Over-The-Counter Human Drugs; Labeling Requirements; Final Rule; Technical Amendment

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 201, 341, and 369

[Docket Nos. 98N-0337, 96N-0420, 95N-0259, 90P-0201]

RIN 0910-AA79

Over-The-Counter Human Drugs; Labeling Requirements; Final Rule;

Technical Amendment

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule; technical amendment.

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SUMMARY: The Food and Drug Administration (FDA) is amending the

regulation that established a standardized format and standardized

content requirements for the labeling of over-the-counter (OTC) drug

products, and is amending several related OTC drug product labeling

regulations. This amendment corrects and conforms several aspects of

the new labeling requirements to other regulatory provisions and

eliminates unnecessary text from the new labeling regulation.

DATES: This regulation is effective January 3, 2000. Submit written

comments by March 18, 2000.

ADDRESSES: Submit written comments to the Dockets Management Branch

(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,

Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Cazemiro R. Martin or Gerald M.

Rachanow, Center for Drug Evaluation and Research (HFD-560), Food and

Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-

2222.

SUPPLEMENTARY INFORMATION:

I. Background

In the Federal Register of March 17, 1999 (64 FR 13254), FDA

published a final rule establishing a standardized format and

standardized content requirements for the labeling of OTC drug

products. The final rule is codified primarily in Sec. 201.66 (21 CFR

201.66). The rule was effective on May 16, 1999 (64 FR 18571, April 15,

1999), but is subject to a detailed implementation plan outlined in the

final rule (64 FR 13254 at 13273 to 13274).

II. Technical Amendments

1. Section 201.66(c) states that the information in paragraphs

(c)(1) through (c)(8) must appear in the order listed. Section

201.66(c)(5)(ii)(A) contains the ``Allergy alert'' warning, followed by

Sec. 201.66(c)(5)(ii)(B), which contains the ``Reye's syndrome''

warning required under Sec. 201.314(h)(1) (21 CFR 201.314(h)(1)). The

order in Sec. 201.66(c)(5)(ii) is not consistent with another FDA

labeling provision.

Under Sec. 201.314(h)(2), the Reye's syndrome warning must be the

first warning listed under the ``Warnings'' heading. To conform

Sec. 201.66(c)(5)(ii) to Sec. 201.314(h)(2), the agency is

redesignating paragraph (c)(5)(ii)(A) as paragraph (c)(5)(ii)(B) and

paragraph (c)(5)(ii)(B) as paragraph (c)(5)(ii)(A). In addition, the

agency is correcting the word ``Reye'' to read ``Reye's'' in

Sec. 201.314(h)(1).

2. Section 201.66(c)(5)(iii) requires the use of the subheading

``Do not use.'' Section 330.1(i)(38) (21 CFR 330.1(i)(38)) allows the

phrases ``give to'' and ``use in'' to be used interchangeably. However,

Sec. 201.66(f) does not allow the use of interchangeable terms in

subheadings. This limitation on the use of interchangeable terms may

cause some confusion when applied to certain monoamine oxidase

inhibitor warnings.

Specifically, the monoamine oxidase inhibitor (MAOI) warning in

Secs. 341.74(c)(4)(vi) (21 CFR 341.74(c)(4)(vi)) and

341.80(c)(1)(ii)(D) (21 CFR 341.80(c)(1)(ii)(D)) provides slightly

different language for products labeled only for children under 12

years of age. The warning states: ``Do not give to a child who * * *''.

Similarly, the warning under the entry ``SODIUM GENTISATE'' in

Sec. 369.21 (21 CFR 369.21) contains a warning that states ``Do not

give to children * * *''. To allow these warnings to conform to the

required subheadings in the new labeling format, the agency is revising

these warnings to replace the words ``give to'' with the words ``use

in.''

3. Section 201.66(d)(3) of the final rule provides, in relevant

part, that the title, headings, subheadings, and information in

paragraphs (c)(1) through (c)(9) must not appear in reverse type, and

that the required labeling must be all black or one dark color, printed

on a white or other light, neutral color, contrasting background.

Section 201.66(d)(3) also provides for the use of a single,

alternative, contrasting dark color to highlight the Drug Facts title

and headings.

Section 201.66(d)(3) is based on the finding that color contrast

between text and background is a significant factor affecting the

legibility of OTC drug product labeling. Generally, high contrast

between the color of the text and the color of the background can

significantly improve legibility. If, however, the text blends into the

background, consumers may have difficulty focusing on and reading the

information.

The final rule recognizes that black text on a white background is

the most common way to achieve high contrast. However, to emphasize the

importance of contrast and to provide more options than black on white

labeling, the agency included the terms ``dark'' text and ``light''

background in Sec. 201.66(d)(3). After receiving several inquiries from

manufacturers about the meaning of these terms, the agency has decided

that the rule would be less confusing if the terms ``dark,'' ``light,''

and ``reverse type'' (i.e., ``light'' type on a ``dark'' background)

were deleted.

Section 201.66(d)(3) is intended to ensure adequate contrast

between text and background. The terms ``dark'' and ``light'' may have

added an unnecessary element of complexity to the rule. Aside from the

difficulty in assigning a fixed meaning to these terms, the agency

acknowledges that there may be combinations of light text on a dark

background that, assuming high contrast, would be consistent with

achieving readable OTC drug product labeling. (See, e.g., Ref. 2 at 62

FR 9024 at 9049 (February 27, 1997), noting that in OTC drug labeling

white text on a brown background may provide good, readable contrast.)

To eliminate possible confusion, while keeping the emphasis in the

final rule on achieving high contrast, the agency is removing the words

``dark'' and ``light'' and the phrase ``shall not appear in reverse

type'' from Sec. 201.66(d)(3). Thus, the amended version of the rule

requires black on white text or, any other combination of a single

color of text on a contrasting background. Generally, the agency

expects the color contrast used in the Drug Facts labeling to be at

least as high as that used in a product's principal display panel or

other promotional labeling.

These amendments institute minor changes and corrections to the

rule and may provide greater flexibility in the implementation of the

new OTC drug labeling requirements. Also, with respect to the third

technical amendment, the agency notes that only few comments submitted

during the rulemaking process addressed the issue of color contrast. Of

these, most supported the need for using good contrast but did not take

a substantive position on whether to require only dark on light

labeling. As discussed above, the agency is retaining the contrast

requirement. Therefore, the agency believes this amendment does not

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present a significant or controversial issue that warrants further

opportunity for notice and comment rulemaking.

For these reasons, the agency finds for good cause that notice and

comment procedures are unnecessary in this instance and that these

changes may go into effect immediately (5 U.S.C. 553(b) and (d) and 21

CFR 10.40(c) and (e)). However, in accordance with 21 CFR 10.40(e)(1),

the agency will accept comments on these amendments to determine

whether they should be modified or revoked.

III. The Paperwork Reduction Act of 1995

FDA analyzed all relevant information collections associated with

this rule in the original final rule document (64 FR 13254 at 13274 to

13276). These amendments do not impose any new requirements and,

therefore, do not require any further analysis and are not subject to

review by the Office of Management and Budget.

IV. Analysis of Impacts

FDA provided a detailed analysis of impacts in the original final

rule document (64 FR 13254 at 13276 through 13285). This technical

amendment provides several clarifications and allows additional

flexibility in the labeling requirements. Thus, no further analysis of

impacts is necessary.

V. Environmental Impact

The agency has determined under 21 CFR 25.30(h) 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.

List of Subjects

21 CFR Part 201

Drugs, Labeling, Reporting and recordkeeping requirements.

21 CFR Part 341

Labeling, Over-the-counter drugs.

21 CFR Part 369

Labeling, Medical devices, Over-the-counter drugs.

Therefore, under the Federal Food, Drug, and Cosmetic Act, the

Public Health Service Act, and under authority delegated to the

Commissioner of Food and Drugs, 21 CFR parts 201, 341, and 369 are

amended as follows:

PART 201--LABELING

1. The authority citation for 21 CFR part 201 continues to read as

follows:

Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 358, 360,

360b, 360gg-360ss, 371, 374, 379e; 42 U.S.C. 216, 241, 262, 264.

2. Section 201.66 is amended by redesignating paragraphs

(c)(5)(ii)(A) and (c)(5)(ii)(B) as paragraphs (c)(5)(ii)(B) and

(c)(5)(ii)(A), respectively, and revising paragraph (d)(3) to read as

follows:

Sec. 201.66 Format and content requirements for over-the-counter (OTC)

drug product labeling.

* * * * *

(d) * * *

(3) The title, heading, subheadings, and information in paragraphs

(c)(1) through (c)(9) of this section shall be legible and clearly

presented, shall have at least 0.5-point leading (i.e., space between

two lines of text), and shall not have letters that touch. The type

style for the title, headings, subheadings, and all other required

information described in paragraphs (c)(2) through (c)(9) of this

section shall be any single, clear, easy-to-read type style, with no

more than 39 characters per inch. The title and headings shall be in

bold italic, and the subheadings shall be in bold type, except that the

word ``(continued)'' in the title ``Drug Facts (continued)'' shall be

regular type. The type shall be all black or one color printed on a

white or other contrasting background, except that the title and the

headings may be presented in a single, alternative, contrasting color

unless otherwise provided in an approved drug application, OTC drug

monograph (e.g., current requirements for bold print in Secs. 341.76

and 341.80 of this chapter), or other OTC drug regulation (e.g., the

requirement for a box and red letters in Sec. 201.308(c)(1)).

* * * * *

3. Section 201.314 is amended by revising paragraph (h)(1) to read

as follows:

Sec. 201.314 Labeling of drug preparations containing salicylates.

* * * * *

(h)(1) The labeling of orally or rectally administered over-the-

counter aspirin and aspirin-containing drug products subject to this

paragraph is required to prominently bear a warning. The warning shall

be as follows: ``Children and teenagers should not use this medicine

for chicken pox or flu symptoms before a doctor is consulted about

Reye's syndrome, a rare but serious illness reported to be associated

with aspirin.''

* * * * *

PART 341--COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC

DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE

4. The authority citation for 21 CFR part 341 continues to read as

follows:

Authority: 21 U.S.C. 321, 351, 352, 353, 355, 360, 371.

5. Section 341.74 is amended by revising paragraph (c)(4)(vi) to

read as follows:

Sec. 341.74 Labeling of antitussive drug products.

* * * * *

(c) * * *

(4) * * *

(vi) For products containing dextromethorphan or dextromethorphan

hydrobromide as identified in Sec. 341.14(a)(3) and (a)(4) when labeled

only for children under 12 years of age. Drug interaction precaution.

``Do not use in a child who is taking a prescription monoamine oxidase

inhibitor (MAOI) (certain drugs for depression, psychiatric, or

emotional conditions, or Parkinson's disease), or for 2 weeks after

stopping the MAOI drug. If you do not know if your child's prescription

drug contains an MAOI, ask a doctor or pharmacist before giving this

product.''

* * * * *

6. Section 341.80 is amended by revising paragraph (c)(1)(ii)(D)

to read as follows:

Sec. 341.80 Labeling of nasal decongestant drug products.

* * * * *

(c) * * *

(1) * * *

(ii) * * *

(D) Drug interaction precaution. ``Do not use in a child who is

taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs

for depression, psychiatric, or emotional conditions, or Parkinson's

disease), or for 2 weeks after stopping the MAOI drug. If you do not

know if your child's prescription drug contains an MAOI, ask a doctor

or pharmacist before giving this product.''

* * * * *

PART 369--INTERPRETATIVE STATEMENTS RE WARNINGS ON DRUGS AND

DEVICES FOR OVER-THE-COUNTER SALE

7. The authority citation for 21 CFR part 369 continues to read as

follows:

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Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 371.

8. Section 369.21 is amended by revising the entry for ``SODIUM

GENTISATE.'' to read as follows:

Sec. 369.21 Drugs; warning and caution statements required by

regulations.

* * * * *

SODIUM GENTISATE. (See Secs. 201.314 and 310.301(a)(2) of this

chapter.)

Warning--Do not use in children under 6 years of age or use for

prolonged period unless directed by physician.

``Keep out of reach of children. In case of overdose, get medical

help or contact a Poison Control Center right away.''

If offered for use in arthritis or rheumatism, in juxtaposition

therewith, the statement:

Caution--If pain persists for more than 10 days, or redness is

present, or in conditions affecting children under 12 years of age,

consult a physician immediately.

* * * * *

Dated: December 22, 1999.

Margaret M. Dotzel,

Acting Associate Commissioner for Policy.

[FR Doc. 99-34040 Filed 12-30-99; 8:45 am]

BILLING CODE 4160-01-F