CARE program: NCI and FDA interagency collaborations to support oncology small business entrepreneurs

The NIH Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs catalyze commercialization of health technologies by small businesses. The National Cancer Institute (NCI) SBIR Development Center provides substantial non-dilutive funding (~$180M in 2021) and commercialization support to oncology startups. Because most cancer technologies ultimately require FDA review to reach the clinic, lack of early regulatory guidance can delay development and waste resources. Recognizing this gap, NCI SBIR, in collaboration with the US Food and Drug Administration (FDA), created the CARE program to connect early-stage, NCI-funded companies with FDA experts for early regulatory input and education on available FDA resources, with the aim of streamlining development paths for oncology products.

Program development and support model: In 2018, external advisors to NCI SBIR recommended adding regulatory assistance for small businesses. NCI SBIR surveyed its portfolio and identified frequent delays stemming from late FDA engagement and lack of regulatory expertise. In response, NCI SBIR and FDA launched the CARE pilot in 2019 (initially with CDRH, later expanded to include CBER, CDER, and OCE) to provide early, informal regulatory feedback and education. Eligibility and application: Annual solicitations invite NCI SBIR/STTR awardees (within past 2 years) who have not yet met with FDA on the product and whose technologies fall under CBER, CDER, or CDRH purview. Applications include development stage, understanding of regulatory path, familiarity with FDA resources, and specific regulatory questions. Triage and expert matching: NCI SBIR reviews applications and routes them to the appropriate FDA Center. CBER, CDER, CDRH, and OCE review questions and match company inquiries to relevant FDA experts (including industry education offices: MATTB, SBIA, DICE). For questions requiring formal processes, FDA directs companies to appropriate meeting pathways (e.g., INTERACT, pre-IND, Q-Submission/Pre-Sub). Education and resources: Early pilots revealed low awareness of FDA resources (e.g., REdI, guidance libraries, center-specific education). NCI SBIR and FDA co-developed a public web portal with curated FDA oncology regulatory resources and routinely present these to new awardees via webinars. Joint funding initiatives: NCI SBIR collaborated with FDA CDRH/OSEL to create targeted SBIR contract topics that support development and potential qualification of Medical Device Development Tools (MDDTs), including quantitative biomarkers (Topic 442), evaluation datasets (Topic 444), and software to evaluate AI/ML devices in oncology (Topic 454). Phase I (up to $400k, 1 year) expects an accepted Qualification Plan; Phase II (up to $2M, 2 years) supports tool development and potential qualification package submission. Assessment: Program outcomes were assessed via post-engagement online surveys approximately one month after FDA responses (response rate 81% for 2020–2022). Website analytics tracked usage of the regulatory resources page. Portfolio metrics were also compiled from publicly available sources regarding FDA submissions, authorizations, and clinical trial starts.

- Participation: 141 companies participated since 2019; 109 participated 2020–2022 (preclinical-stage products). - Regulatory center distribution (2020–2022, n=109): CDER 50% (55/109), CDRH 37% (40/109), CBER 13% (14/109). - Survey response: 88/109 (81%) provided feedback. - Impact on regulatory understanding and planning (2020–2022): - 97% (84/87) learned or identified the appropriate FDA Center for their technology. - 85% (75/88) developed the regulatory strategy for their technology. - 89% (78/88) planned their next regulatory steps. - Planned next actions post-CARE (2020–2022): - 93% (82/88) planned to access FDA website resources on specific regulatory topics. - 91% (80/88) planned to submit a meeting request to FDA. - 81% (71/88) planned to contact FDA industry education offices (SBIA, DICE, MATTB). - Influence on project aims and perceived value: - 81% (71/88) reported information that informed/changed future SBIR/STTR project aims. - 90% (79/88) would recommend CARE to other companies. - Awareness and use of FDA educational resources: - In 2019, 84% (27/32) were unaware of FDA resources. - Familiarity increased from 16% (5/32) in 2019 to 70% (30/43) in 2022 after launch of the NCI regulatory resources webpage. - The webpage (launched Oct 2020) garnered >2000 visitors; returning visitors comprised 30% in the past year; 93% (81/87) of CARE participants found it useful. - Broader NCI SBIR regulatory milestones (2020–2021): - 8 portfolio companies filed INDs or IDEs; 12 clinical trials initiated. - 13 NCI-funded companies received 15 FDA authorizations/clearances for drugs/devices (examples include COSELA, Trodelvy, MARGENZA, LUMAKRAS, CellFX, SoftVue, BeamSite, AAR technology, RefleXion X1, etc.). - Joint NCI–FDA funding topics foster regulatory science tools through the MDDT pathway (Topics 442, 444, 454), aiming to improve predictability and efficiency in device development and review.

Early regulatory engagement is a critical bottleneck for oncology startups lacking in-house regulatory expertise. The CARE program addresses this gap by connecting NCI-funded small businesses with FDA experts during early development, improving understanding of regulatory pathways, informing evidence-generation plans, and aligning SBIR/STTR aims with FDA expectations. High proportions of participants reported clearer regulatory centers and strategies, concrete next steps, and plans to engage with FDA through formal meetings and educational offices. Increased awareness and utilization of FDA resources suggest sustained improvements in regulatory literacy. Complementary efforts by OCE (entrepreneur-focused workshops) and NIH funding mechanisms (TABA, CRP, SEED consultations) further support translation. Together, these activities are likely to reduce time to first-in-human studies and overall time to market, promoting efficient use of public funds and accelerating patient access to safe and effective cancer technologies.

The NCI SBIR–FDA CARE program facilitates early regulatory guidance for oncology small businesses by connecting them with FDA experts and curated educational resources. Incorporating regulatory input early can mitigate development risks, streamline pathways to clinical testing and market, and optimize use of SBIR/STTR funds. As the first NIH program of its kind, CARE showcases the value of interagency collaboration and provides a model for similar initiatives in other priority areas. Future work can continue expanding education, formal meeting readiness, and regulatory science tools (e.g., MDDTs) to further accelerate translation.