NIH PA-27-101: SBIR Phase IIB Strategic Breakthrough Award

NIH PA-27-101: SBIR Phase IIB Strategic Breakthrough Award

NIH PA-27-101 is an active parent Notice of Funding Opportunity for a second Phase II award to advance eligible biomedical products toward commercialization. The first listed receipt date, September 5, 2026, has passed. The next listed application due date is January 5, 2027, by 5:00 p.m. local time of the applicant organization. The NIH notice lists recurring renewal, resubmission, and revision dates through April 5, 2029, and expires April 6, 2029. This is an open continuing opportunity, not a closed historical program. NIH does not accept late applications; dates falling on a weekend or federal holiday move to the next business day.

The National Institutes of Health (NIH) designed this mechanism for a specific financing and development gap: some biomedical technologies need additional research and development after an NIH SBIR or STTR Phase II award before they can reach adoption, regulatory review, or commercialization. PA-27-101 can fund that follow-on work, but it pairs the federal award with a substantial match requirement. A company should assess its prior award, participating NIH component, commercial plan, and funding commitments before investing in a full application.

Current opportunity details

The NIH notice states that the number of awards depends on appropriations and the number and merit of applications. The $30 million figure is a program-level ceiling on total Phase IIB support, not a promise that an applicant can request that amount. Participating Institutes and Centers (ICs) publish lower project budget limits. For example, the notice lists limits of $15 million for NCI, $4.5 million for NHLBI and NIAAA, and $3 million for several other components. Some components instead refer applicants to the applicable Small Business Administration guideline. Applicants must use the limit for the IC whose mission and interests fit the proposal.

What the award supports

Phase IIB is intended to continue a project that has already received NIH SBIR or STTR Phase II support. It is a second Phase II award for further research and development, not an entry point for an untested business idea or a substitute for Phase I or Phase II. The proposed work should address important remaining technical, clinical, regulatory, manufacturing, or market-readiness tasks that stand between the existing Phase II results and successful commercialization.

The notice calls for strong commercial potential: the technology should have a plausible path to becoming an effective and successful product. The research plan should explain what the previous award established, what remains to be proven, and why the additional time, effort, and funds are needed. It should connect proposed tasks and measurable milestones to product development and the needs of customers, patients, or other intended users. A plan that mainly expands exploratory research without explaining the next commercial step is a poor fit for the stated purpose.

The parent announcement covers projects aligned with participating NIH components. Each IC has its own mission, areas of interest, priorities, funding considerations, and contacts. Identify the most appropriate component before committing to a submission plan, and contact program staff early if the fit, budget limit, or clinical-trial rules are unclear. Component alignment matters: eligibility under the parent announcement does not mean every IC will accept every subject area or study design.

Who may apply

Eligible applicants are U.S. small business concerns (SBCs) that previously received an NIH SBIR or STTR Phase II award. The Phase IIB application must be tied to that earlier project, and only one Phase IIB award is allowed per project. The NIH notice says a Phase II grant or contract recipient should submit within the first six due dates after the Phase II budget period expires. Check the specific expiration date and count the applicable receipt dates carefully with the relevant program contact.

The connected Phase II organization must satisfy the applicable SBC requirements. The notice describes a qualifying concern as a for-profit business located in the United States, operating primarily in the United States or making a significant contribution to the U.S. economy, and meeting the ownership and control requirements described in the announcement. It also discusses permitted legal forms, U.S. citizen or permanent-resident ownership paths, and rules for concerns majority-owned by multiple venture capital operating companies, hedge funds, or private equity firms. The concern and its affiliates must have no more than 500 employees. These are detailed tests; do not assume a complicated ownership structure qualifies. Review the full Section III rules and confirm that the connected Phase II award and applicant organization meet them.

The notice also includes HHS SBIR/STTR performance benchmarks. For firms with unusually large Phase I or Phase II portfolios across agencies, a low Phase I-to-Phase II transition rate or insufficient commercialization results can limit eligibility for certain new or additional awards. The applicable thresholds depend on the number of awards and the measurement period described in Section III. Companies with extensive federal SBIR/STTR histories should check their SBA benchmark status before applying rather than treating a prior NIH Phase II award as the only eligibility test.

Foreign organizations and non-U.S. components of U.S. organizations cannot apply. The notice also says applications involving funded foreign subawards or subcontracts are noncompliant for this NOFO. It allows unfunded international collaborations or foreign components as defined by NIH policy, as well as certain foreign consultants or purchases from foreign vendors. If the work involves any international relationship, check the notice’s distinction between an unfunded activity and a funded subaward before including it.

At least one PD/PI must satisfy the SBIR primary-employment requirement at the small business during the award and conduct of the proposed project. The organization and its investigators must also meet NIH registration and submission rules. An organization should resolve questions about ownership, Phase II award status, the six-date submission window, and IC fit before drafting a complete application.

Matching funds and award size

Applicants must secure and document third-party matching funds of at least 100% of the proposed Phase IIB award. If the request is for a given amount, the applicant must demonstrate matching funds at least equal to that amount. The notice permits match from new private capital, such as investment from another company or private investor; new government funding from a program other than SBIR or STTR Phase I or Phase II; or a combination of those sources. NIH SBIR/STTR Phase I or Phase II funds do not qualify as the match.

The match must be available for the Phase IIB project and comply with the federal cost-sharing rules cited in the notice. The application must detail where the funds come from. NIH directs applicants to include letters documenting commitments of matching funds with the Letters of Support; further documentation may be requested during Just-in-Time review. Build a finance plan that identifies each source, the amount and timing available, any conditions on the commitment, and how the funds relate to the proposed project. A statement that the company intends to raise capital later does not, on its own, establish a documented match.

Budget planning must also account for the selected IC’s limit. The broad $30 million ceiling should not be used as a default request amount. Build the budget around reasonable costs and a defined work plan, check component-specific instructions, and discuss the proposed scope and budget with program staff. The project period cannot exceed four years, and the proposed length should be justified by the work required.

Clinical trials and program fit

The parent notice accepts applications that do or do not propose clinical trials. That general designation has exceptions: the NOFO identifies NCATS and the Office of Research Infrastructure Programs (ORIP) as components that do not accept clinical trials, and says a trial application aligned only with either component is not responsive and will not be reviewed. Confirm the fit with the relevant IC before deciding whether the project should include a clinical trial.

When human subjects or a clinical trial are involved, the appropriate PHS Human Subjects and Clinical Trials Information forms and study records are required. The application should describe its regulatory pathway, the timeline for regulatory approval, and discrete milestones. Where approval is required, explain interactions with the relevant regulatory authority and any outside support for the regulatory plan. The notice says supporting evidence of regulatory-authority interactions may be requested, even though letters, emails, and meeting minutes are not submitted with the application by default.

Application types and materials

PA-27-101 allows Renewal (Phase IIB), Resubmission (Phase IIB), and Revision (Phase IIB) applications. A first application connected to a Phase II grant or cooperative agreement is submitted as a Renewal under the notice’s instructions. A New application is allowed only when the connected Phase II award was a contract. For a contract-connected first submission, the notice calls for a cover letter identifying it as a Phase IIB and stating that Phase I was from an NIH SBIR contract. Follow the NOFO and the current NIH SBIR/STTR application guide when selecting the application type; using the wrong type can lead to withdrawal or non-review.

The application uses the SF424 (R&R) SBIR/STTR application package and the required SBIR/STTR (B) instructions, along with PA-27-101’s additional directions. The notice specifically calls for the SBIR/STTR Information Form to identify Program Type as SBIR even when the earlier Phase II award was STTR, and Application Type as Phase IIB. Required materials include the research plan, budget and subaward information as applicable, a commercialization plan, a finance plan explaining the match, and Letters of Support that include matching-fund commitment letters. A regulatory plan of no more than two pages is required; describe the regulatory pathway, requirements, timeline, milestones, and relevant regulatory-authority interactions, or explain why the product does not need regulatory or marketing approval. A separate SBIR application certification is required for concerns majority-owned by multiple venture capital operating companies, hedge funds, or private equity firms. The commercialization plan should address market, customer, and competition information and show through market research that the technology can solve an identified problem. Other forms depend on the proposed work and the general NIH guide.

How to submit

The forms for this notice are available through one of three electronic routes: NIH ASSIST; an institutional system-to-system solution that sends the application to Grants.gov; or Grants.gov Workspace. Regardless of the preparation route, the organization submits electronically to Grants.gov and tracks the application through eRA Commons. Paper applications are not accepted.

All required organization and investigator registrations must be complete before submission. The notice highlights active System for Award Management registration, Grants.gov registration, and eRA Commons accounts for the signing official and PD/PI. It also requires PD/PIs to have an ORCID iD linked to the eRA Commons personal profile. Registration can take six weeks or more, so organizations new to the process should begin early. The organization must use the same Unique Entity Identifier across its application and registrations.

Submit before the deadline so there is time to correct errors and submit a changed application by the due date. Applications are due at 5:00 p.m. local time of the applicant organization, and the notice says late applications will not be accepted. NIH and Grants.gov perform validation checks; after submission, the applicant is responsible for checking the application in eRA Commons to confirm that it is complete and successfully received. A corrected application submitted after the deadline is considered late.

Current timeline and planning

NIH posted PA-27-101 on May 28, 2026, with an earliest submission date of August 5, 2026. The first listed receipt date was September 5, 2026. The next listed renewal, resubmission, or revision date is January 5, 2027; later listed dates are April 5, 2027, September 5, 2027, January 5, 2028, April 5, 2028, September 5, 2028, January 5, 2029, and April 5, 2029. The notice’s expiration date is April 6, 2029. The schedule assigns review and award cycles to those applications, so use the official table to plan a realistic project start. Dates can be affected by NIH’s rule for dates that fall on weekends or federal holidays; check the official notice and NIH calendar when selecting a submission date.

The January 2027 due date leaves a finite preparation period. First confirm eligibility and the six-date window. Then confirm that an appropriate IC participates and accepts the planned project design. Next, obtain program guidance on fit and budget, secure the matching commitment, and build the application around commercial and technical milestones. Finish registrations, forms, and internal review early enough to correct electronic-submission errors. A company that cannot assemble the required match or complete the package by a listed date can plan for a later date shown in the notice, provided it remains eligible and the notice has not expired. The federal application table shows the next dates after January as April 5, 2027, September 5, 2027, January 5, 2028, April 5, 2028, September 5, 2028, January 5, 2029, and April 5, 2029. Each scheduled date is a separate receipt opportunity; the January date is the live deadline currently shown in the page metadata.

Review considerations and common pitfalls

NIH evaluates applications for scientific and technical merit through peer review, while participating components also assess responsiveness to their missions and priorities. Reviewers consider the progress made during the prior Phase II period, whether market research supports the product as an effective solution, and whether post-SBIR development and commercialization milestones are appropriate. They also assess whether the applicant has compelling evidence of the full 100% match. A clear application makes the connection between prior Phase II results, remaining development risks, the proposed milestones, the commercialization pathway, and the resources needed to finish the work.

The NOFO also sets out Strategic Breakthrough criteria used in funding decisions. These include the potential to advance U.S. national security capabilities; to create new technologies or processes, or new applications of existing technologies, that provide alternatives to existing programs; whether a federal customer has expressed intent to purchase and integrate the technology; and whether the technology area is undercapitalized by private investment. NIH also considers security risk through its HHS Due Diligence Program. These factors sit alongside scientific merit, available funds, and demonstrated matching funds. Applicants should explain any relevant federal customer interest or underinvestment with concrete evidence, while keeping claims proportionate to what they can document.

Common avoidable problems include applying without a qualifying NIH Phase II award; missing the program’s submission window tied to Phase II expiration; selecting an application type that does not match the connected grant or contract; proposing a clinical trial to a component that will not accept one; exceeding the applicable IC budget limit; and presenting a match that is neither eligible nor documented. Other weaknesses include vague customer evidence, milestones that do not address commercial barriers, missing commitment letters, inconsistent organization identifiers, and incomplete eRA Commons review after submission.

PA-27-101 is therefore best suited to a company that can show a strong Phase II foundation, a focused plan for the next development stage, a credible market and regulatory path, and confirmed matching resources. The next listed receipt date is January 5, 2027, and the notice remains active through its April 6, 2029 expiration date. Applicants should open the official NIH opportunity listing and revised NOFO and component-specific guidance before submission because the federal instructions and dates govern if a local summary differs.