ISO 10993 – Biological Evaluation of Medical Devices: UpdateJoseph W. Carraway, DVM, MS

Scientific Director, Laboratory Services

NAMSA

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OverviewThis update is specific to the Technical Committee for the ISO 10993 series, TC194, meeting that was held in Japan on April 22-26, 2014.

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ISO 10993

ISO 10993 – Biological evaluation of medical devices

The primary guidance for biocompatibility testing Defines testing required based on end use of product Accepted by most industrialized countries Approximately 20+ parts Parts revised or updated approximated every 5-6

years

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TC194

TC194 is the committee charged with drafting and updating the ISO 10993 series of standards

Composition – 23 member countries Representatives from various interest Usually meet once per year Acceptance of new standard requires approval of

≥75%

US organizational structure & AAMI

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Part 1 – Evaluation and testing within risk management process Last revision in 2009 Reaffirmed by AAMI in 2013

ANSI/AAMI/ISO 10993-1:2009/(R)2013 Did not meet in Japan and currently no NWIP

in progress Will likely meet next year to start an update

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Part 2 – Animal Welfare Requirements

Last revision in 2006 Reaffirmed by AAMI in 2010 Working Group (WG 3) met in Japan

Will start a NWIP to make some updates Update bibliography Make normative for animal use in other ISO parts Other minor revisions

Had two presentations at a joint session, one from Germany on how the new EU Directives make animal studies more difficult to conduct

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Part 3 – Tests for genotoxicity, carcinogenicity & reproductive toxicity

Last revision in 2003 Reaffirmed by AAMI in 2013 Working Group (WG 6) met in Japan

Standard to release this summer/fall as FDIS Companion document, Technical Report (TR)

will release along with the FDIS TR contains detailed methods for common studies

Minor edits to the TR document made during meeting

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Part 4 – Selection of tests for interaction with blood

Last revision in 2002 ANSI/AAMI/ISO 10993-4:2002/(R)2013 &

A1:2006/(R)2013 Working Group (WG 9) met in Japan

Working draft (WD) document reviewed→CD Lots of discussion on tables of recommended tests Discussed recent FDA thrombogenicity test WS Discussion on round robin hemolysis testing and

possible in vitro thrombosis models Possible interim meeting

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Part 5 – Tests for in vitro cytotoxicity

Last revision in 2009 Reaffirmed by AAMI in 2014 Working Group (WG 5) met in Japan

Presentation from one lab comparing a qualitative elution method with the MTT

WG discussed possibly round robin evaluation to compare methods Assays proposed: MTT, Colony assay, Elution,

NRU and BCA

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Part 5 – Tests for in vitro cytotoxicity (continued)

Revision discussed Extraction vehicle changed (not water, DMSO) Extraction at 72 hr discussed Eliminate filter disc test Move MEM elution to annex as a detailed

method An additional table introduced for evaluation of

Quantitative methods (much like Table 2), but no consensus

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Part 6 – Local effects following implant

Last revision in 2007 Reaffirmed by AAMI in 2010 Working Group (WG 10) met in Japan

A CD went out for comments earlier this year Comments were discussed with major revisions

of wording on guidance for selection of implant intervals and combining Annex A into the body

New annex on brain implant Due to major edits, will go out as a CD again

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Part 10 – Test for irritation and sensitization

Last revision in 2010 Working Group (WG 8) met in Japan

Continuing discussion on in vitro irritation models

16 labs have agreed to participate in a RR study

Further discussion of the protocol for RR study No new work items other than round robin study

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Part 11 – Test for systemic toxicity

Last revision in 2005 Reaffirmed by AAMI in 2010 Working Group (WG 6) met in Japan

NWIP to update the standard Several minor edits Modification of Table 1 (group sizes) Discussion of dual extract model Discussion of tiered histopathology

Possibly submit as CD or even DIS

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Part 12 – Sample preparation

Last revision in 2012 Working Group (WG 12) did not meet in Japan No new items in the works

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Part 17 – Allowable limits for leachable substances

Last revision in 2002 Reaffirmed by AAMI in 2012 Working Group (WG 11) held a joint meeting

with WG 6 and 14 along with separate meeting Discussed establishing toxicological equivalence Variables to consider: endpoints, extent of

interaction of complex mixture (extracts), application to device types (small, SA)

NWIP requested

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Part 18 & 19 – Materials characterization

Last revision in 2005 & 2006, respectively Reaffirmed by AAMI in 2011 (Part 18) Working Group (WG 14) met in Japan

Reviewed comments to start a revision Develop Part 19 into a technical standard

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Part 22 – Nanomaterials

WG 17 has been working on this document for several years – still a draft

Questions on how much this will be used? Discussion on whether to propose as a:

Technical report (normative), or Technical specification (informative)

Will have an interim meeting

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NAMSA is now offering seminars on the entire ISO 10993 series Check out

ISO 10993 Biological Evaluation of Medical Devices Series

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