Amend__3_-_Technical_and_Business_Proposal_Q A_9-28-12.pdf

REMINDER: The cut-off for submitting questions regarding this solicitation is 3:00 pm October 5, 2012.

Amendment 3 - Questions and Answers to RFP No. NIHES2012154

Title: Support of the Research Effort to Evaluate Toxicity Following Early Life Exposure to Test Articles For the National Toxicology Program (NTP)

1. Paragraph 1.4. Schedule of the Technical Proposal Instructions (p. 51 of the RFP) states: “Unless the request for proposal indicates that the stipulated schedules are mandatory, they shall be treated as desired or recommended schedules. In this event, proposals based upon the offeror’s best alternative schedule, involving no overtime, extra shift or other premium, will be accepted for consideration.” Please confirm whether or not the schedules are mandatory. Is overtime allowed?

Response: The schedules are mandatory. Overtime is allowed because of the nature of the work where, from time to time, the work process for a day may take longer than 8 hours to complete. Schedules should be managed so that overtime is not excessive and kept to a minimum.

2. For the subchronic mouse study should hematology, clinical chemistry and urinalysis be included in the cost estimate? In the specs it appears that the inclusion of these analyses is test article specific.

Response: Assume that hematology and clinical chemistry are needed and should be included in the cost estimate.

3. For costing purposes on the 2 week range finding study in mice should histology (gross lesions) be included on this study?

Response: Yes

4. For the cost estimates for the in life and histopathology for the F2 generation on the RACB study (study assignment 1), how many animals should be assumed? Assuming 50 mating pairs/group each generating a litter that is culled to 5/sex, this results in 1,000 male and 1,000 female F2 offspring for weaning. Response: For costing purposes, assume that after developmental indices are completed, you will retain 2/sex/litter to 13 weeks of age. For the 3/sex/litter that are not retained past developmental indices, should necropsy, organ weight, and histopathology be done? Response: Yes

5. Sample study assignment #1: Please confirm that audited draft reports are required for the two dose range-finding studies within 6 weeks of the last necropsy.

Response: This is confirmed.

6. Sample study assignment #1, F0 mating and F1 assessment (Phase 3), page 7: Should the cost be for 25 or 20 pregnant females per group?

Response: For this study, assume the contractor will start with 25 females per group. Experience with the HSD rat has shown that it is unlikely that all 25 females will deliver litters, but for costing purposes, assume that 25 rats/group will deliver litters.

7. Sample study assignment #1, F0 mating and F1 assessment (Phase 3), page 7: What is the frequency of food consumption for pregnant and lactating dams?

Response: For costing purposes, align food consumption with body weight intervals during pregnancy and lactation, roughly every three days.

8. Sample study assignment #1, F0 mating and F1 assessment (Phase 3), page 7: How frequently should littering checks be done and on what GD should they begin?

Response: The contractor can propose their best judgment on this question.

During the period of expected parturition, the contractor may check several times during the day for deliveries. Generally deliveries that are completed after 5 pm are considered born on the next day. For HSD rats, most deliveries occur on

PND21-23.

9. Sample study assignment #1, F0 Determination of affected sex (Phase 4), page 9: Should we assume 25 mating pairs for costing of the cross-over mating and the dominant lethal test?

Response: Yes

10. Sample study assignment #1, F0 Determination of affected sex (Phase 4), page 9: It is stated that the dominant lethal test uses all the F0 treated males. Should this be only the high dose F0 males?

11. Sample study assignment #1, F0 Determination of affected sex (Phase 4), page 9: Should these 2 tests be costed together or separately?

Response: They should be costed separately.

12. Sample study assignment #1, F2c necropsy, page 12: Are all F2c pups (up to 10 per litter) retained until 13 weeks of age or are only 2 per sex per litter retained after developmental indices are completed, as with the F1c pups?

Response: See response to #4 above.

13. Sample study assignment #1, F2c necropsy, page 12: Are sperm parameters required for the F2c males, as they are for the F1c males and if so how many F2c males?

Response: For costing purposes, assume that sperm parameters are not required for the F2c males.

14. Sample study assignment #1, Final Report, page 13: The audited report is required within 26 weeks of the final euthanasia. However, the Statement of Work specifies 24 weeks.

Response: For costing purposes, follow the instructions in Study Assignment #1 indicating that an audited draft report is required within 26 weeks of the final euthanasia.

15. Sample study assignment #2, Prenatal developmental toxicity dose range-finding study, page 2: For costing, it is stated to assume that there are 11 pregnant dams per group.

Does this include the 3 pregnant dams used for the GD 18 timepoint?

Response: For costing purposes, assume that of the 14 time mated females per group, only 11 will be pregnant, and of these 11 pregnant animals, the offeror will use 3 for the GD18 timepoint.

16. Sample study assignment #2, Prenatal developmental toxicity dose range-finding study, page 3: It is stated to assume 25 time mated females for costing purposes. For the purpose of costing fetal observations, should we assume that there will be 25 litters on

GD 21?

17. For all studies, what should we assume to be the frequency of formulation/diet preparation?

Response: For costing purposes, assume 42 days. If you know of additional information why 42 days might not be appropriate, please mention this in the technical proposal.

18. Sample study assignment #3, Modified one generation, F0 necropsy, page 8: For costing purposes, how many representative tissues should be retained from controls?

Response: Assume 5.

19. Sample study assignment #3, Modified one generation, F0 necropsy, page 8: It is stated to assume that 2 of the 30 F0 females do not litter and to assume that the other 22 are kept until weaning. These numbers do not add up. Are there 22 or 28 litters?

Response: 28 litters

20. Sample study assignment #3, Modified one generation, Teratology cohort, F1 male necropsy, page 11: Are tissues being preserved for histopathology? A few statements in this section allude to pathology and collection of tissues.

Response: The sample study assignment does not require this but Offerors are free to comment on this in the proposal if they wish.

21. Sample study assignment #3, Modified one generation, Fertility cohort, page 13: For costing purposes, only tissues from high dose and control are being examined microscopically. Is this correct?

Response: For costing purposes, this is correct.

22. Sample study assignment #3, Modified one generation, Neurobehavioral cohort, page 14, section 9.2, second bullet: Body weights are collected for females until evidence of mating. Since there is no information given about mating, gestation, lactation for this cohort, is it correct to assume that this cohort is NOT being mated to produce F2 litters and that all the neurobehavioral assessments at all the timepoints are being done on the F1 pups?

Response: The phrase "until evidence of mating" on page 14 is in error. All the neurobehavior assessments are being done on the F1 pups.

23. Sample study assignment #3, Modified one generation, Neurobehavioral cohort, page 15: Allocation of the F1 animals in this cohort will not be done at weaning (as stated in Section 6.6) but rather on PND 13, when pups are first tested for motor activity. Is this correct?

Response: Yes.

24. Utilizing the mammary gland whole mount preparations, will qualitative and/or quantitative analyses be required for the determination of accelerated or delayed mammary gland development?

Response: Currently, the NTP is evaluating methods for analyses of mammary gland whole mounts so at this time there are no specific required methods. For costing purposes, assume a cursory analysis and provide a short explanation of your assumptions.

25. If there a price reduction for animals for this RFP from the NTP animal supplier?

Response: There is no special government price for rats from any supplier. For mouse studies, the government supplies the B6C3F1 mouse from Taconic at no charge to the Contract Laboratory.

26. For costing purposes, what is the frequency for dose formulation preparation for the sample studies?

Response: For costing purposes, assume 42 day stability.

27. Should Offerors cost for dimorpholinodiethyl ether bulk analysis and formulation or a generic compound for this RFP? Would it be possible to provide methods of dimorpholinodiethyl ether if Offerors are to cost for this compound?

Response: The NTP has no analytical methods developed for this compound. Provide details how you cost this in the proposal.

28. Sample study assignment #1, F1c breeder necropsy, page 12: Necropsy F1c animals after all their F2c offspring have been weaned and vaginal cytology assessment of F1c females is complete. Is this meant to imply that the F1c cytology slides must be read before the F1c females are euthanized?

Response: No

29. Sample Study Assignment 3 for the 13-week cohort for rats specified that vaginal cytology was to begin on PND 77 (±3 days) and continue for 16 days. Should the vaginal cytology evaluations for the female rats actually begin on Study Day 77 instead of PND77? This would put the vaginal cytology on the last 16 days of the study.

Response: Collection of smears for vaginal cytology should begin on Study Day 77 and not PND 77.

30. For rats in the Modified One Generation (MOG) study that progress into the 13-week toxicology cohort, should dosing during the 13-week portion of the study be 5 or 7 days per week?

Response: Dosing for the 13-week gavage study animals in the MOG is 7 days per week.