Food and Drug Administra/on Overview

21st Century Cures Act Sec/on 2041, PRGLAC Task Force

Marjorie Jenkins, M.D., M.Ed.H.P., F.A.C.P. Director, Medical Ini/a/ves & Scien/fic Engagement

Office of Women’s Health

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FDA Mission

•To  protectthe public health by ensuring the safety, efficacy, and security of drugs, products, and medical devices

•To  protectthe safety of our na/on's food supply, cosme/cs, and products thatemit radia/on

•To  regulate the manufacturing, marke/ng, and distribu/on of tobacco products to protect the public health

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Collabora:on

FDA EFFORTS RELATING TO

PREGNANT AND LACTATING WOMEN

Research Communica:on

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Pregnancy and Lacta:on Research Programs at FDA Evaluate a Broad Array of Issues Including:

•Mechanisms of therapies

•Nonclinicalstudies

• PK/PDstudies

• Risk of exposure

• Impact of tobacco use

Drugs

Devices

Biologics

Tobacco

Food

Cosme:cs

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Pregnancy & Lacta:on Research

FDA

Na:onal Centerfor

Toxicological Research (NCTR) Officeof

Women’s Health(OWH)

Centerfor Biologics Evalua:on

and Research (CBER)

Centerfor Drug

Evalua:on and Research

(CDER)

CenterforDevices and Radiological

Health (CDRH)

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CenterforTobacco Products (CTP)

CenterforFood Safety and Applied Nutri:on (CFSAN)

OUR CENTERS

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CenterforBiologicsEvalua:on and Research (CBER)

Mission: Protect and enhance the public health through the regula/on of biological and related products

EXAMPLES OF PRGLAC RESEARCH: BIOLOGICS

• Safety and Efficacy of Vaccines7

• Maternal Immuniza/on7

• Zika infec/on in pregnant women6

• Zika Blood Safety Risk Assessment

• Sen/nel Program (Surveillance Ac/vi/esRelated to the Safety of Vaccines in PregnantWomen)

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Center for Devices and Radiologic Health (CDRH)

Mission: To protect and promote public health through access to safe, effec/ve products, and to provide accessible informa/on to

consumers

EXAMPLES OF PRGLAC RESEARCH: DEVICES

Electromagne/c Exposure9,10,11• Hand-held metal detectors• MRI• RF Exposure and

Temperature Increases inpregnant women from MRI

• RF Exposure

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CenterforDrugEvalua:on and Research (CDER)

Mission: To ensure that safe and effec/ve drugs are available to improve the health of people in the United States

Divisiono fPediatricand Maternal Health (DPMH)

Mission: To develop clinically relevant, evidence-based labeling and other communica/ons that

facilitate informed use of medicines in children and women

of childbearing poten/al

Division of Bone, Reproduc:ve andUrologic Products (DBRUP)

Mission: To assure the safety and efficacy of drugs and therapeu/c biologics aimed at improving bone, reproduc/ve, and urologic health

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CenterforDrugEvalua:on and Research (DPMH, DBRUP, OSE)

EXAMPLES OF PRGLAC RESEARCH: DRUGS

• Medica/on in Pregnancy Risk Evalua/on Program(MEPREP)35

• Pregnancy Registries3

• Collabora/ve research29

• Mechanisms of therapies• U/liza/on of medica/on• Iden/fica/on of therapy for use during

pregnancy• PK/PD studies of therapies during pregnancy

and/or lacta/on 11

 

  

   

Center for Food Safety and Applied Nutri:on (CFSAN)

Mission: To promote and protect the public's health by ensuring that the na/on's food and cosme/c products are safe, sanitary,

and honestly labeled

EXAMPLES OF PRGLAC RESEARCH: FOOD & NUTRITION SAFETY

• Infant Feeding Prac/ces Study13

• Fundedby OWH4,5

• Nervous system dysfunc/on and contaminantexposure

• Contaminants in dietary supplements• Birth Defect poten/al of cosme/c products

containing re/nol

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CenterforTobacco Products (CTP)Mission: To protect Americans from tobacco-related death and disease by regula/on of tobacco products and educa/on of the

public

EXAMPLES OF PRGLAC RESEARCH: TOBACCO

• CTPFunde dQues/onsPregnancy Risk AssessmentMonitoring System (PRAMS)20

• Percep/ons of Health Risk fromSmokeless Tobacco andNico/ne Products22

• Popula/on Assessmentof Tobacco and Health (PATH)21

• Ultrasound Markers ofMaternal Smoking8

• Flavors and DesignFeatures Impac/ngWaterpipe Use andToxicity8

• Low Nico/ne Cigarejes813

 

     

 

Na:onalCenter for ToxicologyResearch (NCTR)

Mission: To func/on as a major research arm to support FDA’s ability to make science-based decisions

EXAMPLES OF PRGLAC RESEARCH

• Preclinical Exposure Impact on Fer/lity,Prenatal and Post-natal Development30

• Pharmacokine/cs of Drugs and Chemicals23

• Biology and Metabolism of BPA25

• Exposure of Thyroid-Disruptor RiskEvalua/on2

• Modeling and Simula/on of Physiology ofPregnancy in order to Test DrugMetabolism30

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OfficeofWomen’sHealth (OWH)

Mission: Protect and advance the health of women through policy, science and outreach

PRGLAC RESEARCH FUNDING

• Annual intramural research programprovides funding across FDA Centersand Offices4,19

• Collabora/ve efforts with Centers onguidance developmentand pregnancyand lacta/on projects

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Crea:on ofPoliciesand Guidances

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FDA Guidances:

Pregnancy and Lacta:on Submission of PremarketN o9fica9ons for Magne9c Resonance

Diagnos9c Devices34

Revised Recommenda9ons for Reducing the Risk of Zika VirusTransmission by Blood and Blood Components6

Considera9ons for Developmental Toxicity Studies for Preven9ve and Therapeu9cVaccines for Infec9ous Disease Indica9ons33

Reproduc9ve and Developmental Toxici9es —Integra9ng Study Results to Assess Concerns32

Evalua9ng the risks of drug exposure in human pregnancies36

Establishing Pregnancy Exposure Registries31

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DraX Guidances • Pregnancy, Lacta/on, and Reproduc/ve Poten/al:Labeling for Human Prescrip/on Drug and BiologicalProducts-Content and Format

• Pharmacokine/cs in Pregnancy - Study Design, DataAnalysis, and Impact on Dosing and Labeling

• Clinical Lacta/on Studies-Study Design, Data Analysisand Recommenda/ons for Labeling

Source: hjps://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInforma/on/Guidances/UCM425398.pdf hjps://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInforma/on/Guidances/UCM072133.pdf hjps://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInforma/on/Guidances/UCM072097.pdf

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Collabora:on EffortsFDA collaborates internally and externally with federal, academic and other organiza/ons to

develop a variety of programs to benefit pregnantand lacta/ng women

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ClinicalPra c:ceInforma:ona nd Recommenda:ons

• FDA does not provide direct clinical care• FDA does

– Regulate prescrip/on drugs, biologics and devices– Communicate through a variety of mechanismssuch as product labelings

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Communica:on

FDA u/lizes various forms of print, digital, and web-based communica/ons related to

pregnancy and lacta/on.

Website Publica/ons Social Media

Conferences, mee/ngs, workshops

Press releases/ News media

Outreach Ac/vi/es

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FDA Pregnancy Registry List

• Connects consumersand healthprofessionals to over40 pregnancyregistries

• Provides links to druginforma/on andeduca/onal resourcesfor pregnant women

www.fda.gov/pregnancyregistries 24

PREGNANCY AND LACTATION LABELING

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Pregnancy and Medica:on Use

• Only a small percentage ofdrugs are contraindicated foruse in pregnancy. – e.g., isotre/noin, mycophenolates

• For the majority of drugs,labeling should provide whatis known in a way thatenables decisions fortreatment.

Theques:on isHOW?

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TheProblemwith Le^ers

 • Overly simplis/c

• Misinterpreted as a grading system

• A drug with adverse informa/on in animalscould be labeled as the same category as a drugwith no animal informa/on

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FDA Solu:on

Replace Pregnancy Le^er Categories with an integrated Risk Summary

– More complete assessment of the known risks

– Considera:onsofmedical/diseasefactors

– Animal data put in context of human exposure

– Humandataaddedwhenavailable

– Explicitlystateswhennodataare available

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Pregnancy and Lacta:on Labeling Rule

• Took effect on June 30, 2015, immediatelyapplicable for drugs approved aler that date

• ALL prescrip/on drugs to remove pregnancylejer categories by June 2020, gradualprocess

• Prescrip/on drugs approved on or aler June30, 2001 must revise content and format ofthe Pregnancy and Lacta/on sec/ons oflabeling

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Summary

1• FDA designs and performs research which will assist in advancingknowledge regarding the safety and efficacy of drugs, devices,biologics, cosme/cs, food, and tobacco

2• FDA's role as a regulatory agency includes development of guidancesandcollabora:onstodevelophealthpolicy and compliance withfederal mandates as appropriate

3• FDA u/lizes a myriad of different forms of print, digital, and web-based communica/ons related to pregnancy and lacta/on.

4• FDA collaborates internally across centers and offices and externallywith federal, academic and other organiza/ons to develop a varietyof programs that will benefit pregnant and lacta/ng women.

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References 1. Oxybenzone Studies hjps://www.niehs.nih.gov/health/materials/ntp_annual_report_fy2012_508.pdf

2. Risk assessmentthyroid ac/ve chemical exposure hjps://www.fda.gov/abouoda/centersoffices/oc/officeofscien/ficandmedicalprograms/nctr/whatwedo/default.htm

3. Health Pregnancy Exposure Registries www.fda.gov/pregnancyregistries

4. OWH funded studies hjp://inside.fda.gov:9003/oc/officeofwomenshealth/ucm270451.htm

5. hjps://www.fda.gov/ScienceResearch/SpecialTopics/WomensHealthResearch/default.htm

6. Blood Safety in Response to Zikahjps://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInforma/on/Guidances/Blood/ UCM518213.pdf

7.  Safety and Efficacy of Vaccineshjp://wcms.fda.gov/FDAgov/AdvisoryCommijees/CommijeesMee/ngMaterials/BloodVaccinesandOtherBiologics/ VaccinesandRelatedBiologicalProductsAdvisoryCommijee/ucm427602.htm

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References 8. Tobacco Regulatory Science Programs hjps://preven/on.nih.gov/tobacco-regulatory-science-program9.  MRI Exposure in Pregnancy

hjps://google2.fda.gov/search?q=FDA+Guidance+for+submission+of+premarket+no/fica/ons+for+magne/c+resonance+diagnos/c+devices&client=FDAgov&site=FDAgov&lr=&proxystylesheet=FDAgov&requiredfields=-archive%3AYes&output=xml_no_dtd&geoields=*

10.  Electromagne/c Exposurehjps://www.ncbi.nlm.nih.gov/pubmed?term=%22Physics+in+medicine+and+biology%22%5BJour%5D+AND+2003%5Bpdat%5D+AND+Kainz+W%5Bauthor%5D&cmd=detailssearch

11. hjps://www.ncbi.nlm.nih.gov/pubmed?term=%22Magne/c+resonance+in+medicine%22%5BJour%5D+AND+2017%5Bpdat%5D+AND+Murbach+M%5Bauthor%5D&cmd=detailssearch

12.  Guidance for Donor Milkhjps://www.fda.gov/scienceresearch/specialtopics/pediatrictherapeu/csresearch/ucm235203.htm

13.  Infant Feeding Prac/ces hjps://www.cdc.gov/breasoeeding/data/index.htm14.  Rules and Guidances for Pregnancy and Lacta/on Labeling

hjps://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInforma/on/Guidances/UCM425398.pdf15. Trea/ng for Two hjps://www.cdc.gov/pregnancy/meds/trea/ngfortwo/index.html

16. hjps://www.cdc.gov/ncbddd/birthdefects/documents/ncbddd_birth- defects_medica/onuseonepager_cdcrole.pdf

17. Na/onal Health and Nutri/on Examina/on Survey hjps://www.cdc.gov/nchs/nhanes/about_nhanes.htm

18. hjps://www.cdc.gov/nchs/nhanes/nhanes_ques/onnaires.htm

19. hjp://inside.fda.gov:9003/oc/officeofwomenshealth/ucm270451.htm

20. PRAMS hjps://www.cdc.gov/prams/ques/onnaire.htm

21. hjps://pathstudyinfo.nih.gov/UI/HomeMobile.aspx

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  Pharmacokine/cs of Internal Drugs and Chemicals

References 22. hjps://www.fda.gov/TobaccoProducts/PublicHealthScienceResearch/Research/ucm405233.htm23. hjps://pathstudyinfo.nih.gov/UI/HomeMobile.aspx24.

hjps://www.fda.gov/abouoda/centersoffices/oc/officeofscien/ficandmedicalprograms/nctr/, hjps://www.fda.gov/downloads/Counterterrorism/UCM399130.pdf

25. Oxybenzone disruptor aci/vity hjps://www.niehs.nih.gov/health/materials/ntp_annual_report_fy2012_508.pdf26. Biology and Metabolism of BPA hjps://www.fda.gov/newsevents/publichealthfocus/ucm064437.htm27. hjps://www.fda.gov/downloads/NewsEvents/PublicHealthFocus/UCM424266.pdf28. hjps://www.cnpp.usda.gov/birthto24months29. hjps://www.ncbi.nlm.nih.gov/pubmed/2450015830. hjps://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm252066.htm31. hjps://www.fda.gov/abouoda/centersoffices/oc/officeofscien/ficandmedicalprograms/nctr/32. hjps://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInforma/on/Guidnces/UCM071639.pdf33. hjps://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInforma/on/Guidances/UCM079240.pdf34. hjps://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInforma/on/Guidances/

Vaccines/ucm092170.pdf35. hjps://www.fda.gov/downloads/medicaldevices/deviceregula/onandguidance/guidancedocuments/ucm454613.pdf36. hjps://link.springer.com/ar/cle/10.1007%2Fs10995-011-0902-x37. hjps://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInforma/on/Guidances/UCM071645.pdf38. Mitchell AA, Gilboa SM, Werler MM, et al., Medica/on use during pregnancy, with par/cular focus on prescrip/on drugs:

1976-2008. AmJ Obstet Gynecol.2011;205(1):51.e1-8.

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