Pennsylvania Code › Title 28 - HEALTH AND SAFETY › Part III - Prevention of Diseases › Chapter 25 - CONTROLLED SUBSTANCES, DRUGS, DEVICES AND COSMETICS › Subchapter A - CONTROLLED SUBSTANCES, DRUGS, DEVICES AND COSMETICS › GOOD MANUFACTURING PRACTICE IN MANUFACTURE, PROCESSING, PACKING OR HOLDING OF DRUGS › Section 25.16 - Production and control procedures

Current through Register Vol. 54, No. 28, July 13, 2024
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).
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).