CDER’s FY 2021 Report on the State of Pharmaceutical Quality (Part 1)

September 7, 2022By Mark I. Schwartz

Last month FDA published its 4th annual report on the state of pharmaceutical quality and, needless to say, there were some interesting statistics, particularly for us FDA nerds.

Number of Manufacturing Sites and Registered Products

The report states that for fiscal year 2021, there were 4,451 CDER drug manufacturing sites, which is a 3% increase over fiscal year 2018, the only comparison year provided.  39% of these manufacturing sites are what is referred to as “no application” sites, meaning that the products manufactured there are without an approved FDA application, which includes over-the-counter (OTC)  products, unapproved prescription drug products and homeopathic products.  The remaining 61% of the sites manufacture at least one application product, meaning either a product resulting from a Biologics License Application (BLA), a New Drug Application (NDA), or an Abbreviated New Drug Application (ANDA).

The countries with the five most manufacturing sites, namely, the United States, India, China, Germany and Canada, all saw net increases in the number of manufacturing sites in inventory over the past three years.

For fiscal year 2021, CDER oversaw 12,428 ANDAs, 3,537 NDAs and 315 BLAs. CDER also oversaw more than 140,000 non-application products, including 75,300 OTC products, and 15,640 homeopathic products.  Presumably the balance of non-application products are unapproved prescription drug products, though that was not specified in the report.

Quality Surveillance with Foreign Regulatory Authority Inspection Reports and Record Requests

Given the problems with performing on-site inspections during COVID over the last year, alternative inspection tools were used by FDA to a greater degree during fiscal years 2021, including review of foreign regulatory authority inspection reports and records requests of the facility at issue.  During fiscal year 2021, FDA reviewed and classified 139 site inspections in 18 Mutual Recognition Agreement (MRA) countries, as we as six other countries.  The latter point about six other countries is particularly interesting because FDA does not appear to have previously acknowledged accepting for review and classification site inspections from non MRA countries.  In addition, during the same period FDA conducted 288 surveillance-based assessments using information from section 704(a)(4)(A) (record review) requests, which resulted in 21 import alerts.

Product Quality Defect Reports

The so-called product quality defect (PQD) reports includes Field Alert Reports (FARs), Biological Product Deviation Reports (BPDRs), MedWatch Reports (MWs) and Consumer Complaints (CCs). During fiscal year 2021, CDER received  4,115 FARs, 205 BPDRs, 11,512 quality related MWs and 273 CCs, which appear to be similar to the number of such product quality defects reported in fiscal year 2020.  According to FDA, in the coming years, the CARES Act will enable FDA to normalize product quality defect reports by the amount of each product manufactured, thereby allowing for a more thorough evaluation of the impact and magnitude of PQDs.

Import Alerts and Recalls

During fiscal year 2021, FDA placed 49 sites on import alert for, among other things, non-compliant laboratory testing, non-compliant findings from inspections, refusing inspections, and refusing 704(a)(4)(A) records requests.  The largest number of import alerts were from sites in China and Latin America, the latter owing to the large number of facilities that manufactured hand sanitizer that were detained at the border.

For the second consecutive year, the total number of recalls increased, from a near historic low in fiscal year 2019 of around 300 (my estimate, based on a review of figure 3 in the report), to around 700 in fiscal year 2020 and around 800 in fiscal year 2021 (the report doesn’t provide precise numbers).  In addition, the number of Class I recalls appears to have nearly doubled in fiscal year 2021 from the prior year, due in large measure to the recalls associated with hand sanitizer products that contained methanol, and the sunscreen products that contained benzene.

In my next blog post, I will summarize FDA’s views from the report on their research into the general state of quality in the pharmaceutical industry, as well as detail the agency’s progress with respect to two initiatives, the New Inspection Protocol Project (NIPP), and the Quality Management Maturity Project (QMM). So stay tuned!