A US Food and Drug Administration inspection completed on Dec. 9, 2010 revealed persistent deficiencies at McNeil Consumer Healthcare’s Fort Washington, Pennsylvania, facility. In a letter to Hakan Erdemir, the company’s vice-president of operations, FDA agents cited problems with complaint handling, process monitoring, and investigations. McNeil Consumer Healthcare is a subsidiary of Johnson & Johnson (J&J, New Brunswick, NJ).
In the letter, inspectors stated that employees at the facility did not adequately follow procedures for handling written or oral complaints related to drug products. For example, complaints about recalled Tylenol that contained reports of stomach pain, diarrhea, or vomiting were labeled “Uncategorized Adverse Event,” but complaints against the same product that contained reports of gastrointestinal illness were categorized as “Digestive/Gastrointestinal.”
According to inspectors, many patients had complained that lots of cherry and grape flavors of Benadryl Children’s FastMelt tablets did not dissolve in children’s mouths. None of McNeil’s complaint investigations, however, addressed the quality information in the out-of-specification (OOS) investigations for content uniformity.
Inspectors also noted that complaint investigations did not always include all relevant quality information available in the investigation system. For example, in February 2010, McNeil staff and an outside contractor detected a haloanisole taint odor in the Fort Washington warehouse. No investigations of off-odor complaints referred to the appropriate quality information, however. As of the inspection report, the lots in question had been distributed to commercial market and had not been recalled.
In addition, the facility had not established control procedures to monitor and validate manufacturing processes that may cause variability in the characteristics of in-process materials and drug products, according to the letter. For example, a particular validation protocol did not explain the scientific rationale for choosing certain parameters, such as target speed, or how they would be monitored. Also, a process-validation report did not discuss hold-time studies to ensure that the final blend maintained uniformity and did not segregate.
Inspectors also observed deficiencies in the plant’s investigations. Personnel failed to review unexplained discrepancies and batches’ failures to meet specifications, whether or not the batches had been distributed already, according to the letter. In addition, the plant continued to produce grape and cherry flavored Benadryl FastMelt tablets after obtaining OOS results without conducting complete investigations. Also, investigations did not include a review of complaint, adverse-event, or lack-of-effect reports received for these products, according to inspectors.
Agents also stated that the plant did not maintain records to enable annual data reviews that would help evaluate the quality standards of each drug product to determine the need for changes in specifications, manufacturing, or control procedures. For example, when certain batches of Sudafed Cold and Cough Caplets were found to be out of trend, the quality-control unit did not initiate investigations as required.
In related news, a Pennsylvania judge found that J&J had failed to report accurate wholesale prices to the state. Commonwealth Court Judge Robin Simpson ordered J&J to repay $45,283,562 to the state’s Medicaid and Pharmaceutical Assistance Contract for the Elderly programs. The judge also ordered the company to pay $6,567,000 in civil penalties, raising J&J’s total liability to nearly $52 million in damages and civil penalties.
In 2004, Pennsylvania’s attorney general sued J&J and several of its subsidiaries for allegedly manipulating the average wholesale price (AWP), a pricing benchmark. The attorney general alleged that J&J had inflated AWP above the true average of wholesale prices to increase drug sales and profits. Government benefit programs, such as Medicaid, reimburse pharmacies for branded drugs using a formula that includes AWP.
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