MEDEC 2016 Workshop Musculoskeletal Division Presentation

Weimin Zhao, Head MSAndrea Katynski, Senior Evaluator

Medical Devices Bureau

Outline

• Workload from the last calendar year

• Performance Summary

• Screening Deficiencies

• Additional Information Requests

• Common Review Deficiencies

• Essentials for inclusion in study summaries

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Licences

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Time To First Decision

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NA

Time To Second Decisions (Average AI Review Time)

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Screening Deficiencies

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Screening Deficiencies

• Labelling: references to unlicensed device names,

indication/contraindication statements…

• Bench Testing: use worst case samples, rationale for not conducting

certain tests…

• Study summary: no summary or simple summaries lacking details

• Clinical Studies: newer technology/claim, materials, no consensus on

S&E

• Shelf-life validation: accelerated aging calculation, use of predicate

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Additional Information Requests

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Additional Information Requests

Frequent AI Requests

• Marketing History

• Preclinical Testing

• Device-Specific Clinical Evidence

• Clinical Literature Summary

• Shelf Life and Packaging

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Common Review Deficiencies• Electronic Information

– Increased volume of background information– File nomenclature

• Descriptive titles in file names and appendices• Avoid files titled by manufacturers’ codes/numbers

– Submissions with multiple validations• Historical validations from product development

phase (shelf life, packaging, process validations)

• Provide the validation relevant to the current application

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Common Review Deficiencies cont.• Market History

– Amendment applications• Unless substantial sales available for the subject

device, provide history for the predicate as well

– Summarize sales information• Provide totals • Sales organized by useful component (ie. If multiple

screws per implant)

– Brief description of the nature of adverse/quality events and any actions required for resolution

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Common Review Deficiencies cont.• Preclinical Testing

– If a representative or predicate device is used, provide a rationale to support the applicability of the results to the subject device

• May include comparison of design / material / intended use

– If the subject device falls outside an approved size range, identify changes to the worst case test scenarios and provide evidence to support the new size/device

- If the formulation of a device changes, provide a clear description and comparison of the formulation of the subject device and predicate (i.e. injectables, absorbables, dental composites etc)

- For devices provided with a syringe/cannula, identify whether these components are licensed; or provide evidence to support their use with the device

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Common Review Deficiencies cont.• Device-Specific Clinical Data

– Novel technology, material, design

– Existing technology with a new or novel claim/indication for use

– Required for certain classes of devices, • e.g. dermal fillers, metal-on-metal hips

• where there is uncertainty and/or inconclusive evidence to support safety and effectiveness

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Common Review Deficiencies cont.• Clinical literature summary

– Provide a summary which clearly outlines the relevance of the literature with respect to the proposed use/indications of the subject device

– Highlight updates or changes to the literature review for each subsequent amendment application

– Tabular comparison of the subject device and representative devices referred to in the literature summary

• Design, material, intended use/indications and licence status

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Common Review Deficiencies cont.• Shelf life and Package Validation

– Shelf life testing• Specify conditions of sterilization and aging methods including

calculation of real time equivalents– Validation based on predicate device

• Include licence/application number• Include the shelf life claim of the predicate• Include justification for “representative” packaging• “packaged similarly” is not sufficient

– Packaging Validation• Provide a description of materials and configuration• Shipping and handling testing (non-sterile and sterile packaging)• Sterile barrier integrity testing (dye penetration/bubble emission) are

often required15

Summaries of Studies (32(3)(f))

• A summary of all studies manufacturer has used to ensure that the device meets the safety and effectiveness requirements (Sec.10-20 MDR)

Suggested Content:– Purpose or Objective – Summary of method including number of units assessed, pass/fail criteria,

stats used, deviations, etc.– Test conditions, patient population, assumptions, limitations– Conclusions drawn– Justification of, or follow-up on failed or unexpected results– Discussion of relevance, context, implications as necessary

Example Studies: Mechanical testing, Stress/Fatigue, Wear, Shelf Life, Biocompatibility, Animal Studies, Clinical Investigations…

Remember reviewer sees many device types, a short narrative or introduction to and between studies helps reviewer follow your timelines…☺

Summaries of Studies (32(3)(f))

Biocompatibility Testing• ISO 10993 series is considered the gold standard• If not using ISO 10993 methods, provide description of method,

sample prep, limitations, etc.• Describe the test article

– was it sterile, prototype, production unit, exact subject device, slightly different?

– If not exact – justify applicability of results

If using Declaration of Conformity: 10993 standards tend not to state pass fail criteria therefore you must clearly state your criteria for pass/fail in addition to result itself

Summaries of Studies (32(3)(f))

Mechanical Studies• Conformity to international standards• Justification of worst case for testing sample selection• Include number of samples tested, mean ± SD, maximal/minimal

values• If comparing with a ‘predicate device’, justify the validity of the

comparison (material, design, intended use…) and provide evidence of Canadian approval for the ‘predicate’

• If your own criteria are used for judging the testing results, justifications are required for the adequacy of the value.

Summaries of Studies (32(3)(f))

Animal Studies and Clinical Studies• Objectives, methodology, results (data), analysis, manufacturer’s

conclusions

• Discussion in context with the published literature or other results

• Adverse reactions observed or commonly known for similar devices should be discussed

Established technology may not require animal/clinical data for approval (i.e. conventional primary hip, knee implants, bone plates/screws, etc. ) assumes no novel or expanded functionality

(Summaries of Studies (32(3)(f))

Sterilization• Information is needed if a component is sold sterile or is to be

sterilized by the end user– Description of the sterilization method– Level of sterility assurance (SAL)– Packaging used to maintain sterility and a summary of testing to

validate it– An attestation that the process has been properly validated &/or

validation report (most reviewers prefer the report)

For devices sold non-sterile but requiring sterilization prior to use, the manufacturer must recommend at least one method for sterilization which they have validated to be safe for the device and effective at sterilization.

Similar information may be requested/expected for disinfection for reusable devices.

Questions ?

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