General administrative rulings and decisions (21 CFR 2.5-2.125)

106 21 CFR Ch. I (4–1–16 Edition) Pt. 2 or the responsible individuals, or both, or request that the drugs be destroyed or otherwise brought into compliance with the Federal Food, Drug, and Cos metic Act under FDA’s supervision. (j) Detention termination. If FDA de cides to terminate a detention or when the detention period expires, whichever occurs first, an FDA representative au thorized to terminate a detention will issue a detention termination notice releasing the drugs to any person who received the original detention order or that person’s representative and will remove, or authorize in writing the re moval of, the required labels or tags. (k) Recordkeeping requirements. (1) After issuance of a detention order under paragraph (d) of this section, the owner, operator, or agent in charge of any factory, warehouse, other estab lishment, or consulting laboratory where detained drugs are manufac tured, processed, packed, or held, must have, or establish, and maintain ade quate records relating to how the de tained drugs may have become adulter ated or misbranded, records on any dis tribution of the drugs before and after the detention period, records on the correlation of any in-process detained drugs that are put in final form under paragraph (h) of this section to the completed drugs, records of any changes in, or processing of, the drugs permitted under the detention order, and records of any other movement under paragraph (h) of this section. Records required under this paragraph must be provided to FDA on request for review and copying. Any FDA request for access to records required under this paragraph must be made at a rea sonable time, must state the reason or purpose for the request, and must iden tify to the fullest extent practicable the information or type of information sought in the records to which access is requested. (2) Records required under this para graph must be maintained for a max imum period of 2 years after the issuance of the detention order or for such other shorter period as FDA di rects. When FDA terminates the deten tion or when the detention period ex pires, whichever occurs first, FDA will advise all persons required under this paragraph to keep records concerning that detention whether further record keeping is required for the remainder of the 2-year, or shorter, period. FDA ordinarily will not require further rec ordkeeping if the Agency determines that the drugs are not adulterated or misbranded or that recordkeeping is not necessary to protect the public health, unless the records are required under other regulations in this chapter (e.g., the good manufacturing practice regulation in part 211 of this chapter). [79 FR 30719, May 29, 2014] PART 2—GENERAL ADMINISTRATIVE RULINGS AND DECISIONS Subpart A—General Provisions Sec. 2.5 Imminent hazard to the public health. 2.10 Examination and investigation sam ples. 2.19 Methods of analysis. Subpart B—Human and Animal Foods 2.25 Grain seed treated with poisonous sub stances; color identification to prevent adulteration of human and animal food. 2.35 Use of secondhand containers for the shipment or storage of food and animal feed. Subparts C–E [Reserved] Subpart F—Caustic Poisons 2.110 Definition of ammonia under Federal Caustic Poison Act. Subpart G—Provisions Applicable to Spe cific Products Subject to the Federal Food, Drug, and Cosmetic Act 2.125 Use of ozone-depleting substances in foods, drugs, devices, or cosmetics. AUTHORITY: 15 U.S.C. 402, 409; 21 U.S.C. 321, 331, 335, 342, 343, 346a, 348, 351, 352, 355, 360b, 361, 362, 371, 372, 374; 42 U.S.C. 7671 et seq. SOURCE: 42 FR 15559, Mar. 22, 1977, unless otherwise noted. Subpart A—General Provisions § 2.5 Imminent hazard to the public health. (a) Within the meaning of the Fed eral Food, Drug, and Cosmetic Act an imminent hazard to the public health VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00116 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 107 Food and Drug Administration, HHS § 2.10 is considered to exist when the evi dence is sufficient to show that a prod uct or practice, posing a significant threat of danger to health, creates a public health situation (1) that should be corrected immediately to prevent injury and (2) that should not be per mitted to continue while a hearing or other formal proceeding is being held. The imminent hazard may be declared at any point in the chain of events which may ultimately result in harm to the public health. The occurrence of the final anticipated injury is not es sential to establish that an imminent hazard of such occurrence exists. (b) In exercising his judgment on whether an imminent hazard exists, the Commissioner will consider the num ber of injuries anticipated and the na ture, severity, and duration of the an ticipated injury. § 2.10 Examination and investigation samples. (a)(1) When any officer or employee of the Department collects a sample of a food, drug, or cosmetic for analysis under the act, the sample shall be des ignated as an official sample if records or other evidence is obtained by him or any other officer or employee of the Department indicating that the ship ment or other lot of the article from which such sample was collected was introduced or delivered for introduc tion into interstate commerce, or was in or was received in interstate com merce, or was manufactured within a Territory. Only samples so designated by an officer or employee of the De partment shall be considered to be offi cial samples. (2) For the purpose of determining whether or not a sample is collected for analysis, the term analysis includes ex aminations and tests. (3) The owner of a food, drug, or cos metic of which an official sample is collected is the person who owns the shipment or other lot of the article from which the sample is collected. (b) When an officer or employee of the Department collects an official sample of a food, drug, or cosmetic for analysis under the act, he shall collect at least twice the quantity estimated by him to be sufficient for analysis, un less: (1) The amount of the article avail able and reasonably accessible for sam pling is less than twice the quantity so estimated, in which case he shall col lect as much as is available and reason ably accessible. (2) The cost of twice the quantity so estimated exceeds $150. (3) The sample cannot by diligent use of practicable preservation techniques available to the Food and Drug Admin istration be kept in a state in which it could be readily and meaningfully ana lyzed in the same manner and for the same purposes as the Food and Drug Administration’s analysis. (4) The sample is collected from a shipment or other lot which is being imported or offered for import into the United States. (5) The sample is collected from a person named on the label of the arti cle or his agent, and such person is also the owner of the article. (6) The sample is collected from the owner of the article, or his agent, and such article bears no label or, if it bears a label, no person is named there on. In addition to the quantity of sample set forth in this paragraph, the officer or employee shall, if practicable, col lect such further amount as he esti mates will be sufficient for use as trial exhibits. (c) After the Food and Drug Adminis tration has completed such analysis of an official sample of a food, drug, or cosmetic as it determines, in the course of analysis and interpretation of analytical results, to be adequate to es tablish the respects, if any, in which the article is adulterated or mis branded within the meaning of the act, or otherwise subject to the prohibi tions of the act, and has reserved an amount of the article it estimates to be adequate for use as exhibits in the trial of any case that may arise under the act based on the sample, a part of the sample, if any remains available, shall be provided for analysis, upon written request, by any person named on the label of the article, or the owner there of, or the attorney or agent of such person or owner, except when: VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00117 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 108 21 CFR Ch. I (4–1–16 Edition) § 2.19 (1) After collection, the sample or re maining part thereof has become de composed or otherwise unfit for anal ysis, or (2) The request is not made within a reasonable time before the trial of any case under the act, based on the sample to which such person or owner is a party. The person, owner, attorney, or agent who requests the part of sample shall specify the amount desired. A re quest from an owner shall be accom panied by a showing of ownership, and a request from an attorney or agent by a showing of authority from such per son or owner to receive the part of sample. When two or more requests for parts of the same sample are received the requests shall be complied with in the order in which they were received so long as any part of the sample re mains available therefor. (d) When an official sample of food, drug, or cosmetic is the basis of a no tice given under section 305 of the act, or of a case under the act, and the per son to whom the notice was given, or any person who is a party to the case, has no right under paragraph (c) of this section to a part of the sample, such person or his attorney or agent may obtain a part of the sample upon re quest accompanied by a written waiver of right under such paragraph (c) from each person named on the label of the article and owner thereof, who has not exercised his right under such para graph (c). The operation of this para graph shall be subject to the excep tions, terms, and conditions prescribed in paragraph (c) of this section. (e) The Food and Drug Administra tion is authorized to destroy: (1) Any official sample when it deter mines that no analysis of such sample will be made; (2) Any official sample or part there of when it determines that no notice under section 305 of the act, and no case under the act, is or will be based on such sample; (3) Any official sample or part there of when the sample was the basis of a notice under section 305 of the act, and when, after opportunity for presen tation of views following such notice, it determines that no other such no tice, and no case under the act, is or will be based on such sample; (4) Any official sample or part there of when the sample was the basis of a case under the act which has gone to final judgment, and when it determines that no other such case is or will be based on such sample; (5) Any official sample or part there of if the article is perishable; (6) Any official sample or part there of when, after collection, such sample or part has become decomposed or oth erwise unfit for analysis; (7) That part of any official sample which is in excess of three times the quantity it estimates to be sufficient for analysis. [42 FR 15559, Mar. 22, 1977, as amended at 63 FR 51299, Sept. 25, 1998] § 2.19 Methods of analysis. Where the method of analysis is not prescribed in a regulation, it is the pol icy of the Food and Drug Administra tion in its enforcement programs to utilize the methods of analysis of the AOAC INTERNATIONAL (AOAC) as published in the latest edition (13th Ed., 1980) of their publication ‘‘Official Methods of Analysis of the Association of Official Analytical Chemists,’’ and the supplements thereto (‘‘Changes in Methods’’ as published in the March issues of the ‘‘Journal of the Associa tion of Official Analytical Chemists’’), which are incorporated by reference, when available and applicable. Copies are available from the AOAC INTER NATIONAL, 481 North Frederick Ave., suite 500, Gaithersburg, MD 20877, or at the National Archives and Records Ad ministration (NARA). For information on the availability of this material at NARA, call 202–741–6030, or go to: http:// www.archives.gov/federallregister/ codeloflfederallregulations/ ibrllocations.html. In the absence of an AOAC method, the Commissioner will furnish a copy of the particular meth od, or a reference to the published method, that the Food and Drug Ad ministration will use in its enforce ment program. Other methods may be used for quality control, specifications, contracts, surveys, and similar non regulatory functions, but it is expected that they will be calibrated in terms of the method which the Food and Drug Administration uses in its enforcement program. Use of an AOAC method does VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00118 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 109 Food and Drug Administration, HHS § 2.35 not relieve the practioner of the re sponsibility to demonstrate that he can perform the method properly through the use of positive and nega tive controls and recovery and repro ducibility studies. [42 FR 15559, Mar. 22, 1977, as amended at 47 FR 946, Jan. 8, 1982; 54 FR 9034, Mar. 3, 1989; 70 FR 40880, July 15, 2005; 70 FR 67651, Nov. 8, 2005] Subpart B—Human and Animal Foods § 2.25 Grain seed treated with poi sonous substances; color identifica tion to prevent adulteration of human and animal food. (a) In recent years there has devel oped increasing use of poisonous treat ments on seed for fungicidal and other purposes. Such treated seed, if con sumed, presents a hazard to humans and livestock. It is not unusual for stocks of such treated food seeds to re main on hand after the planting season has passed. Despite the cautions re quired by the Federal Seed Act (53 Stat. 1275, as amended 72 Stat. 476, 7 U.S.C. 1551 et seq.) in the labeling of the treated seed, the Food and Drug Ad ministration has encountered many cases where such surplus stocks of treated wheat, corn, oats, rye, barley, and sorghum seed had been mixed with untreated seed and sent to market for food or feed use. This has resulted in livestock injury and in legal actions under the Federal Food, Drug, and Cos metic Act against large quantities of food adulterated through such admix ture of poisonous treated seeds with good food. Criminal cases were brought against some firms and individuals. Where the treated seeds are promi nently colored, buyers and users or processors of agricultural food seed for food purposes are able to detect the ad mixture of the poisonous seed and thus reject the lots; but most such buyers, users, and processors do not have the facilities or scientific equipment to de termine the presence of the poisonous chemical at the time crops are deliv ered, in cases where the treated seeds have not been so colored. A suitable color for this use is one that is in suffi cient contrast to the natural color of the food seed as to make admixture of treated, denatured seeds with good food easily apparent, and is so applied that it is not readily removed. (b) On and after December 31, 1964, the Food and Drug Administration will regard as adulterated any interstate shipment of the food seeds wheat, corn, oats, rye, barley, and sorghum bearing a poisonous treatment in excess of a recognized tolerance or treatment for which no tolerance or exemption from tolerance is recognized in regulations promulgated pursuant to section 408 of the Federal Food, Drug, and Cosmetic Act, unless such seeds have been ade quately denatured by a suitable color to prevent their subsequent inad vertent use as food for man or feed for animals. (c) Attention is called to the labeling requirements of the Federal Hazardous Substances Act, where applicable to de natured seeds in packages suitable for household use. § 2.35 Use of secondhand containers for the shipment or storage of food and animal feed. (a) Investigations by the Food and Drug Administration, the National Communicable Disease Center of the U.S. Public Health Service, the Con sumer and Marketing Service of the U.S. Department of Agriculture, and by various State public health agencies have revealed practices whereby food and animal feed stored or shipped in secondhand containers have been ren dered dangerous to health. Such con tamination has been the result of the original use of these containers for the storage and shipment of articles con taining or bearing disease organisms or poisonous or deleterious substances. (b) The Commissioner concludes that such dangerous or potentially dan gerous practices include, but are not limited to, the following: (1) Some vegetable growers and pack ers employ used poultry crates for shipment of fresh vegetables, including cabbage and celery. Salmonella orga nisms are commonly present on dressed poultry and in excreta and fluid exudates from dressed birds. Thus wooden crates in which dressed poultry has been iced and packed are potential sources of Salmonella or other enteropathogenic microorganisms that VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00119 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 110 21 CFR Ch. I (4–1–16 Edition) § 2.110 may contaminate fresh vegetables which are frequently consumed with out heat treatment. (2) Some potato growers and pro ducers of animal feeds use secondhand bags for shipment of these articles. Such bags may have originally been used for shipping or storing pesticide treated seed or other articles bearing or containing poisonous substances. Thus these secondhand bags are poten tial sources of contamination of the food or animal feed stored or shipped therein. (c) In a policy statement issued April 11, 1968, the Food and Drug Administra tion declared adulterated within the meaning of section 402(a) of the Fed eral Food, Drug, and Cosmetic Act shipments of vegetables or other edible food in used crates or containers that may render the contents injurious to health. This policy statement is ex tended so that the Food and Drug Ad ministration will regard as adulterated within the meaning of section 402(a) of the act shipments of vegetables, other edible food, or animal feed in used crates, bags, or other containers that may render the contents injurious to health. Subparts C–E [Reserved] Subpart F—Caustic Poisons § 2.110 Definition of ammonia under Federal Caustic Poison Act. For the purpose of determining whether an article containing ammo nia is subject to the Federal Caustic Poison Act, the ammonia content is to be calculated as NH3. Subpart G—Provisions Applicable to Specific Products Subject to the Federal Food, Drug, and Cosmetic Act § 2.125 Use of ozone-depleting sub stances in foods, drugs, devices, or cosmetics. (a) As used in this section, ozone-de pleting substance (ODS) means any class I substance as defined in 40 CFR part 82, appendix A to subpart A, or class II substance as defined in 40 CFR part 82, appendix B to subpart A. (b) Except as provided in paragraph (c) of this section, any food, drug, de vice, or cosmetic that is, consists in part of, or is contained in an aerosol product or other pressurized dispenser that releases an ODS is not an essen tial use of the ODS under the Clean Air Act. (c) A food, drug, device, or cosmetic that is, consists in part of, or is con tained in an aerosol product or other pressurized dispenser that releases an ODS is an essential use of the ODS under the Clean Air Act if paragraph (e) of this section specifies the use of that product as essential. For drugs, including biologics and animal drugs, and for devices, an investigational ap plication or an approved marketing ap plication must be in effect, as applica ble. (d) [Reserved] (e) The use of ODSs in the following products is essential: (1) Metered-dose corticosteroid human drugs for oral inhalation. Oral pressur ized metered-dose inhalers containing the following active moieties: (i)–(v) [Reserved] (2) Metered-dose short-acting adrenergic bronchodilator human drugs for oral in halation. Oral pressurized metered-dose inhalers containing the following ac tive moieties: (i)–(v) [Reserved] (3) [Reserved] (4) Other essential uses. (i)–(ii) [Re served] (iii) Anesthetic drugs for topical use on accessible mucous membranes of humans where a cannula is used for ap plication. (iv)–(v) [Reserved] (vi) Metered-dose atropine sulfate aerosol human drugs administered by oral inhalation. (vii)–(viii) [Reserved] (ix) Sterile aerosol talc administered intrapleurally by thoracoscopy for human use. (f) Any person may file a petition under part 10 of this chapter to request that FDA initiate rulemaking to amend paragraph (e) of this section to add an essential use. FDA may initiate notice-and-comment rulemaking to add an essential use on its own initia tive or in response to a petition, if granted. VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00120 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 111 Food and Drug Administration, HHS Pt. 3 (1) If the petition is to add use of a noninvestigational product, the peti tioner must submit compelling evi dence that: (i) Substantial technical barriers exist to formulating the product with out ODSs; (ii) The product will provide an un available important public health ben efit; and (iii) Use of the product does not re lease cumulatively significant amounts of ODSs into the atmosphere or the re lease is warranted in view of the un available important public health ben efit. (2) If the petition is to add use of an investigational product, the petitioner must submit compelling evidence that: (i) Substantial technical barriers exist to formulating the investiga tional product without ODSs; (ii) A high probability exists that the investigational product will provide an unavailable important public health benefit; and (iii) Use of the investigational prod uct does not release cumulatively sig nificant amounts of ODSs into the at mosphere or the release is warranted in view of the high probability of an un available important public health ben efit. (g) Any person may file a petition under part 10 of this chapter to request that FDA initiate rulemaking to amend paragraph (e) of this section to remove an essential use. FDA may ini tiate notice-and-comment rulemaking to remove an essential use on its own initiative or in response to a petition, if granted. If the petition is to remove an essential use from paragraph (e) of this section, the petitioner must sub mit compelling evidence of any one of the following criteria: (1) The product using an ODS is no longer being marketed; or (2) After January 1, 2005, FDA deter mines that the product using an ODS no longer meets the criteria in para graph (f) of this section after consulta tion with a relevant advisory com mittee(s) and after an open public meeting; or (3) For individual active moieties marketed as ODS products and rep resented by one new drug application (NDA): (i) At least one non-ODS product with the same active moiety is mar keted with the same route of adminis tration, for the same indication, and with approximately the same level of convenience of use as the ODS product containing that active moiety; (ii) Supplies and production capacity for the non-ODS product(s) exist or will exist at levels sufficient to meet pa tient need; (iii) Adequate U.S. postmarketing use data is available for the non-ODS product(s); and (iv) Patients who medically required the ODS product are adequately served by the non-ODS product(s) containing that active moiety and other available products; or (4) For individual active moieties marketed as ODS products and rep resented by two or more NDAs: (i) At least two non-ODS products that contain the same active moiety are being marketed with the same route of delivery, for the same indica tion, and with approximately the same level of convenience of use as the ODS products; and (ii) The requirements of paragraphs (g)(3)(ii), (g)(3)(iii), and (g)(3)(iv) of this section are met. [67 FR 48384, July 24, 2002, as amended at 71 FR 70873, Dec. 7, 2006; 70 FR 17192, Apr. 4, 2005; 75 FR 19241, Apr. 14, 2010; 73 FR 69552, Nov. 19, 2008; 75 FR 19241, Apr. 14, 2010] PART 3—PRODUCT JURISDICTION Subpart A—Assignment of Agency Com ponent for Review of Premarket Appli cations Sec. 3.1 Purpose. 3.2 Definitions. 3.3 Scope. 3.4 Designated agency component. 3.5 Procedures for identifying the des ignated agency component. 3.6 Product jurisdiction officer. 3.7 Request for designation. 3.8 Letter of designation. 3.9 Effect of letter of designation. 3.10 Stay of review time. Subpart B [Reserved] AUTHORITY: 21 U.S.C. 321, 351, 353, 355, 360, 360c–360f, 360h–360j, 360gg–360ss, 360bbb–2, 371(a), 379e, 381, 394; 42 U.S.C. 216, 262, 264. VerDate Sep<11>2014 14:18 Apr 18, 2016 Jkt 238070 PO 00000 Frm 00121 Fmt 8010 Sfmt 8010 Q:\21\21V1.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B