Adverse event reporting of therapeutic products

Therapeutic product importers, manufacturers, suppliers and registrants are required to report all serious adverse events of their products.

What to report

It is mandatory for companies to report any serious AEs to HSA upon becoming aware of the event, or as soon as possible and no later than 15 calendar days. This includes both spontaneous and solicited reports. These reports should have a causality assessment and should only be submitted if a causal relationship between a therapeutic product and a serious reaction is at least a reasonable possibility, as assessed by either the reporter or the company.

Note: Serious AEs caused by accidental or deliberate overdoses, abuse, misuse and medication errors need not be reported.

The minimum information required for the submission of your initial report is:

  • An identifiable reporter or healthcare professional.
  • An identifiable patient.
  • An AE.
  • A suspected product

Refer to our guides if you are reporting an AE:

How to report

To report serious AEs, companies are to complete the Council for International Organisations of Medical Sciences (CIOMS) I form and send it to HSA via one of the following methods:

When to report

You should report the serious AEs as soon as you are made aware of them and adhere to the reporting timelines below. The initial report of a serious AE should contain as much detail as available but should not be delayed for the sake of gathering more information.

The clock for reporting starts as soon as any personnel in your company, including sales representatives, are made aware of the serious AE. If there is uncertainty about whether the serious AE is reportable, you should still submit a report within the time frame stated.

Adverse event reports Report as soon as possible and no later than  
Initial reports of serious AEs. 15 calendar days
Follow-up reports when additional medically relevant information is received for a previously reported case.

Note: Indicate that it is a follow-up report and link it to the original report. 		15 calendar days

Specific adverse events reporting

Adverse events not subject to reporting requirements

Overseas AEs occurring outside of Singapore and reports of off-label use with no associated AEs need not be reported. Cases that contain only an outcome (e.g. death) as well as local non-serious AEs also need not be reported, unless there is a cluster of AEs indicating a potential safety issue. Records of the events must still be maintained and made available upon request.

Reporting by consumers

Consumers who report AEs should be encouraged to seek medical attention and get the attending healthcare professional to report the AE. Medical confirmation is strongly encouraged to facilitate company’s causality assessment for the purpose of submission to HSA. If a consumer is unwilling or unable to seek medical attention, the company should attempt to obtain as much information as possible from the consumer about the AE. This is to ensure such reports have sufficient information for causality assessment by the company.

Scientific Literature

Cases of local serious AEs from the scientific and medical literature, including relevant published abstracts from meetings and draft manuscripts are reportable provided patients are identifiable.

The regulatory reporting time clock starts as soon as the company has knowledge that the case meets minimum criteria for reportability. A copy of the relevant literature should be provided.

Literature cases may differ from information from other sources, particularly concerning causality, as authors may reference many events and many therapeutic products, and the author may not necessarily suspect the products to be causally related to the events described in the article. If multiple products are mentioned in the literature, a report should be submitted only by the company whose product is suspected by the article’s author to be associated with an AE.  Where the author’s suspicion is not stated or not available, the report should only be submitted if a causal relationship between the product and AE is at least a reasonable possibility, as assessed by the company.

New safety information for therapeutic products pending HSA's review

Where a therapeutic product registration application is pending HSA's review, the applicant must ensure that any new safety information which may impact the benefit-risk balance of the product is immediately submitted to HSA via PRISM or eCTD. The applicant may contact the evaluator of the application to request for the issuance of an Input Request to submit the information.

The new safety information may include but are not limited to the following examples:

  • Tabulation of new or unexpected serious AEs that have not been previously submitted and are not mentioned in the proposed Singapore package insert.
  • Safety reports of new or unexpected serious AEs with evidence of causal relationship.
  • Safety reports where there is suspicion of a change in the frequency or severity of a known effect.
  • Results from studies which may negatively impact the efficacy of the product.     

Adverse events of unregistered products imported via special access route

Importers of unregistered therapeutic products for named patients’ use must report all suspected cases of local serious AEs to HSA if the information is made available to them. They should also follow the requirements on maintaining records of AEs and reporting of AEs in special situations. It should be indicated that the suspected product reported is not registered in Singapore.

Lack of efficacy of a product

Reports of lack of efficacy occurring with no associated AE should not normally be reported but records must be maintained and be provided upon request.

There are special situations where lack of efficacy may be treated as serious AEs for reporting purposes. These include certain classes of therapeutic products that are used in critical conditions or for the treatment of life-threatening diseases, vaccines and contraceptives. Clinical judgment should be used when assessing if a report of lack of efficacy should be submitted. Companies should determine if the lack of efficacy is related to the product as opposed to other factors such as inappropriate treatment or disease progression.

 

Outcomes of use during pregnancy

The company should follow up with the doctor on the pregnancy outcome when the company is aware that a pregnant woman has consumed or been administered a therapeutic product that is not recommended during pregnancy.

If the pregnancy results in an abnormal outcome and the reporting doctor considers that it might have been due to the product, the company must submit the serious AE report to HSA within 15 calendar days upon first knowledge.

Guide for the industry