PHS2013-1_RFP.pdf

OMB No. 0990-0115

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES PHS 2013-1

SOLICITATION OF

THE NATIONAL INSTITUTES OF HEALTH AND

THE CENTERS FOR DISEASE CONTROL

AND PREVENTION

FOR

SMALL

BUSINESS

INNOVATION

RESEARCH

CONTRACT PROPOSALS

Internet: http://sbir.nih.gov

PROPOSAL RECEIPT DATE

NOVEMBER 13, 2012

http://sbir.nih.gov/

PHS 2013-1, Solicitation for SBIR Contract Proposals ii

TABLE OF CONTENTS

PART I INSTRUCTIONS FOR PREPARING AND SUBMITTING A PROPOSAL

1. PROGRAM DESCRIPTION

1.1 PURPOSE OF SOLICITATION

1.2 THREE PHASE PROGRAM

1.3 AWARDING COMPONENTS

NATIONAL INSTITUTES OF HEALTH (NIH)

CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC)

1.4 SBIR PROGRAM ELIGIBILITY

1.5 REPORT FRAUD, WASTE AND ABUSE

2. AGENCY CONTACT FOR INFORMATION

3. DEFINITIONS

4. PHASE I PROPOSAL PREPARATION INSTRUCTIONS AND REQUIREMENTS

4.1 LIMITATIONS ON LENGTH OF PROPOSAL

4.2 TECHNICAL PROPOSAL FORMAT AND CONTENT REQUIREMENTS

4.2.1 TECHNICAL PROPOSAL COVER SHEET

4.2.2 ABSTRACT OF RESEARCH PLAN

4.2.3 RESEARCH PLAN

4.2.4 CURRENT AWARDS AND PENDING PROPOSALS/APPLICATIONS

4.2.5 PRIOR SBIR PHASE II AWARDS

4.2.6 PROPOSED COST BREAKDOWN

4.2.7 STREAMLINING THE CONTRACTING PROCESS

4.2.8 REQUIREMENT FOR ADEQUATE ASSURANCE OF PROTECTION OF HUMAN SUBJECTS

4.2.9 REQUIREMENT FOR ADEQUATE ASSURANCE OF COMPLIANCE WITH THE PHS POLICY ON

HUMANE CARE AND USE OF LABORATORY ANIMALS

4.3 LIMITATIONS ON USE OF APPROPRIATED FUNDS

5. “FAST-TRACK” INITIATIVE

6. FAST-TRACK PHASE II PROPOSAL PREPARATION INSTRUCTIONS AND

REQUIREMENTS

6.1 LIMITATIONS ON LENGTH OF PROPOSAL

6.2 TECHNICAL PROPOSAL FORMAT AND CONTENT REQUIREMENTS

6.3 BUSINESS PROPOSAL FORMAT AND CONTENT REQUIREMENTS

7. METHOD OF SELECTION AND EVALUATION CRITERIA

7.1 EVALUATION PROCESS

7.2 TECHNICAL EVALUATION CRITERIA

7.3 PROPOSAL DEBRIEFING

7.4 AWARD DECISIONS

8. CONSIDERATIONS

8.1 AWARDS

8.2 PROGRESS REPORTS

8.3 FINAL REPORT

8.4 PAYMENT

8.5 LIMITED RIGHTS INFORMATION AND DATA

8.6 PERFORMANCE OF RESEARCH AND ANALYTICAL WORK

8.7 ELECTRONIC AND INFORMATION TECHNOLOGY (SECTION 508)

8.8 ADDITIONAL INFORMATION

9. INSTRUCTIONS FOR PROPOSAL SUBMISSION

9.1 RECEIPT DATE

iii

9.2 NUMBER OF COPIES

9.3 BINDING AND PACKAGING OF PROPOSAL

10. CONTRACTING OFFICERS AND ADDRESSES FOR MAILING OR DELIVERY OF

PROPOSALS

10.1 NATIONAL INSTITUTES OF HEALTH (NIH)

NATIONAL CANCER INSTITUTE (NCI)

NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES (NCATS)

NATIONAL HEART, LUNG, AND BLOOD INSTITUTE (NHLBI)

NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID)

EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN

DEVELOPMENT (NICHD)

NATIONAL INSTITUTE ON DRUG ABUSE (NIDA)

10.2 CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC)

CENTER FOR GLOBAL HEALTH (CGH)

NATIONAL CENTER FOR BIRTH DEFECTS AND DEVELOPMENTAL DISABILITIES (NCBDDD)

NATIONAL CENTER FOR CHRONIC DISEASE PREVENTION AND HEALTH PROMOTION (NCCDPHP)

NATIONAL CENTER FOR EMERGING ZOONOTIC AND INFECTIOUS DISEASES (NCEZID)

NATIONAL CENTER FOR HIV/AIDS, VIRAL HEPATITIS, STD, AND TB PREVENTION (NCHHSTP)

NATIONAL CENTER FOR IMMUNIZATION AND RESPIRATORY DISEASES (NCIRD)

OFFICE OF PUBLIC HEALTH PREPAREDNESS AND RESPONSE (OPHPR)

11. SCIENTIFIC AND TECHNICAL INFORMATION SOURCES

12. RESEARCH TOPICS

NATIONAL INSTITUTES OF HEALTH

NATIONAL CANCER INSTITUTE (NCI)

313 RNAI CANCER THERAPEUTICS USING NANOTECHNOLOGY

314 DEVELOPMENT OF HUMAN TISSUE CULTURE SYSTEMS THAT MIMIC THE TUMOR

MICROENVIRONMENT

315 DEVELOPMENT OF COMPANION DIAGNOSTICS: ENABLING PRECISION MEDICINE IN

CANCER THERAPY

316 DEVELOPMENT OF CTC ISOLATION TECHNOLOGIES ENABLING DOWNSTREAM SINGLE

CELL MOLECULAR ANALYSIS

317 WOUND HEALING PREPARATIONS INCORPORATING NITRIC OXIDE-RELEASING

MATERIALS (NIH TECHNOLOGY TRANSFER)

318 TEST TO PREDICT EFFECTIVENESS OF DOCETAXEL TREATMENT FOR PROSTATE

CANCER (NIH TECHNOLOGY TRANSFER)

319 TECHNOLOGY TO GENERATE ANTI-PEPTIDE CAPTURE REAGENTS FOR AFFINITY-

ENRICHED PROTEOMIC STUDIES

320 HIGH QUALITY CANCER-RELATED STANDARDS FOR METABOLOMICS RESEARCH

321 CHEMICALLY DEFINED GLYCAN LIBRARIES FOR REFERENCE STANDARDS AND

GLYCOMICS RESEARCH (JOINT NCI-NIGMS PROGRAM)

322 REAL-TIME INTEGRATION OF SENSOR AND SELF-REPORT DATA FOR CLINICAL AND

RESEARCH APPLICATIONS

323 DEVELOPMENT OF RADIATION MODULATORS FOR USE DURING RADIOTHERAPY

324 NOVEL IMAGING AGENTS TO EXPAND THE CLINICAL TOOLKIT FOR CANCER DIAGNOSIS,

STAGING, AND TREATMENT

325 INNOVATIVE RADIATION SOURCES FOR ADVANCED RADIOTHERAPY EQUIPMENT

NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES (NCATS)

001 VISUALIZING KNOWLEDGE ABOUT HUMAN HEALTH AND THE PATHWAYS OF TRANSLATION

002 BIOMARKER STUDY FOR CREATINE TRANSPORTER DEFECT DISORDERS

003 AUTOMATED INSTRUMENT TO CLEAN MICROTITER PLATES

004 ASSAY DEVELOPMENT FOR HIGH-THROUGHPUT SCREENING OF CHEMICALS OF

TOXICOLOGICAL CONCERN

NATIONAL HEART, LUNG, AND BLOOD INSTITUTE (NHLBI)

072 NEW METHODS TO DETECT AND ASSESS MYOCARDIAL FIBROSIS

073 EVALUATING OBSTRUCTIVE SLEEP APNEA DENTAL DEVICE TREATMENT COMPLIANCE

iv

074 IMPROVING SAFETY AND EFFICACY OF RED BLOOD CELLS FOR TRANSFUSION

075 DEDICATED PEDIATRIC CARDIAC MRI RECEIVE COILS

076 MRI MYOCARDIAL BIOPSY FORCEPS

077 PASSIVE MRI GUIDEWIRE

078 TRANSTHORACIC CARDIAC ACCESS PORTS AND CLOSURE DEVICES

079 BIOABSORBABLE STENTS FOR PEDIATRIC PULMONARY ARTERY STENOSIS AND

AORTIC COARCTATION

080 FLUORESCENT NANODIAMONDS FOR IN VITRO AND IN VIVO BIOLOGICAL IMAGING

NATIONAL INSTITTUE OF ALLERGY AND INFECTIOUS DISEASES (NIAID)

021 AEROSOLIZED DELIVERY OF ANTI-TUBERCULAR DRUGS

022 DEVELOPMENT OF LONG-ACTING FORMULATIONS OF HIV ANTI-RETROVIRALS

023 IMPROVED FORMULATIONS FOR APPROVED FIRST AND SECOND LINE ANTI-

TUBERCULOSIS (TB) DRUGS

024 INTEGRATED MULTIPLEX MEDICAL DIAGNOSTICS PLATFORMS FOR INFECTIOUS DISEASES

EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

(NICHD)

023 NEURAL INTERFACES: IMPROVING FUNCTIONAL OUTCOMES

NATIONAL INSTITUTE ON DRUG ABUSE (NIDA)

147 A MOBILE APPLICATION TO HELP PATIENTS TAKE THEIR PILL MEDICATIONS AS

PRESCRIBED: IMPROVING MEDICATION ADHERENCE

148 PRODUCTS FOR AT-HOME DEACTIVATION OF PSYCHOACTIVE PRESCRIPTION MEDICINES

149 DEVELOPMENT OF PREDICTIVE IN VIVO SCREENING SYSTEMS FOR PHENOTYPIC

DRUG DISCOVERY FOR SMOKING CESSATION

150 VIDEO GAME TARGETING RELAPSE PREVENTION IN YOUTH WITH SUBSTANCE

USE DISORDERS

CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC)

CENTER FOR GLOBAL HEALTH (CGH)

003 DIAGNOSTIC NEEDS FOR NEGLECTED TROPICAL DISEASES (NTD) PROGRAMS

004 RAPID SCREENING TESTS TO PREVENT CONGENITAL INFECTIONS AND ENSURE

BLOOD SAFETY

005 DEVELOPMENT OF DIAGNOSTIC TESTS FOR STRONGYLOIDIASIS AND SCHISTOSOMIASIS

NATIONAL CENTER ON BIRTH DEFECTS AND DEVELOPMENTAL DISABILITIES (NCBDDD)

016 IMPROVING DATA, IMPROVING CARE, MAKING IT COUNT

017 SMARTPHONE APPLICATION FOR GLOBAL BIRTH DEFECTS SURVEILLANCE

NATIONAL CENTER FOR CHRONIC DISEASE PREVENTION AND HEALTH PROMOTION (NCCDPHP)

033 A MOBILE PHONE APPLICATION (“APP”) FOR ADVANCING TEEN PREGNANCY PREVENTION ... 108

NATIONAL CENTER FOR EMERGING ZOONOTIC AND INFECTIOUS DISEASES (NCEZID)

003 DEVELOPMENT OF NANOPARTICLE DENGUE DIAGNOSTIC TESTS

004 DEVELOPMENT OF TESTS IN A STANDARDIZED KIT FORMAT FOR DIAGNOSIS OF

ARBOVIRAL INFECTIONS IN RESOURCE-LIMITED, PRIMARY HEALTH CARE SETTING

005 REDUCING ANTIMICROBIAL RESISTANCE THROUGH IMPROVED USE OF LABORATORY

TESTING INFORMATION IN HEALTHCARE FACILITIES

NATIONAL CENTER FOR HIV/AIDS, VIRAL HEPATITIS, STD, AND TB PREVENTION (NCHHSTP)

034 DEVELOPMENT OF BIOMEDICAL DEVICES TO ELICIT DURABLE PROTECTIVE IMMUNITY

AGAINST HIV

035 DEVELOPMENT OF A PORTABLE MULTIPLEX ASSAY FOR DETERMINATION OF RECENT

HIV-1 INFECTION

036 TESTING THE EFFICACY OF COMBINATION HIV PREVENTION STRATEGIES IN

NONHUMAN PRIMATES

NATIONAL CENTER FOR IMMUNIZATION AND RESPIRATORY DISEASES (NCIRD)

025 DEVELOPMENT OF AN INACTIVATED ROTAVIRUS VACCINE FOR USE IN GLOBAL

IMMUNIZATION

026 THERMOSTABLE DRY MEASLES VACCINE FORMULATION FOR SUBLINGUAL

ADMINISTRATION

OFFICE OF PUBLIC HEALTH PREPAREDNESS AND RESPONSE (OPHPR)

002 IMPROVED METHODS FOR COLLECTION, PRESERVATION, AND TRANSPORTATION

OF BIOLOGICAL SPECIMENS

v

PART II HUMAN SUBJECTS RESEARCH GUIDANCE AND INFORMATION SUPPLEMENT

1. INTRODUCTION

2. SCENARIOS

3. INSTRUCTIONS FOR PREPARING THE SECTION ON PROTECTION OF HUMAN

SUBJECTS

4. INSTRUCTIONS PERTAINING TO NON-EXEMPT HUMAN SUBJECTS RESEARCH

4.1 PROTECTION OF HUMAN SUBJECTS

4.1.1 RISKS TO HUMAN SUBJECTS

4.1.2 ADEQUACY OF PROTECTION AGAINST RISKS

4.1.3 POTENTIAL BENEFITS OF THE PROPOSED RESEARCH TO HUMAN SUBJECTS AND OTHERS

4.1.4 IMPORTANCE OF THE KNOWLEDGE TO BE GAINED

4.1.5 DATA AND SAFETY MONITORING PLAN

4.1.6 CLINICALTRIALS.GOV REQUIREMENTS

4.2 INCLUSION OF WOMEN AND MINORITIES

4.2.1 ADDITIONAL INSTRUCTIONS AND REQUIREMENTS WHEN NIH-DEFINED PHASE III

CLINICAL TRIALS ARE PROPOSED

4.3 INSTRUCTIONS FOR COMPLETING THE TARGETED/PLANNED ENROLLMENT TABLES FOR

REPORTING RACE AND ETHNICITY DATA FOR SUBJECTS IN CLINICAL RESEARCH

4.4 INCLUSION OF CHILDREN

5. HUMAN SUBJECTS RESEARCH POLICY

5.1 PROTECTION OF HUMAN SUBJECTS

5.2 VULNERABLE POPULATIONS

5.3 DATA AND SAFETY MONITORING PLANS FOR CLINICAL TRIALS

5.4 IRB APPROVAL

5.5 REQUIRED EDUCATION IN THE PROTECTION OF HUMAN RESEARCH PARTICIPANTS

5.6 NIH POLICY ON THE INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH

5.7 NIH POLICY ON INCLUSION OF CHILDREN

5.8 NIH POLICY ON REPORTING RACE AND ETHNICITY DATA: SUBJECTS IN CLINICAL RESEARCH

5.9 RESEARCH ON TRANSPLANTATION OF HUMAN FETAL TISSUE

5.10 RESEARCH USING HUMAN EMBRYONIC STEM CELLS

5.11 CLINICALTRIALS.GOV REQUIREMENTS

APPENDIX A — PROPOSAL COVER SHEET - USE FOR PHASE I AND FAST-TRACK PROPOSALS

MS Word (http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixA.doc) PDF (http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixA.pdf)

APPENDIX B — ABSTRACT OF RESEARCH PLAN - USE FOR PHASE I, PHASE II, AND FAST-TRACK

PROPOSALS

MS Word (http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixB.doc) PDF (http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixB.pdf)

APPENDIX C — PRICING PROPOSAL - USE FOR PHASE I, PHASE II AND FAST-TRACK PROPOSALS MS Word (http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixC.doc) PDF (http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixC.pdf)

APPENDIX D — PHASE II TECHNICAL PROPOSAL COVER SHEET - USE FOR PHASE II AND FAST-TRACK

MS Word (http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixD.doc) PDF (http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixD.pdf) http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixA.doc http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixA.pdf http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixB.doc http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixB.pdf http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixC.doc http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixC.pdf http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixD.doc http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixD.pdf vi

APPENDIX E — STATEMENT OF WORK SAMPLE FORMAT - USE FOR PHASE II AND FAST-TRACK

PROPOSALS

MS Word (http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixE.doc) PDF (http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixE.pdf)

APPENDIX F — SUMMARY OF RELATED ACTIVITIES - USE FOR PHASE II AND FAST- TRACK

MS Word (http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixF.doc) PDF (http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixF.pdf)

APPENDIX G — PROPOSAL SUMMARY AND DATA RECORD - USE FOR PHASE II AND FAST-TRACK

MS Word (http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixG.doc) PDF (http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixG.pdf)

The Appendices noted above are in Microsoft Word and Adobe Acrobat Reader fillable format.

NOTE: Other software packages for completing these proposals may be available from other sources; however, it is essential that the type size and format specifications are met or the proposal may be returned without review.

DISCLAIMER: Reference to these software packages neither constitutes nor should be inferred to be an endorsement or recommendation of any product, service, or enterprise by the National Institutes of Health, any other agency of the United States Government, or any employee of the United States Government. No warranties are stated or implied.

http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixE.doc http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixE.pdf http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixF.doc http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixF.pdf http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixG.doc http://grants.nih.gov/grants/funding/SBIRContract/ContractAppendixG.pdf

U. S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

SOLICITATION OF THE NATIONAL INSTITUTES OF HEALTH AND THE

CENTERS FOR DISEASE CONTROL AND PREVENTION FOR

SMALL BUSINESS INNOVATION RESEARCH

CONTRACT PROPOSALS

PART I INSTRUCTIONS FOR PREPARING AND SUBMITTING A PROPOSAL

1. PROGRAM DESCRIPTION

1.1 PURPOSE OF SOLICITATION

The National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC) invite small business concerns to submit research proposals under this Small Business Innovation Research (SBIR) Contract Solicitation. Firms with the capability to conduct research and development (R&D) in any of the health related topic areas described in Section 12, and to commercialize the results of that R&D, are encouraged to participate.

This solicitation is for Phase I contract proposals and also for Phase I/Phase II Fast-Track contract proposals (see specific topics listed in Section 12 and awarding components identified as accepting Fast-Track proposals).

Included are instructions for offerors to prepare contract proposals, a description of the proposal review process, and some conditions of a contract award. Contract proposals will be accepted only if they respond specifically to a research topic within this solicitation (see Section 12 “Research Topics”). Otherwise, proposals will be returned to the offeror(s) without evaluation.

To apply for an SBIR GRANT rather than an SBIR CONTRACT, use the Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Applications (http://grants.nih.gov/grants/guide/pa-files/PA-12-088.html).

The objectives of the SBIR program include stimulating technological innovation in the private sector, strengthening the role of small business in meeting Federal R/R&D needs, increasing private sector commercialization of innovations developed through Federal SBIR R&D, increasing small business participation in Federal R&D, and fostering and encouraging participation by socially and economically disadvantaged small business concerns and women-owned small business concerns in the SBIR program.

The Federal SBIR program is authorized under Public Laws 97-219, 99-443, 102-564, 106-554, and 112-81. The basic design of the NIH/CDC SBIR program is in accordance with the Small Business Administration (SBA) SBIR Program Policy Directive, 2002. This SBIR Contract solicitation strives to encourage scientific and technical innovation in areas specifically identified by the NIH/CDC awarding components shown in Section 1.3. The guidelines presented in this solicitation reflect the flexibility provided in the Policy Directive to encourage proposals based on scientific and technical approaches most likely to yield results important to the NIH/CDC and to the private sector.

1.2 THREE PHASE PROGRAM

The SBIR program consists of three separate phases. The award amount and contract’s duration listed below represent the guidelines of the SBIR program and, unless the research topic stating the award listed in Section 12 of the solicitation states otherwise, should be followed.

http://grants.nih.gov/grants/guide/pa-files/PA-12-088.html

Phase I: Feasibility; $150,000; 6 months

The objective of Phase I is to determine the scientific or technical feasibility and commercial merit of the proposed research or R&D efforts and the quality of performance of the small business concern, prior to providing further Federal support in Phase II. Phase I awards normally may not exceed $150,000 for direct costs, indirect costs, and profit (fixed fee) for a period normally not to exceed 6 months.

Phase II: Full R/R&D Effort; $1,000,000; 2 years

The objective of Phase II is to continue the research or R&D efforts initiated in Phase I. Funding shall be based on the results of Phase I and the scientific and technical merit and commercial potential of the Phase II proposal.

Phase II awards normally may not exceed $1,000,000 for direct costs, indirect costs, and profit (fixed fee) for a period normally not to exceed two years. Phase I contractors will be informed of the opportunity to apply for Phase II, if not submitted concurrently with the initial Phase I proposal under the Fast-Track procedure (described in Section 5). Only one Phase II award may result from a single Phase I SBIR contract.

Phase III: Commercialization stage without SBIR funds

The objective of Phase III, where appropriate, is for the small business concern to pursue with non-SBIR funds the commercialization objectives resulting from the outcomes of the research or R&D funded in Phases I and II.

Phase III may involve follow-on, non-SBIR funded R&D or production contracts for products or processes intended for use by the U.S. Government.

The competition for SBIR Phase I and Phase II awards satisfies any competition requirement of the Armed Services Procurement Act, the Federal Property and Administrative Services Act, and the competition in Contracting Act. Therefore, an agency that wishes to fund an SBIR Phase III project is not required to conduct another competition in order to satisfy those statutory provisions. As a result, in conducting actions relative to a Phase III SBIR award, it is sufficient to state for purposes of a Justification and Approval pursuant to FAR 6.302-5 that the project is a SBIR Phase III award that is derived from, extends, or logically concludes efforts performed under prior SBIR funding agreements and is authorized under 10 U.S.C. 2304(b)(2) or 41 U.S.C. 253(b)(2).

The NIH is interested in developing products and services via the SBIR program that improve the health of the American people. In its commitment to also support former President Bush's Executive Order 13329, encouraging innovation in manufacturing-related research and development, NIH seeks, through the SBIR program, biomedical research related to advanced processing, manufacturing processes, equipment and systems; or manufacturing workforce skills and protection. This solicitation includes some topic areas that are considered relevant to manufacturing-related R&D. Additional information will be posted on the NIH Small Business Research Funding Opportunities Web site and in the NIH Guide for Grants and Contracts as it becomes available. Small businesses may be interested in reading a U.S. Department of Commerce 2004 report, "Manufacturing in America: A Comprehensive Strategy to Address the Challenges to U.S. Manufacturers".

1.3 AWARDING COMPONENTS

The following awarding components are participating in this SBIR Solicitation for Contract Proposals.

National Institutes of Health (NIH)

• National Cancer Institute (NCI)

• National Center for Advancing Translational Sciences (NCATS)

• National Heart, Lung, and Blood Institute (NHLBI)

• National Institute of Allergy and Infectious Diseases (NIAID)

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) http://edocket.access.gpo.gov/2004/pdf/04-4436.pdf http://sbir.nih.gov/ http://sbir.nih.gov/ http://grants.nih.gov/grants/guide/index.html http://www.ita.doc.gov/media/Publications/pdf/manuam0104final.pdf http://www.ita.doc.gov/media/Publications/pdf/manuam0104final.pdf

• National Institute on Drug Abuse (NIDA)

Centers for Disease Control and Prevention (CDC)

• Center for Global Health (CGH)

• National Center for Birth Defects and Developmental Disabilities (NCBDDD)

• National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP)

• National Center for Emerging Zoonotic and Infectious Diseases (NCEZID)

• National Center for HIV/AIDs, Viral Hepatitis, STD, and TB Prevention (NCHHSTP)

• National Center for Immunization and Respiratory Diseases (NCIRD)

• Office of Public Health Preparedness and Response (OPHPR)

1.4 SBIR PROGRAM ELIGIBILITY

Organizational Criteria: Each organization submitting a proposal under the SBIR program must qualify as a small business concern as defined in Section 3. In determining whether an offeror is a small business concern, an assessment will be made of several factors, including whether or not it is independently owned and operated and whether or not it is an affiliate of a larger organization whose employees, when added to those of the offeror organization, exceed 500. In conducting this assessment, all appropriate factors will be considered, including common ownership, common management, and contractual relationships.

In accordance with 13 CFR 121.103, affiliation exists when “… one concern controls or has the power to control the other … control may be affirmative or negative, …it does not matter whether control is exercised, so long as the power to control exists.” One of the circumstances that would lead to a finding that an organization is controlling or has the power to control another organization involves sharing common office space and/or employees and/or other facilities (e.g., laboratory space). 13 CFR 121.103 also states that control or the power to control exists when “… key employees of one concern organize a new concern … and serve as its officers, directors, principal stockholders, and/or key employees; and one concern is furnishing or will furnish the other concern with subcontracts, financial or technical assistance, and/or other facilities, whether for a fee or otherwise.”

Where there is indication of sharing of common employees, a determination will be made on a case-by-case basis of whether or not such sharing constitutes control or the power to control.

Joint ventures and limited partnerships are eligible provided the entity created qualifies as a small business concern as defined in Section 3 of this solicitation.

If it appears that an offeror does not meet eligibility requirements, the NIH/CDC will request an eligibility determination of the organization from the cognizant SBA Government Contracting Area Office. The evaluation of the proposal for scientific merit will be deferred until the SBA provides a determination.

Project Director/Principal Investigator Criteria. The primary employment of the Project Director/Principal Investigator (PD/PI) must be with the offeror at the time of contract award and during the conduct of the proposed project. The PD/PI is the single individual designated in the proposal with responsibility for the scientific and technical direction of the project. Primary employment means that more than one half of the PD/PI’s time is spent in the employ of the small business concern. Primary employment with a small business concern precludes full-time employment at another organization.

In the event that the PD/PI: (1) is a less-than-full-time employee of the small business, (2) is concurrently employed by another organization, or (3) gives the appearance of being concurrently employed by another organization, whether for a paid or unpaid position, at the time of submission of the proposal, it is essential that documentation be submitted with the proposal to verify his/her eligibility. If the PD/PI also is employed or appears to be employed by an organization other than the offeror (e.g., a university, a nonprofit research institute, or another company), a letter must be provided by the non-offeror organization confirming that the PD/PI will, if awarded an SBIR contract, become a less-than-half-time employee of such organization and will remain so for the duration of the SBIR project. If the PD/PI is employed by a university, the Dean's Office must provide such a letter. If the PD/PI is employed by another for-profit organization, the corporate official must sign the letter. This documentation is required for every proposal that is submitted, even one that is a revision of a previously submitted proposal.

Multiple Principal Investigators. Offerors may propose a multiple Project Director/Principal Investigator (PD/PI) model to direct the project or program to be supported by the contract. The multiple PD/PI model is intended to supplement, and not replace, the traditional single PI model. Ultimately, the decision to submit a proposal using the multiple PD/PI versus single PD/PI is the decision of the investigators and their organizations. The decision whether to employ multiple PDs/PIs should be consistent with and justified by the scientific goals of the project.

The offeror organization may designate multiple individuals as principal investigators (PD/PIs) who share the authority and responsibility for leading and directing the project, intellectually and logistically. When multiple principal investigators are named, each is responsible and accountable to the offeror organization, or as appropriate, to a collaborating organization for the proper conduct of the project or program including the submission of all required reports. The presence of more than one PD/PI on a proposal or award diminishes neither the responsibility nor the accountability of any individual PD/PI.

For Multiple PD/PI proposals: The first PI listed must be affiliated with the small business concern organization submitting the proposal and will serve as the Contact PD/PI. For both SBIR Phase I and SBIR Phase II, the primary employment of the “Contact PD/PI” must be with the small business concern at the time of award and during the conduct of the proposed project.

Performance Site Criteria. For both Phase I and Phase II, the research or R&D project activity must be performed in its entirety in the United States (see Part I, Section 3. Definitions).

Access to special facilities or equipment in another organization is permitted (as in cases where the SBIR awardee has entered into a subcontractual agreement with another institution for a specific, limited portion of the research project). However, research space occupied by an SBIR contractor organization must be space that is available to and under the control of the SBIR contractor for the conduct of its portion of the project.

Whenever a proposed SBIR project is to be conducted in facilities other than those of the offeror, a letter must be submitted with the proposal stating that leasing/rental arrangements have been negotiated for appropriate research space (i.e., space that will be available to and under the control of the SBIR contractor organization).

This letter must be signed by an authorized official of the organization whose facilities are to be used for the SBIR project. It also must include a description of the facilities and, if appropriate, equipment that will be leased/rented to the offeror organization.

Market Research. The NIH/CDC will not support any market research under the SBIR program. Neither will it support studies of the literature that will lead to a new or expanded statement of work. Literature searches where the commercial product is a database are acceptable.

For purposes of the SBIR program, “market research” is the systematic gathering, recording, computing, and analyzing of data about problems relating to the sale and distribution of the subject of the research project. It includes various types of research, such as the size of potential market and potential sales volume, the identification of consumers most apt to purchase the products, and the advertising media most likely to stimulate their purchases. However, “market research” does not include activities under a research plan or protocol that require a survey of the public as part of the objective of the project to determine the impact of the subject of the research on the behavior of individuals.

1.5 REPORT FRAUD, WASTE AND ABUSE

The Office of Inspector General Hotline accepts tips from all sources about potential fraud, waste, abuse and mismanagement in Department of Health & Human Services programs. The reporting individual should indicate that the fraud, waste and/or abuse concerns an SBIR/STTR grant or contract, if relevant.

Report Fraud

2. AGENCY CONTACT FOR INFORMATION

Web Site. The NIH SBIR/STTR Web site at http://sbir.nih.gov offers electronic access to SBIR solicitations, abstracts of ongoing SBIR projects, the latest updates on the SBIR program, hyperlinks to sources of business assistance, and other useful information.

Technical Questions about Solicitation Topics or Contract Administration. Technical questions about a particular contract topic and general questions on the administration of an SBIR contract should be directed to the appropriate contracting officer listed in Section 10. Contracting Officers and Addresses for Mailing and Delivery of Proposals.

General Questions about the NIH SBIR Program

Matthew E. Portnoy, Ph.D.

NIH SBIR/STTR Program Coordinator 6705 Rockledge Drive Rockledge I, Room 3540 Bethesda, MD 20892-7963 Phone: 301-435-2688 Fax: 301-480-0146 E-mail: sbir@od.nih.gov

Robert Vinson NIH SBIR/STTR Program Analyst 6705 Rockledge Drive Rockledge I, Room 3522 Bethesda, MD 20892-7963 Phone: 301-435-2713 Fax: 301-480-0146 E-mail: sbir@od.nih.gov

General Questions about the CDC SBIR Program

Juliana Cyril, Ph.D., M.P.H.

Deputy Director, Office of Science Quality Office of the Associate Director for Science Phone: 404-639-4639 Fax: 404-639-4903 E-mail: JCyril@cdc.gov

Sean David Griffiths, M.P.H.

Science Policy, Office of Science Quality Office of the Associate Director for Science Phone: 404-639-4641 Fax: 404-639-4903 E-mail: SGriffiths@cdc.gov

Listserv. The NIH maintains a ListServ e-mail broadcast service. To stay in touch with SBIR opportunities and receive notices about upcoming conferences and solicitations, subscribe by sending an e-mail to LISTSERV@LIST.NIH.GOV with the following text in the message body: subscribe SBIR-STTR your name.

(LISTSERV will get your e-mail address from the “From:” address of your e-mail message.)

http://oig.hhs.gov/fraud/report-fraud/index.asp http://sbir.nih.gov/ mailto:sbir@od.nih.gov mailto:sbir@od.nih.gov mailto:JCyril@cdc.gov mailto:SGriffiths@cdc.gov mailto:LISTSERV@LIST.NIH.GOV

3. DEFINITIONS

Affiliate. This term has the same meaning as set forth in 13 CFR part 121 – Small Business Size Regulations, §121.103, “What is affiliation?”

Autopsy Materials. The use of autopsy materials is governed by applicable Federal, state and local law and is not directly regulated by 45 CFR part 46.

Child. The NIH Policy on Inclusion of Children defines a child as an individual under the age of 21 years. The intent of the NIH policy is to provide the opportunity for children to participate in research studies when there is a sound scientific rationale for including them, and their participation benefits children and is appropriate under existing Federal guidelines. Thus, children must be included in NIH conducted or supported clinical research unless there are scientific or ethical reasons not to include them.

DHHS Regulations (45 CFR part 46, Subpart D, Sec.401-409 (http://www.hhs.gov/ohrp/humansubjects/ guidance/45cfr46.html#subpartd)) provide additional protections for children involved as subjects in research, based on this definition: "Children are persons who have not attained the legal age for consent to treatments or procedures involved in research, under the applicable law of the jurisdiction in which the research will be conducted." Generally, state laws define what constitutes a “child.” Consequently, the age at which a child's own consent is required and sufficient to participate in research will vary according to state law. For example, some states consider a person age 18 to be an adult and therefore one who can provide consent without parental permission.

Clinical Research. NIH defines human clinical research as research with human subjects that is:

(1) Patient-Oriented Research.

Research conducted with human subjects (or on material of human origin such as tissues, specimens, and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual.

Patient-oriented research includes: (a) mechanisms of human disease, (b) therapeutic interventions, (c) clinical studies, or (d) development of new technologies.

(2) Epidemiologic and Behavioral Studies.

(3) Outcomes Research and Health Services Research.

Studies falling under Exemption 4 for human subjects research are not considered clinical research by this definition.

Clinical Trial. The NIH defines a clinical trial as a prospective biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions (drugs, treatments, devices, or new ways of using known drugs, treatments, or devices).

Clinical trials are used to determine whether new biomedical or behavioral interventions are safe, efficacious, and effective.

Behavioral human subjects research involving an intervention to modify behavior (diet, physical activity, cognitive therapy, etc.) fits this definition of a clinical trial.

Human subjects research to develop or evaluate clinical laboratory tests (e.g. imaging or molecular diagnostic tests) might be considered to be a clinical trial if the test will be used for medical decision making for the subject or the test itself imposes more than minimal risk for subjects.

Biomedical clinical trials of experimental drug, treatment, device or behavioral intervention may proceed through four phases:

• Phase I clinical trials test a new biomedical intervention in a small group of people (e.g., 20-80) for the first time to evaluate safety (e.g., to determine a safe dosage range and to identify side effects).

http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#subpartd

• Phase II clinical trials study the biomedical or behavioral intervention in a larger group of people (several hundred) to determine efficacy and to further evaluate its safety.

• Phase III studies investigate the efficacy of the biomedical or behavioral intervention in large groups of human subjects (from several hundred to several thousand) by comparing the intervention to other standard or experimental interventions as well as to monitor adverse effects, and to collect information that will allow the intervention to be used safely.

• Phase IV studies are conducted after the intervention has been marketed. These studies are designed to monitor effectiveness of the approved intervention in the general population and to collect information about any adverse effects associated with widespread use.

• NIH-Defined Phase III Clinical Trial. For the purpose of the Guidelines an NIH-defined Phase III clinical trial is a broadly based prospective Phase III clinical investigation, usually involving several hundred or more human subjects, for the purpose of evaluating an experimental intervention in comparison with a standard or controlled intervention or comparing two or more existing treatments. Often the aim of such investigation is to provide evidence leading to a scientific basis for consideration of a change in health policy or standard of care. The definition includes pharmacologic, non-pharmacologic, and behavioral interventions given for disease prevention, prophylaxis, diagnosis, or therapy. Community trials and other population-based intervention trials are also included.

Coded. With respect to private information or human biological specimens, coded means that:

(1) identifying information (such as name or social security number) that would enable the investigator to readily ascertain the identity of the individual to whom the private information or specimens pertain has been replaced with a number, letter, symbol or combination thereof (i.e., the code); and

(2) a key to decipher the code exists, enabling linkage of the identifying information with the private information or specimens.

Research that involves only coded private information/data or coded human biological specimens may not constitute human subjects research under the DHHS human subjects regulations (45 CFR 46) if:

• the specimens and/or information/data are not obtained from an interaction/intervention with the subject specifically for the research; and

• the investigator(s) cannot readily ascertain the identity of the individual(s) to whom the coded private information or specimens pertain (e.g., the researcher's access to subject identities is prohibited).

Individuals who provide coded information or specimens for proposed research and who also collaborate on the research involving such information or specimens are considered to be involved in the conduct of human subjects research.

(See the following guidance from the Office for Human Research Protections (OHRP) for additional information and examples: http://www.hhs.gov/ohrp/policy/cdebiol.html.)

Commercialization. The process of developing markets and producing and delivering products for profit (whether by the originating party or by others). As used here, commercialization includes both government and private sector markets.

Consultant. An individual who provides professional advice or services for a fee, but normally not as an employee of the engaging party. In unusual situations, an individual may be both a consultant and an employee of the same party, receiving compensation for some services as a consultant and for other work as a salaried employee. To prevent apparent or actual conflicts of interest, grantees and consultants must establish written guidelines indicating the conditions of payment of consulting fees. Consultants may also include firms that provide paid professional advice or services.

http://www.hhs.gov/ohrp/policy/cdebiol.html

Contract. An award instrument establishing a binding legal procurement relationship between a funding agency and the recipient, obligating the latter to furnish an end product or service and binding the agency to provide payment therefore.

Data and Safety Monitoring Plan. For each clinical trial, NIH requires a data and safety monitoring plan that will provide oversight and monitoring to ensure the safety of participants and the validity and integrity of the data. The level of monitoring should be commensurate with the risks and the size and complexity of the clinical trial. A detailed data and safety monitoring plan must be submitted to the contractor’s IRB and subsequently to the funding IC for approval prior to the accrual of human subjects. The reporting of Adverse Events must be reported to the IRB, the NIH funding Institute or Center, and other required entities. This policy requirement is in addition to any monitoring requirements imposed by 45 CFR part 46 (http://www.hhs.gov/ohrp/humansubjects/guidance/ 45cfr46.html).

Data and Safety Monitoring Board (DSMB). NIH requires the establishment of a Data and Safety Monitoring Board (DSMB) for multi-site clinical trials involving interventions that entail potential risk to the participants, and generally for Phase III clinical trials.

8(a) Small Business Concern. A small business concern that is owned and controlled by a socially and economically disadvantaged individual and that has been approved by the U.S. Small Business Administration as part of the 8(a) Business Development Program (see 13 CFR 124).

Essentially Equivalent Work. This term is meant to identify “scientific overlap,” which occurs when: (1) substantially the same research is proposed for funding in more than one contract proposal or grant application submitted to the same Federal agency; OR (2) substantially the same research is submitted to two or more different Federal agencies for review and funding consideration; OR (3) a specific research objective and the research design for accomplishing that objective are the same or closely related in two or more proposals or awards, regardless of the funding source.

Exemptions. The six categories of research exempt from the DHHS human subject regulations are:

Exemption 1: Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as (i) research on regular and special education instructional strategies, or

(ii) research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.

Exemption 2: Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior, unless:

(i) information obtained is recorded in such a manner that human subjects can be identified directly or through identifiers linked to the subjects and (ii) any disclosure of the human subjects' responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation.

Exemption 2 for research involving survey or interview procedures or observation of public behavior, does not apply to research with children (see 45 CFR part 46, Subpart D (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#subpartd)), except for research involving observations of public behavior when the investigator(s) do not participate in the activities being observed.

Exemption 3: Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under paragraph (b)(2) of this section if: (i) the human subjects are elected or appointed public officials or candidates for public office; or (ii) Federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.

Exemption 4: Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html http://www.access.gpo.gov/nara/cfr/waisidx_06/13cfr124_06.html the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.

The humans subjects regulations decision charts (http://www.hhs.gov/ohrp/policy/checklists/decisioncharts.html) of the Office for Human Research Protection (OHRP) will determine whether the research falls under the human subjects regulations and if so, whether it meets the criteria for Exemption 4. The NIH Office of Extramural Research Web site also contains information that is helpful for determining whether human subjects research meets the criteria for Exemption 4. See http://grants.nih.gov/grants/policy/hs/index.htm.

Research that meets the criteria for Exemption 4 is not considered “clinical research” as defined by NIH. Therefore the NIH policies for inclusion of women, minorities and children in clinical research, and targeted/planned enrollment tables, do not apply to research projects covered by Exemption 4.

Exemption 5: Research and demonstration projects that are conducted by or subject to the approval of Department or Agency heads and that are designed to study, evaluate, or otherwise examine: (i) public benefit or service programs (ii) procedures for obtaining benefits or services under those programs (iii) possible changes in or alternatives to those programs or procedures or (iv) possible changes in methods or levels of payment for benefits or services under those programs.

Exemption 6: Taste and food quality evaluation and consumer acceptance studies (i) if wholesome foods without additives are consumed or (ii) if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural, chemical, or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.

Feasibility. The extent to which a study or project may be done practically and successfully.

Funding Agreement. Any grant, contract, or cooperative agreement entered into between any Federal agency and any small business concern for the performance of experimental, developmental, or research work, including products or services, funded in whole or in part by the Federal Government.

Gender. Refers to the classification of research subjects into either or both of two categories: male and female.

In some cases, representation is unknown, because gender composition cannot be accurately determined (e.g., pooled blood samples or stored specimens without gender designation).

HubZone Small Business Concern. A small business concern that appears on the List of Qualified HUBZone Small Business Concerns maintained by the Small Business Administration (13 CFR 126.103). HUBZone Small Business Concerns are located in historically underutilized business zones, in an effort to increase employment opportunities, investment, and economic development in those areas.

Human Subjects. The DHHS regulations “Protection of Human Subjects” (45 CFR part 46 (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html), administered by OHRP) define a human subject as a living individual about whom an investigator conducting research obtains:

• data through intervention or interaction with the individual or

• identifiable private information

Individually Identifiable Private Information. According to its guidance for use of coded specimens, OHRP generally considers private information or specimens to be individually identifiable as defined at 45 CFR 46.102(f) when they can be linked to specific individuals by the investigator(s) either directly or indirectly through coding systems. Conversely, OHRP considers private information or specimens not to be individually identifiable when they cannot be linked to specific individuals by the investigator(s) either directly or indirectly through coding systems.

http://www.hhs.gov/ohrp/policy/checklists/decisioncharts.html http://grants.nih.gov/grants/policy/hs/index.htm http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html

Innovation. Something new or improved, including research for: (1) development of new technologies, (2) refinement of existing technologies, or (3) development of new applications for existing technologies. For the purposes of PHS programs, an example of “innovation” would be new medical or biological products for improved value, efficiency, or costs.

Intellectual Property. The separate and distinct types of intangible property that are referred to collectively as “intellectual property,” including but not limited to: patents, trademarks, copyrights, trade secrets, SBIR technical data (as defined in this section), ideas, designs, know-how, business, technical and research methods, and other types of intangible business assets, and including all types of intangible assets either proposed or generated by an SBC as a result of its participation in the SBIR program.

Intervention includes both physical procedures by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes. (45 CFR 46.102(f)).

Interaction includes communication or interpersonal contact between investigator and subject. (45 CFR 46.102(f)).

Investigator. The OHRP considers the term investigator to include anyone involved in conducting the research.

OHRP does not consider the act of solely providing coded private information or specimens (for example, by a tissue repository) to constitute involvement in the conduct of the research. However, if the individuals who provide coded information or specimens also collaborate on other activities related to the conduct of the research with the investigators who receive such information or specimens, they will be considered to be involved in the conduct of the research. (See OHRP’s Guidance on Research Involving Coded Private Information on Biological Specimens:

http://www.hhs.gov/ohrp/policy/cdebiol.html.)

Joint Venture. An association of concerns with interests in any degree or proportion by way of contract, express or implied, consorting to engage in and carry out a single specific business venture for joint profit, for which purpose they combine their efforts, property, money, skill, or knowledge, but not on a continuing or permanent basis for conducting business generally. A joint venture is viewed as a business entity in determining power to control its management.

Manufacturing-related R&D as a result of Executive Order 13329. Encompasses improvements in existing methods or processes, or wholly new processes, machines or systems. Four main areas include:

1. Unit process level technologies that create or improve manufacturing processes including:

• fundamental improvements in existing manufacturing processes that deliver substantial productivity, quality, or environmental benefits.

• development of new manufacturing processes, including new materials, coatings, methods, and associated practices.

2. Machine level technologies that create or improve manufacturing equipment, including:

• improvements in capital equipment that create increased capability (such as accuracy or repeatability), increased capacity (through productivity improvements or cost reduction), or increased environmental efficiency (safety, energy efficiency, environmental impact).

• new apparatus and equipment for manufacturing, including additive and subtractive manufacturing, deformation and…