Evolving Mechanisms, Enduring Goals: NICHD OPPTB Support for the Science of Therapeutics in Pregnancy and Childhood (2004–Present)

Abstract

The Obstetric and Pediatric Pharmacology and Therapeutics Branch (OPPTB) of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at the National Institutes of Health (NIH) was formed in 2004 following the enactment of the Best Pharmaceuticals for Children Act (BPCA) of 2002, in recognition of the unique research needs of studying therapeutics in pregnant women and in children of all ages. During the past two decades, the branch has supported basic, translational, and clinical research in maternal and pediatric therapeutics, including the application of emerging technologies and training and career‐development activities. Its portfolio has evolved in response to scientific, regulatory, and legislative changes and has expanded to include pediatric medical devices and a stronger focus on lactation pharmacology. This mini‐review describes the evolution of these programs, selected contributions, remaining limitations, and future scientific priorities.

INTRODUCTION

The Obstetric and Pediatric Pharmacology and Therapeutics Branch (OPPTB; originally the Obstetric and Pediatric Pharmacology Branch) was formed in May 2004 within the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), catalyzed by the 2002 Best Pharmaceuticals for Children Act (BPCA) and recognition of the distinct therapeutic research needs of pregnant women and children. OPPTB consolidated the Pediatric Pharmacology Research Units (PPRU) Network and pediatric pharmacology grants portfolio, established the Obstetric‐Fetal Pharmacology Research Units (OPRUs), advanced National Institutes of Health (NIH)‐specific BPCA mandates, and addressed training and career‐development needs. ¹ Since then, its portfolio and funding mechanisms have evolved to support basic, translational, and clinical research; emerging methods; maternal and pediatric therapeutics across pregnancy, obstetric treatment, postpartum, lactation, and childhood; and pediatric medical‐device research and coordination. ² , ³ Relevant Notices of Funding Opportunities (NOFOs) are summarized in Table S1 .

PROGRESS MADE AND REMAINING GAPS IN PEDIATRIC PHARMACOLOGY

Drug regulation has often been prompted by high‐profile pediatric adverse events, and legislation continues to shape the pediatric therapeutics evidence base (Tables 1 and S2 ). ⁴ , ⁵ In 1994, in response to calls from the American Academy of Pediatrics (AAP) and other advocates to address persistent knowledge gaps in pediatric therapeutics, NICHD established the PPRU Network. ¹ The PPRU Network established multicenter experience in pediatric pharmacology and provided an early platform for studies conducted under the NIH BPCA program.

Table 1.

Landmark legislation and regulatory relevance. Condensed main‐manuscript version of selected US statutes and federal regulations relevant to pediatric and maternal therapeutics and devices

Domain	Authority (years)	Regulatory relevance
Adverse events	Biologics Control Act (1902–1944)	Child antitoxin deaths led to biologics licensing and inspection.
Adverse events	FD&C Act (1938‐)	Elixir sulfanilamide deaths led to premarket drug safety review.
Adverse events	Kefauver‐Harris Amendments (1962‐)	Thalidomide led to proof of efficacy and stronger trials.
Pediatric drugs	Pediatric exclusivity, Sec. 505A (1997‐)	6‐month exclusivity for FDA‐requested pediatric studies.
Pediatric drugs	BPCA (2002‐)	NIH off‐patent studies program; FDA Written Requests.
Pediatric drugs	PREA, Sec. 505B (2003‐)	Pediatric assessments for relevant NDA/BLA filings; waivers/deferrals.
Pediatric drugs	Rare Pediatric Disease PRV (2012‐)	PRV for qualifying products; awards sunset after 9/30/2029.
Pediatric drugs	RACE for Children Act (2017‐)	Pediatric oncology studies tied to relevant molecular targets.
Pediatric devices	PMDSIA (2007‐)	Supports pediatric device consortia, HDE use, and NIH contact point.
Pregnancy/lactation	PLLR (2015‐)	Replaced letter categories with pregnancy/lactation narrative labeling.
Pregnancy/lactation	PRGLAC (2016–2021)	HHS task force on evidence gaps for pregnancy/lactation therapeutics.
Pregnancy/lactation	Revised Common Rule (2019‐)	Removed pregnant women as a categorical vulnerable‐population example.
Pregnancy/lactation devices	None identified	No targeted US authority identified in this review.
RWE/NAMs	Sec. 505(k)(3) (2007‐)	Active postmarket safety surveillance using electronic health data.
RWE/NAMs	Sec. 505(o)(4) (2007‐)	FDA‐required safety labeling changes for new safety information.
RWE/NAMs	Sec. 505F RWE program (2016‐)	RWE may support new indications or post‐approval requirements.
RWE/NAMs	FDORA Sec. 3629 (2022‐)	Directs FDA/HHS guidance on RWD/RWE in regulatory decisions.
RWE/NAMs	Modernization Act 2.0 (2022‐)	IND‐enabling tests may include in vitro/in silico methods.

Note: Full legislative citations and longer rationale can be obtained in Table S2.

Abbreviations: BLA, biologics license application; BPCA, Best Pharmaceuticals for Children Act; FD&C Act, Federal Food, Drug, and Cosmetic Act; FDORA, Food and Drug Omnibus Reform Act; HDE, humanitarian device exemption; HHS, US Department of Health and Human Services; IND, investigational new drug; NAMs, new approach methodologies; NDA, new drug application; PLLR, Pregnancy and Lactation Labeling Rule; PMDSIA, Pediatric Medical Device Safety and Improvement Act; PREA, Pediatric Research Equity Act; PRGLAC, Task Force on Research Specific to Pregnant Women and Lactating Women; PRV, priority review voucher; RACE, Research to Accelerate Cures and Equity; RWD/RWE, real‐world data/evidence.

The Food and Drug Administration Modernization Act (FDAMA) of 1997, utilizing pediatric exclusivity incentives, marked the start of the modern legislative push to encourage studies of drugs in children; however, pediatric labeling gaps remained substantial, particularly for neonates. ⁶ , ⁷ Under BPCA §409I, the NIH, in collaboration with the Food and Drug Administration (FDA), was directed to prioritize pediatric therapeutic needs, sponsor needed pediatric studies, and submit study reports to FDA for possible labeling changes. In the initial years of NIH BPCA 409I implementation, individual, drug‐focused studies were supported through grant mechanisms, including the PPRU Network. As the PPRU Network concluded, scientific and operational knowledge and, in some cases, information from studies initiated during that period were carried forward into the Pediatric Trials Network (PTN), which consolidated BPCA studies within a disease‐agnostic, contract‐based infrastructure. Contracts were awarded in 2010 to the Duke Clinical Research Institute and Emmes Corporation to provide infrastructure for conducting pediatric clinical trials for the BPCA drug development program.

The PTN is an alliance of pediatric pharmacology investigators and clinical sites located around the United States that cooperates in the design and conduct of regulatory‐rigorous pediatric clinical trials intended to close knowledge gaps in drug labels. ⁸ , ⁹ PTN studies emphasize high‐impact gaps, including dosing and safety studies in preterm neonates and children in acute and chronic care settings, as well as trials in breastfeeding mothers and their infants to inform medication use during lactation. As of August 2026, the BPCA/PTN portfolio included 54 studies spanning more than 150 drugs, more than 13,500 participants, and more than 200 peer‐reviewed publications and had informed 26 FDA actions. These comprised 24 drug‐labeling actions involving 23 unique drugs and two pediatric‐device clearances. Among the drug‐labeling actions, at least nine addressed neonates or young infants, four addressed pharmacokinetics or dosing in children with obesity, and two added information concerning medication use during lactation. The relationship between studies and labeling actions is not one‐to‐one, as multiple studies may contribute to a single action, a drug may be the subject of more than one action, and some studies may not generate evidence sufficient for a labeling change or may contribute to a subsequent evidence package. Drug‐, population‐, and action‐specific information is maintained on the PTN website under “FDA Label Changes Informed by the PTN” and the FDA's “NIH Funded Pediatric Labeling Changes for drugs studied under the §409I process” website.

FDA‐approved prescribing information is both a regulatory outcome and an upstream dissemination pathway because pediatric dosing handbooks and electronic drug‐information resources synthesize labeling with primary literature, clinical guidance, and expert review. PTN Results At‐A‐Glance summaries and BPCA Clinical Reports provide complementary public access to study‐level methods and findings. FDA labeling is an important regulatory and dissemination outcome, but a labeling change does not by itself ensure changes in clinical practice. A study of pediatric labeling changes found that subsequent changes in prescribing and drug utilization are variable and, in some settings, modest or absent, underscoring the importance of complementary dissemination and implementation strategies. ¹⁰

Legislative and regulatory innovations, including refinements to the BPCA 409I provisions at 5‐year renewal points, have helped expand pediatric drug development and encourage approaches such as extrapolation and innovative study designs and methods. However, challenges remain, such as the unique needs of neonates and the proximal origin of their health during pregnancy, and further evolution is needed, particularly approaches that leverage innovations in data science and real‐world evidence (RWE). FDA's statutory RWE authorities and implementing guidance provide a framework under which fit‐for‐purpose RWE may support regulatory decisions, including certain postapproval labeling claims, especially for older or off‐patent drugs.

OVERCOMING THE LAG IN MATERNAL AND LACTATION PHARMACOLOGY

Like children, pregnant women have historically been excluded from clinical research and continue to be underrepresented in research. In 2018, a study of actively recruiting NIH‐funded phase III and IV clinical trials found 68% explicitly excluded pregnant women and 47% explicitly excluded lactating women. ¹¹ Reasons for historical exclusion of these populations have largely been due to concerns about the safety and protection for the mother and fetus. Notably, despite longstanding NIH inclusion expectations that require investigators to justify exclusions for some underrepresented groups, there have been no changes to NIH justification criteria and no NIH policy requiring a justification for excluding pregnant women or lactating women from NIH‐funded trials – making default exclusion more likely to persist, as reported in 2022. ¹² Experience with other NIH inclusion policies suggests that explicit inclusion expectations can be associated with measurable changes in trial enrollment; for example, in National Institute of Neurological Disorders and Stroke‐funded phase III trials, enrollment of women and African American participants increased in the period after 1995 when NIH enacted policies on inclusion by sex and race/ethnicity. ¹³

Unsurprisingly, scientific evidence on the safety, efficacy, and dosing guidance for medicinal therapies in pregnant women and lactating women is severely lacking. ³ Pregnant women and lactating women, particularly those with acute or chronic medical conditions, and their clinicians are forced to make decisions about whether to therapeutically treat pre‐existing or emerging medical conditions without adequate scientific knowledge of the safety and efficacy of these treatments. This evidence gap is especially consequential in the United States, which is an outlier among peer high‐income countries for adverse maternal outcomes. ¹⁴

Similar to pediatric pharmacology, progress in maternal pharmacology has been catalyzed by legislative action (Table 1 ). The 21st Century Cures Act (2016) established the Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC) to address the public health and ethical consequences of limited medication data for pregnant women and lactating women. During PRGLAC's operation and since it issued its recommendations, implementation has advanced across multiple federal agencies and within NIH/NICHD, including implementation of revisions to the Federal Policy for the Protection of Human Subjects (aka “Common Rule”) that removed pregnant women as an example of a potentially vulnerable population, as PRGLAC recommended, and the launch of a public–private partnership to qualify biomarkers for preeclampsia. However, additional guidance and policy reforms are still needed to normalize inclusion of pregnant women and lactating women in clinical research. The 2024 PRGLAC Implementation Working Group report underscores the sustained effort and resources required to implement most recommendations at scale.

The NIH continues to pursue the PRGLAC recommendations by encouraging investigator‐initiated applications in these areas through the Translational PAR and through innovative initiatives (Table S1 ). Another initiative is the recently established Transporter Elucidation Network, which focuses on studying understudied perinatal transporters and transport processes for drugs and nutrients in the gut, placenta, and brain. ¹⁵ In parallel, recent RWE legislation and FDA guidance can serve as a near‐term regulatory bridge to support the Pregnancy and Lactation Labeling Rule (PLLR)‐aligned labeling modernization for pregnancy and lactation using fit‐for‐purpose real‐world data.

ENABLING PRECISION THERAPEUTICS AND INNOVATIVE TRIALS

The pursuit of precision application of therapeutics in maternal and pediatric populations necessarily evolves over time as knowledge and technologies advance. ² OPPTB previously supported this goal through initiatives such as the Specialized Centers in Research in Pediatric Developmental Pharmacology (RPDP) and the Obstetric‐Fetal Pharmacology Research Centers/Units (OPRC/Us) (Table S1 ). The Maternal and Pediatric Precision in Therapeutics (MPRINT) Hub was established in 2021 to integrate data, modeling, and research activities relevant to precision therapeutics in pregnant and lactating women and children. ¹⁶ Its structure facilitates collaboration with existing clinical research networks, including the PTN, Maternal‐Fetal Medicine Units (MFMU) Network, and International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network.

To prioritize medications for study and support scalable analyses across literature, RWE, and other data, the publicly available MPRINT Knowledge Portal, hosted through the MPRINT Hub website, maps pharmacological knowledge within an ontological framework. ¹⁷ , ¹⁸ It integrates disparate sources into harmonized, computable “what we know/what we don't know” summaries for drug–population contexts and maps to disease/phenotype and drug‐target ontologies. Panel A of Figure 1 links these knowledge gaps to regulatory relevance and study feasibility; the full pediatric and maternal evidence‐generation framework is discussed under Cross‐Cutting Future Directions.

Figure 1.

Cross‐cutting framework linking candidate‐drug prioritization to pediatric and maternal evidence‐generation pathways for potential labeling updates. Panel (a) shows triage of candidate drugs according to signals and priority, the presence of a label‐actionable question, and regulatory usefulness, followed by a feasibility screen and a go/no‐go decision on whether an FDA‐reviewable evidence package can be built and a labeling decision is plausible. Panel (b) shows the strict pediatric BPCA 409I pathway, in which PTN‐generated prospective/opportunistic PK data, limited PD and safety studies, and selected phase IIb/III trial data are assembled to address accessible pediatric label gaps and submitted for FDA review and lifecycle oversight, with potential pediatric label updates. Panel (c) shows an expanded pediatric pathway in which PTN evidence is integrated with fit‐for‐purpose RWE from NICU EHRs and registries, claims and safety databases, and pragmatic or observational studies; dissemination and implementation activities create a learning loop that strengthens future RWE before submission of a label‐actionable evidence package. Panel (d) shows a parallel maternal pathway in which clinical trial evidence and fit‐for‐purpose RWE are integrated using a similar learning‐loop model to support maternal label updates through FDA review and lifecycle oversight. Across panels, the framework emphasizes starting with defined label gaps, harmonizing endpoints and key covariates, documenting provenance, traceability, relevance, reliability, and auditability, and submitting only when the totality of evidence is sufficiently robust and label‐actionable. BPCA, Best Pharmaceuticals for Children Act; EHR, electronic health record; FDA, US Food and Drug Administration; NICU, neonatal intensive care unit; PD, pharmacodynamics; PK, pharmacokinetics; PTN, Pediatric Trials Network; RWE, real‐world evidence. CFR, Code of Federal Regulations; FD&C Act, Federal Food, Drug, and Cosmetic Act; FDORA, Food and Drug Omnibus Reform Act; PLLR, Pregnancy and Lactation Labeling Rule; SAP, statistical analysis plan.

These outputs support several downstream uses. First, they can inform systematic prioritization of drugs and knowledge gaps for follow‐up studies; for example, a recent analysis integrating the MPRINT Hub's knowledge base with claims and safety datasets identified benzonatate as having recent increases in pediatric prescribing, limited clinical trial data, and a high risk of serious adverse drug events. ¹⁹ Second, the ontology‐linked framework enables discovery workflows – including hypothesis generation and drug repurposing analyses using RWE – and informs trial design by clarifying target populations, endpoints, and the evidence gaps most likely to be addressed with fit‐for‐purpose studies. Finally, the structured links between drugs, targets, phenotypes, and responses provide a foundation for quantitative systems pharmacology (QSP) and related mechanistic modeling approaches. As FDA has clarified expectations for regulatory‐grade RWE derived from registries and electronic health records (EHR) and claims data, these knowledgebase‐driven workflows may be paired with prespecified study designs to assemble evidence packages suitable for regulatory review.

The MPRINT Hub's Centers for Excellence in Therapeutics (CETs) have also played an important role in advancing our understanding of drugs and their use in maternal, pediatric, and lactating populations. One example from the University of California San Diego CET reported associations between maternal antidepressant or anti‐inflammatory medication use and variation in human milk oligosaccharide composition. ²⁰ Whether these associations are causal or affect infant nutrition or outcomes remains unknown and requires further study. At Vanderbilt's VICE‐MPRINT Center, community‐engaged pharmacogenomics (PGx) research found that, despite low baseline familiarity, more than 90% of pregnant participants and parents or guardians in the pediatric cohort viewed PGx as useful for guiding clinical care after receiving a brief definition. ²¹ , ²² This suggests that implementation may depend less on patient acceptance than on clear communication and engagement.

MEDICAL DEVICES

The branch's portfolio has expanded to include maternal and pediatric medical devices. OPPTB holds the congressionally mandated NIH point‐of‐contact role for pediatric medical‐device development and coordinates a trans‐NIH subgroup within the NIH Pediatric Research Consortium (Tables 1 and S2 ). With the National Institute of Biomedical Imaging and Bioengineering (NIBIB), OPPTB also co‐leads a Foundation for the National Institutes of Health‐convened design effort evaluating potential models for national pediatric medical‐device infrastructure. As part of the NIH's Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE) Initiative, OPPTB co‐led with NIBIB the Rapid Acceleration of Diagnostics Technology (RADx® Tech) for Maternal Health Challenge, which focused on technologies for postpartum care in areas with limited access to maternity services.

INVESTIGATOR‐INITIATED APPLICATIONS

OPPTB has also solicited investigator‐initiated applications through successive “Translational Research in Maternal and Pediatric Pharmacology and Therapeutics” Program Announcements with Special Receipt, Referral, and/or Review Considerations (PARs) and other opportunities (Table S1 ). For the Translational PARs, a public NIH RePORTER analysis through August 4, 2026, identified 143 competitive award actions representing 139 distinct projects; 135 were administered by NICHD and eight by three other NIH institutes. RePORTER linked 1,189 unique PubMed‐indexed publications to these projects; 109 projects (78%) had at least one linked publication, including 70 of 76 (92%) whose listed project periods had ended by the cutoff date.

TRAINING AND CAREER DEVELOPMENT

NICHD's OPPTB supports the Clinical Pharmacology Training Network (CPTN), a BPCA‐mandated program to expand the clinical pharmacology and therapeutics workforce, with a major emphasis on pediatrics. CPTN provides interdisciplinary training that spans pediatric—and now maternal—clinical pharmacology, emphasizing model‐informed drug development, pharmacometrics, and “‐omics” approaches to advance precision therapeutics. Since inception, more than 140 participants have graduated across NICHD‐led and co‐funded programs, and many now hold leadership roles in academia, the FDA, and industry. In 2022, CPTN launched a K12 program (Table S1 ) to offer protected research time and national mentorship, supporting scholars—especially at institutions with limited clinical pharmacology infrastructure—as they transition toward independence. Network‐wide, CPTN harmonizes core curricula, promotes cross‐site collaboration, delivers the publicly available Principles of Pediatric Clinical Pharmacology and Therapeutics Lecture Series through the NICHD BPCA Lectures webpage, and sponsors annual meetings. A 10‐year survey of trainees and graduates of CPTN shows strong success and underscores the importance of comprehensive, consistent training and career development opportunities. ²³

CROSS‐CUTTING FUTURE DIRECTIONS

NICHD's 2025–2029 Strategic Plan prioritizes safe and effective therapeutics and devices for pregnant and lactating women, children, and people with disabilities, alongside enabling technologies, partnerships, and reducing health disparities. Several cross‐cutting scientific and implementation gaps remain across pediatric, pregnancy, and lactation therapeutics and reflect areas in which additional research, methods development, and coordination are needed.

Novel therapeutic discovery and translation

Persistent underinvestment in pregnancy‐ and lactation‐specific therapeutics contributes to a thin late‐stage pipeline; as of 2021, only 64 of 444 identified maternal medicine candidates were in active phase 3 development. ²⁴ Earlier incorporation of pregnancy‐, lactation‐, and pediatric‐specific physiology and safety considerations into therapeutic discovery and development could reduce reliance on adult‐first repurposing when suitability for these populations is uncertain.

New approach methodologies (NAMs)

Building on longstanding OPPTB support for NAMs, an emerging priority is the combinatorial use of complementary NAMs to address reproductive and developmental toxicology and exposure questions. These approaches can move key assessments earlier in discovery, supporting faster “go/no‐go” decisions and more informative first‐in‐population studies. A near‐term priority is to strengthen lactation‐relevant NAMs (e.g., mammary models and milk‐transfer platforms) and integrate them with more mature placental systems and model‐informed development. ²⁵

Fetal pharmacology and in utero therapeutics

Advancing methods to quantify fetal exposure and response and to enable targeted delivery and minimally invasive monitoring will improve the quality of data/approaches available to inform parent‐provider prenatal decisions related to fetal treatment interventions, and OPPTB supports research in these areas. Further progress will require harmonized ethical/regulatory approaches, coordinated multicenter infrastructure, and standardized long‐term follow‐up to address heterogeneous datasets and inter‐fetal variability.

New therapeutic modalities

As biologics, nucleic‐acid therapeutics, and gene therapies expand, modality‐specific frameworks are needed to evaluate maternal–fetal and developmental biodistribution, safety, and durability, including in the perinatal period. These modality‐specific considerations could be incorporated early in therapeutic development to support evaluation of emerging options for intractable pediatric diseases and selected prenatal indications.

Real‐world evidence for regulatory utility

Statutory and policy developments (Table 1 ) create opportunities to pair prospective NIH studies with linked real‐world data to produce FDA‐reviewable evidence packages for postmarket labeling updates. Figure 1 integrates candidate prioritization with alternative pathways for generating evidence relevant to regulatory review. Panel (a) depicts the upstream triage of candidate drugs based on knowledge gaps, utilization or safety signals, the presence of a label‐actionable question, and study feasibility. Panel (b) depicts the NIH BPCA pathway based primarily on prospective and opportunistic pediatric studies. Panels (c) and (d) extend the framework by integrating fit‐for‐purpose RWE with pediatric and maternal clinical evidence, respectively, before FDA review. Across the pathways, the framework emphasizes that candidate identification is distinct from the subsequent determination that a sufficiently relevant, reliable, and traceable evidence package can be assembled. Prospective studies can be designed with prespecified questions, cohorts, and endpoints and linked to fit‐for‐purpose real‐world data. Such approaches may be particularly useful for modernizing pregnancy and lactation labeling for older or off‐patent drugs, for which sponsor‐driven updates are less likely.

Risk communication and dissemination and implementation research

Implementation research should assess whether new evidence, including updates to FDA‐approved labeling, is incorporated into dosing references, professional guidelines, formularies, and EHR‐enabled decision support and whether it changes prescribing, dosing concordance, or patient outcomes. Such evaluations are methodologically challenging because labeling actions may coincide with publications, guideline revisions, formulary changes, and secular changes in clinical practice. ²⁶ Implementation research is needed to test scalable dissemination approaches, including clinical decision support and EHR‐enabled tools, and to evaluate the reach and equity of evidence‐to‐practice resources such as PTN summaries and LactMed®.

Partnering and representation

Coordination among FDA, NIH, professional societies, patients, and public–private partners can align scientific standards, ethical guidance, and regulatory pathways while advancing inclusion and health equity.

CONCLUSION

Over the past two decades, OPPTB‐supported programs have been used to address therapeutic evidence gaps in children and in pregnant and lactating populations through clinical research networks, investigator‐initiated studies, training programs, data resources, and medical‐device initiatives. These mechanisms have evolved in response to legislative mandates, scientific advances, and persistent evidence gaps. Remaining priorities include earlier integration of NAMs, innovative trial designs, regulatory‐grade RWE, implementation research, and cross‐sector coordination. Future evaluations should assess not only research and regulatory outputs but also incorporation of evidence into clinical guidance and effects on patient care.

FUNDING

No funding was received for this work.

DISCLOSURE

The opinions expressed in this manuscript are those of the authors and should not be interpreted as the position of the National Institutes of Health.

CONFLICT OF INTEREST

All authors are federal employees of the NIH. Dr. Pileggi is listed as a co‐inventor on the following patent families/applications: (1) Therapeutic hybrid implantable devices / Hybrid implantable therapeutic devices (Google Patents family ID 39495042; PCT/US2008/001433; WO2008097498A1; US20100204683A1; US8702684B2; EP2124815A1; AU2008214423A1; BRPI0808191A2; CA2677082A1; IL200163A/IL200163A0; JP2010517621A; KR20090120473A; MX2009008294A; NZ579362A; RU2009132949A; SMAP200900075A/SMP200900075B; TW200920328A); (2) Macroporous bioengineered scaffolds for cell transplantation (Google Patents family ID 44798999; PCT/US2011/032182; WO2011130322A1; US20130089594A1; EP2558024A1/EP2558024A4/EP2558024B1; TW201204334A); (3) Stable liquid formulations of volatile gas anesthetics (Google Patents family ID 47601532; PCT/US2012/048294; WO2013016511A1; US20140256828A1; US9308269B2; US20160263051A1; US9980923B2); and (4) Methods of treating diabetes and/or promoting survival of pancreatic islets after transplantation (Google Patents family ID 48326412; PCT/US2013/037150; WO2013158868A1; US20150315573A1; US10081809B2; US20190136237A1; US10443056B2; US20200239884A1; EP2839004A1/EP2839004B1; AU2013249191A1/AU2013249191B2; CA2870547A1; CN104487574A/CN104487574B/CN107252492A; DK2839004T3; ES2732252T3; HK1207117A1; IN2014DN08158A; JP2015514778A/JP6348484B2/JP2018131468A; KR20150003824A; MX2014012650A/MX370149B; NZ630914A; RU2014146170A/RU2667960C2).

Supporting information

Table S1 Titles correspond to the most recent solicitation for each program; the Solicitation Number(s) column lists current and prior NOFOs/RFPs associated with that program. Years indicate the span from the first fiscal year of awards under the program's initial solicitation to the most recent fiscal year of awards (or present, for active programs). An asterisk indicates that companion NOFOs for related mechanisms or consortium components are not listed separately.

Table S2 Relevant pediatric and maternal regulatory legislation. Selected US Statutes and federal regulations that have shaped the development, study, labeling, and postmarket evidence generation for drugs, biologics, and medical devices relevant to children and to pregnant and lactating women, including newer authorities related to real‐world evidence (RWE) and new approach methodologies (NAMs). *BPCA's FDA pediatric exclusivity provisions and PREA were made permanent in 2012. BPCA's NIH pediatric studies program under PHSA §409I remains subject to periodic authorization of appropriations; the current authorization extends through FY2028.