FDA Complete Response Letters, 2018–2025
Why the FDA Says No
When the FDA declines to approve a drug or biologic, it issues a Complete Response Letter detailing what fell short. This is an analysis of 202 such letters from 2018 to 2025, surfacing the deficiencies, therapeutic areas, and trends behind the agency's decisions to say no.
202
Total CRLs analyzed
2018–2025
Years covered
152 / 47
NDA vs BLA split
2024
Peak year (38 letters)
What goes wrong
Top deficiency categories
Across 202 letters, deficiencies cluster heavily. Labeling and Risk Management and Clinical Safety dominate, appearing in 96 to 99 percent of all documents and accounting for the bulk of every issue the FDA raises.
Highlighted in amber: the two categories that appear in nearly every letter.
Where it happens
Therapeutic areas
Infectious Disease draws the most Complete Response Letters by a wide margin, followed by Oncology. Together they reflect both the volume of submissions and the regulatory scrutiny these areas attract.
Over time
Year over year
CRL volume climbed steadily and peaked in 2024 with 38 letters, split here into NDA (drug) and BLA (biologic) applications. The 2025 figure is partial and reflects only part of the year.
Go deeper
Explore the letters
Filter the individual letters by year and application type. Sentiment is a normalized tone score (higher is less negative); word count reflects each letter's length.
Type
Showing 169 of 169 letters
| App # | Year | Type | Top deficiency | Top area | Sentiment | Words |
|---|---|---|---|---|---|---|
| 213976 | 2024 | NDA | Labeling Risk Management | Immunology | 0.075 | 2,327 |
| 211321 | 2019 | NDA | Manufacturing CMC | Unspecified | -0.045 | 1,406 |
| 761184 | 2023 | BLA | Labeling Risk Management | Endocrine/Metabolic | 0.022 | 1,263 |
| 761315 | 2025 | BLA | Manufacturing CMC | Endocrine/Metabolic | 0.069 | 6,418 |
| 213931 | 2024 | NDA | Labeling Risk Management | Cardiovascular | 0.024 | 1,913 |
| 207987 | 2018 | NDA | Labeling Risk Management | Cardiovascular | 0.065 | 1,698 |
| 210852 | 2024 | NDA | Labeling Risk Management | Oncology | 0.052 | 5,851 |
| 215064 | 2024 | NDA | Labeling Risk Management | Immunology | 0.059 | 1,000 |
| 761164 | 2022 | BLA | Labeling Risk Management | Unspecified | 0.044 | 1,023 |
| 206966 | 2020 | NDA | Labeling Risk Management | Unspecified | 0.033 | 1,142 |
| 204803 | 2022 | NDA | Clinical Safety | Central Nervous System | 0.169 | 1,635 |
| 761126 | 2025 | BLA | Labeling Risk Management | Oncology | 0.098 | 4,466 |
| 205394 | 2023 | NDA | Labeling Risk Management | Unspecified | 0.026 | 3,235 |
| 210895 | 2019 | NDA | Labeling Risk Management | Unspecified | 0.083 | 727 |
| 205920 | 2018 | NDA | Labeling Risk Management | Respiratory | 0.102 | 4,137 |
| 761166 | 2021 | BLA | Clinical Safety | Unspecified | 0.092 | 1,275 |
| 761066 | 2019 | BLA | Labeling Risk Management | Respiratory | 0.039 | 1,548 |
| 213426 | 2022 | NDA | Labeling Risk Management | Endocrine/Metabolic | 0.087 | 1,871 |
| 216482 | 2024 | NDA | Labeling Risk Management | Immunology | 0.067 | 1,181 |
| 212156 | 2021 | NDA | Labeling Risk Management | Unspecified | 0.077 | 1,444 |
| 202158 | 2018 | NDA | Labeling Risk Management | Unspecified | 0.141 | 1,724 |
| 761180 | 2022 | BLA | Clinical Safety | Immunology | 0.031 | 436 |
| 208564 | 2018 | NDA | Labeling Risk Management | Oncology | 0.086 | 1,965 |
| 210282 | 2022 | NDA | Labeling Risk Management | Infectious Disease | 0.039 | 943 |
| 209529 | 2020 | NDA | Labeling Risk Management | Unspecified | 0.118 | 1,641 |
| 209988 | 2023 | NDA | Labeling Risk Management | Infectious Disease | 0.151 | 11,257 |
| 215092 | 2022 | NDA | Labeling Risk Management | Unspecified | 0.147 | 1,664 |
| 761258 | 2025 | BLA | Labeling Risk Management | Oncology | 0.093 | 1,484 |
| 215212 | 2024 | NDA | Labeling Risk Management | Unspecified | 0.043 | 1,481 |
| 761039 | 2018 | BLA | Labeling Risk Management | Oncology | 0.035 | 1,623 |
| 212905 | 2024 | NDA | Labeling Risk Management | Immunology | 0.050 | 3,567 |
| 208193 | 2019 | NDA | Labeling Risk Management | Unspecified | 0.071 | 2,185 |
| 209510 | 2020 | NDA | Clinical Safety | Unspecified | 0.032 | 2,307 |
| 208042 | 2018 | NDA | Labeling Risk Management | Unspecified | 0.033 | 1,210 |
| 215559 | 2023 | NDA | Clinical Safety | Unspecified | 0.062 | 3,143 |
| 214429 | 2021 | NDA | Labeling Risk Management | Unspecified | 0.071 | 1,105 |
| 211746 | 2023 | NDA | Labeling Risk Management | Respiratory | 0.078 | 1,137 |
| 761133 | 2024 | BLA | Labeling Risk Management | Infectious Disease | 0.108 | 2,512 |
| 217347 | 2024 | NDA | Labeling Risk Management | Immunology | 0.117 | 1,319 |
| 214439 | 2022 | NDA | Clinical Safety | Unspecified | 0.055 | 985 |
| 215040 | 2024 | NDA | Labeling Risk Management | Immunology | 0.036 | 1,570 |
| 212849 | 2024 | NDA | Labeling Risk Management | Unspecified | 0.124 | 4,099 |
| 206968 | 2023 | NDA | Labeling Risk Management | Respiratory | 0.095 | 6,831 |
| 214697 | 2025 | NDA | Labeling Risk Management | Immunology | 0.094 | 1,990 |
| 214952 | 2024 | NDA | Labeling Risk Management | Unspecified | 0.040 | 2,244 |
| 201110 | 2020 | NDA | Clinical Safety | Infectious Disease | 0.042 | 3,463 |
| 208288 | 2018 | NDA | Clinical Safety | Infectious Disease | 0.072 | 4,085 |
| 761355 | 2024 | BLA | Regulatory Compliance | Unspecified | 0.043 | 661 |
| 761081 | 2019 | BLA | Labeling Risk Management | Oncology | 0.080 | 3,426 |
| 202408 | 2019 | NDA | Labeling Risk Management | Infectious Disease | 0.047 | 3,144 |
| 212937 | 2023 | NDA | Clinical Safety | Oncology | 0.039 | 1,548 |
| 211988 | 2022 | NDA | Labeling Risk Management | Respiratory | 0.102 | 2,573 |
| 761275 | 2024 | BLA | Labeling Risk Management | Immunology | 0.051 | 1,131 |
| 214581 | 2022 | NDA | Clinical Safety | Immunology | 0.044 | 767 |
| 216490 | 2024 | NDA | Clinical Safety | Unspecified | 0.048 | 1,408 |
| 215320 | 2024 | NDA | Labeling Risk Management | Unspecified | 0.155 | 1,759 |
| 210526 | 2022 | NDA | Labeling Risk Management | Unspecified | 0.052 | 1,901 |
| 761084 | 2022 | BLA | Labeling Risk Management | Infectious Disease | 0.122 | 1,951 |
| 209354 | 2019 | NDA | Labeling Risk Management | Unspecified | 0.101 | 1,203 |
| 213953 | 2022 | NDA | Labeling Risk Management | Unspecified | 0.085 | 1,528 |
| 210864 | 2021 | NDA | Labeling Risk Management | Unspecified | -0.033 | 3,361 |
| 210605 | 2020 | NDA | Labeling Risk Management | Endocrine/Metabolic | 0.056 | 5,183 |
| 213895 | 2022 | NDA | Labeling Risk Management | Unspecified | 0.054 | 897 |
| 208232 | 2020 | NDA | Labeling Risk Management | Endocrine/Metabolic | 0.025 | 1,348 |
| 206610 | 2021 | NDA | Labeling Risk Management | Unspecified | 0.082 | 5,086 |
| 761088 | 2018 | BLA | Labeling Risk Management | Oncology | 0.109 | 2,422 |
| 761161 | 2023 | BLA | Labeling Risk Management | Unspecified | 0.104 | 1,907 |
| 212854 | 2022 | NDA | Clinical Safety | Unspecified | 0.062 | 4,122 |
| 210583 | 2020 | NDA | Labeling Risk Management | Unspecified | 0.054 | 3,967 |
| 209471 | 2024 | NDA | Labeling Risk Management | Unspecified | 0.036 | 3,167 |
| 761297 | 2025 | BLA | Labeling Risk Management | Unspecified | 0.075 | 1,249 |
| 212304 | 2022 | NDA | Labeling Risk Management | Unspecified | 0.011 | 1,287 |
| 207962 | 2018 | NDA | Regulatory Compliance | Unspecified | 0.146 | 3,935 |
| 210274 | 2023 | NDA | Labeling Risk Management | Infectious Disease | 0.062 | 3,489 |
| 209575 | 2020 | NDA | Labeling Risk Management | Unspecified | 0.115 | 1,416 |
| 214375 | 2023 | NDA | Labeling Risk Management | Unspecified | 0.037 | 1,449 |
| 216962 | 2025 | NDA | Labeling Risk Management | Unspecified | 0.051 | 3,479 |
| 213586 | 2024 | NDA | Labeling Risk Management | Central Nervous System | 0.083 | 1,691 |
| 761248 | 2024 | BLA | Labeling Risk Management | Unspecified | 0.039 | 1,386 |
| 761279 | 2023 | BLA | Clinical Safety | Immunology | 0.022 | 728 |
| 212501 | 2021 | NDA | Labeling Risk Management | Oncology | 0.045 | 2,019 |
| 206927 | 2019 | NDA | Labeling Risk Management | Oncology | 0.030 | 2,308 |
| 210063 | 2019 | NDA | Labeling Risk Management | Oncology | 0.038 | 1,841 |
| 214522 | 2023 | NDA | Regulatory Compliance | Unspecified | 0.069 | 353 |
| 210875 | 2020 | NDA | Clinical Safety | Central Nervous System | 0.080 | 2,311 |
| 217202 | 2024 | NDA | Labeling Risk Management | Oncology | 0.060 | 1,416 |
| 209388 | 2021 | NDA | Clinical Safety | Unspecified | 0.013 | 1,593 |
| 761240 | 2023 | BLA | Labeling Risk Management | Infectious Disease | 0.056 | 1,657 |
| 212122 | 2021 | NDA | Labeling Risk Management | Respiratory | 0.047 | 814 |
| 208276 | 2018 | NDA | Labeling Risk Management | Cardiovascular | 0.184 | 2,505 |
| 204017 | 2020 | NDA | Clinical Safety | Unspecified | 0.092 | 5,660 |
| 212045 | 2021 | NDA | Labeling Risk Management | Unspecified | 0.007 | 3,250 |
| 211039 | 2020 | NDA | Manufacturing CMC | Unspecified | 0.068 | 507 |
| 215000 | 2022 | NDA | Labeling Risk Management | Unspecified | 0.023 | 951 |
| 761082 | 2022 | BLA | Labeling Risk Management | Infectious Disease | 0.085 | 10,420 |
| 761365 | 2024 | BLA | Labeling Risk Management | Unspecified | 0.034 | 954 |
| 761085 | 2019 | BLA | Labeling Risk Management | Infectious Disease | 0.055 | 1,494 |
| 204957 | 2021 | NDA | Labeling Risk Management | Unspecified | 0.043 | 3,027 |
| 209511 | 2021 | NDA | Clinical Safety | Unspecified | 0.142 | 1,607 |
| 211302 | 2020 | NDA | Labeling Risk Management | Unspecified | 0.036 | 1,056 |
| 215352 | 2023 | NDA | Labeling Risk Management | Unspecified | 0.080 | 620 |
| 761198 | 2024 | BLA | Labeling Risk Management | Oncology | 0.106 | 1,699 |
| 211566 | 2024 | NDA | Labeling Risk Management | Endocrine/Metabolic | 0.044 | 1,741 |
| 210933 | 2021 | NDA | Manufacturing CMC | Unspecified | -0.031 | 56 |
| 761225 | 2024 | BLA | Labeling Risk Management | Immunology | 0.071 | 1,458 |
| 210730 | 2020 | NDA | Labeling Risk Management | Unspecified | 0.056 | 2,359 |
| 213135 | 2020 | NDA | Labeling Risk Management | Unspecified | 0.037 | 1,021 |
| 210136 | 2024 | NDA | Labeling Risk Management | Oncology | 0.071 | 7,765 |
| 208419 | 2021 | NDA | Labeling Risk Management | Oncology | 0.050 | 2,368 |
| 215344 | 2024 | NDA | Labeling Risk Management | Immunology | 0.057 | 1,171 |
| 208313 | 2018 | NDA | Clinical Safety | Oncology | 0.044 | 1,451 |
| 214520 | 2023 | NDA | Labeling Risk Management | Unspecified | 0.051 | 2,752 |
| 761183 | 2023 | BLA | Labeling Risk Management | Endocrine/Metabolic | 0.094 | 1,902 |
| 761192 | 2023 | BLA | Labeling Risk Management | Immunology | 0.061 | 1,569 |
| 761151 | 2023 | BLA | Clinical Safety | Immunology | 0.030 | 841 |
| 214927 | 2024 | NDA | Labeling Risk Management | Endocrine/Metabolic | 0.016 | 3,643 |
| 213478 | 2022 | NDA | Labeling Risk Management | Immunology | 0.042 | 1,006 |
| 208969 | 2023 | NDA | Labeling Risk Management | Respiratory | 0.044 | 987 |
| 761219 | 2023 | BLA | Labeling Risk Management | Immunology | 0.058 | 2,102 |
| 209311 | 2018 | NDA | Labeling Risk Management | Unspecified | 0.099 | 1,226 |
| 214860 | 2023 | NDA | Labeling Risk Management | Unspecified | 0.047 | 1,506 |
| 211970 | 2019 | NDA | Clinical Safety | Infectious Disease | -0.042 | 4,371 |
| 214012 | 2022 | NDA | Clinical Safety | Unspecified | 0.069 | 1,019 |
| 211964 | 2021 | NDA | Labeling Risk Management | Unspecified | 0.130 | 859 |
| 213218 | 2022 | NDA | Labeling Risk Management | Unspecified | -0.011 | 723 |
| 202860 | 2019 | NDA | Labeling Risk Management | Cardiovascular | 0.049 | 5,140 |
| 216686 | 2023 | NDA | Labeling Risk Management | Immunology | 0.070 | 1,114 |
| 213260 | 2023 | NDA | Labeling Risk Management | Endocrine/Metabolic | 0.083 | 1,085 |
| 201848 | 2024 | NDA | Labeling Risk Management | Oncology | 0.025 | 4,456 |
| 761148 | 2022 | BLA | Labeling Risk Management | Unspecified | 0.041 | 1,042 |
| 215151 | 2024 | NDA | Labeling Risk Management | Immunology | 0.033 | 851 |
| 215192 | 2024 | NDA | Labeling Risk Management | Central Nervous System | 0.125 | 2,278 |
| 213645 | 2022 | NDA | Labeling Risk Management | Infectious Disease | 0.128 | 1,431 |
| 202049 | 2021 | NDA | Clinical Safety | Respiratory | 0.067 | 2,126 |
| 213972 | 2024 | NDA | Labeling Risk Management | Infectious Disease | 0.049 | 1,774 |
| 213593 | 2023 | NDA | Labeling Risk Management | Immunology | 0.014 | 1,895 |
| 206185 | 2018 | NDA | Labeling Risk Management | Infectious Disease | 0.040 | 2,931 |
| 213072 | 2021 | NDA | Clinical Safety | Endocrine/Metabolic | 0.026 | 1,328 |
| 761306 | 2024 | BLA | Labeling Risk Management | Unspecified | 0.061 | 1,038 |
| 761073 | 2019 | BLA | Labeling Risk Management | Oncology | 0.037 | 1,187 |
| 761127 | 2022 | BLA | Labeling Risk Management | Immunology | 0.048 | 1,035 |
| 214324 | 2022 | NDA | Labeling Risk Management | Unspecified | 0.043 | 1,109 |
| 209191 | 2018 | NDA | Labeling Risk Management | Oncology | 0.040 | 2,901 |
| 761062 | 2019 | BLA | Clinical Safety | Cardiovascular | 0.050 | 1,296 |
| 211363 | 2023 | NDA | Clinical Safety | Cardiovascular | 0.060 | 916 |
| 215179 | 2024 | NDA | Labeling Risk Management | Oncology | 0.032 | 2,022 |
| 210821 | 2019 | NDA | Labeling Risk Management | Unspecified | 0.133 | 644 |
| 208352 | 2020 | NDA | Labeling Risk Management | Respiratory | 0.040 | 2,485 |
| 206976 | 2018 | NDA | Labeling Risk Management | Unspecified | 0.047 | 1,015 |
| 214759 | 2025 | NDA | Labeling Risk Management | Unspecified | 0.053 | 1,354 |
| 211413 | 2024 | NDA | Clinical Safety | Infectious Disease | 0.074 | 3,795 |
| 761045 | 2019 | BLA | Labeling Risk Management | Oncology | 0.150 | 1,827 |
| 761343 | 2024 | BLA | Labeling Risk Management | Immunology | 0.060 | 1,336 |
| 210649 | 2019 | NDA | Labeling Risk Management | Infectious Disease | 0.061 | 1,270 |
| 209863 | 2019 | NDA | Labeling Risk Management | Cardiovascular | 0.057 | 1,634 |
| 214628 | 2022 | NDA | Labeling Risk Management | Unspecified | 0.050 | 922 |
| 218772 | 2025 | NDA | Labeling Risk Management | Unspecified | 0.048 | 893 |
| 204311 | 2024 | NDA | Labeling Risk Management | Infectious Disease | 0.046 | 2,752 |
| 215721 | 2024 | NDA | Labeling Risk Management | Unspecified | 0.039 | 1,034 |
| 206089 | 2019 | NDA | Labeling Risk Management | Cardiovascular | 0.047 | 4,991 |
| 761115 | 2020 | BLA | Labeling Risk Management | Oncology | 0.107 | 2,357 |
| 210735 | 2022 | NDA | Labeling Risk Management | Oncology | 0.060 | 2,816 |
| 761299 | 2024 | BLA | Labeling Risk Management | Immunology | 0.074 | 1,875 |
| 208742 | 2018 | NDA | Labeling Risk Management | Infectious Disease | 0.093 | 1,868 |
| 208647 | 2018 | NDA | Labeling Risk Management | Unspecified | 0.024 | 902 |
| 211950 | 2022 | NDA | Manufacturing CMC | Unspecified | 0.072 | 957 |
| 214273 | 2023 | NDA | Labeling Risk Management | Unspecified | 0.076 | 1,220 |
| 761091 | 2018 | BLA | Clinical Safety | Oncology | 0.049 | 760 |
| 200655 | 2019 | NDA | Clinical Safety | Central Nervous System | 0.076 | 4,226 |