Development of advanced analytical methods for the characterization of complex generics | RFA FD 22 013

Opportunity Information: Apply for RFA FD 22 013

This FDA grant opportunity (RFA-FD-22-013) is focused on strengthening the scientific tools needed to evaluate and develop generic versions of "complex" drug products, specifically synthetic oligonucleotide medicines that are difficult to fully characterize with routine testing. The core idea is that better analytical methods can more clearly connect measurable product attributes to real-world performance factors like quality, safety, and efficacy. By improving how these products are characterized and compared, the FDA aims to reduce uncertainty in generic development and support more reliable assessments of whether a proposed generic is truly comparable to its reference product.

The research objective centers on phosphorothioate (PS) oligonucleotides, a class of modified nucleic acid drugs where replacing a non-bridging oxygen in the phosphate backbone with sulfur creates chiral centers at each PS linkage. That chemistry produces mixtures of diastereomers, and those diastereomeric patterns can matter because they may influence properties such as stability, binding behavior, pharmacokinetics, and potentially biological activity. The grant calls for developing advanced analytical methods capable of analyzing and understanding the diastereomer composition of PS oligonucleotides using either TEGSEDI (inotersen) or SPINRAZA (nusinersen) as the model (reference) product. In practical terms, the funded work is expected to push beyond basic identity or purity tests and instead produce methods that can resolve, measure, and compare these subtle but potentially important stereochemical distributions.

The proposed studies are organized around two main questions. First, applicants are expected to characterize and better understand the diastereomer composition present in the selected model product (either inotersen or nusinersen). That implies building an analytical picture of how the product is distributed across diastereomeric forms, likely including how reproducible that profile is and what features of the molecule or sequence drive the distribution. Second, the project must examine whether, and in what ways, manufacturing processes can shift or shape diastereomeric distributions in the final drug product. This is aimed at identifying process-related sources of variability and determining how sensitive the diastereomer profile is to process choices, which is directly relevant to both generic developers and regulators when evaluating "sameness" or meaningful differences.

A key selling point of the opportunity is transferability: methods developed for these model PS oligonucleotides should be broadly applicable to other synthetic oligonucleotide drugs. The FDA also highlights that the knowledge gained could support quality control, meaning the outputs are expected to be useful not only for one-off research comparisons but also for routine or semi-routine assessment frameworks that improve confidence in product consistency over time.

From an administrative standpoint, this is a discretionary funding opportunity from the Food and Drug Administration using a cooperative agreement mechanism, which typically indicates substantial programmatic involvement from the agency compared with a standard grant. The CFDA/Assistance Listing number is 93.103. The opportunity originally closed on 2022-03-07, was created on 2022-01-12, and listed an award ceiling of $300,000. While the summary text does not specify the number of awards in a clear way, it indicates expected awards information was provided in the source listing.

Eligibility is broad and includes many organization types. Eligible applicants include public and private institutions of higher education (with FDA noting that institutions such as Hispanic-serving institutions, HBCUs, tribally controlled colleges and universities, Alaska Native and Native Hawaiian serving institutions, and AANAPISIs are encouraged to apply), nonprofit organizations with or without 501(c)(3) status (as long as they are not higher education institutions in those categories), for-profit organizations (including small businesses and other than small businesses), and a wide range of government entities (state, county, city or township, special districts, independent school districts, public housing authorities/Indian housing authorities, and federally recognized or other tribal governments and tribal organizations). The opportunity also allows participation by non-U.S. entities: foreign institutions are eligible, non-domestic components of U.S. organizations may apply, and foreign components are allowed as defined by HHS grants policy. Overall, the grant is designed to catalyze advanced measurement science for stereochemical characterization in PS oligonucleotides, with a clear line of sight to improving generic oligonucleotide development and strengthening regulatory-grade quality control approaches.

• The Food and Drug Administration in the consumer protection, health, science and technology and other research and development sector is offering a public funding opportunity titled "Development of advanced analytical methods for the characterization of complex generics" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.103.
• This funding opportunity was created on 2022-01-12.
• Applicants must submit their applications by 2022-03-07. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $300,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA FD 22 013

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