Resubmission of NDA/BLA After CRL: Class 1 versus Class 2 resubmission

If new drug application (NDA) or biological license application (BLA) is not approved by the FDA, the sponsor will receive a complete response letter (CRL). FDA's CRL letter will state something like "the application could not be approved at this time based on [issues and deficiencies]". Receiving a CRL is not the end of the world and the sponsor can address the issues and deficiencies and resubmit the NDA/BLA. Many NDA/BLAs were approved after the resubmission. 

It may take the sponsor months/years to address the issues and deficiencies before NDA/BLA can be resubmitted. However, once the NDA/BLA is resubmitted, the time leading to the PDUFA date is predicable. FDA's policy is to classify the resubmission into one of two classes: class 1 and class 2. 

Resubmission was discussed in 21 CFR Part 314.110 "Complete response letter to the applicant":  

FDA has a MAPP (Manual of Policies and Procedures) specifically about the classification of the NDA/BLA resubmission "Classifying Resubmissions of Original NDAs, BLAs, and Efficacy Supplements in Response to Complete Response Letters". The MAPP listed the items qualifying for class 1 and 2 resubmission.

The review time leading to the PDUFA date is 4 months longer for Class 2 than Class 1 resubmission. Four months seem to be short, but sometimes can be critical if there are competitive NDA/BLA submissions in the same therapeutic area. This is why there is a priority review designation and a priority review voucher program - both will shorten the FDA review time by 4 months. 

Here is an example of resubmission with Class 1 category and an example of resubmission with Class 2 category:

LIPOCINE ANNOUNCES ITS PARTNER RECEIVED FDA ACCEPTANCE OF NDA RESUBMISSION FOR TLANDO® 

"...announcing that the U.S. Food and Drug Administration (“FDA”) has accepted its New Drug Application (“NDA”) resubmission for TLANDO® (testosterone undecanoate). The FDA designated the NDA as a Class 1 resubmission with a two-month review goal period and set a target action date of March 28, 2022, under the Prescription Drug User Fee Act (PDUFA). Lipocine licensed the exclusive U.S. rights for TLANDO® to Antares Pharma."

Ardelyx Announces FDA Acceptance and Six-Month Review for Resubmission of its New Drug Application of XPHOZAH® (tenapanor)

"...the U.S. Food and Drug Administration (FDA) has accepted its resubmission of a New Drug Application (NDA) for XPHOZAH® (tenapanor) for the control of serum phosphate in adult patients with chronic kidney disease on dialysis who have had an inadequate response or intolerance to a phosphate binder therapy. The FDA has determined that the NDA is a class 2 review, which results in a six-month review period from the date of resubmission...."