Dive Brief:
- The Food and Drug Administration has issued warning letters to two over-the-counter (OTC) drugmakers in China: Zhejiang Ludao Technology Co., Ltd. and Nan San Pharmaceutical Factory Ltd in Hong Kong. In both cases, the FDA found the companies' responses to previously identified facility problems inadequate.
- Although addressed to two separate companies, the warning letters to both plants cite similar violations of current good manufacturing practice (cGMP) regulations.
- The expectation going forward is that both firms launch a corrective action plan to address gaps in analytical tests for purity, stability, and potency, and FDA suggested to both firms that they hire a consultant to bring the facilities up to appropriate standards.
Dive Insight:
Two over-the-counter drugmakers from China were hit with FDA warnings from CDER's Office of Manufacturing Quality within the last two months, and they represent the first notices this year to be issued to companies making OTC drugs.
OTC drugmakers in particular will be a renewed target for the agency's manufacturing standards division, according to In-PharmaTechnologist.
That focus already seems to be borne out by the numbers. In 2017, 22 companies that market OTC products were cited for cGMP-related infractions through an FDA warning letter. Thirteen of those 22 companies are located in Asia and seven are specifically situated in China.
This means that 37% (22 of a total of 60 letters) of the warning letters issued in 2017 by the Office of Manufacturing Quality targeted companies that make OTC medications.
At the Zhejiang Ludao plant, data integrity issues and violations of cGMP abounded. Although the firm responded to the inspection and promised to improve its record-keeping protocol, the regulatory agency found the firm's response insufficient overall.
FDA wrote the firm also failed to test the active pharmaceutical ingredient it sourced from a third-party supplier. FDA asked the firm to provide details about lot release and identity testing from all supplier partners and provide identity testing results retrospectively as far back as Sept. 2017.
One of the most notable citations was one for creating certificates of analysis (COA) for four batches of a spray medication prior to them being manufactured and tested. Stability testing was also found to be inadequate, and batches acquired and tested by FDA from Sept. 2016 were "super-potent": one batch had two times the amount of API than was claimed on the spray's label.
For Nan San Pharmaceutical, the warning letter followed a Form 483 the agency issued on November 14, 2017.
According to the regulator, the company did not perform required batch release testing for its topical liquid analgesics, and no validation studies were performed on batches.
Nan San was also found to have inadequately performed stability testing, which impacts the expiration dates listed on their OTC products, such as one called Easy-Flex pain relieving lotion. FDA noticed that data on microbial limit testing for some products were actually collected in 2013, but were used for batches produced in 2016.