doc.nr. ISO/TC 194 WG15 Core Group N1
date 1999-01-13
item nr. supersedes document
Secretariat Nederlands Normalisatie-instituut
Kalfjeslaan 2 P.O. box 5059
Delft 2600 GB Delft
Netherlands
telephone: +31 15 2 690 390
fax: +31 15 2 690 190
Title: CORE GROUP
Secretariat: NNI (Netherlands)
Draft meeting report of December 2, 1998
The following ISO/TC 194/WG 15 experts were
present Barry Page, Mel Stratmeyer, Akitada
Nakamura, Jeremy Tinkler, Victor Dorman-Smith
and Jeannette van Loon.
WG 15/TF1 has prepared a draft report: Principles
and methods for immunotoxiclogy testing of
medical devices. This document is currently
being circulated among some experts for comments.
A meeting is planned for the end of January/beginning
of February to incorporate the comments.
The document will than be circulated to a
wider group of experts. This document will
be presented at the next WG15 meeting in
Copenhagen, probably as a draft technical
report.
In co-operation with TC/194/WG 1 and as discussed
at the WG1 meeting in Alexandria, Barbara
Krug and Jeannette van Loon have prepared
a questionnaire to solicit input from users
of the ISO 10993 series of standards. This
questionnaire has recently been put on Internet.
Dutch experts have been contacted to provide
comments on the readability. Some editorial
changes will be made and the questionnaire
will be send to CEN/TC 206, 1SO/TC 194 and
WG15 members, TC's dealing with vertical
issues, national standardisation institutes,
notified bodies, and authorities. The deadline
for response will be 2 months after receipt.
The results will give information on the
current interpretation of and problems with
the current ISO 10993 standards. It will
also provide input on the guidance to the
format of standards being developed by WG
15/TF2.
WG 15/TF2 has 2 tasks:
a. To prepare a format for guidance on the
application of the individual parts of the
ISO 10993 series of standards. This should
for instance include the background of the
development of the standards, limitations
of test methods proposed in the standard,
how to choose tests out of several choices
and how to interpretate the results.
b. To prepare a general guidance document
to the ISO 10993 series of standards. This
document should give information on the following
issues:
. what do we mean by evaluation of biological
safety
. what comprises an evaluation
. how do we document the evaluation
. how to include risk aspects
The first type of document can be used by
the different WG's to prepare a standard.
The second type of document should have a
more general character, which gives additional
information to the whole ISO 10993 series.
TF2 will continue working on both documents.
First drafts are planned to be available
at the beginning of April. Ron Brown and
David Gott were contacted to give input.
Ron Brown has developed a proposal for using
a conversion factor (CF) of 10 to estimate
toxicologically equivalent doses between
oral and parenteral tip, im, sc) exposure
(valid for long and short time data). A CF
factor of 30 seems to be appropriate when
converting oral to iv doses (at least short
term).
The proposal states that there would be no
need to identify and quantify compounds released
from parenteral exposure devices at doses
less than 0.1mg/day because such amounts
would not be expected to have toxicologically
significant effects.
ISO/TC 194/WGs 7, 11 and 14 should discuss
the implications for introducing such a threshold
within their documents. ISO/TC 194 should
recommend that work should be done on development
of a threshold for systemic toxicity.
During the ISO/TC 194/WG 14 meeting in London
a discussion took place on how to revise
the current Part 18 to include risk assessment
and clause 5 on Principles for judging Toxicological
Equivalency was incorporated. The ISO/TC
194/WG 15 core group generally felt that
clause 5 should be an informative Annex (or
somewhere else) rather than a normative text.
TC 194/WG 15 considers that this clause falls
out of the scope of part 18.
J. Lang will be asked to reconsider how to
proceed with ISO/DIS 10993-18 in view of
these comments.
For the evaluation of biological safety of
specific product groups more/other biological
evaluation tests might be necessary. The
problem is often that within the groups working
on vertical standards not enough expertise
is present on biological evaluation. So there
is a strong need for more effective liaisons
between ISO/TC 194 and vertical TC's and
the knowledge within those TC's that they
can make use of the expertise within ISO/TC
194.
Jeannette van Loon will contact the Chair
of ISO/TC 194, Wolfgang Muller-Lierheim on
his progress in meeting with the Chairpersons
of ISO/TC's dealing with vertical subjects.
As discussed at the plenary session at the
last ISO/TC 194 meeting, Dr. Muller-Lierheim
will discuss biocompatibility testing according
to ISO 10993 and how to incorporate more
specific requirements for biocompatibility
testing in vertical standards when this is
necessary. Akitada Nakamura mentioned that
in Japan during a revision of a vertical
standard a clause was included on biological
evaluation according to the Japanese standards
(which are comparable with the ISO 10993
series).
There is a list of standards recognised by
the FDA. This list does not contain all the
ISO 10993 standards. Acceptance depends on
a technical assessment of each standard and
this includes the confidence of the reviewers
in the standards. The fact that specific
standards are used and how often they are
used plays an essential role.
Within ISO/TC 210 a standard has been prepared
on risk management. Developments in the ISO
10993 standards should be in alignment with
developments in clauses on risk analysis,
risk management and quality assurance. At
the moment no reference is made to the ISO
10993 series in the risk management document.
There was a reference made in the EN 1441.
This should be aligned.
* TF1 will work further on the draft report.
Comments from experts will be collected.
The document will be presented during the
next ISO/TC 194 meeting in Denmark in May
1999.
* The questionnaire will be distributed to
CEN/TC 206, ISO/TC 194 and ISO/TC 194/WG15
members, TC's dealing with vertical issues,
national standardisation institutes, notified
bodies, and authorities. Results will be
presented at the ISO/TC 194 meeting in Denmark
in May 1999.
* Jeannette van Loon will contact Wolfgang
Muller-Lierheim on his progress to inform
TC's, dealing with vertical subjects, about
biocompatibility testing according to ISO
10993 and how to incorporate requirements
on biocompatibility testing in vertical standards.
* TF2 will continue to prepare a guidance
on the format of individual standards and
a guidance document which gives information
on issues like what do we mean by evaluation
of biological safety, what comprises an evaluation,
how do we document the evaluation and how
to include risk aspects.
* ISO/TC 194 should recommend that work should
be done on the development of a threshold
for systemic toxicity.
* J. Lang will be asked to reconsider some
aspects of ISO/DIS 10993-18. Clause 5 should
be an informative Annex rather than a normative
clause. A discussion on this should be initiated
in WG14 (in co-operation with WG11 and 7).
* A liaison should be created between ISO/TC
194 and ISO/TC 210 to align the content of
the ISO 10993 series and the standards written
on risk analysis, risk management and quality
assurance.
The next meeting of the WG15 core group will
take place in Copenhagen (half a day) before
the meeting of the whole WG15 (half a day).
The core group will collect the results from
the TF's and define further steps. This will
be presented to the whole WG15. The final
decisions and recommendations will be presented
to ISO/TC 194.
The meeting was closed at 16:00h.
The following documents were handed out during
the meeting:
. (Draft) Questionnaire on experiences with
the ISO 10993 series of standards
* Report of ISO/TC 194 WG15 TF1 Immunotoxicology
" Principles and methods for immunotoxicology
testing of medical devices".
* Modifications to the list of recognised
standards, Federal register/vol.63, no. 200/October
16, 1998
* Brief minutes of ISO/TC 194 WG14 in London
12, 13 October 1998.
* Letters from Akitada Nakamura and Ron Brown:
Chemical characterisation.
* Slides: progress report for WG15: Risk
Assessment-Based Approach for systemic Toxicity
Evaluation.