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necessary to assure compliance with established specifications and standards, including examinations and assays, as follows:

(1) A description of the sample received for testing with identification of source (that is, location from where sample was obtained), quantity, lot number or other distinctive code, date sample was taken, and date sample was received for testing.

(2) A statement of each method used in the testing of the sample. The statement shall indicate the location of data that establish that the methods used in the testing of the sample meet proper standards of accuracy and reliability as applied to the product tested. (If the method employed is in the current revision of the United States Pharmacopeia, National Formulary, Association of Official Analytical Chemists, Book of Methods, 2 or in other recognized standard references, or is detailed in an approved new drug application and the referenced method is not modified, a statement indicating the method and reference will suffice). The suitability of all testing methods used shall be verified under actual conditions of use.

(3) A statement of the weight or measure of sample used for each test, where appropriate.

(4) A complete record of all data secured in the course of each test, including all graphs, charts, and spectra from laboratory instrumentation, properly identified to show the specific component, drug product container, closure, in-process material, or drug product, and lot tested.

(5) A record of all calculations performed in connection with the test, including units of measure, conversion factors, and equivalency factors.

(6) A statement of the results of tests and how the results compare with established standards of identity, strength, quality, and purity for the component, drug product container, closure, in-process material, or drug product tested.

2 Copies may be obtained from: Association of Official Analytical Chemists, 2200 Wilson Blvd., Suite 400, Arlington, VA 22201-3301.

(7) The initials or signature of the person who performs each test and the date(s) the tests were performed.

(8) The initials or signature of a second person showing that the original records have been reviewed for accuracy, completeness, and compliance with established standards.

(b) Complete records shall be maintained of any modification of an established method employed in testing. Such records shall include the reason for the modification and data to verify that the modification produced results that are at least as accurate and reliable for the material being tested as the established method.

(c) Complete records shall be maintained of any testing and standardization of laboratory reference standards, reagents, and standard solutions.

(d) Complete records shall be maintained of the periodic calibration of laboratory instruments, apparatus, gauges, and recording devices required by §211.160(b)(4).

(e) Complete records shall be maintained of all stability testing performed in accordance with § 211.166.

[43 FR 45077, Sept. 29, 1978, as amended at 55 FR 11577, Mar. 29, 1990]

$211.196 Distribution records.

Distribution records shall contain the name and strength of the product and description of the dosage form, name and address of the consignee, date and quantity shipped, and lot or control number of the drug product. For compressed medical gas products, distribution records are not required to contain lot or control numbers.

(Approved by the Office of Management and Budget under control number 0910-0139) [49 FR 9865, Mar. 16, 1984]

$211.198 Complaint files.

(a) Written procedures describing the handling of all written and oral complaints regarding a drug product shall be established and followed. Such procedures shall include provisions for review by the quality control unit, of any complaint involving the possible failure of a drug product to meet any of its specifications and, for such drug products, a determination as to the need for an investigation in accordance with

§ 211.192. Such procedures shall include provisions for review to determine whether the complaint represents a serious and unexpected adverse drug experience which is required to be reported to the Food and Drug Administration in accordance with §310.305 of this chapter.

(b) A written record of each complaint shall be maintained in a file designated for drug product complaints. The file regarding such drug product complaints shall be maintained at the establishment where the drug product involved was manufactured, processed, or packed, or such file may be maintained at another facility if the written records in such files are readily available for inspection at that other facility. Written records involving a drug product shall be maintained until at least 1 year after the expiration date of the drug product, or 1 year after the date that the complaint was received, whichever is longer. In the case of certain OTC drug products lacking expiration dating because they meet the criteria for exemption under § 211.137, such written records shall be maintained for 3 years after distribution of the drug product.

(1) The written record shall include the following information, where known: the name and strength of the drug product, lot number, name of complainant, nature of complaint, and reply to complainant.

(2) Where an investigation under § 211.192 is conducted, the written record shall include the findings of the investigation and followup. The record or copy of the record of the investigation shall be maintained at the establishment where the investigation occurred in accordance with § 211.180(c).

(3) Where an investigation under § 211.192 is not conducted, the written record shall include the reason that an investigation was found not to be necessary and the name of the responsible person making such a determination.

[43 FR 45077, Sept. 29, 1978, as amended at 51 FR 24479, July 3, 1986]

Subpart K-Returned and
Salvaged Drug Products

$211.204 Returned drug products.

Returned drug products shall be identified as such and held. If the conditions under which returned drug products have been held, stored, or shipped before or during their return, or if the condition of the drug product, its container, carton, or labeling, as a result of storage or shipping, casts doubt on the safety, identity, strength, quality or purity of the drug product, the returned drug product shall be destroyed unless examination, testing, or other investigations prove the drug product meets appropriate standards of safety, identity, strength, quality, or purity. A drug product may be reprocessed provided the subsequent drug product meets appropriate standards, specifications, and characteristics. Records of returned drug products shall be maintained and shall include the name and label potency of the drug product dosage form, lot number (or control number or batch number), reason for the return, quantity returned, date of disposition, and ultimate disposition of the returned drug product. If the reason for a drug product being returned implicates associated batches, an appropriate investigation shall be conducted in accordance with the requirements of §211.192. Procedures for the holding, testing, and reprocessing of returned drug products shall be in writing and shall be followed.

$211.208 Drug product salvaging.

Drug products that have been subjected to improper storage conditions including extremes in temperature, humidity, smoke, fumes, pressure, age, or radiation due to natural disasters, fires, accidents, or equipment failures shall not be salvaged and returned to the marketplace. Whenever there is a question whether drug products have been subjected to such conditions, salvaging operations may be conducted only if there is (a) evidence from laboratory tests and assays (including animal feeding studies where applicable)

that the drug products meet all applicable standards of identity, strength, quality, and purity and (b) evidence from inspection of the premises that the drug products and their associated packaging were not subjected to improper storage conditions as a result of the disaster or accident. Organoleptic examinations shall be acceptable only as supplemental evidence that the drug products meet appropriate standards of identity, strength, quality, and purity. Records including name, lot number, and disposition shall be maintained for drug products subject to this section.

PART 216-PHARMACY COMPOUNDING

Subpart A-General Provisions [Reserved]

Subpart B-Compounded Drug Products

Sec.

216.23 [Reserved]

216.24 Drug products withdrawn or removed from the market for reasons of safety or effectiveness.

AUTHORITY: 21 U.S.C. 351, 352, 353a, 355, and

371.

SOURCE: 64 FR 10944, Mar. 8, 1999, unless otherwise noted.

Subpart A-General Provisions [Reserved]

Subpart B-Compounded Drug Products

§216.23 [Reserved]

§216.24 Drug products withdrawn or removed from the market for reasons of safety or effectiveness.

The following drug products were withdrawn or removed from the market because such drug products or components of such drug products were found to be unsafe or not effective. The following drug products may not be compounded under the exemptions provided by section 503A(a) of the Federal Food, Drug, and Cosmetic Act:

Adenosine phosphate: All drug products containing adenosine phosphate.

Adrenal cortex: All drug products containing adrenal cortex.

Azaribine: All drug products containing azaribine.

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Bromfenac sodium: All drug products containing bromfenac sodium.

Butamben: All parenteral drug products containing butamben.

Camphorated oil: All drug products containing camphorated oil.

Carbetapentane citrate: All oral gel drug products containing carbetapentane citrate. Casein, iodinated: All drug products containing iodinated casein.

Chlorhexidine gluconate: All tinctures of chlorhexidine gluconate formulated for use as a patient preoperative skin preparation. Chlormadinone acetate: All drug products containing chlormadinone acetate.

Chloroform: All drug products containing chloroform.

Cobalt: All drug products containing cobalt salts (except radioactive forms of cobalt and its salts and cobalamin and its derivatives).

Dexfenfluramine hydrochloride: All drug products containing dexfenfluramine hydrochloride.

Diamthazole dihydrochloride: All drug products containing diamthazole

dihydrochloride.

Dibromsalan: All drug products containing dibromsalan.

Diethylstilbestrol: All oral and parenteral drug

products containing 25 milligrams or more of diethylstilbestrol per unit dose. Dihydrostreptomycin sulfate: All drug products containing dihydrostreptomycin sulfate. Dipyrone: All drug products containing dipyrone.

Encainide hydrochloride: All drug products containing encainide hydrochloride. Fenfluramine hydrochloride: All drug products containing fenfluramine hydrochloride. Flosequinan: All drug products containing flosequinan.

Gelatin: All intravenous drug products containing gelatin.

Glycerol, iodinated: All drug products containing iodinated glycerol.

Gonadotropin, chorionic: All drug products containing chorionic gonadotropins of animal origin.

Mepazine: All drug products containing mepazine hydrochloride or mepazine acetate.

Metabromsalan: All drug products containing metabromsalan.

Methamphetamine hydrochloride: All parenteral drug products containing methamphetamine hydrochloride.

Methapyrilene: All drug products containing methapyrilene.

Methopholine: All drug products containing methopholine.

Mibefradil dihydrochloride: All drug products containing mibefradil dihydrochloride.

Nitrofurazone: All drug products containing

nitrofurazone (except topical drug products formulated for dermatalogic application). Nomifensine maleate: All drug products containing nomifensine maleate. Oxyphenisatin: All drug products containing oxyphenisatin.

Oxyphenisatin acetate: All drug products containing oxyphenisatin acetate. Phenacetin: All drug products containing phenacetin.

Phenformin hydrochloride: All drug products containing phenformin hydrochloride. Pipamazine: All drug products containing pipamazine.

Potassium arsenite: All drug products containing potassium arsenite. Potassium chloride: All solid oral dosage form drug products containing potassium chloride that supply 100 milligrams or more of potassium per dosage unit (except for controlled-release dosage forms and those products formulated for preparation of solution prior to ingestion).

Povidone: All intravenous drug products containing povidone.

Reserpine: All oral dosage form drug products containing more than 1 milligram of reserpine.

Sparteine sulfate: All drug products containing sparteine sulfate. Sulfadimethoxine: All drug products containing sulfadimethoxine. Sulfathiazole: All drug products containing sulfathiazole (except those formulated for vaginal use).

Suprofen: All drug products containing suprofen (except ophthalmic solutions). Sweet spirits of nitre: All drug products containing sweet spirits of nitre.

Temafloxacin hydrochloride: All drug products containing temafloxacin.

Terfenadine: All drug products containing terfenadine.

drug

All 3,3',4',5-tetrachloro

3,3′,4′,5-tetrachlorosalicylanilide: products containing salicylanilide.

Tetracycline: All liquid oral drug products formulated for pediatric use containing tetracycline in a concentration greater than 25 milligrams/milliliter. Ticrynafen: All drug products containing ticrynafen.

Tribromsalan: All drug products containing tribromsalan.

Trichloroethane: All aerosol drug products intended for inhalation containing trichloroethane.

Urethane: All drug products containing urethane.

Vinyl chloride: All aerosol drug products containing vinyl chloride.

Zirconium: All aerosol drug products containing zirconium.

Zomepirac sodium: All drug products containing zomepirac sodium.

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that a drug (including a drug contained in a medicated feed) shall be deemed to be adulterated if the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirement of the act as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess.

(b)(1) The provisions of this part set forth the criteria for determining whether the manufacture of a medicated feed is in compliance with current good manufacturing practice. These regulations shall apply to all types of facilities and equipment used in the production of medicated feeds, and they shall also govern those instances in which failure to adhere to the regulations has caused nonmedicated feeds that are manufactured, processed, packed, or held to be adulterated. In such cases, the medicated feed shall be deemed to be adulterated within the meaning of section 501(a)(2)(B) of the act, and the nonmedicated feed shall be deemed to be adulterated within the meaning of section 402(a)(2)(D) of the act.

(2) The regulations in §§ 225.10 through 225.115 apply to facilities manufacturing one or more medicated feeds for which an approved medicated feed mill license is required. The regulations in §§ 225.120 through 225.202 apply to facilities manufacturing solely medicated feeds for which an approved license is not required.

(c) In addition to the recordkeeping requirements in this part, Type B and Type C medicated feeds made from Type A articles or Type B feeds under approved NADA's and a medicated feed mill license are subject to the requirements of § 510.301 of this chapter.

[41 FR 52618, Nov. 30, 1976, as amended at 51 FR 7389, Mar. 3, 1986; 64 FR 63203, Nov. 19, 1999]

$225.10 Personnel.

(a) Qualified personnel and adequate personnel training and supervision are essential for the proper formulation, manufacture, and control of medicated

feeds. Training and experience leads to proper use of equipment, maintenance of accurate records, and detection and prevention of possible deviations from current good manufacturing practices.

(b)(1) All employees involved in the manufacture of medicated feeds shall have an understanding of the manufacturing or control operation(s) which they perform, including the location and proper use of equipment.

(2) The manufacturer shall provide an on-going program of evaluation and supervision of employees in the manufacture of medicated feeds.

[41 FR 52618, Nov. 30, 1976, as amended at 42 FR 12426, Mar. 4, 1977]

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(a) The location, design, construction, and physical size of the buildings and other production facilities are factors important to the manufacture of medicated feed. The features of facilities necessary for the proper manufacture of medicated feed include provision for ease of access to structures and equipment in need of routine maintenance; ease of cleaning of equipment and work areas; facilities to promote personnel hygiene; structural conditions for control and prevention of vermin and pest infestation; adequate space for the orderly receipt and storage of drugs and feed ingredients and the controlled flow of these materials through the processing and manufacturing operations; and the equipment for the accurate packaging and delivery of a medicated feed of specified labeling and composition.

(b) The construction and maintenance of buildings in which medicated feeds are manufactured, processed, packaged, labeled, or held shall conform to the following:

(1) The building grounds shall be adequately drained and routinely maintained so that they are reasonably free from litter, waste, refuse, uncut weeds or grass, standing water, and improperly stored equipment.

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