fda and iso stars aligning on iso 10993 - brandwood ckc · james (morrison) has been a member of...

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FDA and ISO stars aligning on ISO 10993

James Morrison

LIVE WEBINAROctober 2018


James (Morrison) has been a member of ISO/TC 194 for some years and currently serves as Head of the Australian delegation.

Particular expertise in respiratory devices and was very active in the development of the ISO 18562 series.

Currently heavily engaged in Part 17 & Part 18 revisions.

Materials Science and Toxicology background.

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Arthur (Brandwood) has been a member of ISO/TC 194 since just after its inception in 1991 (2nd longest serving member.)

On the drafting committee for 5th Edition Part 1.

BioMaterials and Regulatory background.


ISO 10993-1:2018

Biological evaluation of medical devices -- Part 1: Evaluation and testing within a risk management process

Replaces 4th edition (2009)

Published by ISO, but not yet published nationally.

Gap between publication and acceptance.

Guidance from “authorities having jurisdiction”

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CHANGES

Table A.1 “Endpoints to be addressed in a biological risk assessment” as normative.

New columns:• “physical and/or chemical information” (characterisation)• “material mediated pyrogenicity”• “chronic toxicity”• “carcinogenicity”• “reproductive/developmental toxicity”• “degradation”

“endpoints” to be considered with “E” (NOT “tests” to be conducted with an “X”)

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Table A.1

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CHANGES (cont.)

Annex B “Guidance on the conduct of biological evaluation within a risk management process.”

Additional definitions for terms used throughout the 10993 series.

Categorisation now includes: “Non-contacting” and “Transitory-contacting” devices.

Nanomaterials and Absorbable/Degradable materials.

ISO 18562 (all parts) for “Biocompatibility evaluation of breathing gas pathways in healthcare applications”.

“Significant editing changes throughout” – (rewritten)

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Risk Management

Evaluation is still (or even more so) an exercise in Risk Management.

Annex B, substantial guidance on the whole issue

Risk = Severity of Harm x Probability of Occurrence

Harms are identified in Table A.1

Probabilities are determined from: • firstly, the Physical & Chemical Characterisation or• failing that, the biological testing

Show “Safety Factors” where possible.

Apply consideration of benefit last.

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Toxicological Risk Assessment

The addition of Physical and Chemical Information to Table A.1 drives manufacturers to Chemical Characterisation.

ISO 10993-18 Chemical Characterisation of Materials, currently under extensive revision.

Characterisation allows/drives manufacturers to Toxicological Risk Assessment.

ISO 10993-17 Establishment of allowable limits of leachable substances, currently under extensive revision (“Toxicological risk assessment of medical device constituents”)

TRA ought to reduce the amount of biological testing

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Material Mediated Pyrogenicity

A type of systemic toxicity.

Actually extremely rare/(non-existent?) - Metals (e.g. Nickel salts)

Biologics Mediated Pyrogenicity• Endogenous pyrogens (e.g. IL-1, IL-6, TNFα, INF-γ)• Prostaglandin• Inducers (e.g. polyadenylic, plyuridylic, polybionosinic & polyribocytidylic acids)• Thermoregulatory centre disruptors (e.g. LSD, cocaine, morphine)• Uncoupling agents of oxidativephosphorylation (e.g. 4,6-dinitro-o-cresol, dinitrophenol, piric acid)• N-phenyl-β-naphthylamine & aldo-α-naphthylamine• Bacterial exotoxins (e.g. TSST-1, SEA, Spe F, Spe C)• Neurotransmitters (e.g. noradrenaline, serotonin)

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FDA Guidance

Latest guidance issued: June, 2016.

Probably going to update (long process)

Strong correlation between the FDA & ISO Tables A.1

FDA’s X & O are somewhat confusing. Any box with a mark in it needs to be addressed in the evaluation.

Evaluation reports really need to be very comprehensive documents, not just a list of tests that have passed.

Reminder: Device Specific guidance documents e.g. Medical Gloves

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Evaluation Outline

Device Definition• Intended use• Indications for use• Instructions for use• Principles of operation• Extent of use• Device categorisation

Physical Characterisation

Chemical Characterisation

Toxicological Risk Assessment

Biological Data

Interpretation of Biological Data

Overall Biological Risk Assessment & Evaluation

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fda and iso stars aligning on iso 10993 - brandwood ckc · james (morrison) has been a member of...

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