The ISO 10993 Biological Evaluation of Medical Devices Update covers the revisions/updates that were discussed at the TC194 meeting in Mishima, Japan in April of 2014.

1. ISO 10993 – Biological Evaluation of
Medical Devices: Update
Joseph W. Carraway, DVM, MS
Scientific Director, Laboratory Services
NAMSA

2. 2
Overview
This update is specific to the Technical Committee for
the ISO 10993 series, TC194, meeting that was held in
Japan on April 22-26, 2014.

3. 3
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

4. 4
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

5. Part 1 – Evaluation and testing
within risk management process
5
 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

6. Part 2 – Animal Welfare
6
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

7. Part 3 – Tests for genotoxicity,
carcinogenicity & reproductive toxicity
7
 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

8. Part 4 – Selection of tests for
interaction with blood
8
 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

9. Part 5 – Tests for in vitro
9
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

10. Part 5 – Tests for in vitro
cytotoxicity (continued)
10
 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

11. Part 6 – Local effects following
11
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

12. Part 10 – Test for irritation and
12
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

13. 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
13

14. Part 12 – Sample preparation
 Last revision in 2012
 Working Group (WG 12) did not meet in Japan
 No new items in the works
14

15. 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)
15
 NWIP requested

16. Part 18 & 19 – Materials
16
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

17. Part 22 – Nanomaterials
 WG 17 has been working on this document for
17
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

18.  NAMSA is now offering seminars on the entire ISO 10993
series
 Check out ISO 10993 Biological Evaluation of Medical
18
Devices Series
 For information about the Biocompatibility services NAMSA
can offer you
 Visit our Biocompatibility page
 For additional information
 Download our brochure on Biocompatibility
 Contact us at clientcare@namsa.com.