SAFETY AND

EFFECTIVENESS DATA Over-the-Counter (OTC) Sunscreens

Guidance Summary

Presented by: Sandeepkumar Balabbigari

March 11th 2016

Purpose

Addresses the safety and effectiveness

data needed to determine whether an

OTC sunscreen active ingredient or

combination of active ingredients is

generally recognized as safe and

effective (GRASE)

Regulatory BackgroundThe Sunscreen Innovation Act (SIA) was

designed to amend the Food, Drug, and

Cosmetic Act to spur the review or approval

of OTC sunscreens

Sunscreens are regulated by either the:

• New drug approval process: products may not be

marketed without FDA’s prior review and approval

for each product

• OTC drug monograph process: active ingredients

that are determined to be GRASE in a final

sunscreen order may be marketed in a sunscreen

product without obtaining NDA or ANDA approval

Industry Requirements

Pharmaceutical quality and

manufacturing data

Effectiveness data

Safety data

Pharmaceutical Quality and

Manufacturing DataSponsors must provide information to

characterize the identity of active ingredients

• Compendia status

• Interactions with other sunscreen active ingredients

or commonly used vehicle components

• Particle size information (if micronized or

nanoscale)

• Formulation aspects regarding photostability,

efficacy, or safety

• Other relevant chemical and/or manufacturing

characteristics

Effectiveness Data

FDA requests evidence from at least two

adequate and well-controlled SPF

studies showing that the active

ingredient effectively prevents sunburn

Two adequate and well-controlled SPF

studies of the active ingredient at a

lower concentration than the maximum

requested should also be conducted

Effectiveness DataSPF studies should demonstrate that the

selected concentration provides an SPF value

of 2 or higher

However, FDA strongly encourages

manufacturers to develop OTC sunscreen

products that provide broad spectrum

protection and have an SPF value of 15 or

higher

A broad spectrum testing procedure should be

done to support related labeling claims

Safety Data

Clinical safety testing

• Human dermal safety

studies

• Human absorption studies

• Pediatric considerations

Non-clinical

safety testing

• Carcinogenicity studies

• Developmental and

reproductive toxicity

• Toxicokinetics

Postmarketing

safety data

Clinical Safety TestingHuman Dermal Safety Studies

Recommended to use the repeat insult patch

test with dosing that is more frequent and for

longer duration than clinically proposed

Dermal irritation study

• Substance is applied to the subject’s skin to

determine whether the ingredient causes direct skin

toxicity

• Cumulative irritation studies are recommended

Dermal sensitization study

• Similar to irritation study but are designed to

detect immunologic mediated reactions (require

prior exposure to the allergen)

Photosafety (photoallergenicity

and phototoxicity) testing

• Testing should be done using the highest

concentration for which a GRASE determination is

sought

Clinical Safety TestingHuman Dermal Safety Studies

Maximal usage trial (MUsT)

• Determine the effect of maximal use on systemic

absorption using pharmacokinetic assessments

• Requirements for MUsT varies between NDA

products and GRASE determinations

Study design should allow for steady state

levels to ensure maximum absorption has

taken place

Sponsors are encouraged to discuss MUsT

protocol with FDA before beginning the trial

Clinical Safety TestingHuman Absorption Studies

Young children have a larger ratio of skin

surface to body volume compared to adults,

which can increase a child’s systemic exposure

to topically applied drugs

If a monograph active ingredient’s safety

margin is relatively small, then FDA may

warrant MUsT or other studies in young

children

Clinical Safety TestingPediatric Consideration

Should assess a full panel of tissues

Recommended for any pharmaceutical with an

expected clinical use of at least 6 months

continuously or intermittently

2 year dermal carcinogenicity study in mice or

rats is recommended

Non-clinical Safety TestingCarcinogenicity Studies

FDA recommends evaluating the potential

effects that exposure to the sunscreen active

ingredient may have on offspring

• Identify hormonal disruptions

• Behavioral assessments

Non-clinical Safety Testing

Developmental and Reproductive Toxicity

Data provides the bridge between toxic levels

seen in animals and any potential human

adverse events due to systemic exposure of a

sunscreen’s active ingredients

Non-clinical Safety TestingToxicokinetics

Postmarketing Safety Data

FDA requests a summary of:

• Potential serious and non-serious

adverse drug experiences

• Expected or frequently reported

serious and non-serious side effects

• Individual case safety reports of

serious adverse drug experiences

• Safety information from

safety and effectiveness studies in humans

• Relevant medical literature

describing associated adverse events

Anticipated Final

Formulation Testing

FDA requires final formulation testing of OTC

sunscreen products to ensure effectiveness

FDA anticipates that final sunscreen orders for

sunscreen active ingredients determined to be

GRASE will require final formulation testing

to ensure safety

• In vitro permeation testing prior to marketing

• FDA will not review the results, but records of the

testing must be made available

THANK YOU!

QUESTIONS?