NIH Phase II SBIR Proposal Checklist Guide

Introduction

Preparing a successful NIH Phase II SBIR proposal is a high-stakes endeavor. Phase II represents a critical transition from feasibility to full-scale development—and ultimately commercialization—of your innovation. With millions of dollars potentially at stake, applicants must go beyond good science; they must also prove they can deliver a viable, market-ready solution.

This stage of the Small Business Innovation Research (SBIR) process is not just a continuation of Phase I—it’s an escalation in rigor, scope, and expectations. Reviewers will scrutinize every detail to determine if your company can not only complete the research but also bring the resulting product or service to market.

This checklist is designed to help small businesses navigate the complexities of the NIH Phase II SBIR submission process. Whether you’re submitting a standard Phase II application, a resubmission, or a Fast-Track, this guide ensures your application is thorough, compliant, and competitive.

Confirm Eligibility and Timing

Before diving into the proposal preparation, it’s critical to confirm that your business—and your project—are eligible for a Phase II NIH SBIR award. Failure to meet basic eligibility or timing requirements is one of the most avoidable reasons for application rejection.

NIH Phase II applications are typically a continuation of a successfully completed Phase I project. To be eligible, your small business must:

Be a U.S.-based for-profit business with fewer than 500 employees
Have completed all Phase I milestones satisfactorily
Submit your Phase II application within six due dates after your Phase I award’s budget period ends

In addition to standard renewals, there are other paths to Phase II funding:

Resubmission: If your previous Phase II application was not funded, you can revise and resubmit with a one-page introduction addressing reviewer feedback.
Direct to Phase II: This option allows companies to skip Phase I if they can provide convincing evidence of feasibility from prior, non-SBIR-funded work. However, this route is only available through select FOAs.

Choosing the correct Funding Opportunity Announcement (FOA) is essential. Read it carefully to determine:

Whether it allows Fast-Track or Direct to Phase II submissions
Any institute-specific eligibility criteria or guidance

Submit a Phase II application following successful completion of a Phase I award. Must apply within six standard due dates after the Phase I budget period ends.

Resubmit a revised proposal if your initial Phase II application was not funded. Must include a one-page Introduction responding to prior reviewer comments.

Available through select FOAs, this path skips Phase I if you have strong feasibility data from other sources. Review FOA closely to confirm eligibility.

Complete Mandatory Registrations

Before you can submit your Phase II SBIR proposal, you must complete several mandatory registrations. These are not just technicalities—they’re federal requirements that enable you to legally submit and receive NIH funding. Importantly, these registrations can take several weeks to process, so starting early is essential.

The required registrations include:

SAM.gov (System for Award Management)
Register your entity and obtain a Unique Entity Identifier (UEI). SAM status must be active and renewed annually.
Grants.gov
Create an organizational account linked to your UEI. This is the federal government’s central grant submission portal.
eRA Commons
NIH’s electronic Research Administration system. Both the company and the Principal Investigator (PI) must have individual profiles.
SBA Company Registry
Complete the Small Business Administration’s registry and obtain a Control ID PDF. Attach this to your application.

Each of these registrations must be finalized before you can begin the actual submission process through ASSIST or Grants.gov Workspace. Incomplete or lapsed registrations can halt your submission entirely.

Plan Ahead
Registration delays are one of the top reasons new applicants miss submission deadlines. Start this process 6–8 weeks in advance.

Assemble Core Application Components

The NIH SBIR Phase II application involves a detailed set of documents, each playing a vital role in how reviewers assess your project’s feasibility, scientific rigor, and commercial potential. Missing or improperly formatted components can lead to administrative rejection, regardless of your project’s quality.

SF 424 (R&R) Form

Required for all NIH grant applications. Include your Phase I grant number under “Federal Identifier” if applicable.

Project Summary & Narrative

The Project Summary is a non-confidential overview (≤30 lines); the Narrative explains public health relevance in plain language (≤3 sentences).

Specific Aims and Research Strategy

The Specific Aims page outlines your project goals; the Research Strategy (≤12 pages) covers Significance, Innovation, and Approach. Include Phase I results for renewals.

Commercialization Plan

Up to 12 pages outlining your go-to-market strategy, customer validation, competitive landscape, IP plan, regulatory pathway, and revenue model.

Budget and Budget Justification

Provide a detailed R&R Budget for each year, with a cumulative summary. Justify all costs including personnel, consultants, subawards, equipment, and up to 7% fee.

Biosketches and Key Personnel

Submit updated NIH biosketches (≤5 pages each) for the PI and all key team members, using the current NIH format.

Facilities & Letters of Support

Document available research facilities and resources. Compile letters from collaborators, consultants, or institutions confirming roles or resource access.

Be meticulous: each document must follow NIH formatting, page limits, and file naming conventions. Use the latest NIH SBIR Application Guide to verify current rules before submission.

Address Human Subjects and Animal Use

If your Phase II project involves research with human participants or vertebrate animals, NIH has strict requirements to ensure ethical and regulatory compliance. These requirements are non-negotiable and must be addressed in your application.

Human Subjects Research

If your study involves human subjects, you must include:

Protection of Human Subjects: Describe risk mitigation, informed consent processes, privacy safeguards, and how you’ll ensure participant welfare.
Inclusion Plans: Explain how women, minorities, and children will be included (or provide justification if not).
Data Safety Monitoring Plan (DSMP): If applicable, outline how you’ll monitor data for participant safety and study integrity.

Failing to provide these elements can trigger compliance holds or review delays—even if the science is outstanding.

Animal Use Research

If you’re using live vertebrate animals, you must include:

Vertebrate Animals Section: Justify animal use, describe procedures, and explain veterinary care and minimization of discomfort.
IACUC Approval: Institutional Animal Care and Use Committee approval or pending status must be indicated.

Compliance Warning
Failure to address human or animal subject protections can result in administrative rejection or funding delays under 45 CFR Part 46 and PHS Policy.

Review your FOA carefully, as some institutes require additional certifications or documents for human or animal research.

Utilize NIH Submission Systems

Once your proposal is assembled and all registrations are complete, it’s time to prepare for electronic submission. NIH offers two main platforms:

ASSIST (Application Submission System & Interface for Submission Tracking)

Specifically designed for NIH applications
Provides real-time error checking and validations aligned with NIH rules
Allows collaboration across team members and institutions
Automatically populates information from eRA Commons

Grants.gov Workspace

General federal grant submission platform
Offers collaborative application preparation
Less tailored to NIH-specific requirements

While both systems are acceptable, ASSIST is highly recommended for NIH SBIR applicants because of its built-in NIH compliance tools and smoother integration with eRA Commons.

Before submission:

Run a complete validation to check for missing components
Preview your entire application package as a PDF
Double-check the FOA-specific instructions

Be sure to allow several days for submission and correction of any errors flagged during the validation process.

Implement Best Practices for Submission

Submitting your NIH Phase II SBIR application isn’t just about uploading files—it’s about ensuring every detail has been triple-checked, reviewed, and confirmed for compliance. A single oversight could delay or disqualify your submission.

Key Submission Tips:

Submit Early: Aim to submit at least 48 hours before the deadline to allow time for validation errors and corrections.
Review as a Reviewer: Have someone unfamiliar with the project review your application for clarity, consistency, and completeness.
Cross-Check Forms: Ensure consistency between your Research Strategy, Budget, and Commercialization Plan.
Use the NIH Submission Checklist: Available in the SBIR Application Guide, this list confirms every required document is included.
Engage NIH Program Officials: A pre-submission conversation with your Institute’s SBIR contact can clarify expectations and resolve ambiguities.

Submit Early
Upload your application at least 48 hours before the NIH deadline to fix last-minute errors and avoid Grants.gov lockouts.

Avoid overconfidence—many excellent proposals are rejected due to administrative errors, formatting violations, or overlooked FOA instructions. Treat final submission like a launch checklist: methodical and non-negotiable.

Tagged: applying best practices

Was this article helpful?

Yes No