Inspection Monitor , 11/01/2004 9 11
12-item 483 issued to Yung Shin Pharmaceutical for OOS, multiple validation violations.(Human Drugs)
COPYRIGHT 2004 Washington Information Source
Yung Shin Pharmaceutical Industry, Tachia, Taiwan, Center for Drugs Yung Shin Pharmaceutical Industry, Tachia, Taiwan, was slapped with a 12-item 483 for inadequate systems validation, unacceptable OOS procedures and a lack of a product annual review procedure.
The firm also received a warning letter be-cause the well and city water the firm used in the manufacture of active pharmaceutical ingredients (APIs) had not been demonstrated to be suitable for its intended use.
Investigator George Flynn from Center for Drugs conducted the audit of this manufacturer, which also makes human and veterinary drugs, diagnostics, cosmetics, food supplements, Chinese herbal extracts, and specialty chemicals.
According to the just-released EIR, the 2001 inspection covered validation of the manufacturing process, cleaning validation, batch records, equipment qualification, stability data, reprocessing, solvent recovery, change control procedure, OOS procedure and verification of the manufacturing process.
First, the 483 cited Yung Shin Pharmaceutical because two undisclosed systems were not validated. The firm stated that they had not validated either sys-tem, but stated in their response to Flynn: "The [un-disclosed] systems have been routinely sampled for testing at all the ports. To ensure the consistency of quality, a validation protocol for the [undisclosed] systems was approved on May 25, 2001," the report noted.
The 483 also noted that the firm did not properly validate an undisclosed cycle on a piece of equipment. "Management did the validation without an approved written protocol. I stressed to management that a validation study consisted of a protocol approved prior to start of the study, test results done in accordance with the protocol, and conclusions," the EIR stated.
OOS procedures inadequate, too
The 483 also noted the company's OOS procedure was inadequate. According to the EIR, management stated that OOS procedures had been approved on Feb. 2, 2001, and no OOS investigations had been done since the implementation of the procedure.
"One of the things wrong with this procedure is that a product would be released for sale based on an initial failure and passing retest by the same analysis even though no assignable cause for the initial failure was found. Also, no OOS investigation report would be filled out for this scenario," the EIR noted.
Further: "Another scenario that is objection-able concerns the initial failure and retest failure of the sample performed by the first analyst, and release of the product based on one passing test result by the second analyst without finding an assignable cause for the failures by the initial analyst," the report continued.
Management said they would release the lot based on the test results performed by the second analyst, because the second one was a more experienced chemist. No OOS investigation report would be completed in this scenario. They also said that if the first and second analyst both got OOS results, the lot would be rejected and an OOS investigation report written. "Management was informed that they needed to rewrite this procedure ... and it was suggested to management that a decision tree should be added to the procedure," the EIR stated.
Flynn also cited Yung Shin Pharmaceutical because it had no product annual review procedure. According to the report, "the firm has been manufacturing [an undisclosed product] since March 1999 for the [undisclosed] market. According to management, they do not have a product annual review procedure."
The company replied that a new SOP for annual product reviews was approved on May 14, 2001. "The QA unit will evaluate thoroughly finished products in annual reviews, which include [a] trending table of all test items, yields, all changes carried out to the processes and all products which failed to meet established specifications," the EIR stated.
Further, the 483 stated that Yung Shin did not have an SOP for the calibration of a tool used to measure the containers and closures. "Management confirmed this deficiency," the EIR stated. "The firm has numerous [undisclosed] gauges that are used to measure the dimensions of containers/closures taken as part of release testing. The firm has one [undisclosed] gauge that they send out for yearly calibration."
Additionally, the investigator noted that for an accelerated stability study lot, analysis of the one, two, three and six-month samples were not done in a timely manner. For example, "[a lot] was released and placed on accelerated stability on approximately July 2, 1999. The samples were removed from stability at the designated times but were not tested until approximately nine months after manufacture on March 1, 2000," the EIR stated.
Yung Shin Pharmaceutical Industry, Tachia, Taiwan, 5/4-8/01, Doc. 109642M, $19 plus retrieval.
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