Medical Devices: Post-Market Surveillance, Adverse Events and Recall

What is Post-Market Surveillance (PMS)?

According to the World Health Organization “Post-market surveillance is a set of activities conducted by manufacturers, to collect and evaluate experience gained from medical devices that have been placed on the market, and to identify the need to take any action”¹.

‘Post-market surveillance’ is not to be confused with the term ‘market surveillance’ which refers to the compliance monitoring and response activities carried out by the national authorities in Europe², not activities carried out by the manufacturer.

Why is Post-Market Surveillance required?

ISO 13485:2016 ‘Medical devices — Quality management systems — Requirements for regulatory purposes’ require post-market surveillance activities under various clauses including:

Clause 8.5 “The organization shall identify and implement any changes necessary to ensure and maintain the continued suitability, adequacy and effectiveness of the quality management system as well as medical device safety and performance through the use of … postmarket surveillance…”³.

Clause 8.2.1 “feedback process shall include provisions to gather data from production as well as post-production activities”³.

Clause 7.2.3 “The organization shall plan and document arrangements for communicating with customers in relation to…. c)customer feedback, including complaints; d) advisory notices”³.

ISO14971:2019 ‘Medical devices — Application of risk management to medical devices’ require post-market surveillance activities under various clauses such as:

Clause 10.1 “The manufacturer shall establish, document and maintain a system to actively collect and review information relevant to the medical device in the production and post-production phases”⁴.

Additionally, ‘Essential Principle 14’ states that “Every medical device requires clinical evidence, appropriate for the use and classification of the device, demonstrating that the device complies with the applicable provisions of the essential principles”⁵. The ‘TGA Clinical Evidence Guidelines for Medical Devices’ states that “clinical evidence should be updated and systematically reviewed periodically as new information based on post-market surveillance activities and product experience becomes available”⁶.

Therefore, post-market surveillance activities are conducted as part of the Quality Management System (ISO 13485:2016) which feeds information into and receives information from the Risk Management process (ISO14971:2019) and the Clinical Evaluation process, as seen in diagram 1 below.

Diagram 1: Interaction of the Risk Management, Post-Market Surveillance and Clinical Evaluation processes

What do Post-Market Surveillance activities look like?

Post-market surveillance activities can fall into two categories:

1. Proactive PMS activities
   • Proactive PMS activities seek out information on the medical device so that the potential occurrence of an event can be detected and avoided. Inputs data for the proactive PMS include customer surveys, post market clinical follow-up, etc.
2. Reactive PMS activities
   • Reactive PMS activities involve responding to an event after it has occurred. Reactive PMS activities are also known as vigilance. Input data for the reactive PMS include customer complaints, service reports, in-house device testing, etc.

Although often vigilance is used as synonym for post-market surveillance, it is in fact the reactive type of PMS.

When to report an event, detected by Post-Market Surveillance activities, to the TGA?

According to ISO 13485:2016 ‘Medical devices — Quality management systems — Requirements for regulatory purposes’ clause 8.2.3 states that “if applicable regulatory requirements require notification of complaints that meet specified reporting criteria of adverse events or issuance of advisory notices, the organization shall document procedures for providing notification to the appropriate regulatory authorities”³. In Australia, section 5.7 of the ‘Therapeutic Goods (Medical Devices) Regulations 2002’ outlines that a condition for continued inclusion in the Australian Register of Therapeutic Goods (ARTG) is that ‘adverse events’ or ‘near adverse events’ must be reported to the TGA⁷.

An ‘adverse event’ is an event that involved a medical device and resulted in:

• “death of a patient, health care provider, user or other person; or
• a serious injury or serious deterioration to a patient, health care provider, user or other person, including;
  • a life-threatening illness or injury;
  • permanent impairment of a body function;
  • permanent damage to a body structure; or
  • a condition necessitating medical or surgical intervention to prevent permanent impairment of a body function or permanent damage to a body structure”⁷.

A 'near adverse event' is when:

• “an event associated with the device occurred”; (but death or serious injury did not occur, possibly due to a timely intervention of a healthcare worker or another reason) and
• “if the event occurred again, it might lead to death or serious injury as outlined above”⁷.

Note, when an event is reported to the TGA, it is not an admission of liability⁷.

Are there scenarios where you do not have to report to the TGA?

Yes, there are certain exemption rules that apply that mean reporting to the TGA is not required, including⁷:

1. Deficiencies in a new device that are found by the user prior to its use
2. An adverse event caused solely by the patient’s condition
3. The service life of the medical device is exceeded
4. A design feature safeguarded against a fault becoming a hazardous situation
5. The remote likelihood of an adverse event causing death or serious injury (adverse events that could lead, but have not yet led, to death or serious injury and determined as acceptable in the risk assessment)
6. Foreseeable and expected side effects are documented in manufacturer’s labelling or Instructions for Use
7. Adverse events that occur after the manufacturer has issued an advisory notice (Advisory notices include removals from the market, corrective actions, and product recalls)
8. Reporting exemptions granted by the TGA (A sponsor can request an exemption for common and well-documented events. A periodic report is issued to the TGA instead).

Must an adverse event that occurs outside of Australia be reported when the medical device is supplied in Australia?

If an adverse event happens in Australia it must reported to the TGA.

If an adverse event happens outside of Australia and that same device is supplied in Australia, the adverse event does not need to be reported to the TGA. However, if there is remedial action that occurs outside Australia for devices supplied in Australia this must be reported to the TGA⁷.

How long do you have to report an adverse event?

How do you report an event?

An event can be reported via one of the options below⁸:

Who must report an adverse event?

The sponsor and manufacturer must report adverse events to the TGA. The user of the device (consumer or health professional), although not required, is encouraged to report adverse events to the TGA⁹.

Who is ultimately responsible for the handling an adverse event in Australia?

The sponsor is responsible for handling an adverse event in Australia. However, the manufacturer is responsible for maintaining records on the issues or incidences that occur with a medical device supplied in Australia⁹.

What actions are taken as a result of an adverse event?

Various actions can be taken by the sponsor depending on the outcome of the risk analysis for the adverse event on hand. These actions can be classified into ‘recall actions’ and ‘non-recall actions’¹⁰.

Recall actions can include any of the four actions below¹⁰:

1. Recall: Is used to permanently remove a device from the market. This is usually used if there is a deficiency in presentation, safety, quality, efficacy, or performance.
2. Product defect correction: Is used to correct a device deficiency, which can include temporary device removal to correct the device.
3. Hazard alert: Is used only for implanted medical devices where the device cannot be recalled. It provides precautionary information and on-going management advice where the device has a deficiency related to safety, quality, efficacy, or performance.
4. Product defect alert: Is used where an alternative treatment is not available, therefore, it may be riskier to recall the product and leave the patient without an alternative treatment.

A recall can be classified into the following:

• Class I: Is the most serious safety related recall class. “A situation in which there is a reasonable probability that the use of, or exposure to, the deficient therapeutic good(s) will cause serious adverse health consequences or death”¹⁰.
• Class II: Is a serious safety related recall class. “A situation in which use of, or exposure to, the deficient therapeutic good(s) may cause temporary or medically reversible adverse health consequences, or where the probability of serious adverse health consequences is remote”¹⁰.
• Class III: Is the least serious safety related recall class. “The goods meet acceptable standards of safety and efficacy and the issue does not in itself present an imminent risk. However, if not rectified, the situation may present a hazard in the future”¹⁰.

Additionally, a recall action can be classified into levels, including those seen below. The level refers to the depth of the recall action.

• Wholesale level: Includes purchasing authorities for the states and territories as well as regular wholesalers
• Hospital level: Includes hospitals, nursing homes, ambulance services, etc as well as the previous wholesale level.
• Retail level: Includes pharmacies, dentists, healthcare professionals as well as the two previous levels (wholesale and hospital levels)
• Consumer level: Includes any patient or consumer and the previous three levels (Wholesale, hospital, and retail levels).

Non-recall actions are not considered a recall but are used where there may still be patient safety concerns. Non- recall actions can be used if all device standards are specifications are met and there are no deficiencies in presentation, safety, quality, performance and efficacy. These non-recall actions include¹⁰:

1. Safety alert is used to provide further information, precautions or advice to health professionals on the safe use of a device.
2. Product notification is used to provide information where it is improbably that there might be a significant adverse health consequence.
3. Quarantine can be used at a wholesale, hospital and retail level, if there is a potential issue related to safety, quality, efficacy, or performance. Quarantine cannot be used at a consumer level.
4. Product withdrawal is similar to a recall in terms of removing the device from the market, however, it is not associated with patient risk. The withdrawal of the product is not related to a deficiency in presentation, safety, quality, efficacy, or performance.

Does the sponsor have any other reporting responsibilities in relation to Post-Market Surveillance?

If a medical device falls into one of the four categories below then, yes, the sponsor must also submit an annual report to the TGA for three consecutive years upon medical device inclusion in the ARTG. These annual reports include information on the number of medical device complaints, adverse events, and incident rates both in Australia and globally. The intent of the annual reports are to ensure that:

• “High risk devices that are new to the Australian market continue to meet the Essential Principles for safety and performance; and
• The post-market surveillance system is able to identify any safety or performance issues or signals associated with the device as early as possible"¹¹.

The four categories of medical devices that require three consecutive annual reports to be submitted to the TGA include:

1. Active Implantable Medical Device
2. Class III Medical Device
3. Class IIb Implantable Medical Device or
4. Class 4 In Vitro Diagnostic Device

References

1. World Health Organisation. (2020, December 8). Guidance for post-market surveillance and market surveillance of medical devices, including in vitro diagnostics. Retrieved April 26, 2021, from World Health Organisation: https://www.who.int/publications/i/item/guidance-for-post-market-surveillance-and-market-surveillance-of-medical-devices-including-in-vitro-diagnostics
2. Eurpean Commission. (2021). Product safety and market surveillance. Retrieved April 26, 2021, from https://ec.europa.eu/info/business-economy-euro/product-safety-and-requirements/product-safety/product-safety-and-market-surveillance_en#:~:text=Market%20surveillance%20is%20the%20activity,EU%20health%20and%20safety%20requirements
3. International Organization for Standardization. (2016, March 1). ISO 13485:2016 Medical devices - Quality management systems - Requirements for regulatory purposes. Switzerland: International Organization for Standardization.
4. International Organization for Standardization. (2019, December). ISO 14971:2019 Medical devices — Application of risk management to medical devices. Switzerland: International Organization for Standardization.
5. Therapeutic Goods Administration. (2021, March 22). Essential principles checklist (medical devices). Retrieved April 26, 2021, from Therapeutic Goods Administration: https://www.tga.gov.au/sites/default/files/essential-principles-checklist-medical-devices.pdf
6. Therapeutic Goods Administration. (2021 , March 31). Clinical evidence guidelines Medical devices. Retrieved April 26, 2021, from Therapeutic Goods Administration: https://www.tga.gov.au/sites/default/files/clinical-evidence-guidelines-medical-devices.pdf
7. Therapeutic Goods Administration. (2021, January 15). Adverse event reporting. Retrieved from Therapeutic Goods Administration: https://www.tga.gov.au/adverse-event-reporting#exemption-rules
8. Therapeutic Goods Administration. (2019, October 30). Medical device incident reporting & investigation scheme (IRIS). Retrieved from Therapeutic Goods Administration: https://www.tga.gov.au/medical-device-incident-reporting-investigation-scheme-iris
9. Therapeutic Goods Administration. (2011, May). Australian regulatory guidelines for medical devices (ARGMD). Retrieved April 26, 2021, from Therapeutic Goods Administration: https://www.tga.gov.au/sites/default/files/devices-argmd-01.pdf
10. Therapeutic Goods Administration. (2019, December). Uniform Recall Procedure for Therapeutic Goods (URPTG). Retrieved April 2021, 26, from Therapeutic Goods Administration: https://www.tga.gov.au/sites/default/files/uniform-recall-procedure-therapeutic-goods-urptg.pdf
11. Therapeutic Goods Administration. (2019, October 2019). Annual reports. Retrieved from Therapeutic Goods Administration: https://www.tga.gov.au/annual-reports