In a groundbreaking move for regulatory transparency, the FDA released 89 Complete Response Letters (CRLs) for products that failed to gain approval, offering public access to documents previously shared only with the applicant companies.
This marks a significant milestone in FDA transparency, providing the pharmaceutical industry and the public with unprecedented insight into regulatory decision-making.
Key Findings at a Glance
The dataset reveals several important patterns across 89 CRLs spanning 66 companies. Accord BioPharma Inc. and Accord Healthcare Inc. lead with 5 letters each, suggesting persistent regulatory challenges for these applicants.
The breakdown shows 31 Biologics License Applications (BLA) and 58 New Drug Applications (NDA), representing 77 unique application numbers. Some applications received multiple rejection letters over time—for instance, BLA761147 has three response letters dated April 5, 2024, October 29, 2024, and August 5, 2025, illustrating the iterative nature of the approval process.
Primary Rejection Reasons
Analysis of the CRLs reveals three dominant categories of issues:
- Facility inspection concerns (51 letters)
- Product quality issues (44 letters)
- Clinical issues (31 letters)
These findings underscore that regulatory approval hinges not just on clinical efficacy, but equally on manufacturing quality and facility compliance—areas where companies can proactively invest to improve their approval odds.
What This Means for the Industry
This transparency initiative provides invaluable learning opportunities for pharmaceutical companies. By studying common rejection patterns, applicants can better prepare submissions and address potential issues before they become deal-breakers. The data suggest that robust manufacturing quality systems and thorough facility preparation are just as critical as strong clinical data for regulatory success.
The FDA's commitment to real-time CRL publication represents a fundamental shift toward openness that should benefit the entire pharmaceutical ecosystem through shared learning and improved submission quality.
The complete dataset with application details and letter URLs is available in the table below for further analysis.
| Status | Application Number | Applicant Name | Letter Date | Letter URL |
|---|---|---|---|---|
| Unapproved | NDA 217294 | SQ Innovation, Inc. | 01/12/24 | CRL_NDA217294_20240112.pdf |
| Unapproved | NDA 215291 | BendaRx USA Corporation | 01/17/24 | CRL_NDA215291_20240117.pdf |
| Unapproved | NDA 218258 | Hikma Pharmaceuticals USA Inc. | 01/23/24 | CRL_NDA218258_20240123.pdf |
| Unapproved | NDA 218528 | AFT Pharmaceuticals Ltd | 01/25/24 | CRL_NDA218528_20240125.pdf |
| Unapproved | NDA 214315 | Defender Pharmaceuticals, Inc | 01/25/24 | CRL_NDA214315_20240125.pdf |
| Unapproved | NDA 218470 | Accord Healthcare Inc. | 01/30/24 | CRL_NDA218470_20240130.pdf |
| Unapproved | NDA 217556 | Venatorx Pharmaceuticals, Inc. | 02/22/24 | CRL_NDA217556_20240222.pdf |
| Unapproved | NDA 217002 | Minerva Neurosciences, Inc | 02/26/24 | CRL_NDA217002_20240226.pdf |
| Unapproved | NDA 215749 | Accord Healthcare Inc. | 03/07/24 | CRL_NDA215749_20240307.pdf |
| Unapproved | NDA 218223 | Mapi Pharma Ltd. | 03/08/24 | CRL_NDA218223_20240308.pdf |
| Unapproved | NDA 210168 | Cipla USA, Inc. | 03/22/24 | CRL_NDA210168_20240322.pdf |
| Unapproved | BLA 761303/Original 2 | Regeneron Pharmaceuticals, Inc. | 03/22/24 | CRL_BLA761303Original2_20240322.pdf |
| Unapproved | BLA 761303/Original 1 | Regeneron Pharmaceuticals, Inc. | 03/22/24 | CRL_BLA761303Original1_20240322.pdf |
| Unapproved | BLA 761357 | Gan & Lee Pharmaceuticals | 03/26/24 | CRL_BLA761357_20240326.pdf |
| Unapproved | NDA 218408 | Baxter Healthcare Corporation | 03/27/24 | CRL_NDA218408_20240327.pdf |
| Unapproved | NDA 218224 | Baxter Healthcare Corporation | 03/29/24 | CRL_NDA218524_20240329.pdf |
| Unapproved | BLA 761147 | Accord BioPharma Inc. | 04/05/24 | CRL_BLA761147_20240405.pdf |
| Unapproved | BLA 761356 | Gan & Lee Pharmaceuticals | 04/12/24 | CRL_BLA761356_20240412.pdf |
| Unapproved | NDA 218762 | Accord Healthcare Inc. | 04/17/24 | CRL_NDA218762_20240417.pdf |
| Unapproved | BLA 761376 | Dr. Reddy’s Laboratories SA | 04/19/24 | CRL_BLA761376_20240419.pdf |
| Unapproved | BLA 761187 | Xbrane Biopharma AB | 04/19/24 | CRL_BLA761187_20240419.pdf |
| Unapproved | NDA 216987 | Accord Healthcare Inc. | 05/10/24 | CRL_NDA216987_20240510.pdf |
| Unapproved | NDA 216586 | Elevar Therapeutics, Inc. | 05/16/24 | CRL_NDA216586_20240516.pdf |
| Unapproved | BLA 761308 | Jiangsu Hengrui Pharmaceuticals Co., Ltd | 05/16/24 | CRL_BLA761308_20240516.pdf |
| Unapproved | NDA 218317 | NeuroDerm, Ltd. | 05/24/24 | CRL_NDA218317_20240524.pdf |
| Unapproved | NDA 218698 | XTM Consulting LLC | 06/12/24 | CRL_NDA218698_20240612.pdf |
| Unapproved | NDA 218506 | Bayer HealthCare LLC | 06/13/24 | CRL_NDA218506_20240613.pdf |
| Unapproved | NDA 217379 | Nanocopoeia, LLC | 06/14/24 | CRL_NDA217379_20240614.pdf |
| Unapproved | BLA 125806 | Rocket Pharmaceuticals, Inc. | 06/14/24 | CRL_BLA125806_20240614.pdf |
| Unapproved | BLA 761366 | Daiichi Sankyo, Inc. | 06/26/24 | CRL_BLA761366_20240626.pdf |
| Unapproved | BLA 761377 | CELLTRION, Inc. | 06/27/24 | CRL_BLA761377_20240627.pdf |
| Unapproved | NDA 218345 | Amneal EU, Limited | 07/01/24 | CRL_NDA218345_20240701.pdf |
| Unapproved | BLA 761326 | Novo Nordisk Inc. | 07/10/24 | CRL_BLA761326_20240710.pdf |
| Unapproved | NDA 215029 | MEDRx USA, Inc. | 07/11/24 | CRL_NDA215029_20240711.pdf |
| Unapproved | NDA 217433 | Orexo AB | 07/15/24 | CRL_NDA217433_20240715.pdf |
| Unapproved | NDA 216195 | Xspray Pharma AB | 07/25/24 | CRL_NDA216195_20240725.pdf |
| Unapproved | NDA 217338 | RB Health (US) LLC | 07/26/24 | CRL_NDA217338_20240726.pdf |
| Unapproved | NDA 215455 | Lykos Therapeutics | 08/08/24 | CRL_NDA215455_20240808.pdf |
| Unapproved | NDA 218026 | Antares Pharma, Inc. | 08/16/24 | CRL_NDA218026_20240816.pdf |
| Unapproved | NDA 217724/Original 1; NDA 217724 | Zealand Pharma US, Inc. | 10/08/24 | CRL_NDA217724_20241008.pdf |
| Unapproved | NDA 218923 | Conjupro Biotherapeutics Inc. | 10/10/24 | CRL_NDA218923_20241010.pdf |
| Unapproved | NDA 219045 | Hikma Pharmaceuticals USA Inc. | 10/21/24 | CRL_NDA219045_20241021.pdf |
| Unapproved | NDA 218600 | Bridge Regulatory Affairs, LLC | 10/21/24 | CRL_NDA218600_20241021.pdf |
| Unapproved | NDA 215644 | Sun Pharmaceutical Industries Limited | 10/25/24 | CRL_NDA215644_20241025.pdf |
| Unapproved | BLA 761147 | Accord BioPharma Inc. | 10/29/24 | CRL_BLA761147_20241029.pdf |
| Unapproved | BLA 761212 | Lupin Limited (Biotech Division) | 11/14/24 | CRL_BLA761212_20241114.pdf |
| Unapproved | NDA 219195 | Applied Therapeutics, Inc. | 11/27/24 | CRL_NDA219195_20241127.pdf |
| Unapproved | NDA 218762 | Accord Healthcare Inc. | 12/05/24 | CRL_NDA218762_20241205.pdf |
| Unapproved | BLA 761271 | Sandoz Inc. | 12/05/24 | CRL_BLA761271_20241205.pdf |
| Unapproved | NDA 214610 | Fresenius Kabi USA, LLC | 12/11/24 | CRL_NDA214610_20241211.pdf |
| Unapproved | NDA 212271 | Meitheal Pharmaceuticals Inc. | 12/11/24 | CRL_NDA212271_20241211.pdf |
| Unapproved | BLA 761433 | Janssen Biotech, Inc. | 12/13/24 | CRL_BLA761433_20241213.pdf |
| Unapproved | NDA 218828 | Zealand Pharma US, Inc. | 12/19/24 | CRL_NDA218828_20241219.pdf |
| Unapproved | NDA 210934 | Lexicon Pharmaceuticals, Inc. | 12/20/24 | CRL_NDA210934_20241220.pdf |
| Unapproved | NDA 219357 | Hikma Pharmaceuticals USA Inc. | 12/23/24 | CRL_NDA219357_20241223.pdf |
| Unapproved | NDA 218879 | OWP Pharmaceuticals, Inc. | 01/03/25 | CRL_NDA218879_20250103.pdf |
| Unapproved | BLA 761266 | Tanvex BioPharma USA, Inc. | 01/03/25 | CRL_BLA761266_20250103.pdf |
| Unapproved | BLA 125745 | Atara Biotherapeutics, Inc. | 01/15/25 | CRL_BLA125745_20250115.pdf |
| Unapproved | NDA 219112 | Hospira, Inc. | 01/17/25 | CRL_NDA219112_20250117.pdf |
| Unapproved | BLA 761290 | SFJ Pharmaceuticals, Inc. | 01/31/25 | CRL_BLA761290_20250131.pdf |
| Unapproved | NDA 217719 | Laurus Generics, Inc. | 03/10/25 | CRL_NDA217719_20250310.pdf |
| Unapproved | BLA 761393 | Seikagaku Corporation | 03/11/25 | CRL_BLA761393_20250311.pdf |
| Unapproved | BLA 761424 | Accord BioPharma Inc. | 03/13/25 | CRL_BLA761424_20250313.pdf |
| Unapproved | NDA 216586 | Elevar Therapeutics, Inc. | 03/20/25 | CRL_NDA216586_20250320.pdf |
| Unapproved | BLA 761308 | Jiangsu Hengrui Pharmaceuticals Co., Ltd | 03/20/25 | CRL_BLA761308_20250320.pdf |
| Unapproved | BLA 761377 | CELLTRION, Inc. | 03/26/25 | CRL_BLA761377_20250326.pdf |
| Unapproved | NDA 218571 | Milestone Pharmaceuticals USA, Inc. | 03/27/25 | CRL_NDA218571_20250327.pdf |
| Unapproved | NDA 218345 | Amneal EU, Limited | 04/02/25 | CRL_NDA218345_20250402.pdf |
| Unapproved | NDA 216442 | Aldeyra Therapeutics, Inc. | 04/02/25 | CRL_NDA216442_20250402.pdf |
| Unapproved | NDA 218592 | Telix Pharmaceuticals (US) Inc. | 04/25/25 | CRL_NDA218592_20250425.pdf |
| Unapproved | NDA 218353 | University of California San Francisco | 04/25/25 | CRL_NDA218353_20250425.pdf |
| Unapproved | NDA 215818 | Fresenius Kabi USA, LLC | 04/25/25 | CRL_NDA215818_20250425.pdf |
| Unapproved | NDA 215244 | Stealth BioTherapeutics Inc. | 05/15/25 | CRL_NDA215244_20250515.pdf |
| Unapproved | NDA 219029 | Chemo Research, S.L. | 05/29/25 | CRL_NDA219029_20250529.pdf |
| Unapproved | NDA 217382 | ResQ Pharma | 06/02/25 | CRL_NDA217382_20250602.pdf |
| Unapproved | NDA 210168 | Cipla USA, Inc. | 06/20/25 | CRL_NDA210168_20250620.pdf |
| Unapproved | NDA 215644 | Sun Pharmaceutical Industries Limited | 06/25/25 | CRL_NDA215644_20250625.pdf |
| Unapproved | BLA 761027 | Accord BioPharma Inc. | 06/26/25 | CRL_BLA761027_20250626.pdf |
| Unapproved | NDA 218607 | Unicycive Therapeutics Inc. | 06/27/25 | CRL_NDA218607_20250627.pdf |
| Unapproved | BLA 125845 | Ultragenyx Pharmaceutical Inc. | 07/07/25 | CRL_BLA125845_20250707.pdf |
| Unapproved | BLA 125842 | Capricor, Inc. | 07/09/25 | CRL_BLA125842_20250709.pdf |
| Unapproved | BLA 125827 | Replimune, Inc. | 07/21/25 | CRL_BLA125827_20250721.pdf |
| Unapproved | NDA 205508 | Heritage Pharmaceuticals Inc. d/b/a/ Avet Pharmaceuticals Inc. | 07/28/25 | CRL_NDA205508_20250728.pdf |
| Unapproved | NDA 218923 | Conjupro Biotherapeutics Inc. | 07/30/25 | CRL_NDA218923_20250730.pdf |
| Unapproved | BLA 761385 | Teva Pharmaceuticals, Inc. | 07/30/25 | CRL_BLA761385_20250730.pdf |
| Unapproved | BLA 761303 | Regeneron Pharmaceuticals, Inc. | 07/30/25 | CRL_BLA761303_20250730.pdf |
| Unapproved | BLA 761147 | Accord BioPharma Inc. | 08/05/25 | CRL_BLA761147_20250805.pdf |
| Unapproved | BLA 761211 | Immedica Pharma AB | 08/06/25 | CRL_BLA761211_20250806.pdf |
| Unapproved | NDA 220049 | PTC Therapeutics, Inc. | 08/18/25 | CRL_NDA220049_20250818.pdf |