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U.S. Department of Health and Human Services

CFR - Code of Federal Regulations Title 21

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The information on this page is current as of April 1 2019.

For the most up-to-date version of CFR Title 21, go to the Electronic Code of Federal Regulations (eCFR).

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Help | More About 21CFR
[Code of Federal Regulations]
[Title 21, Volume 4]
[Revised as of April 1, 2019]
[CITE: 21CFR226]





TITLE 21--FOOD AND DRUGS
CHAPTER I--FOOD AND DRUG ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
SUBCHAPTER C--DRUGS: GENERAL
 
PART 226CURRENT GOOD MANUFACTURING PRACTICE FOR TYPE A MEDICATED ARTICLES
 

Subpart C--Product Quality Control

Sec. 226.40 Production and control procedures.

Production and control procedures shall include all reasonable precautions, including the following, to assure that the Type A medicated article(s) produced have the identity, strength, quality, and purity they purport to possess:

(a) Each critical step in the process, such as the selection, weighing, and measuring of components; the addition of drug components during the process; weighing and measuring during various stages of the processing; and the determination of the finished yield, shall be performed by one or more competent, responsible individuals. If such steps in the processing are controlled by precision, automatic, mechanical, or electronic equipment, their proper performance shall be adequately checked by one or more competent, responsible individuals.

(b) All containers to be used for undiluted drugs, drug components, intermediate mixtures thereof, and Type A medicated article(s) shall be received, adequately identified, and properly stored and handled in a manner adequate to avoid mixups and contamination.

(c) Equipment, including dust-control and other equipment, such as that used for holding and returning recovered or flush-out materials back into production, shall be maintained and operated in a manner to avoid contamination of the Type A medicated article(s) and to insure the integrity of the finished product.

(d) Competent and responsible personnel shall check actual against theoretical yield of a batch of Type A medicated article(s), and, in the event of any significant discrepancies, key personnel shall prevent distribution of the batch in question and other associated batches of Type A medicated article(s) that may have been involved in a mixup with it.

(e) Adequate procedures for cleaning of those parts of storage, mixing conveying and other equipment coming in contact with the drug component of the Type A medicated article(s) shall be used to avoid contamination of Type A medicated article(s).

(f) If there is sequential production of batches of a Type A medicated article(s) containing the same drug component (or components) at the same or lower levels, there shall be sufficient safeguards to avoid any buildup above the specified levels of the drug components in any of the batches of the Type A medicated article(s).

(g) Production and control procedures shall include provision for discontinuing distribution of any Type A medicated article(s) found by the assay procedures, or other controls performed to fail to conform to appropriate specifications. Distribution of subsequent production of such Type A medicated article(s) shall not begin until it has been determined that proper control procedures have been established.

Sec. 226.42 Components.

(a) Drug components, including undiluted drugs and any intermediate mixes containing drugs used in the manufacture and processing of Type A medicated article(s), shall be received, examined or tested, stored, handled, and otherwise controlled in a manner to maintain the integrity and identification of such articles. Appropriate receipt and inventory records shall be maintained for 2 years, and such records shall show the origin of any drug components, the manufacturer's control number (if any), the dates and batches in which they were used, and the results of any testing of them.

(b) Nondrug components shall be stored and otherwise handled in a manner to avoid contamination, including cross-contamination from manufacturing operations.

Sec. 226.58 Laboratory controls.

Laboratory controls shall include the establishment of adequate specifications and test procedures to assure that the drug components and the Type A medicated article(s) conform to appropriate standards of identity, strength, quality, and purity. Laboratory controls shall include:

(a) The establishment of master records containing appropriate specifications and a description of the test procedures used to check them for each kind of drug component used in the manufacture of Type A medicated article(s). This may consist of the manufacturer's or supplier's statement of specifications and methods of analyses.

(b) The establishment of specifications for Type A medicated article(s) and a description of necessary laboratory test procedures to check such specifications.

(c) Assays which shall be made of representative samples of finished Type A medicated article(s) in accordance with the following schedule:

(1) Each batch of a Type A medicated article(s) manufactured from an undiluted drug shall be assayed for its drug component(s).

(2) In the case of Type A medicated article(s) which are manufactured by dilution of Type A medicated article(s) assayed in accordance with paragraph (c)(1) of this section, each batch shall be assayed for its drug component(s) with the first five consecutive batches assaying within the limitations, followed thereafter by assay of representative samples of not less than 5 percent of all batches produced. When any batch does not assay within limitations, each batch should again be assayed until five consecutive batches are within limitations.

(d) A determination establishing that the drug components remain uniformly dispersed and stable in the Type A medicated article(s) under ordinary conditions of shipment, storage, and use. This may consist of a determination on a Type A medicated article(s) of substantially the same formula and characteristics. Suitable expiration dates shall appear on the labels of the Type A medicated article(s) to assure that the articles meet the appropriate standards of identity, strength, quality, and purity at the time of use.

(e) Adequate provision to check the reliability, accuracy, and precision of any laboratory test procedure used. The official methods in "Methods of Analysis of the Association of Official Analytical Chemists," 1 methods described in an official compendium, and any method submitted as a part of a food additive petition or new-drug application that has been accepted by the Food and Drug Administration shall be regarded as meeting this provision.

(f) Provisions for the maintenance of the results of any assays, including dates and endorsement of analysts. Such records shall be retained in the possession of the manufacturer and shall be maintained for a period of at least 2 years after distribution by the manufacturer of the Type A medicated article(s) has been completed.

1Copies may be obtained from: AOAC INTERNATIONAL, 481 North Frederick Ave., suite 500, Gaithersburg, MD 20877.

[40 FR 14031, Mar. 27, 1975, as amended at 55 FR 11577, Mar. 29, 1990; 55 FR 23703, June 12, 1990; 70 FR 40880, July 15, 2005; 70 FR 67651, Nov. 8, 2005]

Authority: 21 U.S.C. 351, 352, 360b, 371, 374.
Source: 40 FR 14031, Mar. 27, 1975, unless otherwise noted.

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