Drug Labeling; Warning and Direction Statements for Rectal Sodium Phosphates for Over-the-Counter Laxative Use; Final Rule; Stay of Compliance

SUMMARY: The Food and Drug Administration (FDA) is staying compliance

for the regulation for warning and direction statements for over-the-

counter (OTC) dibasic sodium phosphate/monobasic sodium phosphate

(sodium phosphates) drug products intended for rectal (enema) use until

December 7, 1998. The regulation established conditions under which the

labeling must include warning and direction statements for oral and

rectal sodium phosphates products. This stay of compliance applies only

to rectal sodium phosphates products and is in response to requests and

a citizen petition that the final rule did not allow sufficient time

for relabeling of these products. This final rule is part of the

ongoing review of OTC drug products conducted by FDA.

DATES: Section 201.307(b)(2)(ii) and (b)(3)(i) published on May 21,

1998 (63 FR 27836), are effective September 18, 1998, however,

compliance with Sec. 201.307(b)(2)(ii) and (b)(3)(i) as they relate to

rectal sodium phosphates products is not mandatory until December 7,

1998.

FOR FURTHER INFORMATION CONTACT: Cheryl A. Turner, Center for Drug

Evaluation and Research (HFD-560), Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857, 301-827-2291.

SUPPLEMENTARY INFORMATION:

I. Background

In the Federal Register of March 31, 1994 (59 FR 15139), the

agency proposed to amend the tentative final monograph for over-the-

counter (OTC) laxative drug products to limit the OTC container size

for sodium phosphates oral solution to not greater than 90 milliliters

(mL). The agency also proposed a warning for all sodium phosphates

products not to exceed the recommended dosage unless directed by a

doctor.

In the Federal Register of May 21, 1998 (63 FR 27836), FDA issued

a final rule for OTC laxative drug products containing sodium

phosphates Sec. 201.307(b)(1), (b)(2), and (b)(3) (21 CFR

201.307(b)(1), (b)(2), and (b)(3)) establishing a container size

limitation of 90 mL for oral sodium phosphates (sodium phosphates oral

solution), and new warning and direction statements for OTC oral and

rectal sodium phosphates for relief of occasional constipation, or for

preparing the colon for x-ray or endoscopic examination. On May 21,

1998 (63 FR 27886), FDA also issued a proposed rule to amend the

tentative final monograph for OTC laxative drug products (21 CFR 334.16

and 334.58) to include additional general labeling and professional

labeling for oral and rectal sodium phosphates and a new time-to-effect

statement for rectal products.

The final rule requires manufacturers to add certain new labeling

for rectal sodium phosphates drug products. The new warning in

Sec. 201.307(b)(2)(ii) states: ``Using more than one enema in 24 hours

can be harmful.'' The new directions in Sec. 201.307(b)(3)(i) state:

``Do not'' (``take'' or ``use'') ``more unless directed by a doctor.

See Warnings.'' The final rule specified an effective date of September

18, 1998, for these warning and direction statements for rectal sodium

phosphates products.

In the final rule (63 FR 27836 at 27842), the agency stated that

relabeling costs of the type required by this final rule generally

average about $2,000 to $3,000 per stock keeping unit (SKU) (individual

products, packages, and sizes). At that time, the agency was aware of

three manufacturers that together produce approximately 125 SKU's of

rectal sodium phosphates drug products. The agency mentioned that there

may be a few additional small manufacturers or a few additional

products in the marketplace that are not identified in the sources FDA

reviewed. The agency stated that some entities, especially those

private label manufacturers that provide labeling for a number of the

affected products, may incur significant impacts (63 FR 27836 at

27843).

In response to the final rule, the agency received two comments

(Refs. 1 and 2) and two citizen petitions (Ref. 3). One private label

manufacturer (Ref. 1) stated that the economic impact of the final rule

was severe because it currently had 126 SKU's of rectal sodium

phosphates products. The manufacturer stated that its relabeling cost

was approximately $3,500 per SKU or $441,000. In addition, the cost of

stickering the current inventory of 2 million printed folding cartons

is $160,000 with a capital expenditure of $25,000. The cost of

obsolescence for unused printed folding cartons during the transition

period was estimated to be $100,000, making total costs approximately

$776,000. The manufacturer requested that the implementation date of

the final rule for enema products be 1 year after its effective date. A

major manufacturer of oral and rectal sodium phosphates products (Ref.

2) objected to the content of the final rule and argued that the new

warning and direction statements were not justified for rectal sodium

phosphates products.

On July 15, 1998, at a public meeting between representatives of

FDA and industry (Ref. 4), industry representatives stated the

following concerns: (1) The warning in Sec. 201.307(b)(2)(ii) would be

confusing for consumers because it may conflict with how some

physicians prescribe rectal sodium phosphates for cleansing the bowel

in preparation for a medical procedure, and (2) 120 days is not enough

time for manufacturers to relabel their rectal sodium phosphates

products. Industry representatives suggested that the agency revise the

warning to read: ``Use only one enema in 24 hours unless recommended by

a doctor. Serious side effects may occur from excess dosage.'' No

revisions were

[[Page 67400]]

suggested for the direction statement in Sec. 201.307(b)(3)(i).

Petitions (Ref. 3) for a ``stay of action and reconsideration'' for

OTC enemas containing sodium phosphates, submitted in response to this

meeting, requested: (1) An indefinite stay of the warning and

directions required by Sec. 201.307(b)(2)(ii) and (b)(3)(i), (2)

revision of the warning in Sec. 201.307(b)(2)(ii) to read: ``Do not use

more than one enema in a 24-hour period unless directed by a doctor,''

and (3) revision of the directions in Sec. 201.307(b)(3)(i) to read:

``Use only single daily dose unless directed by a doctor. See

Warnings.''

II. The Agency's Response

The agency acknowledged in its analysis of impacts in the final

rule (63 FR 27836 at 27842) that private label manufacturers that

provide labeling for a number of the affected products may incur

significant impacts. Based on the comment's information (Ref. 1), the

agency agrees that the economic impact for this specific manufacturer

is high. In addition, other industry representatives concurred that 120

days was insufficient time for manufacturers to relabel their rectal

sodium phosphates products. Therefore, the agency is staying compliance

with the regulation for relabeling of rectal sodium phosphates products

until December 7, 1998, to provide manufacturers additional time to

comply with the labeling requirements of the final rule. Industry was

previously informed of this stay of compliance with the regulation

(Ref. 5). The agency is not granting a longer stay of compliance or an

indefinite stay of compliance of this portion of the final rule because

of the safety concerns discussed in the final rule (63 FR 27836 at

27840 to 27841).

The petitioner's request for reconsideration and revision of the

warning and direction statements based on professional uses of these

products is denied (Ref. 5). The warning in the March 31, 1994,

proposed rule (59 FR 15139 at 15142) was intended to promote the safe,

direct consumer use of these products. The agency considers the warning

in Sec. 201.307(b)(2)(ii) and the directions in Sec. 201.307(b)(3)(i)

in the May 21, 1998, final rule consistent with the safe, direct

consumer use of rectal sodium phosphates products as intended in the

proposed rule. The agency may reconsider the wording in this labeling

if convincing data are submitted that demonstrate consumer confusion.

The agency believes that professional labeling for these products,

which will be reproposed in a future issue of the Federal Register,

will address any remaining labeling concerns.

Publication of this document constitutes final action on the

warning and labeling directions for rectal sodium phosphates products

in Sec. 201.307(b)(2)(ii) and (b)(3)(i) under the Administrative

Procedure Act (5 U.S.C. 553). Because this final rule is a stay of

compliance of the regulation, FDA finds that the notice and comment

procedures are unnecessary and not in the public interest (5 U.S.C.

553(b) and (d)). The agency believes that staying compliance with the

regulation, as it relates to rectal sodium phosphates products, until

December 7, 1998, will provide sufficient time for industry to

implement the labeling revisions required for rectal sodium phosphates

products.

III. References

The following references are on display in the Dockets Management

Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm.

1061, Rockville, MD 20852, and may be seen by interested parties

between 9 a.m. and 4 p.m., Monday through Friday.

1. Comment No. C190, Docket No. 78N-036L, Dockets Management

Branch.

2. Comment No. LET176, Docket No. 78N-036L, Dockets Management

Branch.

3. Comment No. PRC1, Docket No. 78N-036L, Dockets Management

Branch.

4. Comment No. MM16, Docket No. 78N-036L, Dockets Management

Branch.

5. Letter from D. Bowen, FDA, to P. Reichertz, Arent Fox

Kintner Plotkin & Kahn, coded LET178, Docket No. 78N-036L, Dockets

Management Branch.

IV. Analysis of Impacts

The economic impact of the final regulation was discussed in the

final rule (63 FR 27836 at 27842 and 27843). A stay of compliance for

the warning and direction statements for rectal sodium phosphates

products will provide additional time for companies to relabel these

products and will reduce label obsolescence, as there will be

additional time to use up more existing labeling. Thus, this final rule

granting a stay of compliance should reduce the economic impact on

industry.

FDA has examined the impacts of the final rule (stay of compliance)

under Executive Order 12866 and the Regulatory Flexibility Act (5

U.S.C. 601-612). Executive Order 12866 directs agencies to assess all

costs and benefits of available regulatory alternatives and, when

regulation is necessary, to select regulatory approaches that maximize

net benefits (including potential economic, environmental, public

health and safety, and other advantages; distributive impacts; and

equity). The agency believes that this final rule is consistent with

the regulatory philosophy and principles identified in the Executive

Order. In addition, the final rule is not a significant regulatory

action as defined by the Executive Order and so is not subject to

review under the Executive Order.

The Regulatory Flexibility Act requires agencies to analyze

regulatory options that would minimize any significant impact of a rule

on small entities. This final rule provides a stay of compliance, which

will provide manufacturers additional time to use up existing product

labeling. Accordingly, the agency certifies that the final rule will

not have a significant economic impact on a substantial number of small

entities. Therefore, under the Regulatory Flexibility Act, no further

analysis is required.

V. Paperwork Reduction Act of 1995

FDA concludes that the labeling requirements in this document are

not subject to review by the Office of Management and Budget because

they do not constitute a ``collection of information'' under the

Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et seq.). Rather, the

labeling is a ``public disclosure of information originally supplied by

the Federal Government to the recipient for the purpose of disclosure

to the public'' (5 CFR 1320.3(c)(2)).

VI. Environmental Impact

The agency has determined under 21 CFR 25.31(c) that this action is

of a type that does not individually or cumulatively have a significant

effect on the human environment. Therefore, neither an environmental

assessment nor an environmental impact statement is required.

Dated: December 1, 1998.

William K. Hubbard,

Associate Commissioner for Policy Coordination.

[FR Doc. 98-32391 Filed 12-4-98; 8:45 am]

BILLING CODE 4160-01-F