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###### Department of Health and Human Services

###### Food and Drug Administration

          - 21 CFR Part 201
          - [Docket No. 1990N-0309]
          - RIN 0910-AF50

# AGENCY:

Food and Drug Administration, HHS.

# ACTION:

Final rule.

# SUMMARY:

                        The Food and Drug Administration (FDA) is issuing a final rule amending the regulations for sodium labeling for over-the-counter (OTC) drug products by extending the sodium content labeling requirement to                               ( print page 69279)                            rectal drug products containing sodium phosphate/sodium biphosphate (sodium phosphates).  FDA is taking this action because people with certain medical conditions are at risk for an electrolyte imbalance to occur when using rectal sodium phosphates products.  Serious adverse events and deaths have occurred because of the high level of sodium present in these products.  This final rule is part of FDA's ongoing review of OTC drug products.                    

# DATES:

This rule is effective November 29, 2005.

# FOR FURTHER INFORMATION CONTACT:

Neel Patel, 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 24, 2004 (69 FR 13765), FDA issued a proposed rule to amend the regulations for sodium labeling for OTC drug products to require sodium content labeling for rectal drug products containing sodium phosphates.  FDA considers it important that consumers be aware of the sodium content of OTC rectal drug products containing sodium phosphates and that this information appear in product labeling so that it will be readily available to consumers, physicians, and other health professionals.  Some OTC laxative drug products intended for rectal administration can contain very high levels of sodium from both active and inactive ingredients.  Significant amounts of some of these products may be absorbed causing an electrolyte imbalance.                

Section 201.64 (21 CFR 201.64) requires orally ingested sodium phosphates products to bear sodium content information.  FDA proposed to add paragraph (k) to § 201.64 to require sodium content information to appear in the labeling of rectal drug products containing dibasic sodium phosphate and/or monobasic sodium phosphate.

## II.  Final Rule Amending Sodium Labeling Regulations

FDA did not receive any comments to its proposed new labeling requirements, its discussion of the statutory authority to require this labeling, or its discussion of this labeling requirement being constitutionally permissible under the first amendment.  Accordingly, FDA is not repeating those discussions in this final rule, but is incorporating the discussions regarding statutory authority and the first amendment by reference (see 69 FR 13766 to 13767).  FDA is finalizing its proposal by requiring sodium content information to appear in the labeling of OTC rectal drug products containing dibasic sodium phosphate and/or monobasic sodium phosphate.

## III.  Analysis of Impacts

                    FDA has examined the impacts of this final rule under Executive Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1501*et seq.*).  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).  Under the Regulatory Flexibility Act, if a rule has a significant economic impact on a substantial number of small entities, an agency must analyze regulatory options that would minimize any significant impact of the rule on small entities.  Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires that agencies prepare a written statement of anticipated costs and benefits before proposing any rule that may result in an expenditure in any one year by State, local, and tribal governments, in the aggregate, or by the private sector, of $100 million (adjusted annually for inflation).                

FDA concludes that this final rule is consistent with the principles set out in Executive Order 12866 and in these two statutes.  As discussed in this section of the document, the final rule will not be economically significant as defined by the Executive order.  With respect to the Regulatory Flexibility Act, FDA concludes that the rule would not have a significant economic impact on a substantial number of small entities.  The Unfunded Mandates Reform Act of 1995 does not require FDA to prepare a statement of costs and benefits for the final rule, because the final rule is not expected to result in any 1-year expenditure that would exceed $100 million adjusted for inflation.  The current inflation adjusted statutory threshold is about $110 million.

The purpose of this final rule is to extend the requirement for sodium content labeling to OTC rectal drug products that contain sodium phosphates so that the information is available to: (1) Health professionals and (2) individuals who need to limit their sodium intake.  The final rule would require minor relabeling of OTC rectal drug products containing sodium phosphates.  There are fewer than five major manufacturers of these products in the OTC drug marketplace.  One company manufactures a nationally branded product with the others producing private label products.  One large manufacturer produces about one-half to two-thirds of the products covered by this final rule.  Three small manufacturers account for the remainder of the market.  There may be other manufacturers/marketers not identified in sources FDA reviewed, but FDA believes there are a limited number and they would be small manufacturers.  FDA concludes that this final rule would not have a significant economic impact on small entities, using the U.S. Small Business Administration designations for this industry (750 employees).  Together, fewer than 300 stockkeeping units (SKUs) are marketed.  The manufacturer of the nationally branded product and some private label manufacturers of these products already include sodium content information in the labeling of their products.  Any necessary relabeling (addition of sodium content labeling) will impose direct one-time costs on some manufacturers.  FDA has been informed that the cost to relabel these products ranges from $500 to $3,500 per SKU.  Using $3,500 per SKU, and assuming all SKUs would need to be relabeled, the total one-time cost to relabel these products would be $1,050,000.  Actual costs will be lower because most of these products already include the sodium content information in their labeling.

Manufacturers that have not voluntarily included sodium content information may also incur one-time costs to test their products to determine the sodium content.  The cost to test for one cation (e.g., sodium) is about $150 for private label manufacturers.  Assuming they repeat the testing, the total one-time costs for an estimated 10 products would be $3,000.

FDA considered but rejected several labeling alternatives:   (1)  A longer implementation period and (2)  an exemption from coverage for small entities.  A longer time period would unnecessarily delay the benefit of the new labeling to consumers who self-medicate with these products.  FDA rejected an exemption for small entities because the labeling is also needed by consumers who purchase products marketed by those entities.

For the reasons stated previously and under the Regulatory Flexibility Act (5 U.S.C. 605(b)), FDA certifies that this final rule will not have a significant economic impact on a substantial number of small entities.
      ( print page 69280)    

## IV. Paperwork Reduction Act of 1995

                    FDA concludes that the labeling requirement in this document is not subject to review by the Office of Management and Budget because it does not constitute a “collection of information” under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501*et seq.*).  Rather, the labeling statements are 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)).                

## V. Environmental Impact

FDA has determined under 21 CFR 25.31(a) 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.

## VI. Federalism

FDA has analyzed this final rule in accordance with the principles set forth in Executive Order 13132.  FDA has determined that the rule does not contain policies that have substantial direct effects on the States, on the relationship between the National Government and the States, or on the distribution of power and responsibilities among the various levels of government.  Accordingly, the agency has concluded that the rule does not contain policies that have federalism implications as defined in the Executive order and, consequently, a federalism summary impact statement is not required.

# List of Subjects in 21 CFR Part 201

      - Drugs
      - Labeling
      - Reporting and recordkeeping requirements

Therefore, under the Federal Food, Drug, and Cosmetic Act and under authority delegated to the Commissioner of Food and Drugs, 21 CFR part 201 is 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 201.64 is amended by adding paragraph (k) to read as follows: 

§ 201.64

* * * * *

(k) The labeling of OTC drug products intended for rectal administration containing dibasic sodium phosphate and/or monobasic sodium phosphate shall contain the sodium content per delivered dose if the sodium content is 5 milligrams or more.  The sodium content shall be expressed in milligrams or grams.  If less than 1 gram, milligrams should be used.  The sodium content shall be rounded-off to the nearest whole number if expressed in milligrams (or nearest tenth of a gram if expressed in grams).  The sodium content per delivered dose shall follow the heading “Other information” as stated in § 201.66(c)(7).  Any product subject to this paragraph that contains dibasic sodium phosphate and/or monobasic sodium phosphate as an active ingredient intended for rectal administration and that is not labeled as required by this paragraph and that is initially introduced or initially delivered for introduction into interstate commerce after November 29, 2005, is misbranded under sections 201(n) and 502(a) and (f) of the act.

Dated: November 18, 2004.

Jeffrey Shuren,

Assistant Commissioner for Policy.

[FR Doc. 04-26269 Filed 11-26-04; 8:45 am]

BILLING CODE 4160-01-S