FDA Warning Letter to API Drug Manufacturer in China

The U.S. Food & Drug Administration has sent a Warning Letter to a manufacturer of active pharmaceutical ingredients (APIs) in China for violations of current good manufacturing practices (cGMPs).

The increased globalization of the pharmaceutical industry means that a finished pharmaceutical obtained by a consume at their local pharmacy can have components manufactured in a number of different countries and the finished dosage form manufactured in another country altogether. Problems with heparin and other drugs manufactured abroad have raised imported drug safety high on the list of FDA’s public health concerns.

FDA imports, drug safety, API

Over 90% of active pharmaceutical ingredients (APIs) used in U.S. drug products are imported

The FDA Warning Letter, dated January 28, 2010, does not indicate if the inspection was initiated by one of the new FDA resident posts in China that have been opened to enhance food safety, drug safety, and the safety of medical devices.

On Tuesday, November 18, 2008 The U.S. Department of Health and Human Services issued a press release that stated:

“FDA has selected eight senior experienced FDA officials to work in its offices in China. The employees are inspectors and senior technical experts in foods, medicines and medical devices. The HHS/FDA office in Beijing will be located in the US Embassy. In Guangzhou, it will be located in the U.S. Consulate General, and in Shanghai it will be part of the U.S. consular mission there, but will be situated in the Shanghai Centre, a well-established business complex in the city where several other U.S. government agencies have staff.”

The FDA Warning Letter has serious concerns regarding the testing for the APIs stating:

“For example, your quality control unit failed to detect that IR spectra were being substituted by a laboratory employee and therefore, misrepresenting the actual results of the tested incoming material. Your response is inadequate in that it does not address the ability of your quality unit to control and detect the manipulation or alteration of laboratory documents.”

Here’s the Warning Letter:


These are serious charges and are a cause for concern by any consumer using drug products. Since 2008 FDA has also issued Warning Letters to a Japanese firm and another Chinese facility for drug safety and failure to follow cGMPs for active pharmaceutical ingredients. This indicates a continuing concern over the quality of APIs. Over 90% of APIs used in drugs in the United States are manufactured abroad. Opening resident posts in China, India, and other countries is part of the effort to ensure their safety.

GxP Perspective:

Regulating APIs is not an easy task. The FDA GMP regulations are for Finished Pharmaceuticals. You will note that most FDA Warning Letters cite FDA regulations found in Title 21 of the Code of Regulations (21 CFR). Warning Letters for APIs however, cite the Food, Drug, and Cosmetic Act and the U.S. Code (U.S.C.). In 2000, when I joined the FDA Foreign Inspection Cadre, FDA headquarters staff actively recruited new API inspectors from the foreign cadre because so few API inspections took place in the United States. When I went to API API Warning Letter FDAschool we were taught to use the International Conference on Harmonization document Q7A as an inspection tool as a replacement for the 1991 “Bulk Pharmaceutical Chemicals” inspection guide. The API Compliance Program Guidance Manual for APIs was issued in 2006 and incorporates Q7A. This is a great step forward, just as the establishment of foreign resident posts improves FDA’s ability to monitor the production of APIs.

I conducted API inspections in Canada, France, Ireland, and the U.S. They are not an easy inspection and should be conducted by specialists. Fortunately I had the opportunity to work with a really great chemist, and that made my job a lot easier.

With the globalization of drug, device, and food manufacturing we want the best inspections possible. Ultimately that will mean increased cooperation and coordination with other regulatory agencies. That is one area that definitely needs improvement. It seems the current FDA leadership senses the need to improve international cooperation. They’ve got a big job in front of them.


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2 Responses to FDA Warning Letter to API Drug Manufacturer in China

  1. […] View original post here:  FDA Warning Letter Sent to Chinese Drug Manufacturer Citing Drug … […]

  2. sid olufs says:

    thank you for spreading the word on this, Carl. It would be good if we had answers to your questions.

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