Responses_to_Questions_RFPnoNIHES2013158.docx

RFP No. NIHES2013158 – Genetic Toxicity Testing Services for NTP Clarifications to RFP – December 11, 2013

Article B.1. Brief Description of Supplies or Services

For the 25 in vivo assays (Annual Approximations):

1) Is this estimate inclusive of both range finding and definitive studies (e.g., assays for 25 chemicals including range finding studies)?

Some studies will include range finding; others will not. For purposes of cost estimation, see section C.3.k, pages 72-75.

2) Please provide specific end points (e.g., MN, Comet, MN & Comet; # tissues) expected to assist in cost estimating.

For purposes of cost estimation, see section C.3.k, pages 72-75.

3) Is this estimate of 25 in vivo assays exclusive of analysis of samples provided by another laboratory?

No, the number of assays estimated on an annual basis includes analysis of blood and tissue samples provided by another laboratory. For purposes of cost estimation, see section C.3.k, pages 72-75.

Study Based Cost Estimate:

1) For costing in vivo Comet assays (pg. 73-74): There is no mention of availability of toxicity information. Should range finding assays be included in the cost estimate?

No range finding studies are requested in this example.

2) For the purpose of costing out the in vivo Comet and MN/Comet studies (pp. 73-75), are the written reports considered to be full reports or abbreviated summary reports?

These are complete (full) study reports, but without statistical analyses because that will be conducted by the NTP.

For purposes of cost estimation, see section C.3.k, pages 72-75.

3) For costing in vivo Comet assays (pg. 73-74): It is requested that additional liver, blood, and gastric stomach samples be collected for and analyzed “histologically” for cytotoxicity. Please provide details as to the expectation for the evaluation of cytotoxicity in blood.

Blood samples cannot be subjected to histopathological analysis so exclude that option from the cost analysis.

4) What study timing distinguishes “concurrently” (2 in vivo comet assays, pg. 73) versus “consecutively” (2 combined MN/Comet assays, pg. 74)? In other words, for consecutive studies, at what point in time during the first study may the second study commence?

In this example, concurrently means that the studies are conducted simultaneously. Consecutive studies are conducted one after the other with no overlap in animal treatments (i.e., the first study is completed and tissue samples have been obtained, processed, and stored for each endpoint as appropriate).

5) For costing of an in vitro MN assay (pg. 73): Is the statement “After concentration range finding tests, seven treatment groups will be run in triplicate in the definitive assay…” intended to imply that dose range finding studies need to be conducted prior to doing the definitive study, and therefore, should be included in the cost estimate?

Yes, include range finding tests in the cost estimate. Please indicate clearly that the cost estimate includes the initial concentration range finding tests and the definitive assay.

6) For costing of the two combined MN/Comet assays (pg. 74-75): Although there is mention of performing histopathology analysis of liver for both studies (the mouse and the rat), for the rat study there is no mention of performing histopathology on the lung and colon tissues additionally assessed for damage using the Comet assay. Should histopathology analysis of the lung and colon for the purpose of assessing cytotoxicity also be included in the cost estimate?

No, only base the cost estimate on exactly what was requested in the example provided. In the cost estimate, clearly indicate the basis of the cost estimate (e.g., the two combined MN/Comet assays and histopathological evaluation of specific tissues).

7) On page 91 of the RFP Number NIHES2013158, it states: “The NTP requires that these studies be conducted in compliance with FDA GLP regulations as specified in Part 58….”. This is a mandatory qualification criterion for all laboratories and subcontractors.

In contrast, the STATEMENT OF WORK (SOW) Attachment 3 December 2012 states: “The Contractor shall keep all laboratory records in accordance with FDA Good Laboratory Practice Regulations…”. The study reporting requirements stated in the SOW (e.g., only summarized data, no data analysis) are also not entirely consistent with 21 CFR Part 58.

The two references to GLP requirements in the RFP and SOW are very different in scope and we are seeking clarity on what is needed for this contract with respect to GLP compliance based on 21 CFR Part 58. Of particular concern is adherence to 21 CFR Part 58; Sec. 58.105 Test and control article characterization (included below), point (a):

“The identity, strength, purity, and composition or other characteristics which will appropriately define the test or control article shall be determined for each batch and shall be documented.”

To meet 21 CFR Part 58; Sec. 58.105 requires analytical determination using validated methods for identity and characterization of each test article and testing and validating the test article concentrations of each dosing solution used for each of the assays. Identity and characterization usually requires determination of mass using mass spectroscopy, and dose formulation analyses can be done with other chromatography methods provided there is an authentic standard. Clearly, this requirement would have a significant impact on the overall costs associated with the studies requested under this support contract.

Since reference to GLP requirements in the SOW and the RFP differ, and it is not stated in the RFP how the analytical services for each study will be accomplished, please clarify if the studies on this contract are to be conducted under strict GLP compliance as described above?

Yes, all work conducted under this contract is to be GLP compliant.

If so:

1) Are hours included in the level of effort for a Quality Assurance professional to audit critical GLP study phases, review data and reports, and audit analytical laboratories and services (there is no mention of a Quality Assurance professional in the staffing requirements)?

The hours given are only an estimate. It shall be up to each individual offeror to propose labor mix and number of hours necessary to complete the requirements outlined in the SOW.

2) Is the Contractor required to provide analytical services (identity, strength, purity, composition, and stability) for all test articles and dose formulations for each study conducted in the Contractor’s laboratory, or will this be done by the NTP?

Chemical analysis will be conducted by the NTP.

3) Are the necessary hours for the Contractor to meet the requirement for analytical determination for all test articles and dose formulations for each study included in the estimated level of effort stated in the RFP (pg. 46)?

The NTP will conduct all required analyses of test articles; the Contractor is responsible for dose formulations (see page 57, “Dose formulation scientist”).