China's Zhuhai United Laboratories bills itself as the world's largest manufacturer of the API for the antibiotic amoxicillin. But the sterile manufacturing for some of its amoxicillin products has been called into question by inspectors in Europe, which is banning the sterile drugs for now, except in limited cases.
According to the European Medicines Agency, in April, inspectors from Romania were in a United plant in Guangdong, China, where they found issues with aseptic manufacturing facilities design, equipment, operations, environmental monitoring and media fill validation. The inspectors said that United's quality assurance operation didn't pick up these problems, leaving them to surmise QA there was "weak and inappropriately implemented."
The EMA has withdrawn the company certificate for selling amoxicillin sodium sterile, potassium clavulanate sterile and amoxicillin sodium and potassium clavulanate sterile mix that it says is sold in Romania, France and the U.K. It said it would give the company a revised certificate for nonsterile products and for "sterile critical medicinal products" for the three countries.
It is the second Chinese API maker that Europe has taken action against this year. In March, it banned products from Huzhou Sunflower Pharmaceutical's plant in Huzhou, Zhejiang Province. That action came after an inspection of the iodine maker by French regulators turned up contamination issues in its manufacturing processes, issues with its purified water system and a piece of testing equipment that may have been put in the facility just for show.
China is the global leader in API production, and it is this kind of weak internal operations as well Chinese government oversight of drugmakers there that has worried Western regulators like the FDA. The FDA intends to more than double its presence in China, expanding the office of 13 to 34, but has been frustrated by Chinese officials who have held up visas for new inspectors. That leaves it having to spend extra money to pay the travel costs of sending inspectors from the U.S. or other countries where they are based.
Problems laid out in a warning letter the agency posted in April for API maker Yunnan Hande Bio-Tech are indicative of issues that it finds with some Chinese drugmakers. The warning letter, its second since 2010, said that during an inspection at its site in Yunnan province, an employee acknowledged altering testing data on an API batch and then using results from that batch to validate product previously manufactured.
- access the EMA notice here