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Substantial changes affecting a TGA conformity assessment certificate and Transfers of certificates

Guidelines for notifying the TGA

29 June 2017

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Appendix A: Examples of substantial changes

Some of the examples below have been modified from the US FDA's draft guidance: Deciding When to Submit a 510(k) for a Change to an Existing Device: Draft Guidance for Industry and Food and Drug Administration Staff (August 2016).

This draft guidance is available from the US FDA's Draft Guidance Documents page.

Labelling, instructions for use and packaging

  1. The Instructions for use (IFU) of a medicated balloon catheter are updated to provide instructions on how to access different vessel types that were not previously addressed in the labelling or IFU. This would change the intended use of the device and hence this is a substantial change that requires notification to the TGA and assessment.
  2. The manufacturer changes the supplier of the polyethylene packaging of their sterile devices; the packaging configuration and specifications remain the same. The manufacturer uses the same package integrity test protocols as that previously approved and an analysis shows the new packaging has no impurities that could affect the devices' biocompatibility. This is not likely to require a substantial change notification to the TGA but it is still a requirement of the Regulations that after any change the manufacturer must ensure its devices continue to meet the requirements of their QMS and the Essential Principles. Documentation of the change would be required and may be followed up for review at a subsequent TGA QMS Inspection. The Technical file for the product should also be updated.
  3. The manufacturer removes a contraindication that has been previously stated for the medical device in the IFU, without making any changes to the device. As this change effectively broadens the indications for the device, this is a substantial change that requires notification to the TGA and assessment. This is also the case if a manufacturer adds a new indication to the IFU.
  4. The manufacturer removes a precaution and/or warning that has been previously stated for the medical device in the IFU, without making any changes to the device. As this change impacts the mitigation of risk, this is a substantial change that requires notification to the TGA and assessment.
  5. The IFU for a pacemaker lead states that the device is safe for conditional use within MR-environments of up to 1.5T. The manufacturer has performed additional testing on the device and test results have shown that the device can be conditionally used within MR-environments of up to 3T. The manufacturer would like to change the IFU to reflect this new information. Given that exposure to higher magnetic field strengths is likely to introduce new risks, this is a substantial change that requires notification to the TGA and assessment.
  6. The manufacturer decides to add certified foreign language translations of the labelling and IFU for use in other regulatory jurisdictions, while no change is to be made to the content of the approved product labelling. Since this change is unlikely to introduce new risks associated with the use of the device, notification to the TGA would not be necessary, but the change should be recorded in the QMS documentation.
  7. After clinical investigations, the manufacturer of a dermal filler decides to add recommendations for use of a certain type of cannula in their IFU as part of the surgical procedure. The manufacturer clarifies that this cannula will not be packaged together with the product, however, this change is likely to be substantial since the new operation procedure or technique will involve specific training and verification. This is a substantial change that requires notification to the TGA and assessment.
  8. Due to real-time aging data becoming available (or further accelerated-aging testing), the manufacturer of a drug-coated stent intends to extend the product shelf-life from 12 months to 24 months. This is a substantial change to the packaging and shelf life of the medical device that requires notification to the TGA and assessment.
  9. The storage temperature of the medical device has changed due to new stability data becoming available. No other changes have been made to the device. This change may possibly affect device performance and hence this is a substantial change that requires notification to the TGA and assessment.
  10. A change in labelling and/or IFU of the medical device to add a statement that the device is non-pyrogenic or endotoxin free. This is a substantial change that requires notification to the TGA and assessment.
  11. The manufacturer decides to change the Unique Product Identifier of the medical device with no other changes to the device, which will result in changes to the device labelling and IFU. This is a substantial change that requires notification to the TGA and assessment.

Design change

  1. A stent manufacturer adds a stent with a larger diameter to a family of coronary stents. This stent diameter is outside the range of the previous approved variants for the stents. Substantial Change notification to the TGA and assessment would be required as the larger diameter could significantly affect device related safety and efficacy. However if the change in diameter was within the previous variant range and there was no other change (i.e. to length of stent) then notification would not be required but documentation of the change to the QMS system and updating of the product technical file would be required.
  2. The manufacturer of a coronary stent increases the thickness of the wire in the stent to reduce the potential for stent fracture. The thickness is important to the performance of the stent and could affect the safety or efficacy of the device. This is a substantial change that requires notification to the TGA and assessment.
  3. The manufacturer of a hemi-arthroplasty femoral stem/head changes the taper/bore angle of the device. Given that this change is likely to affect the biomechanics of the joint replacement device and hence the performance of the device this is considered a substantial change that requires notification to the TGA and assessment.
  4. The manufacturer of a biological surgical repair mesh intends to add an additional manufacturing stage to provide surgeons with pre-cut meshes. This cutting work is currently being done by surgeons in theatre during operations. Given that this design change involves adding a manufacturing process that has not been previously assessed, this is considered a substantial change that requires notification to the TGA and assessment.
  5. The manufacturer of a medical device alters some of the sterilisation process cycle parameters such as process temperature or load size – with no changes to any other aspects of the device. This is considered a substantial change that requires notification to the TGA and assessment since this change is likely to affect the quality and safety of the final product.
  6. The manufacturer decides to change the sterilisation method for the medical device from gamma irradiation to EO without changing any other aspects of the device. The safety of the ethylene oxide residuals remaining on the medical device is of concern, along with potential temperature effects from the sterilisation cycle, and a substantial change application would be required for assessment of this change by the TGA.
  7. The manufacturer of a device intends to implement design changes that are driven by recent changes in the standards that were originally used to demonstrate compliance, or due to recent post-market data becoming available. Since such changes are likely to affect the device safety, performance, and quality this is considered a substantial change that requires notification to the TGA and assessment.
  8. The manufacturer of a hip implant intends to reduce the design tolerances enabling them to manufacture the devices closer to their design specifications without introducing new design features. Since the tightening of acceptance criteria is not expected to raise any new risks and issues, this is not likely to require a substantial change notification to the TGA. However, it is still a requirement of the Regulations that after any change the manufacturer must ensure they continue to meet the requirements of their QMS and the Essential Principles. Documentation of the change would be required and may be followed up for review at a subsequent TGA QMS Inspection. The Technical file for the product should also be updated.
  9. During research and development processes, the manufacturer of an approved active implantable device has found new software algorithms that improve the devices' function and usability. This change requires new design validation and verification; therefore, this is a substantial change that requires notification to the TGA and assessment. If the software only affected the graphical user-interface of the device, notification would not be required.
  10. Using previously approved manufacturing processes, the manufacturer of an intraocular lens (IOL) has made slight changes in the haptic geometry of the IOL. The optical performance specifications of the device have not been changed. However, since such changes are likely to affect the device performance and interaction with internal tissues this is a substantial change that requires notification to the TGA and assessment.

Material change

  1. The manufacturer of a Balloon Catheter changes the material of the polymer tubing used to manufacture the catheter from polymer A to polymer B and the manufacturer has not previously used polymer B (even if there were other similar devices on the market with polymer B). The manufacturer would have no knowledge of the formulation or manufacturing processes of polymer B tubing in the competitors' devices and would be required to assess the biocompatibility and performance of polymer B tubing in its own catheter. This is a substantial change that requires notification to the TGA and assessment. However, if the manufacturer has used polymer B tubing, with the same formulation and processing, in another previously approved catheter with the same type and duration of body contact and the same performance specifications then it may be acceptable to document the change to the QMS and update the technical file only.
  2. The manufacturer of a drug-eluting stent changes the supplier that provides the medicinal substance used in the device. The manufacturer is required to provide evidence (such as Letter of Access for an existing Drug Master File and/or Certificate of Suitability) to support the quality and safety of the medicinal substance used in the device as well as documentation to support the manufacturer's control over the new supplier. This is a substantial change that requires notification to the TGA and assessment.
  3. The manufacturer of a transvenous catheter system decides to change the materials of the guide wire that is supplied with the system. As the guide wire would be in direct contact with the circulatory system, the change in material is likely to affect the biocompatibility of the device; and, the quality and safety of the new materials requires assessment and any impact on performance should be considered. This requires a substantial change notification to the TGA and assessment.
  4. The manufacturer intends to change the sodium hyaluronate raw material specification to accommodate changes proposed by the raw material supplier and validation test results have shown there is an impact on the quality, performance and specification of the finished medical device. This is a substantial change that requires notification to the TGA and assessment. However, if validation test results have demonstrated that the change to the raw material specification have no impact on the quality, performance and specification of the finished medical device, a substantial change application would not be required but the manufacturer should document the changes in the QMS; and the Technical file for the product should be updated.

IVD change

  1. A Manufacturer makes a change to an inactive reagent included in the formulation of an IVD as a result of a change in supplier. The raw material specifications for the replacement reagent are equivalent to the previous reagent. Results of the risk analysis and verification and validation studies conducted by the manufacturer do not indicate any new safety or performance concerns. The manufacturer should document the changes and relevant tests in the QMS; and the Technical file for the product should be updated, without requiring further notification to the TGA or assessment.
  2. An IVD manufacturer makes a material change to a reagent (for example, changing a monoclonal antibody used in an ELISA kit, or the RNA primers included in a NAT assay) and the risk assessment shows that this could result in a change to the performance of the IVD outside the performance changes already approved by the TGA. This change has the potential to affect clinical decision making and this is a substantial change that requires notification to the TGA and assessment.
  3. A Manufacturer changes the design of an IVD for diagnosing HIV 1 to meet less stringent performance specifications. The change affects both sensitivity and specificity. Although the change does not alter how the IVD is used, or require labelling changes, it does alter performance compared to previously approved claims. Therefore, this is a substantial change that requires notification to the TGA and assessment.
  4. The manufacturer of an IVD updates their labelling by adding a new limitation after identifying a new medicine which could interfere with the result. The medicine does not affect the indications for use for the IVD nor significantly affect the risk profile. The manufacturer should document the change in the QMS; and the Technical file for the product should be updated.
  5. A change in the IFU for a Class 4 IVD, to include a new anticoagulant for plasma samples that are to be tested using the IVD, or any other new sample type not previously assessed, requires notification to the TGA and assessment.
  6. A manufacturer intends to add a production line for a new group of IVDs that use nucleic acid technology (NAT) to detect infectious disease markers, whereas previously they only produced immunoassay kits for detecting the same infectious markers. Even though the new NAT assays are the same 'kind of device' as the immunoassay kits that were previously assessed by the TGA, this is a substantial change to the manufacturing process and therefore requires notification to the TGA and assessment.
  7. A manufacturer has previously undergone assessment of three lots of stability data that were generated throughout a storage period of 13 months for a new IVD assay, and obtained approval from the TGA to supply their kits with a 12 month shelf life assigned. The stability studies of the kits were continued for a further 6 months and the manufacturer is satisfied that the kits continue to meet the assigned acceptance criteria, as outlined in the stability protocol. As the ongoing stability studies have reached completion, the manufacturer may assign a longer shelf life of 18 months without notifying the TGA or undergoing further assessment because the previously reviewed stability program has remained unchanged.

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