Attachment No. 26 Q+A BICAN Amendment A00001.pdf

NIH-NIMH-75N95022R00031 A00001

Attachment 26

Request for Proposal Questions and Answers

General:

Question 1: Can you confirm that the proposals are due on Sunday, August 21, 2022? Or are they due the following business day, Monday, August 22?

Answer: The deadline to submit proposals is extended to Tuesday, August 30, 2022, at 1:00 PM

EST.

Question 2: Attachment #6, Additional Technical Proposal Instructions, provides a general sample proposal format. Can you confirm that section A, General Area Proposal, should be comprised of a general technical and business proposal for the max capacity of all task areas offeror is proposing, and that sections B and C are more specific technical and business proposals for each TA that the offeror is proposing?

Answer: Section A is expected to describe the general technical and business capabilities of the offeror, whereas Sections B and C are specific to each Task Area.

Business:

Question 1: We intend to bid the various Tasks on a Fixed-Price basis versus Cost Reimbursement. Please confirm that a fixed-price bid will be acceptable, and therefore would not require offerors to provide the level of financial detail in our response required to support a Cost- Reimbursement proposal.

Answer: It is contemplated that multiple, hybrid IDIQs with cost-reimbursement and fixed price task orders will be awarded.

In accordance with NIH-NIMH-75N95022R00031 Attachment No. 7, Task Order 1 shall be a fixed price contract with a 1-month period of performance and awarded concurrently with the IDIQ contract under General Task Area 1: Manual of Operations.

For subsequent Task Orders, successful Offerors shall have a fair opportunity to compete for additional work under Task Areas 2-7 in which they proposed and received an award. The decision as to whether a given task order will be fixed price, cost-reimbursement, or a hybrid will be made at the time of that specific Task Order Request for Proposal (TO-RFP). Offerors should assume that NIH may determine a Cost-Reimbursement or hybrid task order to be in the best interest of the Government; therefore, offerors are expected to provide the information necessary “to support a Cost-Reimbursement proposal” for the proposed Task Areas. Reference Attachment 8 TO-RFP Task Area One - Manual of Operations and Attachment 9: TO-RFP Sample Tasks Two through Seven.

NIH anticipates that sequencing requirements will ramp up following completion of Phase I pilot studies.

Request for Proposal Questions and Answers Question 2: Is pricing expected to be on a “per Gb output or number of reads” basis, or on a per flow cell basis, or per sample basis? Or is this supplier choice? Any preference from NIH?

Answer: Reference Business Question 1 Answer. Further, in accordance with Section L, Instructions to Offerors, “The business proposal must contain sufficient information to allow the Government to perform a basic analysis of the proposed cost or price of the work.” The Government’s analysis will be applicable to the Task Areas proposed by the offeror.

Examples of expected information include but are not limited to the following: the sequencing platform, unit price per Gb output, price per million reads (by read length), and unit price per flow cell (by sequencer), along with a tiered cumulative discount pricing offer according to the sequencing volume (see below).

A tiered pricing structure with pricing information for these ranges is recommended.

<100 flow cells/year 100-500 flow cells/year 500-1000 flow cells/year >1000 flow cells/year

Question 3: May our “Fixed Pricing” be provided on a tiered basis (per Task) tied to the estimated number of submissions received? I.e. the more sample (libraries) received the lowerac the price.

Example: We were intending to submit a pricing grid that shows how our Fixed-Pricing will change based on the total number of libraries received from the BICAN consortium within a 12-month period. Discounts (going forward) would be realized based on reaching total volume milestones (per Task) within that 12-month period.

Answer: Refer to answers to Business Questions 2 and 5.

Question 4: Would you please advise approximately how many submissions per Task will be submitted to a sequencing provider (per week, or month, or year)?

Answer: The number of submissions will be dependent upon the needs of the BICAN-funded research projects. NIH expects there will be >10 research laboratories submitting sequence ready libraries constructed using a variety of single-cell genomics methods, including 10X Single Cell Multiome, snm3C-seq, Paired-Tag, 10X single-cell RNA-seq, DBiT-seq, SLIDE-seq, smart-seq3.

More information will be provided during Phase I pilot studies. NIH’s current estimated quantities were generated using NovaSeq S4 flow cells, but equivalent platforms are acceptable.

Over 5 years, NIH estimates a total of 7000 flow cells with the following breakdown:

Task Area 2: 500 total flow cells, including scRNA-seq, Slide-seq, smart-seq3, and DBiT-seq Task Area 3: 1700 total flow cells, including snm3C-seq and Paired-Tag

Request for Proposal Questions and Answers Task Area 4: 2800 flow cells for 10X single cell multiome Task Area 5: 1000 flow cells for bulk tissue sequencing Task Area 6: 500 flow cells for whole genome and/or whole epigenome Task Area 7: 500 flow cells for novel omics sequencing (this may include but is not limited to RNA isoform long-read sequencing, subcellular compartment RNA sequencing, ribosome sequencing, and DNA hydroxymethylation sequencing).

Question 5: Attachment #7, Additional Business Proposal Instructions, item #2, states that, “Price proposals for Sample Task Areas 2-7 should include the fixed unit prices for the quantities identified in the sample task orders. There are no quantities identified in Sample Task Area 6 (i.e., exome, genome sequencing). Can you provide minimum and maximum required throughput/year for exome and genome sequencing?

Answer: Reference NIH’s answer to Question 4 (Business). Specific pricing structure, including fixed price or cost-reimbursement, will be determined at the individual task order level.

Attachment #7, Additional Business Proposal Instructions, item #2, is revised as follows:

From: “Price proposals for Sample Task Areas 2-7 should include the fixed unit prices for the quantities identified in the sample task orders.”

To: “Price proposals for Sample Task Areas 2-7 should include the unit prices for the quantities identified in the sample task orders.”

Question 6: Regarding personnel cost, should the effort of individuals be included separately, or should it be loaded into the sequencing cost?

Answer: Personnel costs for the sequencing effort (labor) should be included for the Government’s analysis. Proposed personnel costs may vary depending on Task Areas and associated technical approaches. Costs may include: meetings with BICAN investigators and NIH staff, data delivery coordination to NIH repository, reporting requirements, and overall project management etc.

Question 7: We understand that we should supply “customized sequencing depths and read lengths”. In order to put forth a cost proposal, is it acceptable to provide a menu of read lengths and fully loaded cost per flow cell?”

Answer: It is acceptable to provide a menu of read depths and lengths frequently encountered in the relevant tasks and fully loaded cost per flow cell.

Technical:

Question 1: Will the submissions arrive at contractor locations “ready to sequence”, meaning will the samples be pre-Quantified and Pooled libraries?

Request for Proposal Questions and Answers

Answer: It is expected that the submissions will be ‘ready to sequence’. The requirements for the libraries will be finalized in the pilot phase of each task order.

Question 2: Will the submission be delivered in batches that will fit onto a pre-determined size Illumina flow cell? Or would they be of random number intended to be fit with other submissions multiplexed onto the same flow cell?

Answer: The number of sequencing libraries submissions will be dependent upon the needs of the BICAN-funded research projects. Offerors are expected to anticipate that the submissions will be delivered in batches. NIH staff will coordinate with research laboratories to ensure that batches will fit in predetermined flow cells.

Question 3: Is it acceptable to mix samples from the BICAN project onto the same flow cell, or within the same flow cell lane, with samples from other non-NIH/non-BICAN projects? Note that while that (mix) procedure is not the offeror’s standard practice (due to risk of bar code hopping, etc.) we know that other offerors may pool samples from multiple projects together to reduce price per sample.

Answer: Refer to answer to Technical Question 2.

Question 4: Is the total number of submissions to the sequencing provider fixed?

Answer: No, the total number of submissions will be determined at the time the of a given Task Request for Proposal and dependent upon the needs of the BICAN researchers.

Question 5: Will the submissions arrive on a daily, weekly or monthly basis? Would they be of the same approximate size each time?

Answer: Offerors are expected to describe the ability to accommodate different submission schedules, and submission intervals required to meet the expected task turnaround time. It could be rolling submission without being limited to scheduled biweekly or monthly submission.

Offeror ability for flexible submission scheduling could be evaluated under review criterion c) Throughput: Demonstrated ability to sequence 1-10 trillion short sequencing reads anticipated per year, prepared via a combination of the methods listed in (b).

i. Planned schedule of completion for samples received.

ii. QC/turnaround: A detailed plan on quality control procedures of submitted samples prior to sequencing, and a timeline for generating QC results after sample receipt. Pilot QC of representative study samples are expected within 7 days of the start of the task order period during Phase I.

Question 6: Attachment #2, the Statement of Work, instructs contractors to describe how they will participate in BICAN in-person meetings and conference calls for each Task Area 2-7;

however, on page 25 under Other Considerations, the SOW states that travel is not anticipated

Request for Proposal Questions and Answers for this work. Could you please clarify whether we should include travel costs in our budget proposals?

Answer: The expectation is that the meetings will be virtual using a platform such as Zoom.

Travel is not anticipated; therefore, travel costs do not need to be proposed in response to NIH- NIMH-75N95022R00031. Should travel be determined to be necessary for performance off a future task order, it will be requested, proposed, and evaluated at the task order level.

Question 7: Since the objective of the BICAN Sequencing Core is to perform large-scale DNA and RNA sequencing of libraries generated by BICAN-funded laboratories, Task Areas 2, 3, and 4, differ only in the type of library sequenced. For our CORE, all work would essentially be the same. Could we submit one proposal that encompasses all three Task Areas?

Answer: A separate sample task order proposal/approach should be submitted for each proposed area. Sample task order proposals will be evaluated independently with consideration of potential cross technical area challenges. Evaluations will result in a total possible proposal score, as described in the Technical Evaluation Factors noted in Section M. Duplication of technical approach methodology across various technical areas is permitted provided the applicable page limits are adhered to and cross technical area challenges are addressed.