Tiger Balm External Analgesic Firm Scratched Again On US GMP Violations
Executive Summary
Inspection in February and March found GMP violations including failing to thoroughly investigate unexplained batch discrepancies or failures, regardless of whether it already is distributed, are repeats from 2010 problems FDA found at Haw Par Healthcare.
The Singapore manufacturer of Tiger Balm external analgesics hasn't improved its manufacturing quality-control compliance since it was warned by the US Food and Drug Administration nearly 10 years ago.
Haw Par Healthcare Ltd. also is distributing Tiger Balm Liniment products as misbranded OTC drugs due to noncompliance with the FDA's requirements for warnings about certain ingredients, according to a 19 August warning letter submitted by the offices of manufacturing quality and compliance in the agency's Center for Drug Evaluation and Research.
An inspection in February and March found drug good manufacturing practices violations including failing to thoroughly investigate unexplained discrepancies or failures of a production batch or any of its components to meet specifications, regardless of whether a batch already is distributed, CDER stated.
The firm invalidated out-of-specification test results for assay for an active pharmaceutical ingredient in multiple batches without scientific justification. It also didn't adequately investigate a customer complaint about lack of efficacy and failed to test the returned sample to confirm the amount of active ingredient in the product.
US FDA says GMP violations could render Haw Par's tiger balm liniment products ineffective or contaminated.
"During your initial investigation you determined adequate raw material mixing had not occurred. Even though all sub lots of drug product were made using API from a deficient mixing process, you only rejected portions of the drug product batches that were found to be OOS," according to the letter published 3 September.
In a second laboratory deficiency, Haw Par, which distributes its products in the US through its Tiger Balm US subsidiary, completed forced degradation studies for its OTC drug but didn't use the data to scientifically establish stability acceptance criteria.
It also has equipment problems that trip its GMP compliance. Its computer systems for controlling its analytical instrumentation do not have audit trail capabilities, including gas chromatography instruments for drug product stability analyses and Fourier transform infrared spectroscopy and ultraviolet spectroscopy instruments for raw-material release testing.
Additionally, Haw Par's system to add materials needed to manufacture its product is inadequately designed and could foster development of biofilms and lead to contamination of its manufacturing. Its practice of flushing the system at manufacturing sampling points before sample collection for analysis is not consistent with those points' use in production, potentially causing inaccurate microbial results.
As an OTC drug, Tiger Balm Liniment is misbranded because labeling omits a warning required for drug preparations that contain significant 5% or higher proportions of wintergreen oil, a methyl salicylate of which contains 28%. Labeling must specifically warn that use other than as directed may be dangerous and the article should be kept out of reach of children to prevent accidental poisoning.
In addition to recommending Haw Par hire a consultant to guide its GMP remediations, the FDA asked it for a lengthy list of information including a retrospective review of all invalidated OOS – in-process and release testing for raw materials and finished drug products – results obtained for products in the US and within expiry/retest date.
The agency also asks for drug product specifications established for monitoring impurities; a comprehensive independent review of its entire data system and investigation into the inadequacies in data, records and reporting; and a detailed risk assessment addressing the potential effects of system failures on the quality of all drug product lots currently in U.S. distribution and within expiry.
Similar problems were found in an 2010 inspection at Haw Par's plant in Singapore. The FDA's warning letter that followed the inspection detailed problems including inadequate specificity tests in the method validation reports because they have “not been shown to be capable of detecting potential impurities.” It also failed to investigate unexplained batch failures failed to take representative samples of each shipment of each lot of components for testing. (Also see "Latest FDA Warning Letters Highlight Aseptic Processing Issues" - Pink Sheet, 1 Oct, 2010.)
More recently, Tiger Balm US in 2016 conducted its “Roar Back” national ad campaign of print, digital and videos to encourage athletes and consumers alike to recover from pain faster by using Tiger Balm products. (Also see "Industry Roundup: DXM Bill Moves, CHPA Biz Dev VP, Neurobrands Injunction" - HBW Insight, 25 Apr, 2016.)