Home page

Wednesday, October 24, 2018

What Is Needed for a Regulatory Approval of NDA/ANDA Filings in 90 Days?

Approving pharmaceutical manufacturing NDA/ANDA [New Drug Application/Abbreviated New Drug Application] applications at FDA in three months could be considered a Herculean task for the application filer (company) and the regulators (FDA) and it would be. But, what if, it could be done. If achievable, we would see significant changes on the pharmaceutical landscape (1). Monies would be saved in dealing with regulatory affairs, would reduce the time to market. That would mean higher revenues and profits for the brand and the generic companies. It could also lead to increased competition and potentially improve drug affordability though lower costs. There would be challenges to create and incorporate such a modified filing and approval process but the benefits achieved should outweigh them.  

The existing process of NDA/ANDA filing and approval is cumbersome and a challenge for the regulated and the regulators. I have not been involved but just reviewing the documents, what is expected and needs to be done, the process is cumbersome. I have to admit that I got lost in acronyms (alphabet soup), numbers e.g. xxx (w) (a) etc. and the legal jargon. No disrespect for the creators of the jargon, this alphabet soup gave me indigestion. 

I am sure there is process to accomplish approval in ninety days. For it to happen a precise roadmap (2)has to be created and it has to be so good that it can be followed even with eyes closed.  

Expectations from the Road Map and What would be Expected from the Regulators and the Regulated:

Putting my process development, manufacturing and management hats simultaneously I am proposing a process that would have to be developed by the regulators (FDA) and the companies for their NDA/ANDA approval. I consider filing an NDA/ANDA filing equivalent to a manufacturing process that has to be followed precisely by both sides to create a quality product (3), an approved NDA/ANDA filing. 

Regulators based on their years of experience will write down precise step by step recipe that has to be followed by the NDA/ANDA filing company to get their approval in the slated time. I need to emphasize that if the regulators (FDA) precisely define their expectations, the process will be smooth. There will be no doubts about the expectations in the mind of the filers. Again, information asked has to be precise and cover every detail of type of manufacturing, synthesis as well as formulation, process. It is not going to be easy and can only come from chemists, chemical engineers and other engineering disciplines who have developed, designed, commercialized and reviewed such processes and products from head to toe day in and day out.

Yes, the companies might take their own time to file, their own choice, but the expected information has to be such that there is no finger pointing suggesting “we did not know what was expected”. If companies fulfill and deliver the information as expected and every deliverable is there, company should get their approval/disapproval decision in ninety days or less. That would be a huge win for all involved. There could be some back and forth but it would be minimal and the ninety-day clock, from the day the filing was submitted, will keep ticking. i.e. no stoppage. 

I would call regulator’s road map a quality by design recipe for a perfect process created by the regulators that the filing company will follow. If for some reason the regulator’s (FDA) recipe, the defined road map, cannot be followed or understood by the company, the application process will go from Quality by Design (QbD) to Quality by Analysis, aggravation, (QbA) and that means delays and added costs.  

Once the regulators have defined their needs to approve a filing, chemists and chemical engineers at the companies have to understand the questions and deliver the answers through their submissions. Both entities will have to understand each other’s paper conversation about every process. Only their dialog will produce repeatable quality product through the asked questions and the delivered answers. If this happens, the review process will go smoothly and time reduction mission will be accomplished. 

Companies submitting information will have to have an absolute command and knowledge of their processes and will have to present information so that it will convince the regulatory examiner/s that the product is going to follow every claimed expectation and regulation that has been laid out. In short product will be of consistent and repeatable quality. If this happens I envision that the approval process in the long run will be simpler and quicker than the current process.

Examiners at the regulatory bodies will have to understand the conversed information. In some instances clarification and or additional information might be needed. My expectation is that with time such cases might be few and far in between and the expended time would be significantly less than the present process. 

What would the Showstoppers say or think? 

There will be many who will be apprehensive of the suggested process. Their perspective would be mis-information could be submitted to get fast approval. Yes that is possible but the regulators have a recourse of barring or shutting down such rouge operations. That privilege will have to be used if the current legal system stands in the way. 

I am conjecturing that for the success of this proposal regulators will draw a precise map of what they need to have from the filers. It is going to easier said than done. Regulatory staff will have to be envision and document from their past experiences what all they need for a first-time complete submission. We have to recognize that it can be done but no one is going to welcome a voluminous dissertation. 

Let’s assume that every possible information FDA or any other regulatory body asks/needs for the approval is submitted to the utmost correctness the first time and the regulator have no questions. Would the regulators accept such an application without any apprehension and approve the filing in the 90 days or sooner from the first day of filing? I am sure that there will be doubters on both sides. It will take time to accept this process as it is outside the comfort zone of filers and the regulators.  

We have to accept that will not have a perfect road map from the get go. To get to the perfect stage, I am envisioning there will be lot of obstacles from the legal and consulting firms and even the manufacturing companies. Pilot program might have to be developed by the regulators and tested and over tested. Naysayers and doubters will have their days. However, if successful pharma’s landscape will change. I believe the best minds can create a process that is much simpler than what is being followed. 

I don’t have every “t” crossed and “i” dotted for the proposed process. I may sound repeating myself at times.  Objective here is to use the proposed process to build a system that will expedite the approval process. As stated earlier results will be higher revenue for the brand and the generic companies through speedier introduction of new therapies and out of patent generics, additional competition, possibly lower drug prices and inclusion of better technologies after the products are commercial. Process of continuous improvement would be included more than ever. 

We have an opportunity to play outside the box. It could be a hip-hip hurray moment. 

Girish Malhotra. PE
EPCOT International

1.     Malhotra, Girish: Can the Review and Approval Process for ANDA at USFDA be Reduced from Ten Months to Three Months? Profitability through Simplicity, March 25, 2017

2.     Malhotra, Girish:ANDA (Abbreviated New Drug Application) / NDA (New Drug Applications) Filing Simplification: Road Maps are a Must. Profitability through Simplicity, May 11, 2017

3.     Juran, Joseph M., Juran on Quality by Design, Simon and Schuster, ISBN 9780029166833, May 1992

No comments:

Post a Comment