**Guidance for Industry**

**Drug Products Containing Ensulizole, Hypromellose, Meradimate,
Octinoxate, and Octisalate ---**

**Labeling Enforcement Policy**

**U.S. Department of Health and Human Services**

**Food and Drug Administration**

**Center for Drug Evaluation and Research (CDER)**

**May 2003**

**Procedural**

**Guidance for Industry**

**Drug Products Containing Ensulizole, Hypromellose, Meradimate,
Octinoxate, and Octisalate ---**

**Labeling Enforcement Policy**

*Additional copies are available from:*

*Office of Training and Communications*

*Division of Communications Management*

*Drug Information Branch (HFD-210)*

*5600 Fishers Lane*

*Rockville, MD 20857*

*(Tel) 301-827-4573*

*(Internet) http://www.fda.gov/cder/guidance/index/htm*

**U.S. Department of Health and Human Services**

**Food and Drug Administration**

**Center for Drug Evaluation and Research (CDER)**

**May 2003**

**Procedural**

**TABLE OF CONTENTS**

##  {#section .TOC-2}

# I. INTRODUCTION [1](#introduction) {#i.-introduction-1 .TOC-1}

# II. Background [1](#background) {#ii.-background-1 .TOC-1}

## A. USP Monograph Title Changes [1](#a.-usp-monograph-title-changes) {#a.-usp-monograph-title-changes-1 .TOC-2}

## B. Established Names [2](#b.-established-names) {#b.-established-names-2 .TOC-2}

## C. Citizen Petitions [2](#c.-citizen-petitions) {#c.-citizen-petitions-2 .TOC-2}

# III. Exercise of Enforcement Discretion [3](#iii.-exercise-of-enforcement-discretion) {#iii.-exercise-of-enforcement-discretion-3 .TOC-1}

**Guidance for Industry**[^1]

**Drug Products Containing Ensulizole, Hypromellose, Meradimate,
Octinoxate, and Octisalate --- Labeling Enforcement Policy**

### 

# 

# 

# INTRODUCTION

# 

This guidance discusses how FDA plans to exercise its enforcement
discretion after September 1, 2002, with regard to drug products whose
labeling does not use the established names for ensulizole,
hypromellose, meradimate, octinoxate, and octisalate.

# Background

A series of actions related to the need for labeling changes for certain
drug products has led to the development of this guidance. The actions
are outlined briefly here.

## A. USP Monograph Title Changes

In the May and June 2000 *Pharmacopeial Forum,* Volume 26, No. 3, the
United States Pharmacopeial Convention proposed changes to several
United States Pharmacopeia (USP) monographs. These title changes, which
shortened the names of certain substances, were made to harmonize USP
usage with World Health Organization (WHO) and, in some cases, *European
Pharmacopoeia* usage. These changes were finalized on January 2, 2001,
in the 3rd *USP 24-NF 19 Supplement*. The Supplement generally went into
effect March 1, 2001. However, the monograph title changes discussed in
this guidance were given a delayed effective date of September 1, 2002.
The following title changes were made:

-   *hydroxypropyl methylcellulose* to *hypromellose*

-   *menthyl anthranilate* to *meradimate*

-   *octyl methoxycinnate* to *octinoxate*

-   *octyl salicylate* to *octisalate*

-   *phenylbenzimidazole sulfonic acid* to *ensulizole*

Ensulizole, meradimate, octinoxate, and octisalate are active
ingredients used in sunscreen drug products for over-the-counter (OTC)
human use. Hypromellose is a widely used inactive ingredient and is used
to a lesser extent as an active ingredient in pharmaceutical products.

## B. Established Names

Section 502(e)(1)(A) of the Federal Food, Drug, and Cosmetic Act (the
Act) (21 U.S.C. 352(e)(1)(A)) generally requires the label of a drug
product to bear the established name of the drug product's active and
inactive ingredients. Section 502(e)(3) (21 U.S.C. 352(e)(3)) defines
the established name as:

> \(A\) the applicable official name designated pursuant to section 508
> \[of the Act\], or (B) if there is no such name and such drug, or such
> ingredient, is an article recognized in an official compendium, then
> the official title thereof in such compendium, or (C) if neither
> clause (A) nor clause (B) of this subparagraph applies, then the
> common or usual name, if any, of such drug or of such ingredient \* \*
> \*.

The USP is one of the official compendia recognized in the Act (section
201(j), 21 U.S.C. 321(j)).

Section 508 of the Act (21 U.S.C. 358) authorizes us to designate an
official name for any drug if we determine \"that such action is
necessary or desirable in the interest of usefulness and simplicity.\'\'
We do not, however, routinely designate official names for drug products
under section 508 of the Act. In the absence of designation by FDA of an
official name, the current compendial name will ordinarily be used as
the established name (or if there is no compendial name, the common and
usual name would be considered to be the established name). See 21 CFR
299.4(e). Because we have not designated official names for these
substances, their compendial names (i.e., *ensulizole*, *hypromellose*,
*meradimate*, *octinoxate*, and *octisalate*) would be the established
names of the substances.

## C. Citizen Petitions

On July 26, 2002, the Cosmetic, Toiletry, and Fragrance Association
(CTFA) submitted a petition requesting that we publish a rule amending
§§ 352.10 and 352.20 to provide a September 1, 2003, effective date for
the active ingredient name changes to *ensulizole*, *meradimate*,
*octinoxate*, and *octisalate*.[^2] As an alternative, the CTFA
requested that we provide notice to industry that we will exercise
enforcement discretion and not enforce the requirement that labeling of
drug products subject to the OTC sunscreen monograph bear the new names
until September 1, 2003.

On August 2, 2002, Bayer Health Care, Consumer Health Division also
submitted a petition essentially requesting us to stay, until September
1, 2003, any enforcement action based on a manufacturer's or
distributor's failure to bring its products' labeling into compliance
with the USP monograph title change from *hydroxypropyl methylcellulose*
to *hypromellose*.[^3]

# III. Exercise of Enforcement Discretion

As we discuss in further detail in our response to CTFA\'s petition, we
determined that industry could have experienced uncertainty regarding
our timing for implementation of the USP name changes for sunscreen
products. In addition, we have determined that exercising our
enforcement discretion regarding all of the labeling changes discussed
in this guidance is appropriate to avoid the need for drug manufacturers
and distributors to incur extraordinary expenses in implementing the
labeling changes immediately or to cease marketing certain drug products
whose labeling cannot be changed in a timely manner. As the petitioners
state, these ingredients are found in numerous sunscreen and other
pharmaceutical products.

While harmonization of drug names with WHO and the *European
Pharmacopoeia* is an important goal of both USP and FDA, this limited
use of enforcement discretion should not lead to any significant
confusion. Most pharmacists or other individuals who are knowledgeable
about inactive ingredients or active ingredients in sunscreen and
ophthalmic products are familiar with the names *hydroxypropyl
methylcellulose*, *menthyl anthranilate*, *octyl methoxycinnate,* *octyl
salicylate,* and *phenylbenzimidazole sulfonic acid*. These names have
been used for years, and the continued use of the names for one more
year should not cause any significant problems.

Accordingly, we intend to exercise our enforcement discretion by not
initiating any enforcement action based on a firm's failure to bring its
products' labeling into compliance, before September 1, 2003, with the
USP monograph title changes for ensulizole, hypromellose, meradimate,
octinoxate, and octisalate.

We note, however, that the USP is currently considering a large number
of similar changes. Manufacturers and distributors are responsible for
keeping up to date on these changes and any other changes being
considered for, or made to, the USP. The *USP-NF* and the *Pharmacopeial
Forum* are available by purchase or subscription. The changes will be
first proposed in the *Pharmacopeial Forum*. Interested parties have
opportunities to comment on proposed changes and request appropriate
effective dates. While we intend to exercise our enforcement discretion
in relation to the established names discussed in this guidance,
manufacturers should not assume we will exercise such discretion in the
future with respect to other established name changes.

[^1]: This guidance has been prepared by the Office of Regulatory Policy
    in the Center for Drug Evaluation and Research (CDER) at the Food
    and Drug Administration.

[^2]: See docket number 78N-0038/PSA3.

[^3]: See docket number 02P-0357/PSA1.