Document ID: FDA-2009-N-0146-0004
Agency: fda
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-04-07T04:00Z

Office of Nonprescription Products

Center for Drug Evaluation and Research ( Food and Drug Administration

Silver Spring ( MD 20993

		

CONDITION 	Sodium Shale Oil Sulfonate (SSOS)

	PHARMACOLOGICAL CLASS	Anti-dandruff

	MONOGRAPH	OTC Drug Products for the Control of Dandruff, Seborrheic
Dermatitis, and Psoriasis (21 CFR part 358 subpart H)

	APPLICANT	Dow Pharmaceutical Sciences

	1330A Redwood Way

	Petaluma, CA  94954-1169

	SUBMISSION DATE	November 30, 2007

	REVIEW DATE	February 5, 2008

	REVIEWER	Michael Chasey

	TEAM LEADER	Matthew R. Holman, Ph.D.

	

BACKGROUND

The applicant requests addition of sodium shale oil sulfonate (SSOS) to
the dandruff, seborrheic dermatitis, and psoriasis monograph (21 CFR
part 358 subpart H), in concentrations of:

0.5–2.0% for dandruff leave-on formulations 

4.0% for psoriasis leave-on formulations

0.5–2.0% for dandruff rinse-off formulations

2.0% for psoriasis rinse-off formulations

The applicant does not request any other changes (e.g., labeling,
testing) to the dandruff, seborrheic dermatitis, and psoriasis monograph
other than addition of SSOS.

REVIEWER’S COMMENTS

The applicant provides basic information about SSOS, including a
detailed chemical description as required in 21 CFR 330.14(c)(1)(i), as
well as a detailed description of the method of synthesis and
purification.  A monograph for SSOS has been developed, but is not yet
part of any official pharmacopoeia (USP-NF).  The applicant does note
that the monograph is part of the quality documentation that was
approved by the German Federal Institute for Drugs and Medical Devices
(BfArM) in the scope of registration of OTC drugs containing SSOS as an
active ingredient.

The applicant indicates that SSOS is or has been marketed in 34
countries.  Of these countries, SSOS has been marketed for at least five
continuous years in 26 of them.  The applicant has designated Austria,
France, Germany, Italy and Spain as “selected countries,” in
accordance with 21 CFR 330.14(c)(4).  SSOS has been marketed for over 11
years in each of the “selected countries.”

As indicated in 21 CFR 330.14(b)(2), extent of marketing is determined
by the extent to which sales meets the requirements outlined in 21 CFR
330.14(c)(2)(ii), (c)(2)(iii), and (c)(2)(iv).  These paragraphs
collectively address the adequacy of the markets and marketing to reveal
“infrequent but serious ADEs” (adverse drug events) that may occur
in the U.S. population if FDA finds the condition generally recognized
as safe and effective (67 FR 3060 at 3065).  The applicant is only aware
of 5 reported adverse events for SSOS.  They are only minor skin
irritations.  Because they are not serious, they do not prevent the
ingredient from being eligible for the OTC drug monograph system.

As specified in 21 CFR 330.14(c)(2)(ii), the applicant provides the
“cumulative total number of dosage units . . . sold for each dosage
form of the condition.”  In this case, the applicant reports that
approximately 21 million dosage units of products containing SSOS have
been sold worldwide.  The total dosage units sold worldwide was
calculated using the equation in 21 CFR 330.14(c)(2)(ii)(B), where the
largest package size marketed is reported to be 300 g, and the average
concentration of SSOS in all products marketed is reported to be 1.25%. 
Although the highest concentration (i.e., 2%) is typically used in the
calculation, the applicant includes data demonstrating that using the
average concentration is more accurate in this case.  The applicant
calculated the number of dosage units sold for 13 products from a
leading German finished drug product manufacturer.  The calculation used
the amount of SSOS sold to the finished drug product manufacturer and
the actual (not estimated) volume and concentration of the products. 
Approximately 20 million of these 13 products were sold.  Therefore, it
seems that 21 million is a valid estimate, if not an underestimate, of
the dosage units sold.

The applicant notes that the five “selected countries” market
approximately 85% of all SSOS-containing products.  In addition, the
applicant estimates that rinse-off treatments for dandruff comprise
80-90% of the SSOS marketplace.  Because the rinse-off formulations for
dandruff treatment comprise such a large portion of the marketplace,
there is very little marketing experience with dandruff treatment
leave-on formulations or psoriasis treatment leave-on or rinse-off
formulations.

The applicant notes that in Europe, dandruff products are considered
cosmetics while psoriasis products are considered drugs.  The applicant
describes how cosmetics and drugs are regulated in Europe.  All five of
the applicant’s “selected countries” are members of the European
Union and, as such, are listed in Section 802(b)(1)(A) of the Federal
Food, Drug, and Cosmetic Act (the Act).  Inclusion in this section of
the Act has been interpreted to indicate that the regulatory systems in
these countries are of comparable sophistication to that in the United
States (64 FR 71062 at 71068).

The applicant provides specific demographic information about the
population in each of the five “selected countries.”  This
information complies with 21 CFR 330.14(c)(2)(iii), which requires a
description of population demographics “to ensure that the
condition’s use(s) can be reasonably extrapolated to the U.S.
population.”  The demographics of the 5 selected countries represent a
diverse population of persons that seems to reflect the diversity of the
U.S. population.    

The applicant does not specifically provide an explanation of the “use
pattern,” as required by 21 CFR 330.14(c)(2)(iv).  Use pattern is
defined as how often the product is used (according to the label) and
for how long.  The labeling submitted, however, for currently marketed
products overseas is similar to the labeling currently required in the
dandruff, seborrheic dermatitis, and psoriasis monograph (21 CFR part
358 subpart H).   Therefore, it is assumed that the applicant does not
request any change to the monograph specific for SSOS-containing
products.

RECOMMENDATION

I recommend that sodium shale oil sulfonate (SSOS), 0.5–2.0% in
rinse-off formulations for dandruff treatment, be considered eligible
for review as an active ingredient in the OTC dandruff, seborrheic
dermatitis, and psoriasis monograph (21 CFR part 358 subpart H).  To be
considered eligible for review under the TEA process, a product must
meet the criteria of marketing for a material time and to a material
extent as set forth in 21 CFR 330.14(b)(2).  SSOS meets the requirement
for the material time criteria because SSOS-containing products have
been marketed directly to consumers for over five continuous years in 26
countries.  In addition, ecamsule meets the criteria for marketing to a
material extent because it has been marketed in 34 countries with an
estimated 21 million dosage units sold, of which approximately 80-90%
were sold as rinse-off formulations for dandruff treatment.

TEA 	Sodium Shale Oil Sulfonate (SSOS)	  PAGE  4 

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Time and Extent Application (TEA) Review for Sodium Shale Oil Sulfonate
(SSOS)