OECD Webinar | Training and orientation on validation of methods at the OECD

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orientation on validation of Methods του ΟΟΣΑ.

Είμαστε εδώ στις 14 Νοεμβρίου 2023

2023 and my name is Anon uh and uh I

will give you um just uh one

introductory

slide uh about the objectives of the

this

webinar uh and uh then we will have our

speaker for today miam uh

Jacobs uh first the objectives of this

webinar of first to uh clarify terms

used in the context of validation for

test guidelines development

ATD uh then uh another objective is to

explain

why validation of methods is important

in the context of test guidelines

development uh also uh one objective is

to guide laboratories embarking on

methods

validation uh on how to approach

validation and evaluate uh method

Readiness and how uh relevance and

reproducibility of methods uh can be uh

tested

evaluated and then we will have uh a

moment in this webinar for a Q&A

session uh so you are most welcome to

use the Q&A box uh we will be posting

material resource in the chat uh but the

chat is not accessible to participants

only the the Q&A uh boxer so we will be

selecting uh questions from the Q&A and

raising them to uh uh our speaker and

anyone who would like to uh to

answer uh so also please note uh this

webinar is recorded and it will be made

publicly uh available as a replay on the

o

website so without further Ado I'm going

to hand over um the presenter wres to

our speaker for today uh Miriam Jacobs

uh who is uh uh the national coordinator

for the test guidelines program in the

United Kingdom and Miriam can you hear

us yes I can hear you can you hear me

yes very well

great okay I'll start sharing my screen

now you can see your screen y

okay okay welcome everybody um this is

really a preamble for the workshop that

we will be having on the 14th and 15th

of December uh later this year um and

this is just to get common understanding

with respect to um validation

terminology and um some PR principles

and considerations that that uh are

related to that

so I'm going to go to the next slide

now um so here's an overview of the talk

can you see my slides

okay yes very well yeah okay great um so

there are five aspects to this talk the

first part is to discuss why uh we want

to have uh validation for regulatory

purposes why it's important um so the

per first part is uh looking at the

crisis and reproducibility that we have

and the relevance of to the oecd test

guideline program of the mutual

acceptance of data principle the second

point we look at an overview of

validation terminology focusing

particularly on prospective validation

and more really the early stages of

validation the third aspect we'll look

at examples of what can go wrong and why

and how we can recover from that the

fourth one we'll look at what you can do

um very early on in the process and

finally we'll have some questions and

answers uh questions and discussion

session so the first one crisis and

reproducibility that there's a lack of

reproducibility in research is really

very well known um there was a survey

conducted by nature and published in

2016 where where they reported amongst

their respondents um More than 70% of

the researchers tried and failed to

reproduce other scientists experiments

and many couldn't reproduce their own

experiments and if you have a look here

um unfortunately for us as as working in

toxicology and and biology and

chemistry these were the worst um uh

failures really in chemistry and biology

so um in

biology uh here you can see more than

60% um failed to reproduce their own

experiments and this was from a sample

of over

1,500 um researchers and it was just on

the basis of a brief online

questionnaire but it's really quite

shocking and that really goes to show

how um

uh how one needs to be very careful with

literature

reports

furthermore um in another report uh from

Arrington atal in 2021 they looked at

193 experiments just to look at where at

the protocol status where they were

fully described and what the barriers

were to conducting

replications in the experiments

reported and in this

um uh report you can see here that very

often there was very little help from

the authors when they tried to find out

more about the protocols um in most

cases clarifications were needed often

reagents were offered up to 50% but

often not um and then codes were

sometimes shared but often no

response um and data sharing as well was

really

Limited

something that uh the jrc have reported

on and and given presentations on

recently um uh this promap promoting

reusable open methods and protocols um

so there's a nice pre-print from um

safia Batista leet um online where they

give recommendations on how to report

protocols failure in protocols and

reproducibility in protocols is the

first step in the validation process

that's necessary for improving

reproducibility of

results and being able to transfer the

test method it Fosters confidence in

results that you can obtain with a

certain method and it really facilitates

the use in the weight of evidence Hazard

and risk

assessment and this is also

um supported by an oecd call for Urgent

mobilization of national and Regional

resources to support the valid

validation of new methods for the safety

assessment of of of

chemicals with the need to be able to

have good validation and good

information around first first line um

protocols the mutual acceptance of data

and the practices regards uh the OCD

test

guidelines is the next key element um to

begin

with uh that we need to consider

reproducible data is essential to

support the international Mutual

acceptance of data principle for all

oecd member country chemical regulatory

uh

systems it's critical

for um ensuring there are no trade

barriers it's critical for ensuring

reproducibility of data transfer of data

and the next few slides will'll go

through these in more

detail the reason it was created um was

really in response to fraudulent studies

submitted to Regulators uh the Mad

framework was constructed to ensure the

generation of highquality and reliable

non-clinical test data for regulatory

purposes good lab practice provides the

quality standards and the test

guidelines provide the scientific

standard regulatory author authorities

receiving the data under the mutual

acceptance of data agreement under the

orices of the oecd know that particular

quality and scientific standards have

been followed and they know then that

they don't have to re-evaluate the test

protocol to determine its robustness as

it has a consensus by countries by the

Tes guard guideline program and part of

that approach is really is truly by

consensus every country every member

country needs to agree so it's not by

majority what documents are covered by

the mutual acceptance of

data the OCD test guidelines and the OCD

principles for of good lab practice are

covered by mad they those are the only

documents that are covered by mad all

the other oecd documents are not

guidance documents describing certain

test methods in the series and testing

and assessment aren't covered um an

additional uh in and additional

documents such as detailed review papers

validation reports peer reviews they're

not covered by

mad guidance documents can often be

[Music]

um uh validated test methods um but they

are examples where the scientific

standard wasn't agreed by consensus in

the working group of national

coordinators

and it's considered that the scientific

standard for Mutual acceptance of data

hasn't been

met at that time but that doesn't mean

to say that the guidance documents for

test methods um can't be adopted as test

guidelines at a later date when more

information and more uh relevant

information is available to show

reliability and

reproducibility what does the oecd

council act on the mutual acceptance of

data say it says that the data generated

in the testing of chemicals in an oecd

member country in accordance with oecd

test guidelines and oecd principles of

good lab practice shall be accepted in

other member countries for purposes of

assessment and other uses relating to

the protection of man and the

environment however the data

requirements are government

prerogatives interpretation of test

results is a government

prerogative there can be there is no

need for any repeat testing for the same

data

requirement however acceptance doesn't

to automatically mean the use of the

data by that

country the regulatory use needs data

requirements are country prerogatives

the test guidelines are intended

intended to address and respond to the

existing or foreseeable regulatory needs

in relation to hazard

assessment and the kind of regulatory

needs um that the test guidelines

address um I'm sure you're all very

familiar with these determination of

physicochemical properties environmental

fate and behavior properties chemical

mechanisms of action and

bioactivity um absorption distribution

metabolism and excretion data for model

building toxicity data for screening and

priority setting toxicity data for

identification of a Hazard and or Target

organ and toxicity data for

characterizing a hazard and residues

chemistry

data although data requirements are

country prerogatives and mad is about

avoiding repeat testing if data

requirements diverge extensively between

countries Mutual acceptance of data

principle will erode as test guidelines

data will not be accepted across

countries having different

requirements there therefore the more

compatible and similar the data

requirements are between countries the

more beneficial mad will be

globally and although the interpretation

of test results is a government

prerogative the test guidelines often

integrate the transformation of the raw

experimental data for example through

prediction models data interpretation

procedures to generate a retest result

that addresses more directly a

regulatory need

for example the identification of a

hazard the data transformation and

interpretation procedures implemented in

the test guideline are the outcome of

country's agreement to do so in order to

generate meaningful data and reduce the

room for misinterpretation and maintain

a common Level Playing

Field but it Remains the member

country's prerogative to use the

Standalone test result to to satisfy a

data requirement or to use the test

result de with other sources of

information in combination with other

levels of interpretation or criteria

that meet a country specific regulatory

need and to not use that test result if

their data requirement cannot be

satisfied with that test result alone or

in

combination so that's uh part one um

regarding the crisis in reproducibility

and uh the Mad principle the mutual

acceptance of of data principle um now I

want to move to the section two giving a

brief overview of validation

terminology here I want to look at

standard perspective validation um other

aspects to consider Al also highly

relevant but not not going into any

great detail here our retrospective

validation test guideline revision and

test guideline

augmentation so retrospective validation

for example can happen where if you have

uh a lot of relevant data and you want

to go um uh and uh provide a data

package to show that the test method or

improvements in a test method um can be

done on the basis of data collected

historically and and this is happened

several times for example for inv Vivo

test guidelines um there are a couple of

of examples recently where where we have

done some retrospective

validation test guideline revision also

um Can Happen uh with respect to um more

data being provided um being able to

expand the chemical applicability domain

for example or test guideline

augmentation um when uh there might be a

specific element of a test guideline

that can be expanded further in a

particular direction and the evidence

has been collected to be able to show

how it can be expanded or where a test

guideline may have fail to become

adopted and it because it needs a bit of

further

work um and I will give one example of

of of of that

later uh but mainly the next few slides

really focus on standard perspective um

prevalidation

and these are the main resources that

we're using so the OCD um guidance

document 34 uh published in 2005 and

whilst it is being

revised uh at the moment and work is on

foreseen really for the next year or so

um

it's the basic uh requirements of

validation um I don't imagine will uh uh

change that much not in relation to to

um uh what we're considering here and

then the other resource is um the paper

from efam published in 2004 that was

very much part of this guidance document

205 at the time a modular approach to

the Ean principles on test

validity um these are the modules um so

starting first of all with a test

definition that is what are the

biological process and endpoints that

are modeled by the test system the

second one is the Within lab variability

or reproducibility can the results be

reproduced or replicated in house by a

different operator and over different

part time periods transferability can

others run the method successfully is

the pro protocol sufficiently

detailed number four is the between lab

variability can the results be

reproduced or replicated by others and

um how accurate is it um what is the

sensitivity and specificity of the test

method

um predictive capacity do the

experimental results match with uh

usually literature-based

expectations sometimes in Vivo based

expectations it varies and broader

scientific

consensus what is the chemical

applicability domain what can or can't

be tested um what are the performance

standards what

parameters can be developed that can be

expected from this test method when it's

working as expected based upon on the

historical data and this includes

reference chemicals to demonstrate

demonstrate equivalence in performance

for new me2 test systems compared to the

those that have been previously

validated so these are different modules

and one can come in and out of the

different modules it's not rigid um and

this is the uh from the Harang AEL paper

showing how they're constructed um and

how the mod modes lead when they're

successful they get um discussed by the

validation Management Group lead for and

then they can be taken forward for

peerreview by ex various expert panels

wherever they might be um whether that's

uh esac the European um well efam

scientific advisory committee or efam or

jfam or

oecd um at this

level so really I'm just going to talk

talk a little bit more about these four

modules

reproducibility uh a typical validation

management structure um would be having

a study management team here at the top

independent chemical selection and

expert review um to the side independent

statistical analysis um and then a

number of Labs at least two um sometimes

three and often more it really

depends

for the test definition the objective is

to define the scientific purpose

describe the mechanistic basis

characterize the cell line um there have

been quite a few um uh issues arising

out of cell line characterization or

lack of characterization that I will

mention later the limitations of the

test method the experimental design and

the optimized protocol which includes

the necessary

sop the specifications of endpoints and

endpoint measurements and the derivation

and expression of results and

interpretation um of a preliminary

prediction model uh the prediction Mo

model often needs to be revised um uh on

the subsequent steps that uh uh follow

in the prevalidation aspect and then

there need to be adequate controls

vehicle controls positive controls

negative controls

to begin with also one has requirements

for the initial training or proficiency

set of chemicals and these need to be

well-known chemicals to cover the

relevant mechanism and mode of action of

the test method and with

negatives with the second module one

starts to look at the variability over

time and addressing variability for

different operators but using the same

lab laboratory

setup um and the proficiency set of

chemicals um generally expands uh these

are the most obvious chemicals due to

Quality and quantity of reference

data um addressing the mode of action

the relative potency if possible

physicochemical properties and

appropriate negative controls

availability and representatives of

relevant uh chemical classes for that

particular test

method the s um includes all of these

aspects listed here um and it needs to

be extremely well

detailed

um the first step uh with the protocol

with the

transfer um is often the step where

hiccups are found um Everybody every

Everybody tends to think that that

everybody else does the same sort of pro

process and sop and lab practice that

they do but it really isn't the case so

basic assumptions also need to be

included and these are the sorts of

things that we've really learned over

the years it's much better to include a

lot more detail than less to be able to

ensure that the lab uh that the test

method transfers to the lab

successfully for the module three with

transferability um the robustness of a

test assessment of reproducibility of

data in a second lab is assessed and the

prail practicability the successful

transfer and this is an iterative

process um and with amendments on on the

test definition and the protocol as

needed as the data is generated problems

arise and as they resolved um the

clarifications need to be

made and for the proficiency T of

chemicals now as we move to this they

need to be well understood to cover the

relevant modes of

action for the between lab variability

the objectives are the assessment of

reproducibility of the experimental data

in two to four labs and sometimes more

um the training and proficiency set of

chemicals need to be the most obvious

chemicals again um mode of action

potency physicochemical properties

negative chemicals and availability

considerations there's a slide coming up

that gives a a bit more of an overview

um more detailed overview shortly here

it

is so the Essential Elements for

chemical selection are to address the

sector

diversity um to have a structural

diversity to have a good number of

negatives at least 25% and ideally 50%

and it's actually this data that's often

the hardest to find the negative data

because it's it's often not

published um ideally as we try to use uh

nams and vitro test methods um more in

iarta and defined approaches uh the more

we have information on the range of weak

moderate and strong activity rather than

uh yes no response um the more the

greater applications that we we can use

that test method for um but it's not

always uh it really depends on the

quality of the data that's generated in

the in the study

um sometimes it's just not possible to

do that not at the early stages anyway

ideally also you have uh human invivo

data but um obviously for some classes

of chemicals such as uh pesticides um

it's generally quite unlikely to have

this sort of uh um concentration dose

response information um to a sufficient

degree whereas one might have it for

pharmaceuticals the Pharmaceuticals may

not be um holy relevant to the wider um

chemical um uh world that the test

method is intended to to be looking

at and then there are limitations and

restrictions on International um

transport and use that we need to

consider um uh chemicals that are on the

Stockholm pops convention that are

banned that shouldn't be really used

anymore um they ought to be considered

chemicals with abuse potential it's very

hard to import or export them in a

validation study so for example um well

drugs phob barbital cannabinoids

anabolic steroids and so on and then the

availability it can be very problematic

to have a chemical that it's really rare

and hard to find and there's no

long-term manufacturer or if it's really

expensive um it it becomes really

impracticable impr practical so these

considerations need to be uh included in

the chemical

selection

there is no fixed number of chemicals it

really needs to be on a Case specific

basis depending on the um literature and

data that you have on which you can base

your uh proposals for the the chemical

selection list and it's often a very

good idea to um get that list that you

derive get it peer-reviewed

independently um to and get Buy in um um

as you go forward and that's certainly

something at the oecd level with the

validation management groups and the

expert groups it's really good to have a

good discussion with them um if possible

at the outset to resolve any issues that

might come

later

whoops um designs of a validation study

so um what is not a good idea is to have

loads of Laboratories and just a handful

of chemicals that are being tested um

because then you're not really

demonstrating the applicability the

chemical applicability of the of the

assay however um sometimes you don't

really have a choice about uh the

validation Lab Partners um if if it

depends really on the funding stream but

certainly uh for example if a cro is

interested in participating in a test

method because they want to demonstrate

um well they want to grain gain skills

in in running that assay and they will

have a centel um that will want to use

it um it's not really

uh I mean if they want to participate

it's uh really to be encouraged so

sometimes one cannot Define the number

of uh or or number of Laboratories uh

fully upfront but as long as you have

um a minimum of of three um it's it's uh

encouraged in the expert

groups um for past validation studies

for example the situation on the left

has often been the case where a number

of different chemicals are run in all

three Labs but it was Al it's also been

commonly done to stagger um or have

phases in the validation study so that

the you have your first core uh uh test

chemical or proficiency chemicals in the

labs that are run by everybody and they

all demonstrate that they can reproduce

them well um and then you can expand

your chemical chemical applicability

doain by testing in a number of

different Labs or very often the lead

lab will often test a lot more of the

chemicals um to be able to demonstrate

the chemical applicability domain range

independent statistical support is

needed for within lab variability and

between lab variability and predictive

capacity

um and the TR traditional

process

um uh can take uh well this slide has

been used this interpretations of these

slides have been used um a lot um to

show the length of time that can it can

take um but sometimes it's been used to

show that it can take a very long time

and that's really not necessarily the

case um research and

development can take a great many years

um the prevalidation process um

can include an awful lot of

optimization of that research and

development uh process and sometimes it

sort of goes backwards and you're really

doing

R&D um but on average it can take two

years perhaps sometimes it will take a

bit more especially if there are

problems

arising the validation stage um the

getting to full validation where you

start to have uh blind chemicals um

which I'm not discussing any detail in

this one um that can take a year or it

can take a lot more it really um it it

will really depend on a case-by casee

basis the peer review uh independent

peer review can take a year and then the

oecd regulatory acceptance usually takes

around two years but it can take more

for a number of different reasons which

we will come to in the in the next

section and then um uh acceptance and

writing in to different regulatory

jurisdictions um often happens following

the oecd regulatory

acceptance so so the first stages here

um with the R&D um can happen at the

academic uh uh industry um uh um side um

or agency side as well um and then

really ideally uh these validation steps

um sometimes they are started

independently or by industry groups or

academ MC groups or so but they can

start to enter the um OC OCD test

guideline program at the pre valid valid

prevalidation stage and um it's really

good if if projects do enter um at that

stage to get support from the

international experts and nomin expert

nominations from the working group of

national coordinators that at that sort

of State

agage um because then you know you're

going to be resolving problems that

might come up later with respect to

regulatory acceptance you have a chance

to to be able to address those um and

get

support intellectual property um has

become a bit of a uh an issue also um in

the oecd test guideline program as we

have moved more to inv vitro test

methods um there often are intellectual

property um and patent issues around

some of the test methods it's not a

problem at all now um and uh specific

guidance has been developed regarding

these elements in oecd desk guidelines

it's important to declare whether the

test method contains predicted elements

right at the outset when the project is

submitted to the ACD test guideline

program it needs to be explicitly

indicated and the means foreseen to make

these protected elements available to

users if their method becomes a test

guideline so it's not a handicap it just

needs to be

transparent

um the test method needs to ideally it

will address high priority needs for the

test guideline Pro program um and uh a

guidance document for the development of

oecd guidelines for the testing of

chemicals um uh from

2009 states that

um only that the development or update

of a test guideline is Possible only

when the proposed test method or

modifications to the existing test

guideline has undergone a critical

appraisal concerning its validation and

Regulatory

acceptance including where feasible and

relevant an interlaboratory comparative

study I a ring test or something like

that describing the performance of the

test method and then the current

guidance document um um on validation

from

2005 also states that test method

validation is a process based upon

scientifically sound principles by which

the reliab reliability and relevance of

a particular test approach method or

process

is established for a specific

purpose so now this is the one slide

coming up um giving examples of what can

grow go wrong and why um but this is

what I will spend most of the time

on so some common stumbling blocks or

hurdles in the oecd test guideline

process first of all they can arise with

reproducibility and transfer of the test

method um and experimental Corrections

need to be conducted and there there may

be missing characterization of the test

method and its cell line these have

happened in quite a few um examples of

adopted test guidelines as well as those

uh test methods that have failed uh to

become

adopted so for example one of one of the

um endocrine active uh um test

guidelines early on um uh the test

method um failed to be reproducible in

another lab um even by the test method

developers and the cell line and the

constract had to be changed but then

ultimately it ended up being a

successful uh successfully adopted as a

test guideline it it worked it it was

fine um in another case we've had a um

cases a case of

uh uh well to very early on we didn't do

suff efficient characterization of the

invitra test methods or the cell line

and we had an instance um where another

um test method um was found not to be

the cell line that it was stated to be

um during the validation and at the upon

adoption and it was later found out by

another group um that the

characterization was wrong and the cell

line had been

contaminated the validation had been

successful the cell the test method had

been adopted at a test guideline and um

a clarification sentence was uh provided

within that test

guideline sometimes the material

supporting the performance or validity

of the test method is not

adequate um and so the greater detail

given the better for all of the

evaluations the references the

validation reports and making sure that

they're all accessible some times there

is a lack of adherence to validation

criteria um sometimes there can be

issues regarding reference or

proficiency chemicals so here an example

is the draft sip induction test

guideline where um although successfully

validated uh by the uh the jrc the wnt

wanted to see an expansion of the um

reference uh chemicals um so work on

that is ongoing at the moment but um and

that's it's resolvable um and there were

there was a very strong justification

for the uh chemicals that were used in

the original validation because they

were the only chemicals that were human

data was

available

um so this has slowed down the adoption

unfortunately of this particular test

guideline but it's

resolvable other

um cons considerations might be a poorly

written draft test guideline or

sometimes to be perfectly honest the

adopted test

guideline we find out later it's not

sufficiently clear um for the end users

and we need to go back and revise the

data interpretation procedure we need to

clarify the language but it's really

only after trying it and having it out

there um that we are able to

do those Corrections and we've had to do

that a couple of times recently with the

TG uh 456 for

example sometimes the there's a changed

regulatory purpose of a test guideline

or it's not clearly defined and

increasingly the WT really does want to

see um a clear indication of the

regulatory purpose of the test guideline

and how it can be used how it can fit it

um particularly now for inv vitro test

methods for

nams sometimes there's a low level of

commitment by the lead country um there

can be a staff change or reduction in

res resources and the project needs to

be taken over uh by another country or

or it just gets put to one side for a

year or two until someone is willing or

able um to take the project over or it

will get ultimately dropped if no one is

willing to take it

over um and you know we all move jobs um

uh resources change

so it's it's uh it's it's a realistic um

uh problem that that

occurs sometimes a project proposal is

discussed at the uh working group of

national

coordinators and um further work is

really needed to explore issues within

that work that proposal there might be a

need for an expert consultation then

might be a need for a stronger evidence

base for the proposal and a detailed

review paper might be requested first

and that has happened several times as

well with the test uh test method

proposals going forward to the

w&t so we have that um at the moment for

um uh just thinking of some

um uh with a Maps test for example uh

we've been doing a more detailed report

and having an expert cons independent

expert uh consultation for a project on

the on the work

plan sometimes things go arai because um

of how the expert groups are working

there can be um insufficient briefing or

management of or listening

uh to new review experts or national

coordinators and the interactions there

or the recordkeeping not might not be

sufficiently detailed enough and so

keeping really good records of all of

the record of the discussions and

ensuring uh agreement on those records

as one progresses really makes a

difference uh in achieving

efficiencies and briefing uh new new

reviewers that may may join um because

often there can be circular discussions

that start to occur um as uh uh uh ideas

or concerns expressed earlier and dealt

with um get reiterated um by people who

were not in experts who were not

involved in the work

previously sometimes

um uh it's uh the National

coordinators

don't consider that the test method

addresses a key endpoint Gap or there

are a lack of lead countries coming

forward to address an oecd identified

cap

so for example with a thyroid um

validation effort at the moment on going

um um being led by the jrc but with

there the discussions at the oecd expert

group um countries do need to take a

lead and come forward uh to address to

to to address these assays and these are

assays that were first identified um

over 10 years ago in an oecd thyroid um

scoping document so the delay there has

really been a lack of countries coming

forward to do the work um the jrc came

forward and have done uh um the

preliminary or the prevalidation work

for

a large number of the assays I think 17

or 18 or more um but still uh more

commitment is needed from from lead

countries to take forward some of the

these work these these pieces of work um

and some of them are so for example

Peppa are taking forward at least two I

think of the thyroid assays now but more

countries are needed to take these

forward sometimes there are simp it's

simply conflict of regulatory needs

across R different

countries um and that means that the the

project won't be taken

up sometimes also there can be cultural

safety differences or there can be

issues um around things that you think

are easily available so for example

human serum use in invitro test

guidelines um a UK project proposal that

was made several years ago um uh a cro

came forward and um um uh was able to

adapt some of the skin sensitization

assays

442 um for human serum use and they had

obtained the serum from

Sigma it was openly available it

appeared to be uh

regulated um but actually it turned out

not to be um and the issues that arose

around the discussion at the w&t table

really start started to unpe unpeel or

expose a lot of different issues that we

needed to consider when using human

tissue including competition with

medical use um as well as exploitation

of of donors for example so that led to

a much deeper piece of work and in

including um um workshops to to address

those those problems so and these things

are not obvious when they they first

come so and they need to be resolved um

as we go through the process to be able

to achieve uh full adoption as a test

guideline under mad so there can be this

and here's just this is just a start of

a list really of really common um or

they not I wouldn't say they're really

common but they really concrete examples

of where there have been um

stumblings uh with respect to test

method adoption at the

oecd now let's look at practical

purposes what can be done right to begin

with

um

really it's it's really if validation

needs can be incorporated right at the

outset into research outputs the more we

do that as we develop our work in the

R&D side as it comes as the test methods

come through to um optimization the more

that we have a detailed description of

the

SOP the more we publish the data

associated with the result um the more

that the DAT data is findable accessible

interoperable reusable not as a PDF but

in a machine readable

format the more efficient the whole

process will become and the more

transparent it will become which will

increase Trust there is insufficient

space in scientific literature

manuscripts for all of this sort of

information but there are um websites

where one can um work on protocols

together um there is uh I mentioned

right at the outset this um prom map um

initiative and guidance um developed uh

by staff at the um

efam

um this is most critical step to really

uh

get on top of um right to begin with

with respect to the smooth operation of

of

validation um and the metha transfer is

often delayed at this

step and here are just a list of

resources that one can go to to um

improve the quality of this the SOP and

the data generated so I've just taken

I've taken mainly European examples

um um and oecd examples here and there

are there are a lot more internationally

but here here is just a

selection um the pepper platform has

particularly uh provided some very nice

uh guidance on how to um uh report test

method Readiness for example and there

are a number of different guidance

documents at the oecd the is

critical for test methods

developers um GD 211 for describing

non-guideline inv vitro tests and that's

the basis of uh of these uh test method

Readiness um

um uh

spreadsheets um reusable and open

protocols

um I'm so so on so there's a whole a

whole uh uh list of resources here to to

make use

of and with that thank you for your

attention and um we can have some

discussion and questions

now