Section 25.16. Production and control procedures

Production and control procedures shall include all reasonable precautions, including the following, to assure that the drugs produced have the safety, identity, strength, quality, and purity they purport to possess:

(1) Each significant step in the process, such as the selection, weighing, and measuring of components, the addition of ingredients during the process, weighing and measuring during various stages of the processing, and the determination of the finished yield, shall be performed by a competent and responsible individual and checked by a second competent and responsible individual; or if such steps in the processing are controlled by precision automatic, mechanical, or electronic equipment, their proper performance is adequately checked by one or more competent and responsible individuals. The written record of the significant steps in the process shall be identified by the individual performing these tests and by the individual charged with checking these steps. Such identifications shall be recorded immediately following the completion of such steps.

(2) All containers, lines, and equipment used during the production of a batch of a drug shall be properly identified at all times to accurately and completely indicate their contents and, when necessary, the stage of processing of the batch.

(3) To minimize contamination and prevent mixups, equipment, utensils, and containers shall be thoroughly and appropriately cleaned and properly stored and have previous batch identification removed or obliterated between batches or at suitable intervals in continuous production operations.

(4) Appropriate precautions shall be taken to minimize microbiological and other contamination in the production of drugs purporting to be sterile or which by virtue of their intended use should be free from objectionable micro-organisms.

(5) Appropriate procedures shall be established to minimize the hazard of cross-contamination of any drugs while being manufactured or stored.

(6) To assure the uniformity and integrity of products, there shall be adequate in-process controls, such as checking the weights and disintegration times of tablets, the adequacy of mixing, the homogeneity of suspensions, and the clarity of solutions. In-process sampling shall be done at appropriate intervals using suitable equipment.

(7) Representative samples of all dosage form drugs shall be tested to determine their conformance with the specifications for the product before distribution.

(8) Procedures shall be instituted whereby review and approval of all production and control records, including packaging and labeling, shall be made prior to the release or distribution of a batch. A thorough investigation of any unexplained discrepancy or the failure of a batch to meet any of its specifications shall be undertaken whether or not the batch has already been distributed. This investigation shall be undertaken by a competent and responsible individual and shall extend to other batches of the same drug and other drugs that may have been associated with the specific failure. A written record of the investigation shall be made and shall include the conclusions and followup.

(9) Returned goods shall be identified as such and held. If the conditions under which returned goods have been held, stored, or shipped prior to or during their return, or the condition of the product, its container, carton, or labeling as a result of storage or shipping, cast doubt on the safety, identity, strength, quality, or purity of the drug, the returned goods shall be destroyed or subjected to adequate examination or testing to assure that the material meets all appropriate standards or specifications before being returned to stock for warehouse distribution or repacking. If the product is neither destroyed nor returned to stock, it may be reprocessed provided the final product meets all its standards and specifications. Records of returned goods shall be maintained and shall indicate the quantity returned, date, and actual disposition of the product. If the reason for returned goods implicates associated batches, an appropriate investigation shall be made in accordance with the requirements of paragraph (8).

Notation

Cross References

This section cited in 28 Pa. Code § 25.15 (relating to production and control records); 28 Pa. Code § 25.18 (relating to packaging and labeling); 28 Pa. Code § 25.23 (relating to complaint files).