KV Pharmaceutical — FDA 483 Findings

Examination of packaging and labeling materials for suitability and correctness before packaging operations is not performed.

Rejected closures are not controlled under a quarantine system designed to prevent their use in manufacturing or processing operations for whicb they are unsuitable.

Written records ofinvestigations into unexplained discrepancies and the failure ofa batch or any ofits components to meet specifications do not always include the conclusions and follow-up.

Complete records are not maintained ofany modification ofan established method employed in testing.

Written procedures are not established and followed for the cleaning and maintenance ofequipment, including utensils, used in the manufacture, processing, packing or holding of a drug product.

Returned drug products held, stored or shipped before or during their return under conditions which cast doubt on their safety, identity, strength, quality or purity are not destroyed.

(b) (4) Written production and process control procedures are not followed in the execution ofproduction and process control functions.

Laboratory records are deficient in that they do not include a complete record of all (b) (4) data obtained during testing.

Investigations ofan unexplained discrepancy and a failure ofa batch or any ofits components to meet any ofits specifications did not extend to other batches ofthe same drug product and other drug products that may have been associated with the specific failure or discrepancy.

The responsibilities and procedures applicable to the quality control unit are not fully followed.

Batch production and control records do not include the identification of the persons performing each significant step in the operation, for each batch ofdrug product produced.

Verification ofthe suitability oftbe testing methods is deficient in that they are not performed under actual conditions ofuse.

Written records ofmajor equipment cleaning, maintenance, and use are not included in individual equipment logs.

An NDA-Field Alert Report was not submitted within three working days ofreceipt of information concerning a failure of one or more distributed batches of a drug to meet the specifications established for it in the application.

Laboratory records do not include the initials or signature ofa second person showing that the original records have been reviewed for accuracy, completeness, and compliance with established standards.

Laboratory records do not include complete records of the periodic calibration oflabonnory instruments.

Written records are not always made of investigations into unexplained discrepancies and the failure ofa batch or any ofits components to meet specifications.

Records are not kept for the cleaning and inspection of equipment.

Routine calibration of automatic, mechanical.

The building lacks adequate space for the orderly placement of equipment and materials to prevent mix-ups between different components, in-process materials, and drug products and to prevent contantination.

Changes to written procedures are not reviewed and approved by the quality control unit.

There is a lack of rotation so that the oldest approved stock ofcomponents is used first.

Procedures describing the handling ofall written and oral complaints regarding a drug product are not followed.

Inspection ofthe packaging facilities immediately before use is not done to assure that all drug products have been removed from previous operations.

Equipment and utensils are not cleaned, maintained, and sanitized at appropriate intervals to prevent contamination that would alter the safary, identity, strength, quality or purity ofthe drug product.

There is a failure to thoroughlYTeView any unexplaioed discrepancy and the failUre ofa batch or any of its components to meet any ofits specifications whether or not the batch has been already distributed.

Reports ofanalysis from component suppliers are accepted in lieu oftesting eacb component for conformity with all appropriate wrinen specifications, without establishing the reliability ofthe supplier's analyses through appropriate validation oftbe supplier's test results at appropriate intervals.

(b) (4) Laboratory controls do not include the establishment of scientifically sound and appropriate sampling plans designed to assure that components confonn to appropriate standards of identity, strength, quality and purity.

Procedures for the cleaning and maintenance ofequipment are deficient regarding sufficient detail ofthe methods, equipment, and materials used in the cleaning and maintenance operation, and the methods of disassembly and reassembling equipment as necessary to assure proper cleaning and maintenance.

Control procedures are not established which validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics ofin-process malerial and the drug product.

The written stability program does not assure testing ofthe drug product in the same container-closure system as that in which the drug product is marketed.

Drug product production and control records, are not reviewed and approved by the quality control unit to determine compliance witb all established, approved written procedures before a batch is released or distributed.

Established laboratory control mechanisms are not followed.

An annual report did not include a full description ofthe manufacturing and control changes not requiring a supplemental application, listed by date in the order in which they were implemented.

All processing lines used during the production of a batcb ofdrug product is not properly identified at all times to indicate the phase ofprocessing ofthe batch..