News about GMP/cGMP


FDA Warns OTC Drugmakers in China and Hong Kong, Drug Manufacturer in the US, Sends 483s to Aurobindo and Sun

The US Food and Drug Administration (FDA) released two warning letters sent to over-the-counter (OTC) drugmakers in China and Hong Kong and a third one to a drug manufacturer in the USA. In addition, two Form 483s for India-based Sun Pharmaceutical Industries and Aurobindo Pharma were released.


Zhejiang Ludao Technology

In a warning letter to TaizhouChina-based over-the-counter (OTC) drug manufacturer Zhejiang Ludao Technology Co., Ltd., FDA criticizes the company for data integrity and product testing issues.

FDA inspectors observed "Your firm lacks basic laboratory controls to prevent changes to paper and electronic records." The company admitted to creating certificates of analysis (COA) for four batches of OTC products before the products were manufactured.

Furthermore, FDA said, several computer files of the company's HPLC system were found in the recycle bin. The system did not have audit trail capabilities and the company could not explain why the files were deleted.

The FDA detained and tested samples from a batch of an OTC spray factured by Zhejiang Ludao that had almost twice the amount of active ingredient specified on the label. According to the FDA the company has agreed to reface its test methods to follow the corresponding USP monograph.

Nan San Pharmaceutical

In a warning letter to Hong Kong-based OTC drug manufacturer Nan San Pharmaceutical Factory Limited, FDA claims the company failed to perform adequate laboratory testing and distributed misbranded products to the US.

The company's facility in Kwun Tong Kowloon, Hong Kong was inspected in late September. As a reaction on the inspection findings, the firm was placed on import alert in January.

The FDA says, from 2013 to 2016, Nan San failed to perform microbial limit tests for each batch of one of its products.

"Instead, you performed microbial limit testing on one batch in 2013 and reported the same results to release subsequently-manufactured batches to the United States," FDA states.

The company is also accussed of setting expiration dates for some of its products without adequately assessing the products' stability characteristics.

Two of the company's OTC products, Musflex and Easy-Flex, showed wrong branded labels since they do not declare their active or inactive ingredients.

Philips Medical Systems Inc

At Philips Medical Systems (Cleveland) Inc, several Problems regarding Data integrity and failure management were found. FDA said that many failure codes were not even recognized or processed at all.


Form 483s

The Form 483 for Aurobindo Pharma Limited (India) involved nine observations from February 12-20, 2018 with FDA’s inspectors observing dirt build-ups and not cleaned equipment and utensils causing “potential safety, identity or quality impact on the drug product.”

It also was found that employees in the manufacture, processing and packing are missing training needed for their activities.

Another example for lack of cleanliness was the infestation of the manufacture, processing or packing buildings by rodents, insects and other vermin.

Issues with cleaning and maintenance are again noted in India-based Sun Pharmaceutical Industries’ Form 483 including three observations from a 12-day inspection from February 12-23, 2018.

The three observations can be summed up as follows:

  • Individual areas for securing cleanliness are insufficient for aseptic processing of drug products
  • Written procedures for the installation and maintaining of equipment are not followed for the intention of a risk reduction to product contact surfaces or process materials
  • Other written procedures for sufficient description of sampling, test, approval and rejection of drug product containers and closures are lacking.


FDA Warning Letters