provided on suspected adverse product experiences is treated as confidential. The Adverse Experience Reporting Program is not intended to replace a consumer’s right or responsibility to complain to the registration holder or manufacturer about an adverse experience involving an agricultural chemical or veterinary medicine. In fact, we make it clear to people reporting adverse experiences that they should also report the matter to the registration holder, the manufacturer or to the person from whom they bought the product.