Summary
The Association of Public Health Laboratories (APHL), in cooperation with the US Centers for Disease Control and Prevention (CDC) Division of Tuberculosis Elimination (DTBE), is seeking to recompete the National Public Health Laboratory (PHL) Drug Susceptibility Testing (DST) Reference Center for
Mycobacterium tuberculosis (MTBC)
providing services for PHLs with low to moderate incidences of MTBC. APHL is seeking to identify one (1) state or local public health laboratory to serve as the Reference Center. This Reference Center will serve as an extension of the CDC DTBE Laboratory Branch and provide services that are complementary to those at CDC. Services provided for PHLs with lower volumes of DST (<50 isolates per year) will include:
molecular detection of drug resistance
growth-based first-line and second-line DST, as applicable;
submission of whole genome sequencing data to CDC for national molecular surveillance purposes
Background
Performing DST is technically demanding; maintaining proficiency in performing DST and interpreting results is critical to ensuring testing accuracy. In recent data from CDC’s Model Performance Evaluation Program for DST of MTBC, 77% (46/60) of participants were PHLs.1 Thirty-seven percent (22/60) of the participating laboratories reported performing ≤50 DST per year.1 CDC currently recommends referral testing for laboratories performing DST for fewer than 50 isolates per year 2.
Second-line DST is critical when isolates are resistant to rifampin (RMP) or any two first-line drugs and in situations where additional information is needed to design an effective treatment regimen (e.g., drug intolerance). Second-line DST methods are not standardized and currently, there are no FDA-cleared assays for this purpose. Therefore, laboratories may choose to follow established consensus guidelines (e.g., CLSI or WHO) or evaluate their own in-house test concentrations and interpretive criteria. In the National TB Laboratory Aggregate Report, only 21% (12/58) of PHLs performed second-line DST while other PHLs referred second-line DST to another laboratory for testing.
Molecular detection of mutations associated with drug resistance provides rapid results within hours or days versus the weeks required for growth-based DST. Performing molecular testing such as sequencing requires technical expertise and extensive experience in interpreting test results. Laboratories performing this testing must have competent staff, be able to provide consultative services, and continually adapt to advancements in the field. These requisites may limit the number of laboratories providing molecular testing for drug resistance, however, advancements in the predictive value of genetic determinants are rapidly progressing3 with some laboratories choosing to provide molecular testing as a primary methodology.
Eligibility
Eligible laboratories include all PHLs with the following capabilities, resources, and facilities in place. Specific expectations regarding the methodologies to be used by the Reference Center are outlined in Appendix A: Expectations for National PHL DST Reference Center for MTBC. All applicants are required to agree to the following minimum requirements (as outlined in Appendix B: Minimum Requirements for National PHL DST Reference Center for MTBC):
1. Availability of necessary equipment (e.g., MGIT) or ability to purchase additional equipment if necessary, anticipating testing for up to 500 samples per year (molecular and first-line DST);
2. Availability of adequate laboratory space (including infrastructure for unidirectional workflow for molecular testing) or space to accommodate additional equipment if necessary, anticipating up to 500 additional samples per year (molecular and first-line DST);
3. Sufficient workforce capacity for expanded testing volume or ability to hire additional qualified staff;
4. Established capacity for MTBC culture and both first- and second-line phenotypic DST methods;
5. Established capacity to perform molecular susceptibility testing for MTBC
a. Applications that include molecular testing as the primary method are preferred;
b. Whole genome sequencing (WGS) must be available in the laboratory for MTBC
- Applicants may have established WGS for surveillance purposes with an intent to fully implement for CLIA-compliant molecular susceptibility testing by the date of contract award
6. Participation in CDC’s Model Performance Evaluation Program (MPEP);
7. Willingness to alter or amend existing testing protocols;
8. Willingness to increase frequency of performing certain methods (if required) to meet expected turnaround times;
9. Willingness to amend specimen submission form(s) to include additional variables;
10. Willingness to alter existing reporting language to a standardized reporting language with input from APHL/CDC;
11. Willingness to share copies of QA or biosafety documentation associated with relevant procedures to APHL and CDC upon request;
12. Informatics capabilities:
a. Laboratory Information Management System in place and able to be enhanced or modified to meet susceptibility test algorithms, workflows, submission requirements, and reporting language and Electronic Test Order and Results (ETOR)
b. Proven capability to support ETOR, either through an existing web portal or through standardized messaging
OR
c. Ability to adopt APHL’s LabWeb Portal Solution, hosted on the APHL Informatics Services platform (AIMS) using LIMSConnect
13. Ability to perform and report results from laboratory developed tests according to applicable regulatory requirements including those from FDA.
Anticipated RFP Schedule
August
5, 2024 – RFP Issued
August 26, 2024 – Letter of Intent Due to APHL (see below)
August 29, 2024 – Informational Teleconference, if necessary (Q&A)
September 27, 2024 – RFP Responses Due
October
11, 2024 – Proposal
Reviews
Completed
October 14-16, 2024 – Follow-up
Interviews and
Updated
Proposals
Due (as needed)
October
18, 2024 – Final
Review
Completed and
Awardee
Selected
Spring 2025 – Site visit,
Harmonization, Validations, and
Other Pre-Planning (as needed)
July 1, 2025 – First
Year
Contract
Awarded
APHL will communicate any modification to this anticipated schedule on APHL’s procurement website (www.aphl.org/rfp) and via email blast to PHLs.
Final Response
APHL must receive complete responses by
11:59 pm EST on
September 27, 2024.
Please see Proposal-Required Submissions section for items that must be included in the completed proposal. Applicants may send proposals
via email to
sarah.buss@aphl.org
with copy to
infectious.diseases@aphl.org.
RFP Materials
The Official RFP Document will provide detailed information. APHL will post all RFP-related documents, current schedule information, and answers to submitted questions and clarifications on APHL's procurement site, www.aphl.org/rfp.
Questions and Answers
The RFP mentions that “Applications that include molecular testing as the primary method are preferred”. Should universal molecular testing be performed on every specimen and if so should algorithms always include phenotypic drug susceptibility testing or are algorithms that rely solely upon molecular testing acceptable?
A:The expectation is that universal WGS will be performed for all isolates submitted to the reference center. Alternative algorithms that rely upon molecular drug susceptibility testing with reflex to phenotypic testing in certain situations are acceptable, as are algorithms that incorporate both routine molecular and phenotypic testing. However, every applicant must have the ability to perform whole genome sequencing, molecular detection of drug resistance (by WGS +/- tNGS or Sanger sequencing) and growth-based first-line and second-line DST.
Are algorithms that involve molecular testing followed by reflex phenotypic testing only in certain situations preferred?
A:There is no preference, but please include a detailed description of your proposed algorithms.
When calculating the budget, should you include estimations of the volumes based on previous years numbers (if current reference center) or on a general number of 500 samples a year.
A:Calculation of testing cost per specimen (and per method) is preferred. To generate this per specimen testing figure, it would be advisable to use the volume estimate of 500 samples a year if necessary.
Should a one year or five-year budget be prepared?
A:A one-year budget should be prepared. However, as the RFP states, “By accepting this award, the laboratory agrees to the negotiated rate for up to a five (5) year time span barring substantive changes in scope or material expenses at APHL’s discretion.”
As cost of living continues to rise, are salaries subject to the same budgetary requirements.
A:As the RFP states, “By accepting this award, the laboratory agrees to the negotiated rate for up to a five (5) year time span barring substantive changes in scope or material expenses at APHL’s discretion.”
You mentioned that proposals should be 10 double-spaced pages, but the application says 10 single-spaced pages. Which is it?
A:I misspoke. It should be what is stated in the RFP “no more than ten (10) single spaced pages (font size >11pt, 1 inch margins)”
The RFP questions ask about procedures used for validating LDTs. How are laboratories expected to address the FDA LDT Rule?
A:We do not expect laboratories to detail their plans for maintaining compliance with the FDA LDT rule or have a plan in place, as there are too many unknowns at this time. However, applicants should address their general experience with evaluation and implementation of new methods, including validation procedures. Applicants should also express their awareness of and willingness to meet requirements associated with the FDA LDT rule.