Recently, the CDER warning letter issuance skyrocketed from 70 in FY2014 to 128 in FY2018, an increase of 83%. What types of firms are taking the heat? And where are they located?

Here we answer these questions and more with a review of CDER warning letter trends in regard to facility type, including:

  • Year-over-year analysis since 2014
  • Trends in foreign enforcement
  • Overview of over-the-counter (OTC) manufacturing facilities
  • And an overview of pharmaceutical manufacturing facilities

CDER Issuance by Facility

Taking totals from 2014 to 2018*, CDER warning letters comprised of:

  • 41% pharmaceutical manufacturing facilities
  • 34% compounding pharmacies
  • 13% OTC manufacturers
  • 7% GCP
  • 5% unapproved drugs and others

*Please note that this article uses fiscal year data rather than calendar year.


As seen in Figure 1, this increase in CDER warning letters is primarily made up of warning letters issued to OTC and compounding pharmacies. Although OTC warning letters only account for 14% of the five year total, the past two years have seen a surge with them contributing to a third of the CDER warning letters issued in 2018.

OTC Manufacturer Issuance

In 2016 there were six warning letters issued to OTC manufacturers; in 2018 there were 45, amassing a 650% increase within three years and showing a drastic expansion into foreign markets (see Figure 2).

73% of 2018’s OTC warning letters were issued to three countries: U.S., China, and South Korea.


China is a major factor in this increase of OTC enforcement. After two years of no OTC warning letters, FDA began shifting focus with 16% of warning letters attributed to those facilities in 2017.

In 2018, there was a 256% increase year-over-year with OTC manufacturers receiving 57% of warning letters and pharmaceutical manufacturers receiving 43% (see Figure 3).

While China may be receiving more attention in this area, it should be noted that FDA focus on OTC manufacturers within the U.S. continues, as we see a steady increase year-over-year in warning letter issuance.

[NOTE: Don’t forget the data. Download your own copy of this report here.]

Pharmaceutical Manufacturer Issuance

As seen in both Figures 3 and 4, the countries receiving the majority of pharmaceutical warning letters are the U.S., India, and China.


From 2017 to 2018, the U.S. saw a 75% decrease in issuance here, as well as a 39% decrease in overall issuance. Taking into account that issuance to OTC manufacturers tripled in this same timeframe, we can assume a clear recent adjustment of focus from the FDA.


There is a significant increase in CDER warning letters since 2014. Based on this data, we are likely to see the following in 2019:

  • OTC enforcement will continue to be a focus for FDA.
  • Asia Pacific will continue to see attention from the FDA. Out of the nine CDER warning letters that have been issued to facilities since January 1, 2019, five have been issued to facilities in APAC countries: four in India, and one in China.
  • Refocusing of staff and resources will continue to have an effect on other areas of enforcement.
  • The decline in warning letters to pharmaceutical manufacturers does not necessarily indicate more compliance; rather it shows that the FDA is refocusing their efforts and resources.