All opinions are my own.

Thursday, May 11, 2017

ANDA (Abbreviated New Drug Application) / NDA (New Drug Applications) Filing Simplification: Road Maps are a Must.

Excellence is expected from every task we humans do. Definition of excellence differs between humans. Due to lack of product quality consistency and excellence in pharmaceutical produced products, US FDA was created in 1906 (1). If we review the history of the US Food and Drug Administration its prime motive is to assure consistently excellent quality products (food, pharmaceuticals and cosmetics) that deliver the same performance all the time.  

Going fast forward, since I had not been involved in ANDA filings, I recently started to learn the task. I found it an extreme challenge. The process is cumbersome and even a priority approval takes time (2). I spent significant time to understand, determine and accumulate what all is needed to simplify a filing and create an ANDA application to have an approval in three months from the current expectation of ten months. FDA’s goal of approval in ten months from past practices would be a significant improvement (3, 4).  

Being a chemical engineer, I am trained to follow and communicate using a process flow diagram for the process at hand. Block process flow diagrams (5) are one of the way chemical engineers communicate information about the processes to their colleagues. Such process flow diagrams have been in use since 1840 (6).

Hoping to find a similar diagram for ANDA filings, I searched FDA websites. Yes I did find many documents that tell the readers what all is needed but I could not find a single document (showing a process flow diagram) that would tell me or anyone precisely what are the documents and information needed and their sequence. [If anyone knows existence of such road map at FDA site, please let me know.] There are lots of guidelines and guidances but during discussion with fellow professionals, I found they have different interpretation of requirements.

Simply said these documents (guidances) suggest that if five different companies were filing an ANDA for the same drug it is quite possible that none of the submissions would be exactly the same. I wonder how FDA staff will do if asked to file ANDA for a generic drug. FDA site has links that link to different documents but there are no simple flow diagrams (7). One can get lost in the maze. I would not be surprised if the number of pages in these guidances could exceed an ANDA filing application.

Since I could not find a flow chart for ANDA approval process, I thought a flow chart for New Drug Approval (NDA) (8) might exist. To my chagrin I was disappointed. Again, there were links.

The US FDA has done an excellent job in documenting and guiding what paper work is needed but I am afraid that paperwork as stated earlier can lead to personal interpretation of what all is needed and it most likely is the main cause of variations and inadequacies in filed applications and leads to delays in ANDA and NDA approvals.  

Best way to simplify the process, my perspective, would be to create/draw a road map that details each marker at every step of the way and nothing is left for interpretation. Each desired parameter has to be defined and even illustrated if need be. Simplicity is needed.

Process of filing approval for the Brand and Generic drugs is similar to any manufacturing or a service process. Every filer desires to produce a quality product (aka QbD “quality by desire”) filing. However, the current filing process can be labeled a QbA product “quality by analysis = aggravation” as it is based on individual interpretation of guidances and guidelines. I believe as stated earlier is the cause of delays and resubmissions.

I hope that once the road map for ANDA/NDA filing is created someone at USFDA will follow the road map and a file an application. Such filings should then be reviewed internally and the roadmap/ flow diagram tweaked to assure perfection. Such a process will define discrepancies and simplify the filing process. There could exceptions but in general the process will assist everyone. If done, it will lower the effort and costs related to filings. Another latent but a magnificent benefit will be that the companies will create an excellent document that is based on filers desire to create excellence. It will be a QbD (design/desire/diligence) document based on a quality by design process. I am confident that it will also assist companies to create repeatable and excellent processes that will produce quality product.

Girish Malhotra, PE
EPCOT International

  1. US FDA History Accessed May 10, 2017

  2. Malhotra, Girish: Can the Review and Approval Process for ANDA at USFDA be Reduced from Ten Months to Three Months? Accessed May 10, 2017

  3.  Generic Drug User Fee Act Reauthorization (GDUFA II) Accessed May 10, 2017

  4. Testimony of Drs. Woodcock, Marks and Shuren Accessed May 10, 2017

  5. Process Flow Diagrams Accessed May 10, 2017

  6. Cotton Processing Flowchart, Accessed May 10, 2017

  7. Abbreviated New Drug Application (ANDA): Generics Accessed May 10, 2017

  8. New Drug Application Accessed May 10, 2017