21 C.F.R. § 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(b) On and after April 20, 1972, a number of notices were published in the Federal Register concerning previously unpublished OTC drugs reviewed by the National Academy of Sciences-National Research Council Drug Efficacy Study Group.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. (1) The requirements of the following DESI announcements are not deferred (the reference document may also pertain to prescription drugs):
  1. (i) Certain Surgical Sutures (DESI 4725), published in the Federal Register of November 11, 1971 (36 FR 21612).
  2. (ii) Absorbable Dusting Powder (DESI 6264), published in the Federal Register of May 25, 1971 (36 FR 9475).
  3. (iii) Certain Insulin Preparations (DESI 4286), published in the Federal Register of April 9, 1971 (36 FR 6842).
  4. (iv) Sulfo-Van Ointment (DESI 2230), published in the Federal Register of October 8, 1970 (35 FR 15860).
  5. (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.
  6. (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).
  7. (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. (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. (i) 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).
  2. (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).
  3. (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.
  4. (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).
  5. (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).
  6. (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.
  7. (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).
  8. (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).
  9. (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).
  10. (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).
  11. (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).
  12. (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).
  13. (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).
  14. (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. (1) The addition to the labeling of warning, contraindications, side effects, and/or precaution information.
2. (2) The deletion from the labeling of false, misleading, or unsupported indications for use or claims of effectiveness.
3. (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. (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.