Post-market responsibilities (II) Post-Market Vigilance Activities

Jorge Garcia Principal Scientific Adviser Office of Product Review

Sponsor Information & Training Day – 9 September 2014

Session C4: IVDs

Overview • The TGA’s Role • Regulation of medical devices and TGA’s Regulatory Authority • The Reporting and Investigation of Medical Device Adverse Events

- What is an adverse event - When to report - How to report

• Sponsor Obligations • IRIS: Incident Report Investigation Scheme

- Role, functions and responsibilities - What happens to an incident report - Some statistics

• Post Market Monitoring/Review • Vigilance Exchange

Session C4: IVDs – Post-market Vigilance Activities

Role of the TGA in market vigilance and surveillance

The TGA’s role is to continually monitor and evaluate the safety and efficacy or performance of therapeutic goods that are available on the market and to manage any risks associated with individual products.

We regulate therapeutic

goods throughout

their lifecycle in a number of

ways

Assess evidence

Enforce compliance

Register

Monitor

Changes to product information, safety alerts, recalls

Session C4: IVDs – Post-market Vigilance Activities

Regulation of Medical Devices • Post market regulation of devices is monitoring to ensure the device

continues to be “free from unacceptable risk”

• At all times the supplier & manufacturer must demonstrate continued compliance with “essential principles” that describe the safety & performance of a medical device

• Proof of compliance is demonstrated through a conformity assessment procedure

Session C4: IVDs – Post-market Vigilance Activities

Device Safety Monitoring Three major components of device safety monitoring:

• Ensuring that the manufacturer complies with the TGA’s required post-market surveillance system

• Post-market monitoring of compliance by the TGA • Vigilance programs, such as incident reporting

TGA monitors and regulates devices throughout their life cycle

Session C4: IVDs – Post-market Vigilance Activities

The TGA has authority to…

• Ask questions of sponsors and manufacturers. There are penalties for providing false and misleading information

• Seize products & inspect premises • Cancel/suspend products from supply • Mandate a recall of a therapeutic product.

Manufacturer/Sponsor is obliged to gather and report certain information.

Session C4: IVDs – Post-market Vigilance Activities

Medical Device Adverse Events

• What is an adverse event?

• When to report an adverse event

• How to report an adverse event

Session C4: IVDs – Post-market Vigilance Activities

Medical Device Adverse Events

• An event that resulted in, or could have resulted in (had effective intervention not taken place) serious injury, illness or death to patient, healthcare worker or other person

• A medical device adverse event is an event associated (caused or partially attributable) with the use (or misuse) of a medical device.

What is an adverse event/incident?

Session C4: IVDs – Post-market Vigilance Activities

Serious Injury Serious injury (also known as serious deterioration in state of health) is: • a life threatening illness or injury, • a permanent impairment of a body function,

(The term “permanent” means irreversible impairment or damage to a body structure or function. The term excludes minor impairment or damage.)

• 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. (In this context, medical intervention is not in itself a serious injury. It is the reason that motivated the medical intervention that should be used to assess whether an event should be reported)

Session C4: IVDs – Post-market Vigilance Activities

Medical Device Adverse Events Difficulties and Malfunctions; • Problems with getting device to operate

• Repeated repairs

• Difficulty of use

• Difficulty of cleaning after use

• Many different faults that may affect the quality, timeliness and cost -effectiveness of health care. Events or other information in relation to the quality, performance and safety of medical devices (eg device design)

• The TGA encourages users to report issues of concern with the devices that they use. The TGA understands that under reporting both to the TGA and /or suppliers is an issue.

Session C4: IVDs – Post-market Vigilance Activities

It is often difficult to determine whether an adverse event was caused by a medical device. When in doubt it is better to report than not to report.

Session C4: IVDs – Post-market Vigilance Activities

Sponsor – mandatory obligations

• Sponsors must report the details of events associated with their device(s) that have resulted or could have resulted in serious injury or death. – Guidance allows certain exemptions from reporting. Further information can

be found in the guidance document Australian regulatory guidelines for medical devices (ARGMD)

– Guidance stipulates the amount of information that constitutes a complete report.

– These are conditions of inclusion set out in the Therapeutic Goods (Medical Devices) Regulations (2002)

• Within two days of becoming aware of an issue of serious public health threat or concern that will require prompt action to reduce the hazard.

• Within ten days of becoming aware of a death or serious injury. • Within thirty days of becoming aware of an event that might have led to

serious injury or death.

When to report n to report

Session C4: IVDs – Post-market Vigilance Activities

Medical Device Adverse Events How to report • Log into eBS • Select medical device

adverse event reporting • List of all reports

submitted by the sponsor

• Complete new report, update follow-up or final report

• Device Incident Report reference number available immediately

• Save or print report

Session C4: IVDs – Post-market Vigilance Activities

Common Issues noted with reports submitted • Proof Reading – check accuracy, be careful of cut and paste

• Lack of Information or Relevancy – ensure all the information is made available, accurate and relevant to the event as it makes assessment easier and reduces the need of further information being requested

• Duplicates – Ensure all parties in your company are aware of what has already been sent to the TGA.

- The TGA makes every effort to match any user report it receives to a corresponding sponsors report.

- If you have been sent a questionnaire for a user report and you have not reported it to the TGA- there is no need to do so separately

• Similar event rates

- Similar events are based on the clinical event description and not the cause of an event.

- The rate should preferably be provided in the form of an incidence rate or percentage.

Further information on how to fill in the report can be found in the FAQs on the TGA website.

Session C4: IVDs – Post-market Vigilance Activities

IRIS - (Medical Device) Incident Report Investigation Scheme

“A scheme intended to help maintain the standard of devices used in health care through the voluntary cooperation between users government and industry through the investigation of adverse events and incidents”

Session C4: IVDs – Post-market Vigilance Activities

Safety monitoring process

• Every adverse incident reported entered into the database and reviewed by professional and medical staff

• Data is analysed to identify safety signals that may indicate a problem

• A signal is a preliminary indication of a safety issue and by itself does not indicate a causal association with the product

• When a signal is identified, a detailed evaluation is undertaken to establish if the product contributed to the root cause of the incidents reported

Session C4: IVDs – Post-market Vigilance Activities

What happens to reports? Initial risk assessment... • All reports are entered into the Scheme’s database so that they

may be easily referenced in the future. • Urgent reports are addressed immediately by the Scheme

coordinator. • Focus is on unusual problems, potentially serious problems, or

problems that have high levels of incidence. • Isolated incidents or problems that are not likely to lead to injuries

or have a detrimental effect on effectiveness are recorded but not necessarily further investigated.

Session C4: IVDs – Post-market Vigilance Activities

What happens to reports? (cont.) • Scientific, engineering and clinical experts assess the reports.

They then determine what level of investigation will take place • The TGA investigator contacts the sponsor (company) and works

with them to resolve any issues • Reports are treated as confidential and the reporter and sponsor

are informed of the outcome of the investigation • Most reports are placed onto the Database of Adverse Event

Notifications (DAEN). This is done after a final report is received & every three months.

Session C4: IVDs – Post-market Vigilance Activities

Outcomes of investigations If action is necessary it may involve any of the following: • Recall - removal of goods from sale or use, or for correction • Safety Alert - urgent information to inform those using the device, or

affected by the problem • Report in the TGA News, TGA website or other appropriate journal/s. • Product improvement • Referral to other TGA Sections for regulatory action.

Session C4: IVDs – Post-market Vigilance Activities

Source of Reports

0

50

100

150

2002012 Total: 22632013 Total; 3309

Sponsor Reports: – 2012: 1824 – 2013: 2456

Patient, Surgeon reports up (178, 310 respectively) in 2013 due to the PIP silicone breast implant issue

20

Session C4: IVDs – Post-market Vigilance Activities

Outcome of Investigations Other Outcomes: • Reviewed, trending purposes

only – 2012: 1442 – 2013: 1245

• Reviewed, No Further Action Required – 2012: 611 – 2013: 1334

TGA publication was high in 2013 because of the 500+ reports received regarding the PIP issue.

020406080

100120 2012 Total: 2263

2013 Total: 3309

Session C4: IVDs – Post-market Vigilance Activities

Post Market Review Process For safety and performance • Conducted for but not exclusively for the following criteria:

− Trends from the Medical Device Incident Report Investigation Scheme − Recurrent breaches of the Advertising Code − Unresolved/repeated recalls − Information received from other regulatory agencies

• Reviews are conducted on one or all of the following criteria: − Sponsor − Manufacturer − Ingredient − Product − Kind of Device

• Reviews for safety and performance may be conducted at any point in the product’s life-cycle.

Session C4: IVDs – Post-market Vigilance Activities

Post Market Review Process (cont.) • TGA usually requests that the sponsor provide the following information:

- Labels - IFU - Advertising material - Technical documentation describing mechanism of action - Declaration of Conformity and certification of the manufacturing process and the

product - Risk assessment - Ingredients and formulations of medicated/formulated devices, - Post market data such as the number of problems, complaints, adverse events that

have been reported. Details about what the sponsor and manufacturer has done about these issues.

- Clinical evidence • Dependant on the issue under review

Session C4: IVDs – Post-market Vigilance Activities

Number of Reviews

Year No. ARTG entries reviewed

No. Reviews completed

Cancelled by Sponsor

Cancelled by TGA

2011 237 202 48 11

2012 551 186 122 6

2013 130 90 21 3

Session C4: IVDs – Post-market Vigilance Activities

Sponsor Annual Reporting In addition to the adverse event reports required under the vigilance provisions, it is a condition of inclusion that the sponsor of a medical device that is: • an AIMD • Class III • implantable Class IIb

And • Provides three consecutive annual reports to the TGA following inclusion

of the device on the ARTG. (5.8 Regs) • Annual reports are due on 1 October each year. • Reports should be for the period 1 July to 30 June

Session C4: IVDs – Post-market Vigilance Activities

Vigilance Exchange • TGA exchanges vigilance information through the National Competent

Authority Reporting (NCAR) Program. Information will be exchanged on incidents and events where: - corrective action, including recalls, is to be taken - there is a serious risk to the safety of patients or other users, but where

no corrective action has yet been established although measures are under consideration, or where there is not yet a final report from the sponsor.

• The TGA will consult the sponsor when preparing a report. It is the responsibility of the sponsor to ensure that the manufacturer is aware of the TGA vigilance report, and that any comments that are made by the manufacturer are passed on to the TGA for consideration. The TGA will only consider changes that address inaccuracies in the report.

Session C4: IVDs – Post-market Vigilance Activities

Questions?

Session C4: IVDs – Post-market Vigilance Activities

Recalls of Therapeutic Goods In vitro diagnostic medical devices

Simon Waters Deputy Recall Coordinator

Sponsor Information & Training Day – 9 September 2014

Session C4: IVDs

The URPTG (current) 2004 edition Available online at:

www.tga.gov.au/industry/recalls-urptg.htm

Terminology and definitions found in the URPTG must be applied to market actions undertaken in Australia

Session C4: IVDs – Recalls of Therapeutic Goods

What is a recall action? Two distinct types of recall actions applicable to IVDs are included in the URPTG: • Recall: permanent removal of deficient goods from the market or from use;

and • Recall for Product Correction: correction, which may involve temporary

removal from the market or from use. A recall action is required where a defined deficiency has been identified. Legislative context for what is considered to be a defined deficiency is referenced in section 41KA of the Therapeutic Goods Act 1989 and includes: • Non-compliance with the Essential Principles • Failure to apply the Conformity Assessment Procedures • Device determined to be not fit to be used for its intended purpose • Unacceptable quality, safety or performance

Session C4: IVDs – Recalls of Therapeutic Goods

Recall vs product correction • Appropriate recall action is determined on a case by case basis:

– Nature of the deficiency – Incidence of complaints – Consumer/Patient safety – Distribution networks – Availability of alternatives

Session C4: IVDs – Recalls of Therapeutic Goods

Quarterly Trend of Recall Actions – all therapeutic goods

Session C4: IVDs – Recalls of Therapeutic Goods

Quarterly Trend of Recall Notifications - IVDs

Session C4: IVDs – Recalls of Therapeutic Goods

Questions?

Post-market responsibilities (II) Recalls and Adverse events

Sally Jennings RA QA Affairs & IBP Manager

Abbott Diagnostics

Uniform Recall Procedure For

Therapeutic Goods

System for Australian Recall Actions (SARA)

Global Terminology Title of customer communications

recall Urgent Medical Device Recall

(mandated)

Urgent Field Safety Notice – Product Recall

(mandated)

Product Recall (example only)

(not mandated)

Product Recall (example only)

(not mandated)

Australia

Europe

Australia

Europe

USA

Canada

corrective action Urgent Medical Device Recall for Product Correction

(mandated)

Urgent Field Safety Notice – Product Correction

(mandated)

Product Correction (example only) (not mandated)

Product Correction (example only)

(not mandated)

Australia

Europe

Australia

Europe

USA

Canada

Global Terminology Title of customer communications

Global Terminology

advisories (no mandated terminology)

Safety Advisory or Alert

Advice Notices/Recommendations (depends on country)

Safety Alert/Safety Communication

Advisory

Australia

Europe

Australia

Europe

USA

Canada

What is a Recall?

Wrong reagent in bottle

Stability drop during routine testing

Shift in on-market performance

Wrong label on bottle

Control Solution

recall from market recall from market

Recall or Recall for Product Correction?

What isn’t (or may not be) a Recall?

Restandardization of the assay

Instrument System software

upgrade to enhance usability

Known sample interferent documented in Instructions for

Use

Recall or Recall for Product Correction?

Lot number on-market for 12 months – recall

Does the control detect the shift and can the assay be recalibrated?

Recall for product correction – notify customer and include notification in future kits until Instructions for Use updated

If yes, no action required

Lot number on-market for 5 months - correction

If no, recall Control range

Every Recall is Unique

• Every recall is unique • Each one should be assessed on a case-by-

case basis – Reportability – Recall v Recall for Product Correction – Impact on the market v risk – Actions to be taken

Don’t assume what you did last time will apply this

time!

Field action – when do I notify?

• You must pro-actively notify the TGA whenever an IVD product supplied in Australia is the subject of an action in the field unless…..

– The affected batch number or serial number was not received in Australia.

– The issue/event is deemed to be not-reportable because there is no increased risk or potential risk to patients or users from the event.

– The action is part of routine maintenance or troubleshooting.

Information to be provided to TGA

• Email to recalls@tga.gov.au: – Summary of issue – Draft letter – Health hazard assessment – List of customer locations – Exported product?

Actions post TGA review • Send letter to customer

– Within 48 hours (2 working days) – Head of institution – Paper and electronic – special envelopes

• ACCC (Minister) – Safety related (Class I and II) – recalls@recalls.gov.au

• Obtain customer acknowledgements • Ongoing reporting

– 2 week, 6 week, 3 month – TGA – Until close-out of corrective action

• Agreed timeframes

• TGA close-out letter

Adverse Events

Global Terminology Adverse Event Schemes

Adverse Event IRIS – Incident Report Investigation Scheme

Device Incident Report (DIR)

Medical Device Incident Reporting System Medical Device Incident (MDI) (Report)

MDR – Medical Device Reporting Medical Device Report (MDR)

CV-MD - Canada Vigilance - Medical Device Problem Reporting Program Medical Device Problem Report (MDPR)

Australia

Europe

Australia

Europe

USA

Canada

Death or Serious Injury

• What does this mean for an IVD? • ‘Adverse impact to patient management’

– Patient - result lead to, or might have lead to, a patient management decision that resulted in death or serious deterioration in the health of the patient

– User – death or serious injury or potential death or serious injury

Scenario 1 • Public Health

– H1N1 pandemic – Government decides to use Acme Enterprises

PoC test for H1N1 to screen all persons arriving in Australia by plane and boat!!

– Doctors begin to report cases of recent travellers falling ill with H1N1

• Reportability – Potential for spread of H1N1 from infected people – Public Health threat

Timeframe for reporting – 48 hour reportable Let’s hope it never happens!!

Scenario 2

• Patient impact – Person with diabetes presented to emergency

department in a coma and later dies – Patient had tested glucose levels using a self-

testing glucose meter and administered insulin prior to ED admittance

• Reportability – patient death – Glucose meter results may have lead to an

incorrect patient management decision

Timeframe for reporting –10 day reportable

Scenario 3 • User impact

– Incidents were reported by Laboratory personnel of an IVD instrument overheating and, in one case, catching fire

– Fire was contained within instrument – No injury to laboratory personnel in reported cases

• Reportability – Potential injury (burns) to users if fire is not

contained

Timeframe for reporting –30 day reportable

Scenario 4 • Patient Impact

– Patient sample is tested by a laboratory for creatinine and protein level

– Creatinine reads high at 150 umol/L and the protein level read 140 g/L

– Results are released to the treating physician who queries the creatinine result

– No change to patient management

• Reportability – Potential for change to patient management if results acted on, BUT – Proteins are known to interfere with creatinine at concentrations

above 100 g/L and this is clearly stated in the Instructions for Use of the creatinine assay.

Timeframe for reporting – not reportable

How do I report an Adverse Event?

MDIR Form – Initial report – Final report

• By modification of the initial report – Interim updates can be added as

required. The event must have occurred in Australia

Finding Adverse Event Notifications

• DAEN

– Database of Adverse Event Notifications – Publically available – Searchable

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