Amendment 5_7591024R00006.pdf

Offers must acknowledge receipt of this amendment prior to the hour and date specified in the solicitation or as amended, by one of the following methods:

(a) By completing items 8 and 15, and returning or (c) By separate letter or electronic communication which includes a reference to the solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGMENT TO BE

RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of this amendment you desire to change an offer already submitted, such change may be made by letter or electronic communication, provided each letter or electronic communication makes reference to the solicitation and this amendment, and is received prior to the opening hour and date specified.

E. IMPORTANT: Contractor is not is required to sign this document and return copies to the issuing office.

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT

1. CONTRACT ID CODE

2. AMENDMENT/MODIFICATION NUMBER 3. EFFECTIVE DATE 4. REQUISITION/PURCHASE REQUISITION NUMBER 5. PROJECT NUMBER (If applicable)

7. ADMINISTERED BY (If other than Item 6) CODE

STANDARD FORM 30 (REV. 11/2016)

Prescribed by GSA FAR (48 CFR) 53.243

FACILITY CODE

9A. AMENDMENT OF SOLICITATION NUMBER

9B. DATED (SEE ITEM 11)

10A. MODIFICATION OF CONTRACT/ORDER NUMBER

10B. DATED (SEE ITEM 13)

11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

The above numbered solicitation is amended as set forth in Item 14. The hour and date specified for receipt of Offers is extended. is not extended.

12. ACCOUNTING AND APPROPRIATION DATA (If required) copies of the amendment; (b) By acknowledging receipt of this amendment on each copy of the offer submitted;

13. THIS ITEM APPLIES ONLY TO MODIFICATIONS OF CONTRACTS/ORDERS.

IT MODIFIES THE CONTRACT/ORDER NUMBER AS DESCRIBED IN ITEM 14.

CHECK ONE A. THIS CHANGE ORDER IS ISSUED PURSUANT TO: (Specify authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT ORDER

NUMBER IN ITEM 10A.

B. THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office, appropriation data, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF FAR 43.103(b).

C. THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF:

D. OTHER (Specify type of modification and authority)

Except as provided herein, all terms and conditions of the document referenced in Item 9A or 10A, as heretofore changed, remains unchanged and in full force and effect.

15C. DATE SIGNED

15A. NAME AND TITLE OF SIGNER (Type or print)

16C. DATE SIGNED

16A. NAME AND TITLE OF CONTRACTING OFFICER (Type or print)

14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF section headings, including solicitation/contract subject matter where feasible.)

PAGE OF PAGES

6. ISSUED BY CODE

8. NAME AND ADDRESS OF CONTRACTOR (Number, street, county, State and ZIP Code) (X)

CODE

15B. CONTRACTOR/OFFEROR

(Signature of person authorized to sign)

16B. UNITED STATES OF AMERICA

(Signature of Contracting Officer)

Previous edition unusable

NCI-EXEC

Mandie S. White

The purpose of this amendment is to respond to questions regarding Solicitation No. 75N91024R00006 that were received by the applicable due date and time. See attached Q&A under General for further details. The due date for the submission of proposals is unchanged.

Offerors are required to acknowledge EACH Solicitation Amendment by including EACH Standard Form 30 (SF-30) signed by your organization's signature authority and are required to be submitted with your proposal.

PROPOSAL DUE DATE: FEBRUARY 29, 2024, 5:00PM EDT (Unchanged)

National Institute of Health National Cancer Institute Bethesda, MD 20892-7511

To all potential offerors 75N91024R00006

1 9

02/26/2024

Mandie S. White -S Digitally signed by Mandie S. White -S Date: 2024.02.26 15:23:58 -05'00'

2/26/2024

ARPA-H SBIR SOLICITATION 75N91024R00006

Amendment #5 Questions and Answers

1. QUESTION: For ARPA-H 05 Saving Baby Hearts, If the product has an AI component for the acquisition (e.g. after placement the US beam steered towards the heart), does that component need to be part of the system prior to the 600 neonate clinical trial, or can it be developed during the study period (e.g. having the beam manually steered during the trial)?

ANSWER: There is no defined requirement on this and is therefore subject to your organization’s proposed method.

2. QUESTION: For Topic ARPA-H 05 - Saving Baby Hearts, .RE: Patents and Invention Reporting (Pg 47, 7.18): States “…and requires that anyone exclusively licensed to sell the invention in the United States must normally manufacture it domestically.” Does this provision apply only to groups licensed to sell our device in the US, or does it also apply to us as well, as the manufacturer of record?

a. Our team is collaborating with two separate academic medical institutions as part of our R&D and clinical work. It is highly unlikely that IRBs will be in place prior to submission deadline, but they are in progress. Is it acceptable to detail this in the application and provide the IRB upon finalization? Both institutions as proposed sub-grantees/ project partners have active OHRP FWAs. These are clinical studies by definition, not clinical trials.

i. If not included in the funding request, would our project be able to include study data and technical development from clinical partner sites outside the US? We would still comply with any stated international reporting requirements.

ANSWER: Regarding the provision to manufacture in the U.S., yes, it does apply to manufacturer of record. It is also advisable to detail the status of the IRB approval in your proposal.

All research or research and development work must be performed by the SBC and its subcontractors in the United States (assuming “study data and technical development” is included in the research). Yes, if not included in the funding request, it is possible to include study data and technical development from clinical partner sites outside the United States, so long as international reporting requirements are met.

3. QUESTION: After reviewing all attachments from SAM, we have compiled a list of questions we would like to get clarifications on in order to assemble a competitive proposal to topic ARPA-H 02 – LymphoLab ProDiscover Kit.

• What inspired the writing of this solicitation? Does ARPA-H have a direct need for this kit, or is ARPA-H more concerned about the kit being marketed to other stakeholders?

ANSWER: This solicitation is primarily concerned with marketing the kit to other stakeholders to enable novel research, preclinical models, etc.

• Our company has preliminary and published data using low-throughput PDMS chips demonstrating the recapitulation of various lymphatic functions listed as desired in the topic description. Would a Fast-Track proposal focused more on device scale up and translation be responsive? Or should proposals mainly focus on demonstrating lymphatic vessel function in low-throughput device kits?

ANSWER: All proposals should include some R&D objectives to improve the technology’s capabilities or costs. Later stage, Phase II, proposals may allocate significant costs to manufacturing, translation, and clinical trials activities.

• Does the kit imply that incubation systems be developed as potential parts of the kit?

ANSWER: This is left up to the proposer based on their technology and approach. We encourage proposals to be mindful of price, accessibility, and ease of use.

• May the kit suggest licensing necessary materials for LEC culture (for example, cells and/or culture medium)? Or can the proposer assume that the customer will already have these materials on-hand?

ANSWER: The proposer should decide what makes sense for the kit that they are developing. We encourage proposers to assess, and then outline, how their approach balances novelty, cost and accessibility to ensure commercial success and enable impactful studies into the lymphatic system.

• The solicitation mentions, “Design choices should reflect a strong fit to a specific lymphatic anatomy and regional microenvironment”. Does this imply that a tissue-specific platform might be more responsive than a one-size-fits-all platform? Or might proposers suggest methods and materials to achieve morphological qualities relating to different tissues?

ANSWER: The proposed approach will be left up to the proposer based on their approach and technical justification. Pre-clinical impact and usefulness should be a strong design consideration.

• When ARPA-H calls for a design that “facilitate[s] the study of at least one phenotypic marker”, do they expect that the kit itself contain materials to measure these markers or that the kit can enable the collection of effluent and cells that can be analyzed by other downstream platforms?

ANSWER: The proposed approach will be left up to the proposer based on their approach and technical justification. Proposers must balance innovative approaches with ease of use and affordability and make a strong case justifying their design choice while following the technical evaluations factors defined in the solicitation.

• Does ARPA-H desire a modular kit meaning that individual chips might be assembled into larger platforms (for example, building blocks to a 96-well plate), or does ARPA-H desire a one-size-fits-all solution where users can customize their cell compartmentalization according to their experimental needs?

ANSWER: The proposed approach will be left up to the proposer based on their approach and technical justification.

• Both cell extraction and multi-cellular cultures were listed as strong design considerations. Does ARPA-H expect that tools within the kit be able to separate cell populations extracted from a multi-cellular system? Or can the proposer assume customers have cell sorting capabilities?

ANSWER: Proposers can assume that customers will have cell sorting capabilities.

• How does ARPA-H define a “standardized” assay? Are there functional or morphological metrics that an engineered lymphatic system needs to meet? Does ARPA-H expect the proposer to define these?

ANSWER: The solicitation includes “design considerations” which outline a bare minimum of physiological guidelines that approaches must meet. We encourage proposals to go above and beyond those guidelines where feasible. Further, we encourage designs to be either modular or tailored to assess tissue bed or organ specific lymphatic morphology and functions.

• Are there reproducibility metrics that fall within ARPA-H’s definition of a “standardized” assay kit?

ANSWER: No reproducibility metrics were given in the solicitation, but we encourage proposals to consider the reproducibility and variability of existing commercial in-vitro assays and organ-chip platforms as a reference.

• Are there any specific use cases or disease modalities that ARPA-H is more likely to align with for testing and design purposes or is the submission intended to be as modular as it can be? Is disease-specificity of the kit likely to increase the response of any application?

ANSWER: The is no specific disease that ARPA-H is more likely to align with compared to others. We do encourage strong consideration of how the design may enable studies useful for pre-clinical modeling.

• Is there any rationale behind the term “ProDiscover” in the solicitation title? Does this pertain to any specific requirements that the kit should have?

ANSWER: Broadly we anticipate this kit to enable advanced discovery of “drugs, cells, and factors of the microenvironment on the function and formation of lymphatic vasculature” as outlined in the solicitation.

4. QUESTION: Questions regarding ARPA-H 06 IAM SBIR Solicitation Section 1:

• Does the intended scope encompass primarily access to health IT systems/applications or is it to also included medical devices with embedded IT (e.g., heart rate monitors, x-ray machines, EKGs)?

ANSWER: Both hospital IT systems and medical devices are in scope.

• Please clarify what is encompassed in “hospital operational technology” as meant in this context?

ANSWER: “Hospital operational technology” encompasses all technology currently in operation within the hospital infrastructure.

• Please clarify if the intent is focused on non-person entities (NPEs), individual persons, or both interacting with the IAM capability.

ANSWER: The intent is to minimize the burden on individual medical providers and support staff.

• Please clarify what ARPA/CMS consider “limited overhead IAM model” (i.e., what characteristics define “limited”) or what characteristics would be key to demonstrate in a prototype?

ANSWER: The intent is to provide an integrated vendor- agnostic IAM model. The proposer is encouraged to make this as lightweight as possible to encourage timely and efficient integration.

• Please clarify the scope and parameters of a “simulated small scale medical environment” that is differentiated from “the scale and IT complexity of a twenty-five (25) bed critical access hospital.”

ANSWER: A simulated small scale medical environment is a representative sample of the types and complexity of devices and configurations that would be found in a 25-bed critical access hospital.

• What is included in the environment? What are the boundaries of the environment? What is not included in the environment? Will CMS/the government provide this environment, or would the offeror be required to construct it as part of the effort?

ANSWER: The proposer will provide and determine what is needed in this environment.

• Please clarify if CMS can help facilitate the identification and participation of the types of “small, rural hospitals” for feedback, or if that burden falls solely on the Offeror.

ANSWER: ARPA-H/CMS can likely assist in making connections between the performer and small, rural hospitals.

• Objective: Please elaborate on the definition, types and examples of misconfigurations and their origins desired for detection by leveraging artificial intelligence.

ANSWER: The proposer shall identify examples of misconfigurations in their proposal response.

• “Today, healthcare I.T. environments have minimal connectivity between all the layers of the access control “stack”, from network access controls (NAC) up through clinical application-specific permissions.” Please elaborate on the layers of the access control stack, the clinical applications in-use and the necessary permissions within.

ANSWER: There are a lot of different ways to manage and enforce IAM. The following sentence under Topic 6 has been revised to, “Today, healthcare I.T. environments have minimal connectivity between the different layers of access control, from network access controls (NAC) up through clinical application-specific permissions.

• Is there a list of required APIs the IAM capability must support, and can those be shared?

ANSWER: No specific APIs are required. The solution should provide or enable IAM in a novel and/or uniquely impactful manner.

• Is there a list of required automated workflows the IAM capability must support, and can those be shared?

ANSWER: There is no list of required automated workflows that the IAM must support.

• Who are the individual user types of the system? And what are the goals of the users in/of the system?

ANSWER: The users are hospital staff (nurses/doctors/laboratory staff/etc.) that all have varying levels of access to different clinical systems across a hospitals network. This includes access to electronic medical record systems, laboratory information systems, various medical devices, etc. Implementation of identity and access schemas vary widely across hospitals from centrally managed (Active Directory approach) to disparate/fragmented access schemas. The goal is to develop an approach that maximizes security and the appropriate assignment of access without negatively effecting a hospital staff’s ability to seamlessly deliver patient care.

• For Appendix A, Technical Proposal - Please clarify the request in the Objectives—is it objectives of the Phase I effort being proposed, or a theoretical/potential Phase II/ (is the reference to Phase II a “cut and paste” error?

ANSWER: I believe your question is concerning a typographical error in the Objectives section of Appendix A, Phase I Technical Proposal that was identified and in which incorrectly referenced Phase II. A revised Appendix A Phase I Technical Proposal was provided via Amendment 4 that fixed this error.

• For Appendix A, Technical Proposal - In the Abstract of the Research Plan, where it refers to “long-term objectives” please confirm that this means beyond the period of performance for the Phase 1 effort.

ANSWER: Yes.