Amendment_1_Genetox_SOW_Dec2012.pdf

PDF 179 KB Posted Dec 4, 2012

Attached to: Genetic Toxicity Testing Services for the NTP Federal contract opportunity
Solicitation number: NIHES2013158
Issued by: Department of Health and Human Services National Institutes of Health

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Amendment 1 Genetox SOW December 2012

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Amendment_1_PACKAGING_AND_DELIVERY_OF_PROPOSALS.pdf	PDF	Dec 4, 2012
Amendment_00001_to_RFPNIHES2013158.pdf	PDF	Dec 4, 2012
RFPNoNIHES2013158_SOW.pdf	PDF	Nov 16, 2012
RepsAndCerts.pdf	PDF	Nov 16, 2012
PROPOSAL_INTENT_RESPONSE_SHEET.pdf	PDF	Nov 16, 2012
PACKAGING_AND_DELIVERY_OF_PROPOSALS.pdf	PDF	Nov 16, 2012
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Genetic	Toxicity	Testing	Contract	Attachment	3
Solicitation	no:	NIEHS2013158		December	2012

STATEMENT OF WORK

Independently

and

not

agent

the

Government,

the

Contractor

shall

furnish

services,

qualified

personnel,

material,

equipment,

and

facilities,

not

otherwise

provided

the

government

under

the

terms

this

contract

needed

perform

the

work

set

forth

below.

This

contract

will

provide

support

the

government

examine

variable

number

chemicals

annually,

depending

the

needs

the

government

and

available

funding,

for

induction

genetic

changes

(e.g.,

mutations,

chromosomal

changes,

DNA

damage)

animal

human

cells.

Approximately

vivo

assays

may

conducted

annually.

The

contract

will

also

provide

the

government

the

capability

examine

chemicals

for

ability

induce

genetic

changes

(e.g.,

chromosomal

changes,

DNA

damage)

cultured

mammalian

cells.

addition

eukaryotic

test

systems,

the

contract

will

provide

the

capability

test

approximately

chemicals

per

year

for

induction

gene

mutations

bacterial

tester

strains.

The

Contractor

must

have

the

capability

conducting

the

assays

described

this

Statement

Work

(SOW)

site.

The

number

and

type

assays

may

vary

from

year

year,

and

the

contractor

must

have

the

ability

conduct

multiple

assays

the

same

time.

Chemicals

tested

for

potential

genotoxicity

under

this

contract

will

supplied

the

COR

through

the

NTP

chemistry

contracts

will

identified

the

COR

for

purchase

the

Contractor.

The

Contractor

shall

perform

all

work

accordance

with

standard

operating

procedures

(SOPs)

and

test

article

specific

protocols

approved

the

COR.

Standard

protocols

for

each

assay

type

must

place

before

testing

initiated,

and

shall

approved

the

COR

within

days

after

the

award

made.

For

each

chemical,

the

COR

will

identify

the

specific

assays

performed.

Not

all

chemicals

test

articles

will

tested

every

assay.

The

Contractor

shall

have

written

Quality

Management

Plan

available

for

inspection

the

COR

(see:

http://www.epa.gov/quality/qmps.html).

The

Contractor

shall

keep

all

laboratory

records

accordance

with

FDA

Good

Laboratory

Practice

Regulations

(originally

published

Federal

1978,

pp.

(21

CFR

Section

58)).

The

Contractor

shall

perform

all

work

manner

compatible

with

the

attached

NTP

Health

and

Safety

Minimum

Requirements.

The

COR

will

determine

the

test

articles

examined

and

the

assay(s)

used.

Test

protocols

and

protocol

amendments

will

approved

signature

the

Genetic	Toxicity	Testing	Contract	SOW	–	Attachment	3	2
December	2012

COR.

The

COR

may

change

the

protocols

keep

current

with

state

the

art

technology

improvements/changes

assay

design,

meet

specific

Program

needs.

Assay

types

shall

include

but

are

not

limited

to:

Assay	1	–	in	vivo	micronucleus	assay,	exposures	conducted	at	an
alternate	laboratory	or	site

The

Contractor

shall

measure

micronucleated

erythrocyte,

reticulocyte,

and/or

lymphocyte

frequencies

coded

bone

marrow

blood

samples

obtained

from

animals,

typically

mice

and

rats,

occasionally

humans

exposed

chemical(s)

alternate

laboratory

site.

Typically,

the

animal

exposures

will

conducted

NTP

contract

laboratory

that

conducts

short‐term

toxicity,

2‐year

cancer

bioassay,

other

studies

rodents.

Blood

samples

from

these

animals

will

collected,

chilled,

and

packaged

for

overnight

shipment

cold

packs

the

Contractor.

necessary,

expedite

receipt,

the

Contractor

may

choose

collect

the

packaged

samples

the

courier’s

facility

and

transport

them

the

Contract

Laboratory

ensure

sample

quality.

Upon

arrival

the

Contract

Laboratory,

the

samples

will

processed

and

stored

minus

80°

freezer.

Typically,

samples

will

evaluated

using

flow

cytometric

procedures.

noncommercial

collaborating

laboratory,

within

outside

the

NIH

(e.g.,

NCI,

CDC,

DOD)

typically

provides

coded

human

blood

samples

evaluated

for

micronuclei.

personal

identifiers

shall

attached

any

human

samples.

Assay 2 – in vivo micronucleus assay, exposures conducted by the Contractor

The

Contractor

shall

measure

micronucleated

erythrocyte,

reticulocyte,

and/or

lymphocyte

frequencies

blood

(or

occasionally

bone

marrow)

samples

obtained

from

animals,

typically

mice

and

rats,

exposed

chemical(s)

the

Contract

Laboratory.

Treatment

regimens

and

sample

times

will

determined

the

COR.

occasion,

directed

the

COR,

other

dividing

cell

populations

may

assessed

for

frequency

micronuclei.

Procedures

shall

consistent

with

those

described

OECD

Guideline

474.

Samples

shall

collected,

processed,

stored

necessary,

and

evaluated.

For

these

in‐house

studies,

the

Contractor

shall

perform

dose‐ranging

studies

unless

the

COR

instructs

otherwise.

The

Contractor

shall

perform

all

assays

using

appropriate

solvent

and

positive

controls

(where

appropriate).

Flexibility

methods

data

collection

(slides

flow

cytometry)

requirement,

although

emphasis

will

the

use

flow

cytometry

for

evaluating

frequency

micronucleated

cells.

Genetic	Toxicity	Testing	Contract	SOW	–	Attachment	3	3
December	2012

Assay 3 – in vivo comet assay

The

Contractor

shall

quantitate

DNA

damage

(e.g.,

single

and

double

strand

breaks,

oxidative

damage,

alkali

labile

sites,

and

DNA‐DNA

and

DNA‐protein

crosslinks)

using

the

single

cell

gel

electrophoresis

(comet

assay)

method

tissues

designated

the

COR

animals,

typically

mice

and

rats,

occasionally

humans

exposed

chemical(s).

personal

identifiers

shall

attached

any

human

samples.

Exposures

may

occur

either

alternate

laboratory

site

(e.g.,

NTP

contract

laboratory),

for

laboratory

animals

only,

the

Contract

Laboratory.

Treatment

regimens

and

sample

collection

times

may

vary.

Examples

tissues

cells

that

may

examined

for

chemical‐induced

DNA

damage

animals

include

but

are

not

limited

blood

leukocytes,

liver,

kidney,

stomach,

ileum,

colon,

and

brain.

Human

samples

would

limited

peripheral

blood.

Single

cell

suspensions

samples

generated

alternate

laboratory

shall

prepared

that

laboratory

and

frozen

minus

80°C

balanced

salt

solution

supplied

the

Contractor.

Subsequently,

the

coded

samples

shall

shipped

overnight

courier

the

Contractor;

the

Contractor

shall

collect

them

the

courier’s

facility,

transport

them

the

Contract

laboratory,

catalogue

the

samples,

and

store

them

minus

80°C

freezer

until

they

are

thawed

and

evaluated.

Tissue

samples

obtained

from

animals

exposed

the

Contract

Laboratory

shall

prepared

appropriately

(methods

differ

tissue

type)

and

either

analyzed

immediately

frozen

minus

80°C

for

future

analysis.

Slides

shall

prepared

and

electrophoresed

following

published

methods.

image

analysis

system

shall

used

locate

and

evaluate

cells

for

DNA

damage.

Electronic

images

each

cell

that

evaluated

shall

stored.

There

additional

requirement

that

the

Contractor

perform

cytotoxicity

measurement

for

tissues

selected

for

DNA

damage

assessment.

Assay 4 – combined in vivo micronucleus/comet assay

The

Contractor

shall

simultaneously

measure

micronucleus

frequencies

erythrocytes

and/or

reticulocytes,

and

DNA

damage

tissues

selected

the

COR,

laboratory

animals

(typically

mice

rats)

exposed

chemical(s)

the

Contract

Laboratory.

This

combined

micronucleus/comet

assay

shall

adhere

published

protocols

although

alternate

dosing/sampling

regimens

may

specified

the

COR

for

particular

chemicals.

Blood

and

tissue

samples

shall

collected

the

Contract

Laboratory

and

processed

appropriate

for

the

endpoint.

Blood

samples

(and/or

bone

marrow

samples)

for

micronucleus

analysis

shall

prepared

described

for

Assays

and

tissue

samples

for

the

comet

assay

shall

prepared

and

analyzed

described

for

Assay

Genetic	Toxicity	Testing	Contract	SOW	–	Attachment	3	4
December	2012

Assay 5 – Pig‐a gene mutation assay

The	Contractor	shall	measure	the	frequency	of	X‐linked	Pig‐a
(phosphatidylinositol	glycan,	Class	A) gene	mutations	in	peripheral	blood
erythrocytes	and	reticulocytes	obtained	from	animals,	typically	mice	and
rats,	or	occasionally	humans,	exposed	to	a	chemical(s).	Animal	exposures
may	occur	at	the	Contractor’s	laboratory	or	an	alternate	laboratory	such	as
an	NTP	contract	laboratory.	A	noncommercial	collaborating	laboratory,
within	or	outside	the	NIH	(e.g.,	NCI,	CDC,	DOD)	typically	provides	coded
human	blood	samples	to	be	evaluated	for	frequency	of	cells	bearing	Pig‐a
mutations.	No	personal	identifiers	shall	be	attached	to	any	human	samples.
For	the	animal	studies,	peripheral	blood	samples	shall	be	obtained	from	each
animal	using	an	approved	method	and	blood	samples	shall	be	immediately
processed	following	accepted	protocols	for	evaluation	of	the	frequency	of
cells	with	aberrant	GPI	anchor	expression	(CD59‐negative	cells),	which	is	a
direct	measure	of	Pig‐a	gene	mutation.

Assay 6 – in vitro micronucleus assay

The

Contractor

shall

measure

the

frequency

micronucleated

cells

culture,

following

treatment

with

test

article

the

presence

and

the

absence

exogenous

metabolic

activation.

The

procedure

followed

the

Contractor

shall

consistent

with

that

outlined

OECD

guideline

487.

The

test

article

and

cell

type

will

chosen

the

COR.

initial

range

finding

study

shall

conducted

set

test

article

concentrations.

Cytotoxicity

must

quantified

the

range

finding

study

and

toxicity

levels

shall

not

excessive

the

highest

concentration

selected

for

the

definitive

study.

the

definitive

study,

appropriate

vehicle

and

positive

controls

shall

included.

The

use

cytochalasin

shall

considered,

particularly

for

asynchronously

dividing

cell

populations.

Assay 7 – in vitro comet assay

The

Contractor

shall

measure

chemical‐induced

DNA

damage

cultured

cells

using

the

single

cell

gel

electrophoresis

(comet

assay)

method.

Cells

shall

treated

and

examined

the

Contract

Laboratory.

Cell

type

and

test

article

will

determined

the

COR.

The

duration

chemical

exposure

well

other

technical

aspects

the

exposure

and

slide

preparations,

including

the

concentration

low

density

agarose

and

the

electrophoresis

characteristics,

shall

selected

the

COR

consultation

with

the

Contractor.

some

cases,

the

COR

may

request

that

specific

protocol

designed

measure

chemical‐induced

oxidative

damage

followed.

Cells

shall

evaluated

for

DNA

damage

using

image

analysis

platform.

Genetic	Toxicity	Testing	Contract	SOW	–	Attachment	3	5
December	2012

Assay 8 – bacterial mutagenicity assay

The

Contractor

shall

measure

gene

mutation

frequencies

(evaluated

number

mutant

colonies

per

plate)

tester

strains

Salmonella

typhimurium

and/or

Escherichia

coli

following

chemical

exposures

carried

out

with

and

without

source

exogenous

metabolic

activation.

The

test

article(s)

shall

provided

the

NTP.

Concentration

range

finding

studies

shall

conducted

select

test

concentrations.

Appropriate

vehicle

and

positive

controls

shall

included

each

experiment.

Examination

chemicals

typhimurium

strains

TAl00,

TA98,

and

the

coli

strain

WP2

(uvrA,

pKM101)

core

requirement

for

each

bacterial

mutagenicity

assay.

Tests

using

additional

different

strains

may

requested

the

COR

meet

specific

informational

needs

the

Government.

The

Contractor

shall

perform

least

one

repeat

experiment

confirm

the

results

from

the

initial

experiment.

The

COR

shall

determine

which

experiments

not

meet

quality

control

criteria

and

when

necessary,

shall

request

additional

repeat

tests

beyond

the

two

trials

specified.

Assay development and protocol refinement

addition

the

assays

described

above,

directed

the

COR,

the

Contractor

shall

engage

research

and

development

activities

required

for

assay

development

and

refinement

pertinent

technology

improvements

and

innovations

occur

during

the

course

this

contract.

For

example,

over

the

past

decade,

methods

for

measuring

micronucleated

erythrocyte

frequencies

changed

from

primarily

slide‐based

data

acquisition

use

flow

cytometry

for

evaluating

blood

samples.

This

change

data

acquisition

methods

necessitated

development

expertise

flow

cytometric

analysis

blood

samples

and

demonstration

that

results

from

flow

cytometric

analyses

were

consistent

with

results

from

slide‐based

methods

both

rats

and

mice.

These

types

research

and

development

activities

may

require

550

the

total

effort

annual

basis.

The

Principal

Investigator

and

other

key/critical

personnel

shall

visit

the

NIEHS

consult

with

the

COR

and

other

NIEHS

staff,

directed

the

COR.

addition,

the

Principal

Investigator

shall

attend

one

scientific

meeting

conference

annually

present

data

and

discuss

results

genetic

toxicity

tests

performed

under

the

contract,

directed

the

COR.

occasion,

key

critical

personnel,

defined

this

SOW,

may

asked

the

COR

travel

acquire

specific

contract‐related

training

enhance

technological

capabilities

methods

used

the

field

advance.

Training‐related

travel

requirements

may

vary

from

year

year,

but

are

not

anticipated

exceed

one

trip

per

year

for

one

member

the

Contract

Laboratory

staff.

required

training

session

should

considered

single

day,

running

from

PM.

addition,

the

COR

may

direct

that

one

member

the

Contractor’s

Genetic	Toxicity	Testing	Contract	SOW	–	Attachment	3	6
December	2012

staff

travel

another

NTP

contract

laboratory

other

site

for

one

workdays

for

the

purpose

providing

training

collect

tissue

samples

for

analysis

the

Contractor.

directed

the

COR,

the

Contractor

shall

ship

animal

tissues,

slides,

other

biological

material

information

including

(but

not

limited

to)

protocols

and

data

the

NIEHS

another

location

the

U.S.

Some

the

shipments

may

require

dry

ice

shipment

wet

ice

cold

packs.

The

Government

shall

arrange

for

receipt

tissues

cell

samples

associated

with

conducting

the

assays

described

this

SOW.

The

Government

shall

also

provide

the

B6C3F1

mice

required

for

any

the

vivo

studies

described

this

SOW;

Harlan

Sprague

Dawley

rats

shall

purchased

the

Contractor

needed

for

the

vivo

assays

described

this

SOW.

occasion,

the

Contractor

may

directed

the

COR

obtain

animals

from

outside

sources

used

assays

conducted

the

Contract

Laboratory.

Cell

lines

and

bacterial

strains

used

the

vitro

genetic

toxicity

tests

shall

obtained

the

Contractor,

the

direction

the

COR.

All

facilities,

practices,

and

procedures

husbandry,

care,

and

maintenance

animals

used

the

performance

this

contract

shall

accordance

with

the

latest

issue

effect

the

''Guide

for

the

Care

and

Use

Laboratory

Animals."

The

most

current

version,

the

Eighth

Edition,

(Reference

HHSAR

370.401

and

http://grants.nih.gov/grants/olaw/Guide‐for‐the‐Care‐and‐Use‐of‐Laboratory‐ Animals.pdf)

10.

The

Contractor

shall

accredited

the

Association

for

the

Assessment

and

Accreditation

Laboratory

Animal

Care

(AAALAC)

International.

The

Contractor’s

animal

care

and

use

committee

(ACUC)

shall

approve

the

animal

care

and

use

protocols

for

all

assays

conducted

with

animals

performance

this

contract.

The

ACUC‐approved

protocols

shall

submitted

the

COR

prior

the

initiation

studies.

DELIVERABLES/TECHNICAL REQUIREMENTS

To accomplish this SOW, the Contractor must have:

Macintosh

computer

running

the

most

recent

operating

systems

and

web

browsers

(Safari

Explorer)

available,

with

capability

upgrade

newer

software

programs

become

available.

2. An Internet connection: high‐speed cable access is required.

Genetic	Toxicity	Testing	Contract	SOW	–	Attachment	3	7
December	2012

Other

Software:

and

Microsoft

Excel

(as

part

the

Adobe

Acrobat

Professional

Microsoft

Office

suite

software)

the

most

advanced

versions

available.

4.	A computer system to capture the in-life portion of the study data unless one is
	provided by the NTP.

Note:

the

internet

browsers

are

free

software.

The

required

software

should

upgraded

software

improvements

become

available.

The

above

equipment

and

software

required

each

workstation

where

technician

recording

data

that

the

data

can

entered

directly

into

the

web

application.

This

equipment,

software,

and

internet

accessibility

also

required

for

the

Laboratory

Director,

the

Principal

Investigator,

and

all

key

personnel.

REPORTING REQUIREMENTS AND DELIVERABLES

Electronic Data Collection and Submission

The

Contractor

shall

submit

data

from

the

assays

the

NTP

within

days

the

completion

testing.

The

Contractor

shall

not

include

detailed

data

the

annual

final

reports

(described

below).

There

are

three

types

data:

endpoint

data,

in‐life

data,

and

images.

The

Contractor

shall

always

submit

endpoint

data

(i.e.,

the

results

the

assay)

the

NTP

data

file.

The

data

file

must

NTP

approved

and

standardized

format

that

the

data

can

easily

incorporated

into

NTP

databases.

Additionally,

depending

the

assay,

the

Contractor

shall

submit

in‐life

data

and/or

image

files.

The

following

table

outlines

data

submission

requirements

assay.

Assay Endpoint Data In‐life Data

Imag es

1	–	in	vivo	micronucleus	assay,	exposures
conducted	at	an	alternate	laboratory	or	site

Yes

2	–	in	vivo	micronucleus	assay,	exposures
conducted	by	the	Contractor

Yes Yes

3	–	in	vivo	comet	assay	Yes Yes	when
conducted	by

Contractor

Yes

4	–	combined	in	vivo	micronucleus/comet	assay Yes Yes	when
conducted	by

Contractor

Yes

5	–	Pig‐a	gene	mutation	assay	Yes Yes	when
conducted	by

Contractor

6	–	in	vitro	micronucleus	assay	Yes
7	–	in	vitro	comet	assay	Yes
8	–	bacterial	mutagenicity	assay Yes

Genetic	Toxicity	Testing	Contract	SOW	–	Attachment	3	8
December	2012

The	NTP	will	provide	directions	to	the	Contractor	regarding	compatible	file
preparation	required	to	submit	data	files	to	the	NTP.

The

NTP

expects

specify

NTP

system

for

collecting

the

in‐life

portion

assay

data

some

point

during

the

lifetime

the

Contract.

Should

the

NTP

offer

any

NTP

system

process

for

collecting

the

in‐life

portion

assay

data

some

point

during

the

lifetime

the

Contract,

the

NTP

will

provide

training

and

access

the

Contractor.

Otherwise,

the

Contractor

shall

use

their

internal

system

for

collecting

the

in‐life

portion

the

assay

data

where

appropriate.

1. Study

reports

For

each

assay

conducted

with

test

article

for

the

NTP

the

Contract

Laboratory,

written

report

shall

submitted.

This

report

shall

summarize

the

protocol

that

was

followed;

including

any

approved

amendments,

and

shall

summarize

the

results

and

other

important

findings

and

observations

(data

analysis

not

required,

all

study

data

will

analyzed

the

NTP).

Summary

data

shall

included

the

study

report.

With

this

report,

summary

costs

associated

with

each

study

shall

submitted.

These

costs

shall

include,

but

not

limited

total

per

assay

cost,

well

materials,

supplies,

shipping

costs,

etc.

associated

with

each

individual

study.

2. Biannual/Annual Reports

a) The

Contractor

shall

submit

biannual

(6‐month)

reports

beginning

months

after

the

date

contract

award

and

the

end

each

month

period

performance.

b) Biannual	and	Annual	reports	shall	include	a	summary	of	results	from
each	chemical/assay	conducted,	status	of	chemicals	on	test	or	to	be
tested,	problems	encountered,	problem	resolution,	and	anticipated
problems.		The	Biannual	and	Annual	reports	shall	not	contain	the	assay

data.

3. Final Reports

The

Contractor

shall

electronically

submit

final

report

within

days

completion

the

contract.

The

Final

report

shall

include

summary

all

samples

tested

and

the

assay

results.

4. Summary of Salient Results

The

Contractor

required

prepare

and

submit,

with

the

final

report,

summary

(not

exceed

200

words)

salient

results

achieved

during

the

performance

the

contract.

This

report

shall

due

before

the

expiration

date

the

contract.

The

Contractor

shall

submit

6‐month,

annual

and

final

reports

electronically,

one

copy

the

COR

and

one

the

Contracting

Official,

PDF

unless

Genetic	Toxicity	Testing	Contract	SOW	–	Attachment	3	9
December	2012

otherwise

directed

the

COR.

electronic

copy

the

Draft

Final

Report

shall

due

the

COTR

days

before

the

completion

date

the

contract,

with

the

Final

Report

due

the

time

contract

completion.

All

electronically

submitted

reports

must

508

compliant.

except

drafts

Personnel needs to be met by the contractor: See RFP Section L

Oversight

animal

experiments:

Contractor

must

have

experienced

Animal

Care

and

Use

Committee

(ACUC)

for

approval

vivo

animal

experiments

addition

showing

strict

adherence

NIH

guidelines

for

animal

care

and

use.

The

contractor

must

also

have

approved

animal

welfare

assurance

plan

file

with

the

NIH

Office

Animal

Welfare

prior

contract

award.

The

Contractor

must

compliance

with

Public

Health

Service

policies

concerning

animal‐related

activities.

For

all

in‐life

animal

studies

conducted

the

Contract

Laboratory

described

this

SOW,

euthanasia

shall

accomplished

70:30

CO2/O2

anesthesia

followed

exsanguination

ensure

death

prior

sample

collection.

Invoicing schedule

Invoicing

schedule:

The

Contractor

shall

submit

detailed

monthly

invoices

that

include

the

name

each

employee

who

charged

hours

the

Contract,

the

project

study

which

the

employee

worked,

and

the

task(s)