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
President
EPCOT International
- US
FDA History Accessed May 10, 2017
- Malhotra, Girish: Can
the Review and Approval Process for ANDA at USFDA be Reduced from Ten
Months to Three Months? Accessed May 10, 2017
- Generic
Drug User Fee Act Reauthorization (GDUFA II) Accessed May 10, 2017
- Testimony
of Drs. Woodcock, Marks and Shuren Accessed
May 10, 2017
- Process Flow
Diagrams Accessed May 10, 2017
- Cotton
Processing Flowchart, Accessed May 10, 2017
- Abbreviated
New Drug Application (ANDA): Generics Accessed May 10, 2017
- New
Drug Application Accessed May 10, 2017