TGA Blueprint, page-35

Hi @Tobybreslin, I'm not a medical expert, however, I do have experience meeting complex government health and safety certifications within the construction industry. The language used in the report may seem daunting to a person not familiar with these types of processes. However, on closer reading, it simply addresses a range of detailed criteria and is requesting more information and data on various points. Additional lab testing and additional batches of kits are required.

If one were to step back from the emotion and drama of this year and look at the big picture, what we have here is an advanced-stage medical research company, with exceptional results across 7 studies, culminating in a large clinical trail. On top of this, they now hold valuable and detailed 'instructions' from the TGA detailing exactly what is required to gain approval. In hindsight, it is very unlikely any company could have met the stringent TGA requirements first time around, bearing in mind this is an innovative population screening device, not just any old cholesterol test or similar.

Here is a summary, which I distilled from the TGA report, of what RHY need to 'provide' to achieve TGA approval -

1) ManufacturerRelationships

Additional information regarding the relationship between Biotem andRhythm Biosciences

2) EP1 - Use of medical devices not to compromise health and safety, EP2 - Design andconstruction of medical devicesto conform with safety principles, EP 3 - Medical devices to be suitable forintended purpose, EP 6 - Benefits of medical devices to outweigh anyundesirable effects

• The final version of the risk assessmentfor the Device

• A discussion of risks and analyticalprocess

• Possible introduction of additionalcontrol measures,

• Clarification software inputs canpossibly determine error

• Clarification regarding record keepingand traceability;

3) EP 4 - Long‑term safety and EP 5 - Medical devices not to beadversely affected by transport or storage

• Clarification regarding whether theDevice is a single-assay device, or multiple

• Replacement validation data for stabilityat different temperatures

• Data log process for temperatures duringtransport

4) EP 13 – Information to be providedwith medical devices

Additional detailed lab data fordilution/concentration of samples.

5) EP 14 - Clinical Evidence and EP15 -Principles applying to IVD medical devices only

• The raw results for Study 9 presented as CRCstages 1,2,3 and 4 and controls sets with the risk classification for eachsample identified as positive likelihood, negative likelihood or indeterminate.

• Appendix D of the CER; and

• Any additional clinical validationdocumentation that has been generated since the release of the device tomarket.

6) EP 15- Principles applying to IVDmedical devices only

Sample Stability

• Validation of the stability of the serumsample for storage at three days at 4 oC for each Biomarker.

• A sample equivalence study that verifies theuse of frozen samples.

Biomarker Accuracy

• Validation of the accuracy of eachBiomarker assay using various ELISA comparator devices.

• Validation of between-user, between-day,between-instrument and between-lot (a minimum of three lots)

Precision

• Detailed additional data required for inter-assayprecision based on a minimum of 20-measurements.

Limit of Detection

• Additional data for each biomarker’sperformance at or below normal range.

Interference

• Repeat interference studies forhaemoglobin, bilirubin, lipid, total protein, paraprotein and rheumatoid factorwith a reported concentration of Biomarker in a sample with quantitated low,medium and high levels of potential interferent.

• Interference studies for exogenoussources of interference that may impact the Device performance.

Cross Reactivity

• Validation of the risk of carry-over or ajustification as to why this is not a requirement; and

• Validation of any prozoning or ajustification as to why this is not a requirement.

• Repeat cross-reactivity studies thatinclude the concentration of the measured result for the sample containingpotential interferent measures.

Measuring Range

• Validation of the high ‘decimal’ as beingappropriate

• Repeat linearity/parallelism studies for eachBiomarker to provide a number of data points ranging from the upper limits andlower limits of quantitation. The information to be provided must include theassayed values.

Recovery

• Replacement recovery studies that includethe theoretical concentration of Biomarker tested and the assayed resultexpressed as U/mL or ng/mL and which include concentrations below S5; and

• If recovery for samples below theconcentration of S5 are poor, a discussion on the recovery in the context ofthe expected (normal or abnormal concentration of Biomarker) must be provided.

Calibrator and Control Information

• Clarification if each and every lot hasan identical target mean value and the same acceptance range and, if theinformation is the same, how the manufacturing process ensures that the valuesdo not change;

• Clarification if the supplementary IFU islot specific.

• Certificates of analysis for the proteinsused in the and information regarding the sourcing and standardisation of eachlot of manufactured ;

• Discussion how the preanalytical dilutionstep can be verified for each Biomarker in the absence of any direct measure;and

• Justification for the use of a singlecontrol value for each Biomarker (in comparison to three levels). Thejustification must include evidence that the single control value providesquality assurance for the full measuring range.