B.12 - PWS (Updated) PR# 54561.pdf

Performance-Based Work Statement

Title: Broad SARS-CoV-2 Genomic Sequencing

I. BACKGROUND:

Large-scale viral genomic surveys for SARS-CoV-2 can provide important baseline information for national and state-level surveillance, defining important changes in transmission, identifying unusual or emerging variants, and ultimately: improving public health responses and decision-making with better laboratory data. Even so, routine sequencing of viruses can be challenging in many public health laboratories, due to a number of factors, including the complexity of sequencing and bioinformatic workflows, and limited access to timely remnant samples for sequencing and analysis.

In this work, CDC will conduct genomic surveillance using a random set of samples from across the United States collected by laboratories that also have the capacity to conduct SARS-CoV-2 sequencing.

II. DEFINITIONS

The following definitions are used throughout this work statement.

Jurisdictions under surveillance: Those jurisdictions, which may include some or all fifty (50) states, Washington DC, Puerto Rico and major US territories and possessions, from which the contractor commits to obtaining specimens for surveillance. For this contract, there are two categories of samples representing jurisdictions under surveillance:

CRSP Diagnostic samples:

Remnant specimens obtained from Broad’s Clinical Research Sequencing Platform (CRSP). Currently represents samples from MA, VT, NH, ME, CT, RI, and NY.

External Diagnostic samples:

Specimens obtained from third party clinical, public health, and commercial diagnostic labs with whom we have existing partnerships. These include: Flow Health Diagnostics (primarily southern CA and DCA, and to a lesser extent NY (metro NYC), GA (Atlanta), and WA (Seattle)), COVID Check Colorado (CO), Rhode Island Department of Health (RI), Partners Massachusetts General Brigham Network (mainly Boston area, MA) and University of Massachusetts Medical Center (Worcester, MA). These samples are not tested through the Broad CRSP platform.

Maximum weekly sequencing capacity: The number of SARS-CoV-2 sequences the contractor agrees to provide capacity for under the contract. For this contract, the overall weekly (Sunday 12:00am – Saturday 11:59pm) sequencing target for CRSP Diagnostic samples and External samples will increase over a 6 week period (see table below).

Minimum Jurisdictional weekly sequencing target: The minimum number of SARS-CoV-2 sequences the contractor agrees to provide from each of the jurisdictions under surveillance. For this contract, the jurisdictional weekly sequencing target is: 15 samples each jurisdiction (State) covered by CRSP. It assumes that the sum of these minimums for all jurisdictions will be less than the overall weekly available sequencing capacity.

For this contract, the jurisdictional weekly sequencing target is based only on samples for which contractor can guarantee access (CRSP Diagnostic samples).

Sample source Target Week 1-3 3/1-3/21

Target Week 3-6 3/22-4/11

Target Week 6+-

4/12-TBD

Minimum Weekly Target

Maximum Available Capacity (attempts)

Minimum Weekly Target

Maximum Available Capacity (attempts)

Minimum Weekly Target

Maximum Available Capacity (attempts)

Internal -

CRSP

specimens

Total of 525 samples per week

550 Samples per week2

Total of 1050

2496 Samples per week

Total of 1050

5576 Samples per week

External - Specimens sourced from external testing facilities1

0 samples per week1

1. For External Diagnostic Samples, we currently have active sequencing collaborations and regular sample flow with several partners where diagnostic testing is not performed at the Broad CRSP. These include: Flow Health Diagnostics (primarily southern CA and DCA), COVID Check Colorado (CO), RIDOH (RI), Partners MGB Network (Boston, MA) and UMMC (Worcester, MA). We are in the process of formalizing these sample flows for contractual purposes. In the meantime we are not reporting minimum weekly targets from these sources, although samples will continue to flow and we anticipate weekly coverage from these sources.

We will keep the CDC updated on contractual arrangements with these sources.

2. We are currently reviewing a key process improvement that could increase our capacity by up to 2x in the short term (through 3/21). We will keep the CDC updated on changes to our capacity and actual genomes processed.

III. PROJECT OBJECTIVE:

The contractor must submit regular weekly sequence data from all jurisdictions where it has agreed to provide SARS-CoV-2 sequencing data, including all required metadata. During the course of this contract, CDC may also work with the contractor to designate additional and/or specific geographic regions, time periods, patient populations, settings or outcomes for increased sampling and sequencing, based on evolving scientific and public health priorities, and subject to the capabilities and assessed feasibility of the contractor.

IV. DESCRIPTION OF WORK:

The contractor is expected to provide: rapid access to timely samples that meet surveillance requirements, laboratory processing and sequencing of samples, data and metadata management, and data delivery to CDC according to parameters and specifications in this PWS.

Task 1: SARS-CoV-2 Baseline Genomic Sequencing

Task 1.1 Selection of Residual SARS-CoV-2 Positive Specimens for Sequencing

The contractor shall commit to providing no less than the overall weekly sequencing capacity and the Jurisdictional weekly minimum sequencing target of completed sequences each week for the duration of this contract. In collaboration with CDC, contractor will identify samples from sites to attempt to fill additional available capacity each week. All sequences must meet the delivery and quality expectations set forth below:

a. Contractor(s) shall identify excess, remnant, or residual SARS-CoV-2 positive specimens from PCR diagnostic testing, or nucleic acid extracts, from Clinical Research Sequencing Platform (CRSP)or External Diagnostic sources (tbc). In collaboration with CDC, contractor will work to identify additional external testing sites to receive samples from. From this list, unless otherwise directed, the contractor shall choose generally representative positive samples from each jurisdiction to achieve at least the jurisdictional weekly sequencing target for each jurisdiction to which the contractor is agreeing. Cycle threshold (Ct) values may be consulted in selecting samples for sequencing, and Ct values (or an appropriate surrogate) should be reported to CDC along with other required metadata.

b. The contractor shall select a representative set of SARS-CoV-2 PCR positive samples for genomic sequencing each week. The contractor will be expected to deliver no fewer than the jurisdictional weekly sequencing target, and no greaterthan the maximum available capacity of complete (as defined by Task 1.3) genome sequences and associated metadata to CDC per jurisdiction per week, and with mutual agreement, contractor may deliver additional samples if available. It may be necessary for the contractor to set aside and to process/sequence more than the minimum number of PCR samples in order to consistently meet data delivery requirements of the contract.

c. Samples and data shall be provided to CDC completely de-identified, but with requested metadata attached (see details in Task 1.3.1 and Attachment A). Any concerns over inadvertent re-identification of patient samples should be addressed during regular calls and data exchanges between the contractor(s) and CDC technical staff.

While it is not anticipated that any identifying information for these samples will need to be exchanged during the course of this project, all contractor(s) should retain, where available, the necessary accession numbers and linking information, in the event that future, authorized record linkages and analyses are required. It is anticipated that public health officials from individual state and local jurisdictions may request the necessary linking information to re-identify patient samples, and the contractor should anticipate being able to respond to authorized requests for information as specified in Task 3.

d. Unless otherwise specified, no sample shall be submitted for sequencing if more than 10 days have elapsed since the original patient sample was taken.

Task 1.2 Viral Genomic Sequencing of SARS-CoV-2 from Positive Residual Specimens

a. The contractor(s) shall provide CDC with complete and up-to-date written documentation of any laboratory protocols for sample extraction, nucleic acid quantification, targeted amplification, library construction and sequencing.

b. The contractor(s) shall provide CDC with complete and up-to-date written documentation of any and all sequencing process controls and quality assurance measures.

c. Sequencing runs may be batched as necessary to optimize efficiency, but should be done with the anticipation of ongoing, weekly data delivery to CDC.

d. The Contractor(s) shall retain all extracts, samples and sequencing libraries for a period of 30 days, in the event that repeat sequencing is required, or that a specific virus sample is required for further characterization and culture.

Task 1.3 Sequence Data Formats and Quality Assessment

The contractor(s) shall provide CDC with raw read (FastQ, Fast5, or BAM ) and consensus sequences for SARS CoV-2 viruses from each geographic region/jurisdiction (US State, territory, federal district or possession) each week according to the specifications below:

1. For raw read sequence data:

a. Sequence data shall be assessed for quality trimmed, and submitted to CDC (via the CDC AWS S3) as FastQ, or BAM files.

b. Sequence data and metadata shall be submitted to CDC as available but at minimum on a weekly basis, and by an agreed-upon format and mechanism.

c. All completed sequences shall be delivered to CDC within 14 days of sample submission to Broad for sequencing.

2. For consensus sequences:

a. The reference sequence to be used, unless otherwise specified, is Wuhan-Hu-1 (NC_045512.2)

(https://www.ncbi.nlm.nih.gov/nuccore/NC_045512 ).

b. Consensus sequences failing to meet the following acceptability criteria will not be counted towards sequencing totals. The acceptable consensus sequences shall:

i. measure no less than 26,700 bases.

ii. be composed solely of IUPAC standard characters. “N” should be used to represent ambiguous positions—positions where there is a nucleotide that can’t be determined and will be referred to as indeterminate bases. Consensus sequences shall not consist of over 1.0% indeterminate bases.

Where appropriate, ambiguous positions may be marked at a 25% minor allele frequency with the appropriate IUPAC ambiguity code.

iii. Not consist of over 10% gap filling Ns. A gap filling N is defined as positions in the consensus where the coverage is too low to make a consensus call. Gap filling Ns should represent the estimated length of the gap.

iv. Under no circumstances shall submitted consensus sequences include synthetic backfill from primer or reference sequences when filling gaps. (Note: some common bioinformatic tools may insert these automatically)

v. Consist of a single contig assembly or mapping. The average data coverage of 50x is required if using all the reads. If upstream protocol uses duplicate removal then the average coverage of 10x will be acceptable. CDC recognizes that multiple technologies may be used to accurately sequence SARS-CoV-2 and will review protocols that use other coverage standards.

vi. be well-supported with an average Phred score ≥Q30.

vii. not include markup for suspected indels.

Details on bioinformatic workflows and variant calling approaches shall be provided to CDC and discussed in detail with contract technical staff upon the start of sequencing and bioinformatic activities. CDC shall be notified in writing of any significant change to sequencing or bioinformatic workflows.

3. For sequence-associated metadata:

a. The contractor(s) shall provide CDC with an up-to-date table of detailed sequence metadata for all submitted samples by AWS S3 upload, or other mutually agreed-upon mechanism. It is expected that a complete line list of sample metadata shall accompany each set of BAM/FastQ/FastA files submitted.

b. File format may be tab-separated-values (TSV) or comma-separated-values (CSV) in accordance with the format shown in Attachment A.

Task 1.4 Deposition of SARS-CoV-2 Genomic Sequence Data to CDC and/or Designated Public Sequence Repositories

At CDC’s discretion, and with the agreement and acceptance of the contractor, the contractor may be requested and authorized to submit sequence data directly to public repositories on CDC’s behalf. In the case that both CDC and the contractor agree that the contractor shall submit the sequence data directly to public repositories, the following guidance will apply:

1. Upon completion and quality assurance, all sequences meeting basic acceptability requirements (detailed in Task 1.3 above) shall be deposited immediately by the contractor(s) to GISAID EpiCoV (https://www.gisaid.org), NCBI GenBank and NCBI SRA (https://www.ncbi.nlm.nih.gov/sars-cov-2), with https://www.ncbi.nlm.nih.gov/nuccore/NC_045512 minimum metadata (isolate name, country, state, organism and collection date). Submission of additional metadata fields to public sequence repositories is at the discretion of the contractor.

a. For public sequence submissions, contractors shall simultaneously and immediately deposit approved sequences:

i. Consensus sequences to GISAID EpiCoV and NCBI Genbank.

ii. Raw reads to NCBI Sequence Read Archive (SRA)

iii. Reference (Wuhan-Hu-1)-aligned BAM files to NCBI SRA (optional/if available).

b. The SPHERES umbrella BioProject (PRJNA615625) should be used to link all SRA submissions.

c. Isolate names and sample IDs for each sample must follow the following naming convention: two-letter state/territory abbreviation for the jurisdiction where the virus was collected, an abbreviated designation for the contractor organization, and a unique identifier, all separated by hyphens. (eg: GA-CDC-12345;

PR-CDC-67890). Naming conventions shall be discussed and confirmed at the contract kickoff meeting.

Task 1.5 Sequencing and Submission Report

The contractor will submit a Sequencing Report every 4 weeks on sequencing activities organized by batch/run, jurisdiction. If applicable, the report will also include submission statistics for GISAID, NCBI Genbank, and SRA.

See example report in Attachment B.

Task 2: Directed Sequencing of Designated Geographic Regions, Patient Populations and Outcomes

Task 2.1

1. As required, contractor(s) shall stand ready to identify and sequence specific types of samples from the CRSP based on CDC designations as described below, providing relevant metadata to identify such samples is available to contractors (namely date and location of collection). Performance factors, such as turnaround time, data delivery and sample annotation shall be discussed and negotiated in advance, along with any concerns over data privacy, ethics or inadvertent identification of specific patients or groups.

2. Contractor(s) shall remain capable of implementing a directed sequencing strategy for additional samples from designated geographic regions or patient populations, within one week of written notification from CDC contracting staff. CDC may require additional focused sequencing, based on the following sample criteria:

a. Geographic location of sample collection (state or region);

b. Specific interval or period of time (eg: March 2022);

c. Selection criteria may be combined, and contractors shall indicate which variables may be reliably included for the selection of samples for additional sampling. (eg: specific age ranges within a specific geographic area during a specific period of time).

3. Data delivery, process/performance documentation, metadata expectations, acceptability criteria, turnaround time and deposition requirements remain as specified in Task 1.

Task 3: Laboratory Reporting to States

In accordance with deliverables and tasks as listed and in compliance with the CARES Act, the Contractor(s) is required to report each sample sequenced that identifies SARS-CoV-2 variants to the appropriate state health department. The table in Attachment C provides details and examples for implementation of variant reporting to states. Example messaging formats for variant reporting to state health departments are shown in Attachment D.

The technical implementation guidance is subject to change as new variants of interest are identified and standard codes are added/updated. A website is currently in development that will contain the most current guidance. CDC will inform the contractor when this is available.

V. Performance Requirements Summary

Service Required

Measures of Success

Indicators

Standards – Criteria for Acceptance

Method of Surveillance

“Incentives” Positive or Negative

Task 1.1 Contractor shall perform all tasks/services in accordance with (IAW) what is stated in Task 1.1

100% of Services/tasks adhere to applicable requirements as stated in Task 1.1. With CDC approval, less than 100% may be accepted if the incidence of SARS-CoV-2 infection in the population drops to a point where the minimum # of

COR or Technical assignee approval and observation.

Positive: Past Performance and Evaluation will be used in determining awards for future contracts for similar services;

Negative: Performance evaluations will include any required samples can not be obtained.

services that failed to meet acceptable standards and will be used in determining awards for future contracts for similar services.

Task 1.2, 1.3, 1.4, 1.5, 2, 3

Contractor shall perform all tasks/services in accordance with (IAW) what is stated in Task 1.1, 1.3, 1.4, 1.5, 2, 3

100% of Services/tasks adhere to applicable requirements as stated in Task 1.1, 1.3, 1.4, 1.5, 2, 3

COR or Technical assignee approval and observation.

Positive: Past Performance and Evaluation will be used in determining awards for future contracts for similar services;

Negative: Performance evaluations will include any services that failed to meet acceptable standards and will be used in determining awards for future contracts for similar services.

VI. DELIVERABLES:

Milestone/Deliverable Task Section

Reference

Planned Completion/Due Date

Initial Kickoff Meeting Within 5 calendar days after award

Sample Selection Strategy Description 1.1 At kickoff meeting

Bioinformatic and Sequencing Protocols and SOPs 1.1, 1.2 At kickoff meeting, and when changes are implemented

Progress Meetings 1, 2, 3 Weekly or as requested by CDC

Deposition of raw sequences, consensus, and metadata files.

1.3 As available, but at minimum, weekly

Submission of sequence data to GISAID/NCBI 1.4 Optional, and after approval from CDC

Sequencing and Submission Report 1.5 Within 5 calendar days after each 4 week period

Variant Report Table delivered to State Health Lab 3 As requested by State, with 3 days of request

Final Sequencing and Submission Report Within 10 calendar days of end of contract

VII. SPECIAL REQUIREMENTS/CLAUSES:

VIII. HUMAN SUBJECTS

The test results are not intended to be used as a diagnostic tool and instead identify a marker for past infection with SARS-CoV-2 at some previous undetermined time. It will not be useful to the health or well-being of any individual. Remnant/excess/residual specimens will have all personal identifying information removed. Final results will be presented in aggregate, stratified by location, and it will not be possible to link results to an individual.

IX. HHSAR Provision, 352.239-73: Electronic and Information Technology Accessibility Notice

(a) Section 508 of the Rehabilitation Act of 1973 (29 U.S.C. 794d), as amended by the Workforce Investment Act of 1998 and the Architectural and Transportation Barriers Compliance Board Electronic and Information (EIT) Accessibility Standards (36 CFR part 1194), require that when Federal agencies develop, procure, maintain, or use electronic and information technology, Federal employees with disabilities have access to and use of information and data that is comparable to the access and use by Federal employees who are not individuals with disabilities, unless an undue burden would be imposed on the agency. Section 508 also requires that individuals with disabilities, who are members of the public seeking information or services from a Federal agency, have access to and use of information and data that is comparable to that provided to the public who are not individuals with disabilities, unless an undue burden would be imposed on the agency.

(b) Accordingly, any offeror responding to this solicitation must comply with established HHS EIT accessibility standards. Information about Section 508 is available at http://www.hhs.gov/web/508. The complete text of the Section 508 Final Provisions can be accessed at http://www.access-board.gov/sec508/standards.htm.

(c) The Section 508 accessibility standards applicable to this contract are: 1194.

205 WCAG 2.0 Level A & AA Success Criteria 302 Functional Performance Criteria 502 Inoperability with Assistive Technology

504 Authoring Tools 602 Support Documentation 603 Support Services

In order to facilitate the Government's determination whether proposed EIT supplies meet applicable Section 508 accessibility standards, offerors must submit an HHS Section 508 Product Assessment Template, in accordance with its completion instructions. The purpose of the template is to assist HHS acquisition and program officials in determining whether proposed EIT supplies conform to applicable Section 508 accessibility standards. The template allows offerors or developers to self-evaluate their supplies and documentation detail - whether they conform to a specific Section 508 accessibility standard, and any underway remediation efforts addressing conformance issues. Instructions for preparing the HHS Section 508 Evaluation Template are available under Section 508 policy on the HHS Web site http://hhs.gov/web/508.

In order to facilitate the Government's determination whether proposed EIT services meet applicable Section 508 accessibility standards, offerors must provide enough information to assist the Government in determining that the EIT services conform to Section 508 accessibility standards, including any underway remediation efforts addressing conformance issues.

(d) Respondents to this solicitation must identify any exception to Section 508 requirements. If a offeror claims its supplies or services meet applicable Section 508 accessibility standards, and it is later determined by the Government, i.e., after award of a contract or order, that supplies or services delivered do not conform to the accessibility standards, remediation of the supplies or services to the level of conformance specified in the contract will be the responsibility of the Contractor at its expense.

(e) Electronic content must be accessible to HHS acceptance criteria. Checklist for various formats are available at http://508.hhs.gov/, or from the Section 508 Coordinator listed at https://www.hhs.gov/web/section 508/additional-resources/section-508-contacts/index.html. Materials that are final items for delivery should be accompanied by the appropriate checklist, except upon approval of the Contracting Officer or Representative.

(End of provision)