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M-23: Analysis of FDA Warning Letters (2013-2017) of Active Pharmaceutical Ingredients (APIs) Made in China and India

Poster Presenter

      Nahae Hannah Kim

      • Undergraduate Researcher
      • University of Southern California
        United States


The objective of the study was to identify areas of regulatory compliance challenges for manufacturers of active pharmaceutical ingredients (APIs) located in China or India; by analyzing warning letters issued by the United States Food and Drug Administration (FDA) during the past years (2013-2017).



FDA warning letters from 2013-2017 were retrieved from www.FDA.gov and identified by country of origin (China or India) and stratified by provinces/states. The contents of each warning letter were analyzed using a systematic approach and the quality elements categorized and ranked.


During 2013-2017, there were 23 companies from China and 19 companies from India that received warning letters from the FDA. Review of the documents identified seven general quality related categories: data integrity, problem resolution, cleanliness, systemic issues, verification, inspection, and storage and shipment. The "Data Integrity" category includes data alterations, inadequate maintenance of data, and lack of promptness in recording of data. The "Problem Resolution" category includes investigating out-of- specification (OOS) results and implementing CAPA. The "Cleanliness" category includes maintaining clean buildings and equipment. The "Systemic Issues" include having a quality unit and implementing quality management systems. The "Verification" category includes ensuring compliance with cGMP and adequately monitoring suppliers. The "Inspection" category includes providing information during inspection. The "Storage and Shipment" category includes API repackaging, relabeling, and holding operations. The southeast regions of China and southwest regions of India were issued the most warning letters with significant quality findings. In China, Zhejiang province had the highest warning letter count of five. This was followed by Shandong and Jiangsu provinces with three each. In Zhejiang, data integrity was the most common quality issue followed by both verification and problem resolution. In India, Maharashtra had the highest warning letter count of nine followed by Gujarat and Andhra Pradesh with four each. In Maharashtra, data integrity was the most common quality issue followed by both verification and problem resolution. The study found that there are overlapping quality issues of data integrity, verification and problem resolution across China and India.


In this era of globalization, approximately 80% of active pharmaceutical ingredients (APIs) used in U.S. are sourced abroad, from either China or India. A deeper understanding of the quality issues faced by the local manufacturers in these two countries may help to identify key areas that need improvement. According to the findings from this research, quality issues associated with APIs manufactured in China and India are most frequently observed in the category of data integrity. This would be of a great concern to companies looking to outsource manufacturing of their APIs in these countries. Further investigations into why the foreign manufacturers are having difficulties in this area would be important in identifying ways to intervene and minimize data integrity risks. Understanding common quality issues across the two countries will also allow companies and regulators to take action through better education, training, or guidance documents. Greater transparency and access to timely information from U.S. and foreign agency inspection findings are needed to help inform companies looking to manufacture their APIs abroad. But investigation into quality systems in China and India has been challenging. Companies typically do not publicly disclose countries of origin for APIs used in their products. Hence, it is difficult to take warning letter findings from the FDA website and search for corresponding actions taken by foreign agencies. The other agencies are less transparent with their inspection findings and language barriers limit the access of even available information to a broader audience. Sharing of inspection findings between US and foreign regulatory agencies and with the public would provide transparency, facilitate collaboration, and increase efficiency.