Regulatory Considerations for the Mother, Fetus and Neonate in Fetal Pharmacology Modeling
The regulatory framework for considering the fetal effects of new drugs is limited. This is partially due to the fact that pediatric regulations (21 CFR subpart D) do not apply to the fetus, and only US Health and Human Service (HHS) regulations apply to the fetus. The HHS regulation 45 CFR Part 46...
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doaj-a64124a612a143cabac0ab7f159759802021-07-26T07:57:12ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602021-07-01910.3389/fped.2021.698611698611Regulatory Considerations for the Mother, Fetus and Neonate in Fetal Pharmacology ModelingDionna J. Green0Kyunghun Park1Varsha Bhatt-Mehta2Donna Snyder3Gilbert J. Burckart4Office of Pediatric Therapeutics, Office of the Commissioner, US Food and Drug Administration, Silver Spring, MD, United StatesOffice of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, United StatesOffice of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, United StatesOffice of Pediatric Therapeutics, Office of the Commissioner, US Food and Drug Administration, Silver Spring, MD, United StatesOffice of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, United StatesThe regulatory framework for considering the fetal effects of new drugs is limited. This is partially due to the fact that pediatric regulations (21 CFR subpart D) do not apply to the fetus, and only US Health and Human Service (HHS) regulations apply to the fetus. The HHS regulation 45 CFR Part 46 Subpart B limits research approvable by an institutional review board to research where the risk to the fetus is minimal unless the research holds out the prospect of a direct benefit to the fetus or the pregnant woman (45 CFR 46.204). Research that does not meet these requirements, but presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health of pregnant women, fetuses, or neonates, may be permitted by the Secretary of the HHS after expert panel consultation and opportunity for public review and comment (45 CFR 46.407). If the product is regulated by the US Food and Drug Administration (FDA), FDA may get involved in the review process. The FDA does however have a Reviewer Guidance on Evaluating the Risks of Drug Exposure in Human Pregnancies from 2005 and this guidance does discuss the intensity of drug exposure. Estimation of that exposure using physiologically based pharmacokinetic (PBPK) modeling has been suggested by some investigators. Given that drug exposure during pregnancy will impact the fetus, a number of new guidances in the last 2 years also address inclusion of pregnant women in clinical drug trials. Therefore, the drug-specific information on fetal pharmacology will increase dramatically in the next decade due to interest in drugs administered in pregnancy and with the assistance of model-informed drug development.https://www.frontiersin.org/articles/10.3389/fped.2021.698611/fulldrug developmentfetalregulatorypediatricsFood and Drug Administrationmodel-informed drug development |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dionna J. Green Kyunghun Park Varsha Bhatt-Mehta Donna Snyder Gilbert J. Burckart |
spellingShingle |
Dionna J. Green Kyunghun Park Varsha Bhatt-Mehta Donna Snyder Gilbert J. Burckart Regulatory Considerations for the Mother, Fetus and Neonate in Fetal Pharmacology Modeling Frontiers in Pediatrics drug development fetal regulatory pediatrics Food and Drug Administration model-informed drug development |
author_facet |
Dionna J. Green Kyunghun Park Varsha Bhatt-Mehta Donna Snyder Gilbert J. Burckart |
author_sort |
Dionna J. Green |
title |
Regulatory Considerations for the Mother, Fetus and Neonate in Fetal Pharmacology Modeling |
title_short |
Regulatory Considerations for the Mother, Fetus and Neonate in Fetal Pharmacology Modeling |
title_full |
Regulatory Considerations for the Mother, Fetus and Neonate in Fetal Pharmacology Modeling |
title_fullStr |
Regulatory Considerations for the Mother, Fetus and Neonate in Fetal Pharmacology Modeling |
title_full_unstemmed |
Regulatory Considerations for the Mother, Fetus and Neonate in Fetal Pharmacology Modeling |
title_sort |
regulatory considerations for the mother, fetus and neonate in fetal pharmacology modeling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pediatrics |
issn |
2296-2360 |
publishDate |
2021-07-01 |
description |
The regulatory framework for considering the fetal effects of new drugs is limited. This is partially due to the fact that pediatric regulations (21 CFR subpart D) do not apply to the fetus, and only US Health and Human Service (HHS) regulations apply to the fetus. The HHS regulation 45 CFR Part 46 Subpart B limits research approvable by an institutional review board to research where the risk to the fetus is minimal unless the research holds out the prospect of a direct benefit to the fetus or the pregnant woman (45 CFR 46.204). Research that does not meet these requirements, but presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health of pregnant women, fetuses, or neonates, may be permitted by the Secretary of the HHS after expert panel consultation and opportunity for public review and comment (45 CFR 46.407). If the product is regulated by the US Food and Drug Administration (FDA), FDA may get involved in the review process. The FDA does however have a Reviewer Guidance on Evaluating the Risks of Drug Exposure in Human Pregnancies from 2005 and this guidance does discuss the intensity of drug exposure. Estimation of that exposure using physiologically based pharmacokinetic (PBPK) modeling has been suggested by some investigators. Given that drug exposure during pregnancy will impact the fetus, a number of new guidances in the last 2 years also address inclusion of pregnant women in clinical drug trials. Therefore, the drug-specific information on fetal pharmacology will increase dramatically in the next decade due to interest in drugs administered in pregnancy and with the assistance of model-informed drug development. |
topic |
drug development fetal regulatory pediatrics Food and Drug Administration model-informed drug development |
url |
https://www.frontiersin.org/articles/10.3389/fped.2021.698611/full |
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