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person may file with the Dockets Management Branch, Food and Drug Administration, written objections specifying with particularity the provision of the tentative order to which objection is made. These objections are to be supported by a brief statement of the grounds therefor. A request for an oral hearing may accompany such objections.

(iii) Within 12 months after publishing a tentative order pursuant to paragraph (a)(7)(i) of this section, any interested person may file with the Dockets Management Branch, Food and Drug Administration, new data and information to support a condition excluded from the monograph in the tentative order.

(iv) Within 60 days after the final day for submission of new data and information, comments on the new data and information may be filed with the Dockets Management Branch, Food and Drug Administration.

(v) New data and information submitted after the time specified in this paragraph but prior to the establishment of a final monograph will be considered as a petition to amend the monograph and will be considered by the Commissioner only after a final monograph has been published in the FEDERAL REGISTER unless the Commisisoner finds that good cause has been shown that warrants earlier consideration.

(8) Oral hearing before the Commissioner. After reviewing objections filed in response to the tentative final monograph, the Commissioner, if he finds reasonable grounds in support thereof, shall by notice in the FEDERAL REGISTER Schedule an oral hearing. The notice scheduling an oral hearing shall specify the length of the hearing and how the time shall be divided among the parties requesting the hearing. The hearing shall be conducted by the Commissioner and may not be delegated.

(9) Final monograph. After reviewing the objections, the entire administrative record including all new data and information and comments, and considering the arguments made at any oral hearing, the Commissioner shall publish in the FEDERAL REGISTER a final order containing a monograph establishing conditions under which a cat

egory of OTC drugs is generally recognized as safe and effective and not misbranded. The monograph shall become effective as specified in the order.

(10) Administrative record. (i) All data and information to be considered in any proceeding pursuant to this section shall be submitted in response to the request for data and views pursuant to paragraph (a)(2) of this section or accepted by the panel during its deliberations pursuant to paragraph (a)(3) of this section or submitted to the Dockets Management Branch as part of the comments during the 90-day period and 30-day rebuttal comment period permitted pursuant to paragraph (a)(6) of this section or submitted to the Dockets Management Branch during the 12-month period or as part of the comments during the 60-day period permitted pursuant to paragraph (a)(7) of this section.

(ii) The Commissioner shall make all decisions and issue all orders pursuant to this section solely on the basis of the administrative record, and shall not consider data or information not included as part of the administrative record.

(iii) The administrative record shall consist solely of the following material: All notices and orders published in the FEDERAL REGISTER, all data and views submitted in response to the request published pursuant to paragraph (a)(2) of this section or accepted by the panel during its deliberations pursuant to paragraph (a)(3) of this section, all minutes of panel meetings, the panel report(s), all comments and rebuttal comments submitted on the proposed monograph and all new data and information submitted pursuant to paragraph (a)(6) of this section, all objections submitted on the tentative final monograph and all new data and information and comments submitted pursuant to paragraph (a)(7) of this section, the complete record of any oral public hearing conducted pursuant to paragraph (a)(8) of this section, all other comments requested at any time by the Commissioner, all data and information for which the Commissioner has reopened the administrative record, and all other material that the

Commissioner includes in the administrative record as part of the basis for the Commissioner's decision.

(11) Court appeal. The monograph contained in the final order constitutes final agency action from which appeal lies to the courts. The Food and Drug Administration will request consolidation of all appeals in a single court. Upon court appeal, the Commissioner may, at his discretion, stay the effective date for part or all of the monograph pending appeal and final court adjudication.

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(12) Amendment of monographs. (i) The Commissioner may propose on the Commissioner's own initiative amend or repeal any monograph established pursuant to this section. Any interested person may petition the Commissioner for such proposal pursuant to §10.30 of this chapter. The Commissioner may deny the petition if the Commissioner finds a lack of safety or effectiveness employing the standards in paragraph (a)(4) of this section (in which case the appeal provisions of paragraph (a)(11) of this section shall apply), or the Commissioner may publish a proposed amendment or repeal in the FEDERAL REGISTER if the Commissioner finds general recognition of safety and effectiveness employing the standards in paragraph (a)(4) of this section. Any interested person may, within 60 days after publication of the proposed order in the FEDERAL REGISTER, file with the Dockets Management Branch, Food and Drug Administration, written comments in quadruplicate. Comments may be accompanied by a memorandum or brief in support thereof. All comments may be reviewed in the Dockets Management Branch between the hours of 9 a.m. and 4 p.m., Monday through Friday. After reviewing the comments, the Commissioner shall publish a final order amending the monograph established under the provisions of paragraph (a)(9) of this section or withdraw the proposal if comments opposing the amendment are persuasive. A new drug application may be submitted in lieu of, or in addition to, a petition under this paragraph.

(ii) A new drug application may be submitted in lieu of a petition to amend the OTC drug monograh only if

the drug product with the condition that is the subject of the new drug application has not been marketed on an interim basis (such as under the provisions of paragraph (a)(6)(iii) of this section), all clinical testing has been conducted pursuant to a new drug application plan, and no marketing of the product with the condition for which approval is sought is undertaken prior to approval of the new drug application. The Food and Drug Administration shall handle a new drug application as a petition for amendment of a monograph, and shall review it on that basis, if the provisions of this paragraph preclude approval of a new drug application but permit the granting of such a petition.

(b) Regulatory action. Any product which fails to conform to an applicable monograph after its effective date is liable to regulatory action.

(c) Information and data submitted under this section shall include, with respect to each nonclinical laboratory study contained in the application, either a statement that the study was conducted in compliance with the good laboratory practice regulations set forth in part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance.

(d) [Reserved]

(e) Institutional review and informed consent. Information and data submitted under this section after July 27, 1981, shall include statements regarding each clinical investigation involving human subjects, from which the information and data are derived, that it either was conducted in compliance with the requirements for institutional review set forth in part 56 of this chapter, or was not subject to such requirements in accordance with §§ 56.104 or 56.105, and that it was conducted in compliance with the requirements for informed consent set forth in part 50 of this chapter.

(f) Financial certification or disclosure statement. Any clinical data submitted under this section must be accompanied by financial certifications or

disclosure statements or both as required by part 54 of this chapter.

[39 FR 11741, Mar. 29, 1974, as amended at 39 FR 39556, Nov. 8, 1974; 42 FR 19141, Apr. 12, 1977; 42 FR 54800, Oct. 11, 1977; 46 FR 8460, 8955, Jan. 27, 1981; 46 FR 14340, Feb. 27, 1981; 46 FR 21360, Apr. 10, 1981; 46 FR 47738, Sept. 29, 1981; 50 FR 7516, Feb. 22, 1985; 55 FR 11581, Mar. 29, 1990; 63 FR 5253, Feb. 2, 1998]

EFFECTIVE DATE NOTE: At 63 FR 5253, Feb. 2, 1998, § 330.10 was amended by adding new paragraph (f), effective Feb. 2, 1999.

§ 330.11 NDA deviations from applicable monograph.

A new drug application requesting approval of an OTC drug deviating in any respect from a monograph that has become final shall be in the form required by $314.50 of this chapter, but shall include a statement that the product meets all conditions of the applicable monograph except for the deviation for which approval is requested and may omit all information except that pertinent to the deviation.

[39 FR 11741, Mar. 29, 1974, as amended at 55 FR 11581, Mar. 29, 1990]

§ 330.12 Status of over-the-counter (OTC) drugs previously reviewed under the Drug Efficacy Study (DESI).

(a) There were 420 OTC drugs reviewed in the Drug Efficacy Study (a review of drugs introduced to the market through new drug procedures between 1938 and 1962). A careful review has been made of the reports on these drugs to determine those drugs for which implementation may be deferred without significant risk to the public health, pending review by appropriate OTC drug advisory review panels and promulgation of a monograph.

(b) On and after April 20, 1972, a number of notices were published in the FEDERAL REGISTER Concerning previously unpublished OTC drugs reviewed by the National Academy of Sciences-National Research Council Drug Efficacy Study Group. Only the evaluations and comments of the panels were published, with no conclusions of the Commissioner of Food and Drugs. Those publications were for the purpose of giving interested persons the benefit of the Academy's opinions. For those products, and also for OTC

drug products previously published with the Commissioner's conclusions (except for the products listed in paragraphs (b) (1) and (2) of this section, all requests for data, revised labeling, requests for new drug applications, abbreviated new drug applications, updating supplements, data to support less than effective claims, if any, etc., are deferred, and such OTC drug products are instead subject to the OTC drug review in their appropriate classes pursuant to the procedures established in this subpart.

(1) The requirements of the following DESI announcements are not deferred (the reference document may also pertain to prescription drugs):

(i) Certain Surgical Sutures (DESI 4725), published in the FEDERAL REGISTER of November 11, 1971 (36 FR 21612).

(ii) Absorbable Dusting Powder (DESI 6264), published in the FEDERAL REGISTER of May 25, 1971 (36 FR 9475).

(iii) Certain Insulin Preparations (DESI 4286), published in the FEDERAL REGISTER of April 9, 1971 (36 FR 6842).

(iv) Sulfo-Van Ointment (DESI 2230), published in the FEDERAL REGISTER of October 8, 1970 (35 FR 15860).

(v) Antiperspirants and Deodorants Containing Neomycin Sulfate (DESI 11048) for which an order revoking provisions for certification or release was published in the FEDERAL REGISTER of December 5, 1972 (37 FR 25820) and has been stayed by the filing of objections.

(vi) Thorexin Cough Medicine (DESI 11160) for which a notice of opportunity for hearing was published in the FEDERAL REGISTER of February 2, 1973 (38 FR 3210).

(vii) Antibiotic susceptibility discs (DESI 90235) for which an order providing for certain discs to be certified and removing provisions for certification of other discs was published in the FEDERAL REGISTER of September 30, 1972 (37 FR 20525) and has been stayed by the filing of objections notice of which was published in the FEDERAL REGISTER of March 15, 1973 (38 FR 7007).

(2) Deferral of requirements is not appropriate when an announcement has been published and has been followed by a final order classifying a drug either as lacking substantial evidence of effectiveness or as not shown to be safe. These products will be removed

from the market, if they have not already been removed. Regulatory action will also be undertaken against identical, similar and related products (21 CFR 310.6). Deferral of requirements is not appropriate for the following (the referenced document may also pertain to prescription drugs):

(1) Certain Sulfonamide-Decongestant Nasal Preparation (DESI 4850), for which notice of withdrawal of approval of new drug applications was published in the FEDERAL REGISTER of October 24, 1970 (35 FR 16605, 16606).

(ii) Eskay's Theranates, containing strychnine, sodium, and calcium glycerophosphates, thiamine hydrochloride, alcohol, and phosphoric acid (DESI 2220), for which notice of withdrawal of approval of the new drug application was published in the FEDERAL REGISTER of February 18, 1971 (36 FR 3152).

(iii) The following topical drugs (DESI 1726), for which notice of withdrawal of new drug applications was published in the FEDERAL REGISTER of August 28, 1971 (36 FR 17368):

(a) Rhulitol Solution, containing tannic acid, chlorobutanol, phenol, camphor, alum, and isopropyl alcohol.

(b) Zirnox Topical Lotion, containing phenyitoloxamine citrate and zirconium oxide.

(iv) Menacyl Tablets, containing aspirin, menadione, and ascorbic acid (DESI 6363), for which notice of withdrawal of approval of the new drug application was published in the FEDERAL REGISTER of July 23, 1970 (35 FR 11827).

(v) Curad Medicated Adhesive Bandage containing sulfathiazole (DESI 4964), for which notice of withdrawal of approval of the new drug application was published in the FEDERAL REGISTER of December 31, 1969 (34 FR 20441).

(vi) Drugs Containing Rutin, Quercetin, Hesperidin, or any Bioflavonoids (DESI 5960), for which notice of withdrawal of approval of new drug applications was published in the FEDERAL REGISTER of July 3, 1970 (35 FR 10872, 10873) and October 17, 1970 (35 FR 16332). A further notice of opportunity for hearing with respect to the drugs covered by the October 17, 1970 FEDERAL REGISTER notice will be published at a later date.

(vii) Antibiotics in Combination with Other Drugs for Nasal Use (DESI 7561), for which an order revoking provision for certification was published in the FEDERAL REGISTER of August 6, 1971 (36 FR 14469) and confirmed in the FEDERAL REGISTER of October 28, 1971 (36 FR 20686).

(viii) Antibiotic Troches (DESI 8328), for which an order revoking provision for certification was published in the FEDERAL REGISTER of July 14, 1971 (36 FR 13089) and confirmed in the FEDERAL REGISTER of October 9, 1971 (36 FR 19695).

(ix) Certain Drugs Containing Oxyphenisatin or Oxyphenisatin Acetate (DESI 10732), for which notices of withdrawal of approval of new drug applications were published in the FEDERAL REGISTER of February 1, 1972 (37 FR 2460), and March 9, 1973 (38 FR 6419).

(x) Curad Medicated Adhesive Bandage containing tyrothricin-nitrofurazone (DESI 6898), for which an order revoking provision for certification was published March 14, 1972 (37 FR 5294), and confirmed in the FEDERAL REGISTER of July 6, 1972 (37 FR 13254).

(xi) Candette Cough Gel (DESI 11562), for which notice of withdrawal of approval of the new drug application was published in the FEDERAL REGISTER of November 19, 1972 (37 FR 25249).

(xii) Certain OTC Multiple-Vitamin Preparations for Oral Use containing excessive amounts of vitamin D and/or vitamin A (DESI 97), for which notice of withdrawal of approval of the new drug applications was published in the FEDERAL REGISTER of November 29, 1972 (37 FR 25249).

(xiii) Certain Sulfonamide-Containing Preparations for Topical Ophthalmic or Otic Use (DESI 368, for which a notice of withdrawal of approval was published in the FEDERAL REGISTER Of February 2, 1973 (38 FR 3208).

(xiv) Those parts of the publication entitled "Certain Mouthwash and Gargle Preparations” (DESI 2855) pertaining to Tyrolaris Mouthwash, containing tyrothricin, panthenol, and alcohol, for which an order revoking provision for certification was published in the FEDERAL REGISTER of February 2, 1967 (32 FR 1172) prior to the drug efficacy study implementation.

(c) Manufacturers and distributors should take notice that the information on OTC drugs provided by the Drug Efficacy Study review is valuable information as to the deficiencies in the data available to support indications for use. They are encouraged to perform studies to obtain adequate evidence of effectiveness for the review of OTC drugs which is already in progress. In the interim it is in the public interest that manufacturers and distributors of all OTC drugs effect changes in their formulations and/or labeling to bring the products into conformity with current medical knowledge and experience.

(d) Manufacturers and distributors of OTC drugs may be reluctant to make appropriate formulation and/or labeling changes for fear of losing the protection of the so-called "grandfather" provisions of the 1938 Federal Food, Drug, and Cosmetic Act (sec. 201(p)(1)) and the 1962 amendments to the act (sec. 107(c) of those amendments). To encourage and facilitate prompt changes, the Food and Drug Administration will not take legal action against any OTC drug, other than those not deferred, based on a charge that the product is a new drug and not grandfathered under the act as a result of the changes if the changes in formulation and/or labeling are of the following kind:

(1) The addition to the labeling of warning, contraindications, side effects, and/or precaution information.

(2) The deletion from the labeling of false, misleading, or unsupported indications for use or claims of effectiveness.

(3) Changes in the components or composition of the drug that will give increased assurance that the drug will have its intended effect, yet not raise or contribute any added safety questions.

(4) Changes in the components or composition of the drug which may reasonably be concluded to improve the safety of the drug, without diminishing its effectiveness.

(e) The forbearance from legal action for lack of grandfather protection is an interim procedure designed to encourage appropriate change in formulation and/or labeling during the time period

required to review the various classes of OTC drugs. At such time as an applicable OTC drug monograph becomes effective, the interim procedure will automatically be terminated and any appropriate regulatory action will be initiated.

§ 330.13 Conditions for marketing ingredients recommended for overthe-counter (OTC) use under the OTC drug review.

(a) Before the publication in the FEDERAL REGISTER of an applicable proposed monograph, an OTC drug product that contains: (1) An active ingredient limited, on or after May 11, 1972, to prescription use for the indication and route of administration under consideration by an OTC advisory review panel, and not thereafter exempted from such limitation pursuant to §310.200 of this chapter, or

(2) An active ingredient at a dosage level higher than that available in an OTC drug product on December 4, 1975, shall be regarded as a new drug within the meaning of section 201(p) of the act for which an approved new drug application is required.

(b)(1) An OTC drug product that contains: (i) An active ingredient limited, on or after May 11, 1972, to prescription use for the indication and route of administration under consideration by an OTC advisory review panel, and not thereafter exempted from such limitation pursuant to §310.200 of this chapter, or

(ii) An active ingredient at a dosage level higher than that available in an OTC drug product on December 4, 1975, which ingredient and/or dosage level is classified by the panel in category I (conditions subject to § 330.10(a)(6)(i)) shall be regarded as a new drug within the meaning of section 201(p) of the act for which an approved new drug application is required if marketed for OTC use prior to the date of publication in the FEDERAL REGISTER of a proposed monograph.

(2) An OTC drug product covered by paragraph (b)(1) of this section which is marketed after the date of publication in the FEDERAL REGISTER of a proposed monograph but prior to the effective date of a final monograph shall be subject to the risk that the Commissioner

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