Guidance Snapshots are a communication tool and are not a substitute for the guidance document. 

To learn more about general clinical pharmacology considerations for neonatal studies, read the guidance: 

https://www.fda.gov/media/129532/download

www.fda.gov

Why Is This Guidance Important?

• Neonates present unique absorption, distribution,

metabolism, and excretion (ADME) characteristics.

• Many drugs administered in neonatal intensive care

units (NICUs) are used in an off-label capacity.

• Pharmacokinetics (PK) and pharmacodynamics

(PD) are affected by multiple factors in the neonatal

population (e.g., size, growth and physiologic

maturation, underlying illnesses, and concomitant

medications) and may differ between neonates and

older children and adults.

• Pharmacogenomics has not been extensively studied in

the neonatal population.

General Clinical Pharmacology Considerations for

Neonatal Studies for Drugs and Biological Products

Final Guidance for Industry

What Is Covered in This Guidance?

This final guidance addresses the clinical pharmacology 

considerations for any planned studies in neonates submitted in 

new drug applications (NDAs), biologics license applications (BLAs), 

and supplements.

What Is the Age Range for Neonates? 

This guidance defines the neonatal period for the term and post-term 

newborn as the day of birth plus 27 days, and for the preterm newborn as 

the day of birth through the expected date of delivery plus 27 days. When 

designing studies, it is important to consider stratifying the neonatal 

population to decrease variability. While neonates can be grouped by 

gestational age and/or weight at birth, postnatal age is another important 

variable to consider for stratification, as it can significantly affect ADME.

27
Prior to Neonatal Study Initiation: 

Sponsors should assess the available scientific information regarding the neonatal condition, 

mechanism of action, PK, PD, and the ontogeny of any organs and tissues that are involved in the 

predicted response to the drug and or its metabolites.

Neonatal 

Study Design 

Considerations

Dose range selection is critical

for deriving rational dosing

recommendations for the

neonatal population. All

existing PK and PD data,

including from other

populations, should

be used to help

determine an

initial dose.

DOSE 

SELECTION

FORMULATION

SAMPLE 

SIZE

SAMPLING

BIOANALYTICAL 

METHODS

DATA ANALYSIS

CLINICAL 

STUDY REPORT

ETHICS

SAFETY AND

EFFECTIVENESS

STUDY

POPULATION

An 

ageappropriate

dosage formulation is 

required for neonates.1

 Sponsors 

should consider the potentially 

small unit doses and 

ensure accurate 

dosing. Consider 

the necessary 

number of neonates in various 

subpopulations to establish accurate 

dosing and provide justification for the 

sample size selected. The precision of 

PK and PD parameters in the 

sample size calculation 

is critical. Use the smallest 

possible blood sample 

volume to minimize risk to the 

patient. It is essential to use all 

available information on the 

ontogeny of relevant organ 

and enzyme systems, 

as well as PK 

data, including 

from other 

populations.

An 

accurate, 

precise, 

sensitive, 

specific, and 

reproducible

analytical method to 

quantify the parent drug 

and metabolites in 

the biologic fluids 

of interest is 

essential.

Two 

recommended 

approaches are:

(1) standard

noncompartmental

PK and (2) PopPK.1

Neonatal models 

should consider all ADME 

factors for subgroups and 

be supported by additional 

scientific data.

In 

addition to clinical 

pharmacology information, it is 

important to capture safety 

data in all the clinical study reporting 

for neonatal studies.1

The 

2014 FDA 

draft guidance 

on general clinical 

pharmacology considerations for 

pediatric studies recommends that 

an institutional review board 

reviewing neonatal research 

have specific expertise in 

neonatal trials.1

Regardless 

of the 

approach used to 

provide evidence of 

effectiveness, safety 

data should be obtained 

for all drugs studied in 

neonates.

The 

neonates 

enrolled 

should have 

(or in some cases 

be at risk for) the 

disease or condition of 

interest. It may also be 

necessary to enroll a 

wide spectrum of 

developmental 

age subgroups.

1

 Please see the 2014 FDA draft guidance titled General Clinical Pharmacology Considerations for Pediatric Studies for 

Drugs and Biological Products that can be accessed at the following link: https://www.fda.gov/media/90358/download

Guidance Snapshots are a communication tool and are not a substitute for the guidance document. 

To learn more about general clinical pharmacology considerations for neonatal studies, read the guidance:

https://www.fda.gov/media/129532/download
Guidance Snapshots are a communication tool and are not a substitute for the guidance document.

To learn more about the general clinical pharmacology considerations for neonatal studies for drugs and biological 

products, read the guidance: https://www.fda.gov/media/129532/download

To see additional Guidance Snapshots, check out the pilot program: 

https://www.fda.gov/drugs/guidances-drugs/guidance-snapshot-pilot

www.fda.gov

Background About the Guidance 

This guidance supplements the FDA draft guidance titled General 

Clinical Pharmacology Considerations for Pediatric Studies for 

Drugs and Biological Products (December 2014). The agency issued 

this guidance as part of an ongoing effort to support sponsors and 

investigators who are planning neonatal trials. Currently, many 

drugs are used off-label in NICUs, and there have been cases where 

adult drugs have been ineffective or even harmful to neonates. The 

FDA would like to spread the message that therapies designed 

specifically for neonates need to be developed, and neonates can 

be protected through inclusion in clinical research. 

Guidance Recommendations Apply Throughout the Drug Development Timeline 

This guidance provides recommendations for neonatal clinical pharmacology studies. Before 

initiating neonatal clinical pharmacology studies, the sponsor should assess the available scientific 

information regarding the mechanism of action and PK of the drug, as well as the ontogeny of any 

organs and tissues that are involved in the predicted response to the drug or its metabolites. This 

scientific information can be derived from several sources, including applicable animal models, 

in vitro studies, and other potentially relevant clinical studies. This guidance does not discuss the 

timing to initiate neonatal studies. Sponsors should direct questions on the initiation of neonatal 

studies with the relevant FDA review division. 

Guidance Recap Podcast – Hear Highlights Straight From FDA Staff

and 

Speakers: Elimika Pfuma Fletcher, PhD, policy lead for the Office of Clinical 

Pharmacology, Gerri Baer, MD, team lead for pharmacovigilance and 

neonatology in the FDA’s Office of Pediatric Therapeutics (OPT)

Click here to listen Click here to read transcript