RFQ_75F40126Q00206.pdf

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75F40126Q00206

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19.

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This is small business Set-Aside Firm Fixed Price purchase order using Simplified Acquisition Procedures for " Bioinformatics Analysis of Livestock Genomics

1 Bioinformatics Analysis of Livestock Genomics

1 Variant validation 2000 variants 2 CRISPRme ready VCF generation 2 pig breeds 3 *additional pig breeds 0

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23.

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SCHEDULE OF SUPPLIES/SERVICES

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ITEM NO.

4 *additional species/breed 4

Period of Performance: 07/15/2026 to 06/14/2027

32f. TELEPHONE NUMBER OF AUTHORIZED GOVERNMENT REPRESENTATIVE

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45 2 of

Bioinformatics Analysis of Livestock Genomics Request for Quotations (RFQ) No 75F40126Q00206

1. BACKGROUND

CVM possesses significant bioinformatics expertise; however, personnel with the specific skills to perform these tasks are currently allocated to other high-priority agency projects.

To meet the urgent timelines for this analysis, CVM requires external, focused support to perform the necessary visual validation of swine variants from an already generated list of candidate variants and the generation of CRISPRme input files for cattle, chicken, and swine. This approach will allow the project to proceed efficiently while enabling CVM's internal experts to provide oversight and ensure the validated variants and CRISPRme input files meet their precise scientific requirements.

2. COMMERCIAL SERVICES PROCUREMENT

This acquisition is being conducted using simplified acquisition procedures in accordance with FAR Part 13 and commercial services procedures under FAR Part 12. This requirement is a Total Small Business Set-Aside under FAR 19.502-2.

3. NOTICE OF FAC

This solicitation incorporates FAR clauses in effect through Federal Acquisition Circular (FAC) 2026-01, effective March 13, 2026. This Purchase Order incorporates clauses by reference. The full text of clauses may be accessed electronically at www.acquisition.gov.

See also https://www.acquisition.gov/far-overhaul/far-part-deviation-guide/far-overhaulpart- 52.

The Department of Health and Human Services (HHS) Acquisition Regulation (HHSAR) clauses referenced in this solicitation can be found on the following website:

https://www.hhs.gov/grants/contracts/contract-policies-regulations/hhsar/index.html. See also https://www.hhs.gov/grants-contracts/contracts/contract-policies-regulations/hhsaroverhaul/index.html.

4. PURCHASE ORDER REQUIREMENTS

See Section 8, Performance of Work Statement, for a full description of the services to be acquired.

http://www.acquisition.gov/ https://www.acquisition.gov/far-overhaul/far-part-deviation-guide/far-overhaulpart-52 https://www.acquisition.gov/far-overhaul/far-part-deviation-guide/far-overhaulpart-52 https://www.hhs.gov/grants/contracts/contract-policies-regulations/hhsar/index.html https://www.hhs.gov/grants-contracts/contracts/contract-policies-regulations/hhsaroverhaul/index.html https://www.hhs.gov/grants-contracts/contracts/contract-policies-regulations/hhsaroverhaul/index.html

5. ORDER TYPE

The Government anticipates awarding one (1) Firm Fixed Price type Purchase Order.

6. PERIOD OF PERFORMANCE

The anticipated period of performance for this contract is a single one-year base period from July 15, 2026, to July 14, 2027. There are no option years.

The actual period of performance will be determined at the time of award.

7. Pricing Schedule

Base Period: July 15, 2026, to July 14, 2027

CLIN Description QTY Total Price

1 Variant validation variants

2 CRISPRme ready VCF generation 2 pig breeds 3 *additional pig breeds 0 4 *additional species/breed 4

Total FY cost

8. Performance Work Statement (PWS) for the Bioinformatics Analysis of Livestock Genomics 1 General

1.1 Introduction

The mission of the FDA's Center for Veterinary Medicine (CVM) is to protect human and animal health by ensuring animal drugs are safe and effective and that food from treated animals is safe to eat. In support of this mission, the Office of Applied Science’s Veterinary Research Branch (VRB) requires specialized bioinformatics services. This acquisition is to procure the services needed to validate genomic variants in CRISPR/Cas9 gene-edited swine samples and generate breed-specific naturally occurring cattle, chicken, and swine variant resources to improve the robustness of in silico off-target predictions, both of which are critical for evaluating the safety and efficacy of intentional genomic alterations in animals.

1.2 Objective

The primary objective of this contract is twofold. First, to perform visual validation of genomic variants in whole genome sequencing (WGS) data of CRISPR/Cas9 gene-edited swine samples, confirming the presence and characteristics of both on-target and off-target variants. Second, to generate CRISPRme-ready input files, including breed-specific variant call files (hereinafter, “breed-specific VCFs”) for cattle, chicken, and swine, representing at least two breeds per species, using known databases of naturally occurring variants. A successful outcome will result in the delivery of a comprehensive dataset of visually validated variants with supporting evidence, the breed-specific VCFs that are directly compatible with CRISPRme software, the scripts and workflow to generate the breed-specific VCFs so they can be reused to generate comparable files for additional breeds, and a detailed final report that meets the quality and accuracy standards defined herein.

1.3 Scope of Work

The scope of this contract is to provide specialized bioinformatics services for (1) visual validation of genomic variants identified in CRISPR/Cas9 gene-edited swine whole genome sequencing data, and (2) generation of CRISPRme-compatible breed-specific VCFs and CRISPRme input files for cattle, chicken, and swine. This work does not include initial DNA sequencing, variant calling of the WGS data, experimental validation of variants, or long-term data storage beyond the contract period.

1.4 Type of Contract Contemplated

Firm Fixed Price

1.5 Place of Performance

The work shall be performed at the contractor's own facility. The principal place of performance, and the location of all data processing and storage, must be within the United States.

1.6 Applicable Documents

The following documents, standards, and resources are applicable to this contract.

Contractors shall comply with the requirements specified in these documents as they relate to the performance of work under this contract. All documents are incorporated by reference and made part of this contract.

1.6.1 Technical Standards and Specifications

a. VCF Format Specification v4.2 or later Available at: https://samtools.github.io/hts-specs/VCFv4.2.pdf Application: All variant call files delivered under this contract must conform to VCF format specifications version 4.2 or later.

b. SAM/BAM Format Specification Available at: https://samtools.github.io/hts-specs/SAMv1.pdf Application: For guidance on interpretation of alignment files provided by the government.

c. Bos taurus ARS-UCD2.0 Reference Genome.

Available at: https://ftp.ensembl.org/pub/release-115/fasta/bos_taurus/ Application: All analyses shall use this reference genome build for consistency.

d. Gallus gallus bGalGal1.mat.broiler.GRCg7b Reference Genome.

Available at: https://ftp.ensembl.org/pub/release- 115/fasta/gallus_gallus/ Application: All analyses shall use this reference genome build for consistency.

e. Sus scrofa 11.1 Reference Genome.

Available at: https://ftp.ensembl.org/pub/release-115/fasta/sus_scrofa/ Application: All analyses shall use this reference genome build for consistency.

1.6.2 Software and Analytical Tools

a. CRISPRme Software

Available at: https://github.com/pinellolab/CRISPRme Application: VCF files generated under Task 2.4 must be compatible with CRISPRme software for off-target prediction analysis.

Contractors should familiarize themselves with CRISPRme input requirements.

b. Integrative Genomics Viewer (IGV) or equivalent Available at: https://software.broadinstitute.org/software/igv/ Application: For guidance only. Visual validation may be performed using IGV or other industry-standard genome browsers capable of displaying BAM and VCF files.

1.6.3 Data Security and Transfer

a. PrecisionFDA Cloud Computing Platform

Available at: https://precision.fda.gov/ Application: All data transfers between the government and contractor must occur through precisionFDA. Contractors must establish an account and comply with platform terms of use.

1.6.4 Federal Acquisition Regulation (FAR) Clauses

The following FAR clause is applicable to this contract and are incorporated by reference:

a. FAR 52.239-1 Privacy or Security Safeguards

Application: The contractor shall implement appropriate administrative, technical, and physical safeguards to protect government data from unauthorized access, use, or disclosure.

1.6.5 Industry Best Practices

Contractors are expected to follow current industry best practices for:

a. Bioinformatics workflow documentation and reproducibility

b. Version control for computational scripts and pipelines (e.g., Git)

c. Containerization and dependency management (e.g., Docker, Conda)

1.6.6 Document Availability

All publicly available documents listed above can be accessed via the provided URLs. The contractor is responsible for obtaining and reviewing all applicable documents. Questions regarding interpretation or application of these documents should be directed to the TPOC.

1.6.7 Document Precedence

In the event of conflict between this Performance Work Statement and any referenced document, the requirements of this PWS shall take precedence unless otherwise specified by the TPOC in writing.

2 Specific Requirements/Tasks

2.1 Task One: Project management and collaboration

2.1.1 Conduct a post-award kickoff meeting with CVM personnel to review project goals, establish communication protocols, and define a detailed timeline.

2.1.2 Deliver a formal Project Management Plan within 15 business days of the kickoff meeting, outlining the schedule, milestones, risk management, and key personnel.

2.1.3 Provide monthly written status reports summarizing progress, any issues encountered, and plans for the next reporting period. Reports shall be submitted by the 5th business day of each month.

2.1.4 Participate in bimonthly virtual progress review meetings with CVM technical experts to discuss status, address issues, and review findings.

2.2 Task Two: Data Receipt and Initial Processing

2.2.1 Securely receive the following files from CVM via precisionFDA:

a. Filtered VCFs from FreeBayes and LUMPY variant callers

b. Corresponding binary alignment map (BAM) files for each of the 73 swine samples (70 cases and 3 controls).

c. Sample metadata for 73 swine samples.

2.2.2 Perform comprehensive Quality Control (QC) analysis of the received sequencing data files to verify data integrity, completeness, and suitability for analysis.

2.3 Task Three: Visual Validation of Genomic Variants

2.3.1 Develop and document a standardized validation protocol and submit to

CVM for approval within 20 business days of data receipt.

2.3.2 Apply the approved validation protocol consistently across all variants.

2.3.3 Perform manual visual inspection of genomic variants in the VCFs in the sample(s) for which they occur and the three controls (n= 3). The dataset characteristics are:

a. 70 case samples and 3 control samples

b. 15 of the case samples have low-level mosaic variants

c. 20-70X sequencing coverage

d. Paired-end Illumina sequencing data (150bp x 2)

e. Reference genome: Sus scrofa 11.1 (Ensembl)

2.3.4 The scope of visual validation includes

a. All variants at four CRISPR/Cas9 target sites in 55 of the case samples

(some of the samples have multiple variants) – two of the sites have a high degree of homology

b. Approximately 2,000 variants at other sites in the genome – a combination of short variants and large structural variants; most are unique to one sample

2.3.5 Visual validation shall include:

a. Manual inspection of read alignments in BAM files using IGV

b. Confirmation of variant absence in all three control samples.

c. Assessment of variant quality and confidence, including but not limited to: bidirectional read support, split reads, discordant read pairs, alternate allele observations, and sequencing depth of coverage. Note that genotype is not an accepted filter.

2.3.6 Documentation of findings in a structured format suitable for regulatory and scientific reporting.

2.3.7 For visually confirmed variants, note if they are a known naturally occurring variant and if so, provide an identifier and/or source.

2.3.8 Deliver a progress report summarizing validation results for the first 15 variants, allowing CVM to provide feedback on the validation approach.

2.3.9 Deliver the validation results for all variants at least 30 business days before the end of the contract period.

2.3.10 Deliver a comprehensive validation report documenting all findings and methods at least 30 business days before the end of the contract period.

2.4 Task Four: Generation of CRISPRme-Ready Input Files

2.4.1 Demonstrate the ability to perform CRISPRme analysis without a VCF for each of the three reference genome builds from Ensembl (cattle: ARS- UCD2.0, chicken: bGalGal1.mat.broiler.GRCg7b, and swine: Sus scrofa 11.1) using the most recent CRISPRme version, one gRNA sequence (provided by CVM), one PAM, three mismatches, one bulge RNA, and one bulge DNA. Deliver to CVM the version-stable docker, script, and results via precisionFDA within 20 business days after receipt of data (gRNA sequence).

2.4.2 Identify databases of naturally occurring variants in cattle, chicken, and swine breeds.

2.4.3 Develop and document plan, including sources of naturally occurring variants in cattle, chicken, and swine breeds and indication of which are proposed to be used in this contract, and submit to CVM for approval within 40 business days of data receipt.

2.4.4 Perform all necessary pre-processing steps including but not limited to:

variant normalization, left-alignment, filtering, annotation, and format standardization to ensure compatibility with CRISPRme.

2.4.5 Generate breed-specific VCFs representative of variants in at least two breeds in each of the three species (swine, cattle, and chicken), using genomic coordinates in Ensembl ARS-UCD2.0 (cattle), bGalGal1.mat.broiler.GRCg7b (chicken), and Sus scrofa 11.1 (swine) reference genome builds. These breed-specific VCFs must be formatted and structured for direct use as input into CRISPRme software, analogous to the 1000 Genomes Project or GNOMAD VCFs currently used by CRISPRme.

2.4.6 Generate supplementary required input files, for each species (swine, cattle, and chicken):

a. Genomes from Ensembl chromosome fastas (including autosomes, unplaced contigs, mitochondria, and sex chromosomes)

b. Gene Annotation (--gene_annotation; --annotation)

c. VCFs

d. SampleIDs

2.4.7 Develop and document all scripts and computational workflows used to generate the VCF and supplementary input files, to enable the reuse of these tools for additional species and breeds in the future.

2.4.8 Provide comprehensive documentation including:

a. Data sources used for each species and breed

b. All preprocessing and filtering steps applied

c. Instructions for reproducing the workflow

d. Instructions for applying the workflow to additional breeds and/or species

2.4.9 Perform CRISPRme analysis for each of the three species using the breed-specific VCFs, one gRNA sequence each (provided by CVM), one PAM, three mismatches, one bulge RNA, one bulge DNA, and the generated input files listed under 2.4.6.

2.4.10 Deliver a demonstration of the CRISPRme-ready breed-specific VCFs to CVM technical experts, showing successful integration with CRISPRme software, by virtual meeting, at least 60 business days before the end of the contract period.

2.4.11 Deliver version-stable docker, script, compressed tarball (.tar.gz) of all input files in appropriate subdirectory structure, and full documentation required to execute the most recent CRISPRme version for cattle, chicken, and swine using the compressed tarball, to CVM via precisionFDA at least 30 business days before the end of the contract period. These files will be used by CVM; CVM will also make the files publicly available using precisionFDA or a similar platform.

2.5 Task Five: Final Deliverables and Data Transfer

2.5.1 Prepare and deliver a final, comprehensive analysis report detailing the methodologies, findings, and interpretations for both Task Three (Section 2.3) and Task Four (Section 2.4).

2.5.2 Securely transfer all final deliverables to CVM using precisionFDA. This includes:

a. Complete variant validation results in structured format

(spreadsheet(s))

b. Supporting documentation and evidence for all validated variants

c. CRISPRme-ready breed-specific VCFs and input files for cattle, chicken, and swine.

d. All scripts, workflows, and computational pipelines with full documentation

e. The comprehensive final report.

2.5.3 Ensure all scripts and workflows are executable on Linux operating systems and include dependency management using containerization (Docker) or environment management (Conda) to ensure reproducibility.

2.5.4 Provide all deliverables in formats specified in Section 4 and according to the schedule in Table 1.

3 Contractor Quality Assurance The contractor shall implement and maintain a quality assurance program to ensure all deliverables meet the performance standards specified in this PWS. The contractor's quality assurance program shall include:

3.1 Validation Protocol Standardization: Development and consistent application of documented protocols for variant validation to ensure reproducibility and minimize subjective bias.

3.2 Peer Review: Internal technical review of validation results and workflows by qualified bioinformatics personnel not directly performing the analysis.

3.3 Documentation Standards: Maintenance of detailed records of all analytical decisions, including rationale for variant classification and any deviations from standard protocols.

3.4 Data Integrity: Implementation of version control for all scripts and workflows, and verification procedures to ensure data accuracy during transfer and processing.

3.5 Reproducibility Testing: Verification that all delivered scripts and workflows execute successfully in a clean environment using the provided documentation.

3.6 The contractor shall submit a Quality Assurance Plan describing these procedures within 15 business days of contract award as part of the Project Management Plan (Section 2.1 Task 1).

4 Deliverables

4.1 All deliverables are the property of the FDA. The contractor shall not use the outcomes of this contract for their own purposes or publicize any results without written approval from the TPOC.

4.2 All deliverables shall be submitted via precisionFDA unless an alternative method is approved in writing by the TPOC. Deliverables shall be provided according to the schedule in Table 1 (Due Dates for Key Deliverables) and meet the acceptable quality levels defined in Table 2 (Performance Standards for Key Deliverables).

Table 1: Due Dates for Key Deliverables

Deliverable Frequency Due Date

Project Management & Quality Assurance Plans (2.1.2)

One-Time Due 15 business days after kickoff meeting.

Monthly Status Report (2.1.3) Recurring Due 5th business day every month after kickoff meeting.

Validation Protocol (2.3.1) One-Time Due 20 business days after receipt of data.

CRISPRme Analysis (No VCF) (2.4.1) One-Time Due 20 business days after receipt of data.

Plan to assess naturally occurring variants in cattle, chicken, and swine (2.4.3)

One-Time Due 40 business days after receipt of data.

Progress report for variant validation task (2.3.8)

One-Time Due upon completion of the first 15 variants.

Demonstration of CRISPRme Analysis (With VCF) (2.4.10)

One-Time Due 30 business days before end of contract.

CRISPRme Full Deliverable Package (2.4.11)

One-Time Due 30 business days before end of contract.

Final Validation Results – All Variants (2.3.9)

One-Time Due 30 business days before end of contract.

Final Comprehensive Validation Report (2.3.10)

One-Time Due 30 business days before end of contract.

Table 2: Performance Standards for Key Deliverables Deliverable Performance Standard Acceptable Quality Level (AQL) Surveillance Method Final Validation Results – All Variants

Must include validation results for all variants with clear classification (confirmed/rejected) and supporting evidence, in suitable format (Excel or csv formats).

Dataset is complete, properly formatted, and validation decisions are scientifically defensible based on provided evidence.

100% inspection; CVM will review a random sample of 10% of variants in detail

Final Comprehensive Validation Report

Must accurately describe all methodologies, provide clear interpretation of findings, and include sufficient detail for regulatory review.

Report delivered on time and requires no more than one round of major revisions.

100% inspection by CVM technical experts

CRISPRme Full Deliverable Package

Breed-specific VCFs must be directly usable in CRISPRme without modification and must include variants for all specified breeds.

All code must be executable following provided documentation on a Linux system. Must include dependency management.

Breed-specific VCFs successfully load and execute in CRISPRme during demonstration. Files pass format validation using vcf-validator or bcftools.

Scripts execute successfully in a clean test environment.

Documentation is sufficient for reproduction without contractor assistance.

Functional testing by CVM technical experts

5 Inspection and Acceptance

5.1 General Inspection and Acceptance Procedures

All deliverables under this contract are subject to inspection and acceptance by the Government. The TPOC is the authorized Government official responsible for inspecting deliverables and recommending acceptance or rejection to the Contracting Officer. Only the Contracting Officer has authority to accept deliverables on behalf of the Government.

5.2 Inspection Standards

Deliverables will be inspected against the performance standards and acceptable quality levels (AQLs) specified in Section 4 Table 2 (Performance Standards for Key Deliverables). The Government will use the surveillance methods identified in that table to assess contractor performance.

5.3 Submission and Review Process

5.3.1 The contractor shall submit all deliverables to the TPOC via the method specified in Section 4 (precisionFDA for data deliverables; email for reports and documentation). Upon receipt of each deliverable, the following process applies:

5.3.2 For Written Deliverables (Reports, Documentation, Plans):

a. Acknowledgment of Receipt: The TPOC will acknowledge receipt of the deliverable within 2 business days.

b. Government Review Period: The Government will complete its review and provide written feedback to the contractor within 15 calendar days from the date of receipt for draft deliverables, and within 10 calendar days for final deliverables.

c. Contractor Revision Period: If revisions are required, the contractor shall submit a revised deliverable within 10 business days from receipt of Government comments, unless a different timeframe is specified by the TPOC.

d. Acceptance or Rejection: The Contracting Officer will issue written acceptance or rejection within 5 business days of receiving the TPOC’s recommendation.

5.4 Acknowledgment of Receipt:

The TPOC will acknowledge receipt of the deliverable within 2 business days.

5.5 Government Inspection Period

The Government will complete functional testing and inspection within 20 calendar days from the date of receipt.

5.6 Deficiency Correction Period

If deficiencies are identified (e.g., scripts fail to execute, VCF files are improperly formatted, data is incomplete), the contractor shall correct all deficiencies and resubmit within 10 business days from receipt of the Government's written notice of deficiencies.

5.7 Acceptance or Rejection

The Contracting Officer will issue written acceptance or rejection within 5 business days of receiving the TPOC’s recommendation following successful inspection.

5.8 Inspection Criteria: The Government will inspect deliverables using the following criteria.

5.8.1 Timeliness: Deliverables must be submitted by the due dates specified in

Section 4 Table 1 (Due Dates for Key Deliverables). Late deliverables may be rejected at the Government's discretion.

5.8.2 Completeness: All required elements specified in the PWS must be included. Data deliverables must include all specified files and documentation. Reports must address all required topics and questions.

5.8.3 Technical Accuracy: Methodologies must be scientifically sound and appropriate for the data type. Variant validation decisions must be supported by clear evidence. VCF files must conform to format specifications and be compatible with CRISPRme. Scripts and workflows must execute successfully as documented.

5.8.4 Quality and Clarity: Reports must be well-organized, clearly written, and free of significant errors. Documentation must be sufficient for a qualified bioinformatician to understand and reproduce the work. Data must be properly formatted and labeled.

5.8.5 Format Compliance: All deliverables must be submitted in the formats specified in Section 4. File naming conventions must be logical and consistent.

5.9 Acceptance

Acceptance of a deliverable will be documented in writing by the Contracting Officer. Acceptance constitutes the Government's agreement that the deliverable meets the requirements of this PWS and satisfies the associated performance standards. Payment for deliverables on a Firm Fixed Price contract will be made only after formal acceptance by the Contracting Officer.

5.10 Rejection

5.10.1 If a deliverable does not meet the requirements of this PWS or fails to satisfy the performance standards in Section 4, the Government may reject the deliverable. Rejection will be documented in writing and will specify:

a. The deficiencies identified

b. The corrective action required

c. The timeframe for resubmission

5.10.2 The contractor shall correct all deficiencies at no additional cost to the Government and resubmit the deliverable within the specified timeframe.

Rejected deliverables will be subject to re-inspection using the same criteria.

5.11 Conditional Acceptance

5.11.1 In limited circumstances, the Government may conditionally accept a deliverable that contains minor deficiencies that do not substantially impair its usefulness. Conditional acceptance will be documented in writing and will specify:

a. The minor deficiencies identified

b. The corrective action required

c. The deadline for final correction. The contractor must correct all identified deficiencies by the specified deadline. Final acceptance will be issued only after all deficiencies are corrected.

5.12 Final Inspection

5.12.1 Prior to contract closeout, the TPOC will conduct a final inspection to verify that:

a. All deliverables have been submitted and accepted

b. All data has been properly transferred via precisionFDA

c. All contract requirements have been satisfied

d. All Government-furnished information has been returned or destroyed as directed

5.12.2 The contractor shall cooperate fully with the final inspection and provide any additional documentation or information requested by the TPOC.

5.13 Quality Assurance Surveillance Plan (QASP)

The Government will monitor contractor performance using the Quality Assurance Surveillance Plan (QASP) shown in Table 3. The QASP identifies performance standards, acceptable quality levels, and surveillance methods for key performance areas.

Table 3: Quality Assurance Surveillance Plan (QASP)

Performance Area Performance Standard Acceptable Quality Level

(AQL)

Surveillance Method Frequency

Timeliness of Deliverables

All deliverables submitted by due dates specified in Section 4 Table 1 100% on-time delivery Review of submission dates Each deliverable

Quality of Written Reports

Reports are complete, accurate, well-organized, and address all required elements

No more than one round of major revisions required for any report

100% inspection by TPOC and technical experts

Each report deliverable

Accuracy of Variant Validation

Variant validation decisions are scientifically defensible and supported by clear evidence

Government review of 10% random sample finds ≥95% agreement with contractor's validation decisions

Random sampling inspection

Upon delivery of validated variants dataset

Functionality of VCFs

VCF files are properly formatted and successfully load into CRISPRme without errors

100% of VCFs pass format validation and function correctly in CRISPRme

Functional testing Upon delivery of VCF files

Reproducibility of Scripts/Workflows

All delivered scripts execute successfully following provided documentation in a clean test environment

100% of scripts execute without critical errors

Functional testing in government test environment

Upon delivery of scripts

Responsiveness to Government Feedback

Contractor addresses Government comments and questions in a timely and thorough manner

Revised deliverables submitted within specified timeframes and adequately address all Government comments

Review of resubmissions

Each revision cycle

Performance Area Performance Standard Acceptable Quality Level

(AQL)

Surveillance Method Frequency

Meeting Participation

Contractor personnel attend scheduled meetings and provide meaningful updates and technical discussion

100% attendance at required meetings; substantive participation

Attendance records and meeting notes

Each scheduled meeting

5.14 Contractor Notification of Issues

5.14.1 The contractor shall immediately notify the TPOC in writing of any issues that may impact the quality, completeness, or timeliness of deliverables, including but not limited to:

a. Data quality problems with government-furnished information

b. Technical challenges that cannot be resolved using standard methods

c. Resource constraints or personnel changes

d. Any circumstances that may cause delays

5.14.2 Early notification allows the Government to work collaboratively with the contractor to resolve issues and minimize impacts to the project schedule.

6 Meetings The contractor shall participate in the following meetings with CVM personnel. All meetings will be conducted virtually unless otherwise specified by the Government. The contractor shall ensure that appropriate technical personnel with direct knowledge of the work are available to participate in all meetings.

6.1 Post-Award Kickoff Meeting

A virtual kickoff meeting shall be held within 15 business days of contract award.

The purpose of this meeting is to:

a. Introduce key personnel from both the Government and contractor teams

b. Review project objectives, scope, and deliverables

c. Establish communication protocols and points of contact

d. Discuss the data transfer process via precisionFDA

e. Review the project timeline and key milestones

f. Address any initial questions or concerns

Required Contractor Attendees: Project Manager and lead technical personnel (bioinformaticians) Government Attendees: Technical Point of Contact (TPOC), and other CVM technical experts as appropriate Duration: Approximately 1 hour

6.2 Mid-Project Technical Review Meeting

A virtual mid-project technical review meeting shall be held approximately 60 business days after data receipt (or as scheduled by the TPOC), coinciding with the delivery of the Mid-Project Validation Progress Report (Section 4). The purpose of this meeting is to:

a. Review preliminary variant validation results for the first 15 variants

b. Discuss the validation methodology and any refinements made during initial analysis

c. Allow CVM technical experts to provide detailed feedback on the validation approach

d. Review progress on CRISPRme breed-specific VCF generation

e. Assess overall project status and timeline

f. Make any necessary adjustments to approach or priorities

Required Contractor Attendees: Project Manager and lead bioinformatics personnel performing variant validation Government Attendees: TPOC and CVM technical experts with expertise in genomics and variant analysis Duration: Approximately 1 hour Contractor Responsibilities: Prepare a detailed technical presentation showing:

a. Examples of validated variants with supporting evidence

b. Methodology and decision criteria used

c. Any challenging cases or ambiguous results

d. Statistical summary of validation results to date

e. Progress on breed-specific VCF generation

f. Be prepared for in-depth technical discussion and questions

6.3 CRISPRme Breed-Specific VCF Demonstration Meeting

A virtual demonstration meeting shall be held at least 30 business days before the end of the contract period, as specified in Section 2.4. The purpose of this meeting is to:

a. Demonstrate the CRISPRme-ready breed-specific VCFs

b. Show successful integration and functionality with CRISPRme software

c. Walk through the workflow and scripts used to generate the breed-specific VCFs

d. Discuss data sources and preprocessing steps

e. Address any questions about reproducibility or application to additional breeds or species Required Contractor Attendees: Project Manager and technical personnel who developed the breed-specific VCF generation workflow Government Attendees: TPOC and CVM bioinformatics personnel who will use the VCFs Duration: Approximately 1 hour Contractor Responsibilities:

a. Prepare a live demonstration showing:

• Breed-specific VCF files loading into CRISPRme

• Example CRISPRme analysis using the swine VCFs

• Overview of the generation workflow

b. Provide demonstration materials (test data, example commands) to CVM in advance

c. Be prepared to troubleshoot any technical issues during the demonstration

6.4 Final Review and Closeout Meeting

A virtual contract closeout meeting shall be held within 10 business days before the contract end date, or as scheduled by the TPOC. The purpose of this meeting is to:

a. Review all final deliverables and confirm completeness

b. Verify that all contract requirements have been met

c. Discuss any outstanding issues or final revisions needed

d. Confirm successful transfer of all data and materials via precisionFDA

e. Review lessons learned and feedback for potential future work

f. Discuss final administrative requirements for contract closeout

Required Contractor Attendees: Project Manager and key technical personnel Government Attendees: TPOC, Contracting Officer (optional), and other CVM personnel as appropriate Duration: Approximately 1 hour

6.5 Ad Hoc Technical Discussions

In addition to the scheduled meetings above, the Government may request ad hoc technical discussions via phone, video conference, or email to address specific questions or issues as they arise. The contractor shall make reasonable efforts to accommodate such requests and respond within 5 business days of the Government's request. These informal discussions do not replace the required meetings specified above and are not considered formal deliverables.

6.6 Virtual Meeting Platform

All virtual meetings will be conducted using a Government-approved platform (i.e., Microsoft Teams). The Government will provide meeting invitations and connection information. The contractor is responsible for ensuring their personnel have the necessary technology and internet connectivity to participate effectively in virtual meetings.

6.7 Meeting Summary Table

For quick reference, Table 4 summarizes all required meetings

Table 4: Required Meetings Summary

Meeting Timing Duration Key Purpose Contractor Deliverable

Kickoff Meeting

Within 15 business days of award

1 hour Project initiation, establish protocols

None (participation required)

Mid-Project Technical Review

~60 days after data receipt

1 hour

Review preliminary validation results and CRISPRme breed-specific VCFs, get feedback

Detailed technical presentation with validation examples and status of generation of breed-specific VCFs for CRISPRme.

CRISPRme VCF Demonstration

30 business days before contract end

1 hour Demonstrate VCF functionality

Live demonstration with test materials

Final Review/Closeout

Within 10 business days before contract end

1 hour Confirm completion, closeout

None (participation required)

Ad Hoc Discussions As needed Variable Address specific technical questions Response within 5 business days

7 Required Travel and Other Direct Costs (ODCs)

No travel is required.

8 Constraints and Special Instructions

8.1 Data Transfer and Computing Environment Requirements

8.1.1 PrecisionFDA Requirement: The contractor shall use precisionFDA

(https://precision.fda.gov/) for all data receipt from and delivery to CVM.

The contractor must establish a precisionFDA account prior to contract award or within 5 business days of award. Alternative methods of data transfer will not be accepted unless approved in writing by the TPOC.

8.1.2 Data Security: The contractor shall implement appropriate security measures to protect all government-furnished data from unauthorized access, modification, or disclosure. Data shall be stored on encrypted systems with access limited to authorized personnel only.

8.2 Subcontracting Prohibition

The contractor shall not subcontract any portion of the work under this contract without prior written approval from the Contracting Officer. All work must be performed by the prime contractor's personnel.

8.3 Software and Computational Requirements

8.3.1 All scripts and workflows delivered under this contract must be executable on Linux operating systems (CentOS 7 or later, or Ubuntu 20.04 or later).

The contractor shall use widely adopted, well-supported languages and tools for all bioinformatics analysis. Acceptable options include, but are not limited to:

a. Scripting languages: Bash, Python, R

b. Standard Unix/Linux utilities: sed, awk, grep, cut, sort, uniq, and other

POSIX-compliant command-line tools

c. Domain-specific tools: Established bioinformatics software packages

(e.g., samtools, bcftools, bedtools)

8.3.2 All software dependencies must be managed using containerization

(Docker preferred) or environment management tools (Conda/Mamba acceptable).

8.3.3 All delivered code must include a README file with clear installation and execution instructions.

8.4 Data Rights

All data, reports, software, and other materials produced under this contract are the sole property of the U.S. Government. The contractor shall not publish, present, or otherwise disclose any information related to this contract without prior written approval from the Contracting Officer.

8.5 Personnel Qualifications

The contractor shall assign personnel with demonstrated expertise in:

a. Bioinformatics analysis of whole-genome sequencing data

b. Variant calling and validation methodologies

c. Structural variant analysis

d. VCF file format specifications and manipulation

e. CRISPR/Cas9 genome editing technologies (preferred)

f. Swine genomics (publications preferred)

8.6 Continuity of Services

Key personnel assigned to this contract shall remain assigned for the duration of the contract. Any proposed changes to key personnel must be submitted to the TPOC for approval at least 15 business days prior to the proposed change, along with qualifications of proposed replacement personnel.

9 Government Furnished Property/Equipment/Information

9.1 The Government will furnish the following information and data to the contractor:

Table 5: Government-Furnished Information and Data

Item Description Format Quantity Delivery Method Timing

Whole genome sequencing alignments

BWA-MEM alignments of paired-end Illumina sequencing data for 73 swine samples (70 cases, 3 controls; 20-70X sequencing depth of coverage) and index files.

BAM format with indices 73 sets precisionFDA

Within 10 business days of contract award

Variant call files

Filtered VCF files from FreeBayes variant caller (one multi-sample VCF)

VCF format 1 file precisionFDA Within 10 business days of contract award

Variant call files

Filtered VCF files from LUMPY structural variant caller (one/sample)

VCF format 73 files precisionFDA Within 10 business days of contract award

Item Description Format Quantity Delivery Method Timing

Sample metadata

Sample identifiers, case/control status, sex, and relevant experimental information

Spreadsheet (Excel or

CSV)

1 file precisionFDA Within 10 business days of contract award

Reference genomes

ARS-UCD2.0,

bGalGal1.mat.broiler.GRCg7b, and Sus scrofa 11.1 reference genomes from Ensembl release

FASTA

format 3 files

Public URLs:

https://ftp.ensembl.org/pub/release- 115/fasta/sus_scrofa/dna/ https://ftp.ensembl.org/pub/release- 115/fasta/bos_taurus/dna/ https://ftp.ensembl.org/pub/release- 115/fasta/gallus_gallus/dna/

Within 10 business days of contract award https://ftp.ensembl.org/pub/release-115/fasta/sus_scrofa/dna/ https://ftp.ensembl.org/pub/release-115/fasta/sus_scrofa/dna/ https://ftp.ensembl.org/pub/release-115/fasta/bos_taurus/dna/ https://ftp.ensembl.org/pub/release-115/fasta/bos_taurus/dna/ https://ftp.ensembl.org/pub/release-115/fasta/gallus_gallus/dna/ https://ftp.ensembl.org/pub/release-115/fasta/gallus_gallus/dna/

9.2 Condition of Government-Furnished Information

All government-furnished data is provided "as-is." The contractor is responsible for performing quality control checks upon receipt and notifying the COR immediately of any data quality issues or missing files.

9.3 Contractor Responsibilities

The contractor shall:

a. Acknowledge receipt of all government-furnished information within 2 business days of delivery

b. Maintain the security and integrity of all government-furnished data

c. Return or securely destroy all government-furnished data upon contract completion or termination, as directed by the Contracting Officer

10 Glossary of Abbreviations and Acronyms

Abbreviation/Acronym Definition

AQL Acceptable Quality Level

BAM Binary Alignment Map (file format for storing sequence alignment data) bp Base pair

CDRL Contract Data Requirements List

CRISPR Clustered Regularly Interspaced Short Palindromic Repeats

Cas9 CRISPR-associated protein 9

CSV Comma-Separated Values (file format)

CVM Center for Veterinary Medicine

FAR Federal Acquisition Regulation

FASTA Text-based format for representing nucleotide or protein sequences gRNA Guide RNA used in CRISPR/Cas9 editing

IGV Integrative Genomics Viewer

PSC Product or Service Code

PWS Performance Work Statement

QC Quality Control

QASP Quality Assurance Surveillance Plan

SOO Statement of Objectives

SOW Statement of Work

TPOC Technical Point of Contact

VCF Variant Call Format (file format for storing gene sequence variations)

WGS Whole Genome Sequencing

GOVERNMENT POINTS OF CONTACT

Contracting Officer (CO)

• Name and Position: Ian Weiss, Contracting Officer

• Phone: 240-402-2773

• Email: ian.weiss@fda.hhs.gov

Contract Specialist (CS)

• Name and Position: Samad Sahil, Contract Specialist

• Email: samad.sahil@fda.hhs.gov

Contracting Officer’s Representative (COR)

• Name and Position: Tina Crosby, Contracting Officer’s Representative

• Phone:

• Email: tina.crosby@fda.hhs.gov

Contracting Officer’s Authority

The Contracting Officer (CO) identified above has responsibility for ensuring the performance of all necessary actions for effective contracting, ensuring compliance with the terms of the Purchase Order, and safeguarding the interests of the United States in its contractual relationships. The CO is the only individual who has the authority to enter into, administer, or terminate this Purchase Order and is the only person authorized to approve changes to any of the requirements under this Purchase Order; notwithstanding any provision contained elsewhere in this Purchase Order, this authority remains solely with the CO.

No statement, whether oral or written, by anyone other than the CO, shall be interpreted as modifying the terms and conditions of the Purchase Order. It is the Contractor’s responsibility to contact the CO immediately if there is even the appearance of any technical direction that is or may be outside the scope of the Purchase Order. The Government will not reimburse the Contractor for any work not authorized by the CO.

COMPLIANCES

Contractor Compliance mailto:ian.weiss@fda.hhs.gov mailto:Amanda.Lusk@fda.hhs.gov mailto:tina.crosby@fda.hhs.gov

The Contractor shall be responsible for knowledge of, and compliance with all applicable federal information technology and information management laws, regulations, policies, and standards at the government-wide, HHS, and FDA levels. At the government-wide level, these include Office of Management and Budget (OMB), National Institute of Standards and Technology (NIST), and General Accounting Office (GAO). These can be primarily found at or through the Federal CIO Council website at: http://www.cio.gov/. HHS documents are found at:

http://www.hhs.gov/

GOVERNMENT CLOSURES AND FEDERAL HOLIDAYS

Recognized Federal Holidays – The Contractor is not required to provide on-site services on the following days that are Federal Holidays or on any other day designated as a Federal holiday for the Washington, D.C. area:

• New Year’s Day

• Martin Luther King, Jr.’s Birthday

• Washington’s Birthday

• Memorial Day

• Juneteenth National Independence Day

• Independence Day

• Labor Day

• Columbus Day

• Veterans Day

• Thanksgiving Day

• Christmas Day

Inclement Weather – The Contractor is not required to provide on-site service on days when the Federal Government is closed due to inclement weather. The Contractor is required to follow, as a minimum, other directives issued by the U.S. Office of Personnel Management (OPM) or other such official for late arrivals due to inclement weather (unless otherwise specified in the Purchase Order).

In the event the Federal Government is closed by order of the President of the United States or OPM for any reason, or the agency, the Center or the building is closed for administrative or safety reasons, the Contractor shall follow directives issued by the COR or Contracting Officer concerning reporting for work. In the event of early closings, the Contractor may be approved to leave early at the discretion of the COR and/or local policy.

http://www.hhs.gov/

INVOICING INSTRUCTIONS AND REQUIREMENTS

11. Department of Health and Human Services (HHS) Acquisition Regulation (HHSAR) 352.232-71 - Electronic Submission of Payment Requests (FEB 2022)

(a) Definitions. As used in this clause-

Payment request means a bill, voucher, invoice, or request for contract financing payment with associated supporting documentation. The payment request must comply with the requirements identified in FAR 32.905(b), "Content of Invoices" and the applicable Payment clause included in this contract.

(b) Except as provided in paragraph (c) of this clause, the Contractor shall submit payment requests electronically using the Department of Treasury Invoice…