Immune Assay BAA 8.4 Questions and Responses.pdf

April 17, 2023 1

Responses to Questions: BARDA BAA AOI 8.4 COVID-19 Immune Assays(s)

Development and Implementation Question

Questions/Concerns/Assumptions Responses

1 While our company does not quantitate antibodies using electrochemiluminescence, we use a Luminex based platform for isotype/subclassing and Fc receptor binding of antigen-specific antibodies. Our company has extensive experience performing these analyses against large multiplexed SARS-CoV2 antigens panels. Does our technology meet the funding requirements?

No, the scope of this solicitation is limited to MSD-ECL platform.

Please refer to the requirements for the MSD binding assay 8.4.1.

(iii).

2 Does BARDA have access to/provide materials for assay development/qualification or is our company responsible for sourcing these materials (e.g., serum, nasal secretions, antigens)?

The contractor is responsible for sourcing the materials for assay development.

3 Our company offers functional profiling of antigen-specific antibodies in 9 different assays.

Does BARDA have interest in this technology as part of our proposal?

No. The scope is limited to assays as stated in the BAA AOI 8.4.

4 Given that our assays are antigen-specific and changes to the antigen panel have impact on our assays, does the government expect to cover the qualification cost of new antigens? For example, should we build into project price the cost of assay qualification of new antigen panels or does the government expect to cover this on a separate basis?

Yes. Plans to change the virus strain should be included. The offeror can provide a per strain change" price with the assumption of 3 strain changes. Please refer to AOI 8.4.1.i, 8.4.1.ii, 8.4.1.iii, 8.4.1.iv, and 8.4.1.v for items stating that "Offerors shall include plans to update the assay target virus as needed based on SARS-CoV-2 variant emergence and evolution....".

5 For AOI 8.4.1., is there a specific technology type that is expected or desired or does Offeror have innovative freedom to propose novel approaches for the immune assays? For example, for 8.4.1.ii, can a technology other than

No, the scope is limited to MSD-ECL platform. Please refer to the requirements for the MSD binding assay 8.4.1. (iii).

April 17, 2023 2 electrochemiluminescence that enables the same multiplexed be accepted or would be less desirable.

6 For 8.4.1, is it expected that Offerors secure off-the-shelf or existing equipment or conduct development activities with novel technologies that may improve multiplex ability, capacity, and sensitivity? Are there any restrictions on timelines for development of immune assays based on novel approaches?

It is expected that the offeror secures off-the-shelf or existing equipment for the development and establishment of immune assays. We are not specifying a particular timeline as it varies from project to project in assay development. It is incumbent on the Offeror to provide a justifiable timeline. Offerors who meet realistic accelerated timelines will receive higher consideration during the evaluation trade-off process.

7 For 8.4, are there specific laboratory classifications or certifications that are expected?

Yes, assays have to be in compliance with GCLP. Please refer to the NIH guidance (https://www.niaid.nih.gov/sites/default/files/gclpstandards.pdf).

Data from these assays should meet regulatory requirements as data may be used to support a U.S. FDA Biological License application (BLA).

8 For AOI 8.4.2, are multiple awards expected? Do Offerors need to have an established laboratory, or can laboratory setup activities be proposed?

Multiple awards are expected. The offeror is required to have an established lab but additional systems to increase sample throughput will be considered. The offeror may sub-contract to a lab with the appropriate facilities.

9 Do Offerors need to address all items under 8.4.1?

No. Offerors can propose establishment of one, all or any combination of selected assays (8.4.1.i through vi).

10 For AOI 8.4.1.vi, are sample collection units only desirable or may point-of-care immune assays be or relevance towards decentralized clinical trial testing?

Would

Decentralized sample collection methods for clinical trials supported by central labs will be considered. Samples collected using the proposed devices/methods should be qualified for testing in USG-developed immune assays. Point of care immune assays will not be considered.

11 What is the expected timeline for developing assays under 8.4.1 and setting up laboratory capacity under 8.4.2?

It is incumbent on the offeror to provide a justifiable timeline for the activities including but not limited to assay development (including qualification and validation), partial validation, strain change (upon USG request), evaluation and high throughput testing. Offerors who meet realistic accelerated timelines will receive higher consideration in the evaluation trade-off process.

12 Are there certain characteristics or capabilities expected by Offerors proposed solutions for 8.4.1 and/or 8.4.2?

Yes, assays have to be in compliant with GCLP. Please refer to the NIH guidance (https://www.niaid.nih.gov/sites/default/files/gclpstandards.pdf) . Data from these assays should meet regulatory requirements as data may be used to support a U.S. FDA Biological License application (BLA).

13 Are there any budgetary guidelines and timelines for review time?

Aside from the instructions provided in the BAA solicitation, there are no additional budgetary guidelines for AOI 8.4. For the AOI #8.4 the USG's goal is to award a contract on an accelerated timeline.

April 17, 2023 3

14 For 8.4.2.i, is multiplexing of more than 4 variants desirable?

Yes, they will be considered.

15 Throughout 8.4., there are multiplex requirements for updating assays and performing vaccine-product specific partial validation pending FDA requirements? How should these activities be proposed as there is uncertainty in scope, budgetary requirements, timeline.

For the partial validation requirement, USG will provide the incurred (40-50) samples for each new candidate vaccine and the validations will be performed sequentially.

16 For 8.4.2, how long should budgets last after laboratories have been established? How long should personnel be retained under this program? Is this a multi-year contract following the establishing of labs?

AOI#8.4 is not to establish a laboratory it is to establish assay capability. Assay capability will be maintained for the duration of the contract period of performance.

17 How will contracting to be done between USG and Offeror once capacity is established? Will new contracts be made or is it expected that such contracts should be proposed herein.

The USG requirement is for a single contract for each immune assay establishment (including qualification and validation) and high throughput sample evaluations. At this time, there are no plans for contracts beyond this requirement.

18 Is there an expected or desired timeframe for updating assays?

Offerors shall include plans to update the assay target virus as needed based on SARS-CoV-2 variant emergence and evolution, within 2 months of USG request (and availability of appropriate reagents).

19 Will 8.4.2 provide funding to expand laboratory space and purchase equipment designed for automation?

No. No construction or renovation will be supported. The offeror is required to have an established lab but additional systems to increase sample throughput will be considered.

20 Are the target weekly capacities reflective of the expected target capacity or would more volume of relevance?

The throughput listed is reflective of the maximum surge capacity that the labs should have; testing volumes will fluctuate and elastic throughput is desirable.

21 I was wondering if the submission would be confidential?

Also, what is the scope and expected budget for this proposal?

See FAR 3.104-4 Disclosure, protection, and marking of contractor bid or proposal information and source selection information.

For scope, please refer to the requirements listed in the BAA

8.4.1 and 8.4.2. The offeror is expected to propose a budget based on their approach.

22 A highly complex laboratory has developed quantitative IgG assays for SARS-CoV-2 RBD, S1, and Nucleocapsid proteins. These assays were submitted for EUA to the FDA and denied because of low priority. Would these assays, submissions attached, be

No, the scope of this solicitation is limited to MSD-ECL platform.

Please refer to the requirements for the MSD binding assay 8.4.1.

(iii)

April 17, 2023 4 acceptable candidates for this offering?

23 Does BARDA agree that the proposal can include studies correlating the SARS-CoV-2 neutralizing antibody levels (semi-quantitative or quantitative) with immuno-protection would be valuable in the evaluation of the efficacy of COVID-19 vaccines, assessing herd immunity and for screening of convalescent plasma?

No. Please refer to the requirements for the PSV binding assay 8.4.1(i).

24 Can BARDA clarify that for the Qualification and Validation studies, “sensitivity and specificity” on page 50 of BAA-18- 100-SOL-00003 refers to analytical or clinical sensitivity and specificity? If referring to clinical sensitivity, would a validated PRNT assay serve as the comparator method?

BARDA clarifies that qualification and validation studies refer to antibody functional levels and should include parameters such as analytical and clinical, sensitivity, precision and dilutional linearity. A validated PRNT comparator could be considered.

25 Please confirm whether BARDA will be responsive to novel serological assays that uses different detection technologies than electrochemiluminescence (MSD) or Chemiluminescent (ELISA) based detection technologies?

No, the scope of this solicitation is limited to MSD-ECL platform.

Please refer to the requirements for the MSD binding assay 8.4.1.

(iii)

26 Please confirm whether BARDA will be responsive to including other respiratory pathogens in our Multiplex assay, in addition to COVID-19 and its variants?

No. This AOI is limited to SARS-CoV-2 and its variants

27 Section 1 iii requests multiplex MSD antibody binding assays be developed.

Can alternative platforms such as Luminex be proposed as opposed to the Meso Scale Discovery (MSD- ECL) method?

No, the scope of this solicitation is limited to MSD-ECL platform.

Please refer to the requirements for the MSD binding assay 8.4.1.

(iii).

28 Section 1 iv. requests establish MSD-based multiplexed angiotensin-converting enzyme 2 (ACE2) receptor blocking assays to the SARS-CoV-2 Spike and RBD antigens, including variants of the

No. Please refer to the requirements for the MSD based receptor blocking assay 8.4.1.(iv).

April 17, 2023 5

SARS-CoV-2 virus for sera and mucosal samples.

Can alternative platforms, including ELISA, be proposed as opposed to the MSD-based multiplexed platform?

29 What is the minimum TRL required for a successful submission for each of the subsections of AOI 8.4?

There are no minimum TRLs. Proposals with feasibility data will receive higher consideration in the evaluation trade-off process.

30 Is it mandatory that solutions for 8.4.1.ii. use electrochemiluminescence, rather than alternative detection technologies of sufficient sensitivity and specificity?

Yes, it is mandatory to use MSD-ECL platform. Please refer to the requirements for the MSD binding assay 8.4.1.(ii and iii).

31 For 8.4.1.iii., would pilot data restricted to IgG be sufficient for a competitive proposal?

Proposals with IgG and IgA feasibility data will receive higher consideration in the evaluation trade-off process.

32 Is it mandatory that solutions for 8.4.1.v. use intracellular staining, rather than alternative detection technologies of sufficient sensitivity and specificity?

Yes, it is mandatory to use intracellular cytokine staining (ICS).

Please refer to the ICS requirements listed in 8.4.1.(v).

33 For the T cell assay against SARS- CoV-2, am I correct to interpret the instructions that there is no initial Quad Chart/White Paper, but that a full application is due May 3?

AOI #8.4 is open until May 17, 2023 at 4:30 PM Eastern Time (unless amended). An initial Quad Chart/White Paper will not be sought for this area of interest. Offerors must submit Full Proposals in accordance with the instructions provided in Part VI Full Proposal Instructions of the BAA.

34 For exploratory assays, is there interest in characterizing potential changes in B cell epitope profiles with neutralization with new variants?

No.

35 Is there interest in assays characterizing longitudinal responses using epitopes

No.

36 How do previous exposures/vaccinations affect/or not new epitope profiles and neutralization

No.

37 What throughput is expected for exploratory assays?

Throughput requirement is described in 8.4.2 (i through iv).

38 Please inform about the fit of such development and application to the Area of Interest 8.4. Please inform about contact with relevant program directors prior to submission and mechanism of

The scope is described in AOI# 8.4.1 and 8.4.2. There will be no contact with program prior to submission of the proposal unless a TechWatch is approved and scheduled. Please submit full proposals by the due date as indicated in the deadline in the BAA.

April 17, 2023 6 submitting the proposal.

Is there an invitation required and how to obtain it?

39 Will a meeting by teleconference be available prior to the submission deadline?

There will be no contact with program prior to submission of the proposal unless a TechWatch is approved and scheduled.

40 Do you consider highly sensitive multiplexed lateral flow tests?

No.

41 Do you consider a 12 channel (available) or 48 channel (under development) dry fluorescence lateral flow reader a high throughput assay?

No.

42 Do you accept classical nanobeads based quantitative lateral flow test plus a 12 channel reader?

No.

43 We would like to inquire as to whether a point of care testing platform for quantifying neutralizing antibody titer against all SARS-CoV-2 variants, and designed to provide normalized results across all testing sites, would be within the goals of this AOI?

No. The scope of this solicitation is limited to lentivirus- based psedovirus assay. Please refer to the requirements in 8.4.1. (i).

44 Is there a preference or expectation for the type of Offeror? I.e., university, laboratory company, diagnostics company?

That is to ask, will there be a preference between a large or small company proposing activities? What bearing does Offeror type have on proposal favorability?

There is no preference or expectation for type of offeror. The offeror is required to have an established lab with quality systems in place, capacity for high throughput sample evaluations, and regulatory compliance as required in this solicitation.

45 Is the Topic more focused on the development and novelty aspect of immune assays (for example, assays with improved performance and flexibility to modification updates) or the innate need to increase immune assay capacity, regardless of the novelty.

The scope and focus are described in AOI# 8.4.1 and 8.4.2.

46 The Subject Test is being developed with a focus on IgG but can be easily adapted to read IgA titer by changing the certain reagent(s). Does this have to be

There are no TRL requirements. Proposals with IgG and IgA feasibility data will receive higher consideration.

April 17, 2023 7 demonstrated prior to submission of application for award? If so, what TRL should be demonstrated?

47 The Subject Test is being developed for ELISA and IFA but can be easily adapted to other formats such as:

chemiluminescence, time-resolved fluorescence, and electrochemiluminescence. What TRL should be demonstrated prior to application of award?

There are no TRL requirements. Only proposals with MSD-ECL platform will be considered.

48 For multiplex capability, are you looking exclusively for MSD multiplex (V-Plex) capability or would an alternative multiplex single-well system be considered?

How about multiple wells each with a single target?

For this AOI, MSD multiplex V-plex capability is being sought.

49 The company has done development work for the tests focused on serum and plasma as sample types. Are you requiring feasibility work to be completed with mucosal swabs and saliva prior to application for award? If so, what TRL should be demonstrated?

There are no TRL requirements. Proposals with feasibility data will receive higher consideration in the evaluation trade-off process.

50 We recognize that the AOI#8.4 Full Proposal submission deadline is 3 May 2023 and that a BARDA response will be issued within 120 days of the submission deadline.

Please confirm.

The full proposal submission deadline is extended to May 17, 2023. BARDA anticipates responding on an accelerated timeframe.

51 What start date should AOI#8.4 offerors assume for initial contract award?

For the AOI #8.4 the USG's goal is to award a contract on an accelerated timeline; no firm dates are available at this time.

52 What full period of performance (i.e., 3 years, 5 years, etc.) should AOI#8.4 offerors assume?

It will be a multi-year award(s). Currently, the period of performance depends on the unique features of the proposed effort.

53 Please confirm the number of AOI#8.4 contract awards anticipated (i.e., single-award, multiple-award).

Multiple awards are expected.

54 For AOI#8.4 Key Personnel, can offerors utilize our own company-specific CV format or is the NIH Biosketch format required for each Key person?

NIH biosketch format is required.

April 17, 2023 8

55 Please clarify which assays (and matrices) will support regulatory submission and should be validated and which one are exploratory?

Please proceed with the expectation that all assays and matrices as listed in the AOI will support regulatory submission thus potentially will need to be validated.

56 Will BARDA provide matrices for the development, qualification and validation of all those assays?

The contractor is responsible for sourcing the materials for assay development. For the partial validation requirement, USG will provide the incurred (40-50) samples for each new candidate vaccine and the validations will be performed sequentially. USG will provide samples from decentralized sample collection devices/methods for testing in the offeror's immune assays.

57 Could you please indicate the estimate timeframe for samples analysis (Est. start and end time) for each assays.

It is incumbent on the offeror to provide a justifiable timeline for the activities including but not limited to assay development (including qualification and validation), partial validation, strain change (upon USG request), evaluation and high throughput testing. Offerors who meet realistic accelerated timelines will receive higher consideration in the evaluation trade-off process.

58 Please clarify how many matrices the SARS-CoV-2 pseudovirus neutralization assay is expected to support. Do all the different matrices need to be validated?

Please proceed with the expectation that all matrices listed in

8.4.1. will need to be supported and validated for 8.4.1.(i).

59 Can you please specify if the “testing (of) self-collected samples from various sources” and the subsequent assay modification to support the specific matrices can be done under assay development without fit for purpose qualification or validation?

Please proceed with the expectation that all assays and matrices will support regulatory submision and thus potentially will need to be validated. Research grade assays are not acceptable for sample testing.

60 Are section 8.4.II and 8.4.IV referring to the same assay and can be combined?

This question appears to be in error. There is no 8.4.II and 8.4.IV.

61 Concerning the qualification of methods and devices for collection of clinical samples for use in the immune assays described above.

Can you clarify if the feasibility data will be generated with different assays than described in section 8.4?

Offerors must provide preliminary feasibility data for the methods and devices demonstrating that adequate sensitivity and specificity are achievable in relevant clinical matrices (i.e., sera, blood, nasal secretions and saliva etc.). Feasibility data may include testing with surrogate assays (e.g., metabolic testing or other relevant disease analytes).

Offerors shall provide a qualification strategy that includes sample size calculations and study populations details for a clinical study design. Once the samples are collected as part of these studies, the methods and devices for collection will be qualified in the immune assays described in 8.4.1.

62 We are pleased to offer our current immunoassay, which is an ELISA assay designed to provide qualitative measurements of neutralizing antibodies against COVID infection and immunization. We would like to

The scope of this solicitation is limited to receptor blocking assays based on the MSD platform. Please refer to the requirements in

8.4.1. (iv).

April 17, 2023 9 know if this product fits the scope of your current process.

Responses to Questions: BARDA BAA AOI 8.4 COVID-19 Immune Assays(s) Development and Implementation