We Read 445 FDA Rejection Letters. Most Are About the Factory.

FDA began publishing Complete Response Letters in 2025. As of the 13 August 2026 update there are 445 of them in the openFDA transparency API, issued between 2002 and 2026.

We parsed the full text of all 445 letters, not just the metadata.

In 236 of 445 letters (53%), FDA raised a manufacturing problem and no clinical deficiency at all. Only 42 letters (9%) were the reverse.

How we counted, and why it matters

Every CRL is organized under FDA's own ALL-CAPS section headings: FACILITY INSPECTIONS, PRODUCT QUALITY, CLINICAL, NONCLINICAL. We extracted those headings from each letter rather than searching the text for keywords.

We did it that way because most of a CRL is boilerplate, and keyword matching on this corpus produces nonsense. Search for "labeling" and you will find it in 99% of letters, and conclude that labeling is the great unsolved problem in drug development. It is not. It is a standard paragraph.

Here is how often each heading appears:

The first five are near-universal. SAFETY UPDATE is a standing request to include a safety update when you resubmit. PROPRIETARY NAME and CARTON AND CONTAINER LABELING are procedural. OTHER is the closing section about the one-year clock.

The headings that do not appear every time are the ones that say why an application failed.

Manufacturing versus clinical deficiencies

We grouped the bolded headings with their variants: FACILITIES counts as a facility inspection; PRODUCT QUALITY MICROBIOLOGY and MICROBIOLOGY count as product quality; CLINICAL/STATISTICAL, CLINICAL PHARMACOLOGY and similar headings count as clinical. That is why these counts run higher than the single-heading counts above.

96 letters (22%) carry no substantive deficiency heading at all. Those are applications held up on labeling, naming or procedural grounds.

This corroborates The FDA Group's analysis of 89 letters, which found 56% with facility issues and 41% with product quality problems. Our numbers come from a sample five times larger and from FDA's own section headings rather than a reading of the prose, and they land in the same place.

If your CRL cites a facility, it will not tell you what is wrong

Facility sections are almost entirely formulaic. Here is one in full, from a 2018 letter to AB Pharmaceuticals:

During a recent inspection of the Macleods Pharmaceuticals Limited (FEI # 3007517881) manufacturing facility for this NDA, our field investigator observed objectionable conditions at the facility and conveyed that information to the representative of the facility at the close of the inspection. Satisfactory resolution of the observations is required before this NDA may be approved.

And a 2016 letter to Salamandra, LLC:

During a recent inspection of Sun Pharmaceutical Industries Limited, Halol-Baroda 389350, Gujarat, India, our field investigator conveyed deficiencies to the representative of the facility. Satisfactory resolution of these deficiencies is required before this application may be approved.

Neither says what the deficiencies were. They were conveyed at the close of the inspection, which means they are in the Form 483, not in the CRL.

If you are responding to a facility CRL, work from the 483, not the letter. You need it from the site, which is often a contract manufacturer you do not control. If you are reading a competitor's CRL to learn what went wrong at their plant, the letter will not tell you.

A trap in the approval status field

Every record carries an approval_status field. Aggregating it produces a dramatic result that isn't real:

Read naively, first-cycle outcomes collapsed after 2023. They did not. The two release batches were selected on opposite criteria: the earlier release covered CRLs for products that went on to be approved, the later one products still unapproved. That split measures FDA's publication policy, not industry performance.

Any "percentage of CRLs that end in approval" drawn from this dataset measures publication policy, not approval rates.

Other corpus statistics

The 445 letters went to 311 companies, and 79 companies appear more than once. Accord Healthcare leads with six; Tanvex BioPharma, Eli Lilly, Fresenius Kabi and Regeneron have five each. Large, experienced sponsors get CRLs too.

The corpus has 328 NDAs and 103 BLAs, so biologics are 23%. The median letter is about 8,700 characters and the longest is over 45,000. 438 of the 445 carry a company_rep, the sponsor's named regulatory contact.

Caveats

The texts are OCR'd from scanned PDFs and the quality varies. Redactions appear as artifacts, so facility names and FEI numbers are sometimes unreadable. Our heading extraction found at least one heading in 438 of 445 letters; the remaining seven are OCR casualties.

This is also not a random sample of CRLs. It is the set FDA has chosen to publish, and as the table above shows, that choice was not neutral. Everything here describes the published corpus, not the population.

Using the corpus

In this corpus, a first-cycle rejection is more often a manufacturing problem than a clinical one. Manufacturing is also the part of a program most often run by someone else. If a contract manufacturer makes your product, its inspection history is part of your application.

The more practical use is to read the letters your own review division has issued for products like yours. A CRL states, in the division's own words, what it found insufficient. Before 2025 those letters were not public.

For the mechanics, see our glossary entry on Complete Response Letters: what a CRL is, the three options that follow one, the one-year clock, and Class 1 versus Class 2 resubmissions.