US FDA recently finalized “Guidance for Industry on Applications for Drugs with Inadequate Generic Competition” (1). and it tells us it is the same play with different buntings. This guidance/process is totally inadequate as it is mired in FDA’s current lethargic and controlling practices. It renames the existing ANDA approval process and suggests it will create competition. However, except for minor tweaks and window dressing it is no different from what has been and is the practice.
FDA has a unique opportunity to create a legacy, bring manufacturing jobs home and address national security issue dues to potential drug shortages. It can also at the same time let the companies innovate manufacturing technologies, lower manufacturing costs, improve profits and improve affordability. Unless a process of “nondestructive creation” outlined below is adopted and implemented, the new proposal is a useless exercise of no value. In the outlined proposal there will be challenges but compared to sending man to the moon, the process would be a cake walk. There is no financial relationship with any entity.
Following proposal/road map will not only create generic competition but also assure continued strategic drug supplies to the residents of United States. Under this scenario FDA has to grant or deny ANDA applications in 90 DAYS from the date of filing if they are properly filled and submitted (2,3). For this to come to fruition FDA has to create ANDA a simple filing process and environment. FDA would use the current fee structures for ANDA application filings and approvals.
For 90 day approvals to happen FDA has to tell the industry the exact information it needs so that the ANDA can be granted or denied in the allocated time. Application will be equivalent “process operating instructions” given to any applicant filing ANDA and if followed as designed, will result perfect application (quality product) that will be approved 90 days or less. With any filing applicant guarantees that is will produce quality products.
Such filing process will be equivalent to FDA writing operating instructions that any operator (company) can follow to create a perfect product (ANDA application). I equate this exercise to be QUALITY BY DESIGN operating instructions. If any applicant company decides to produce the API or formulate in the United States
US Government should give companies preferential ANDA approval time of 30 days vs. the proposed 90 days which includes inspection if they manufacture drugs in the United States. US has used such preferential treatments in the past (4).
Regulators and companies cannot have any meetings prior to filings to address/answer any questions. Once the application is filed no new additional information except for minor clarifications can be asked by the regulators.
Companies participating in this process have make sure that they will produce the quality product that has been approved by US FDA and follow FDA cGMP requirements on continued basis. If on random testing or inspection their products in US market does not meet quality specifications which they had committed to in their granted application, NO 483s will be issued and their production shut down for the next TWO years.
FDA’s filing instructions (operating instructions) that would be detailed but general enough to apply to every API and formulations application (5,6) . It will necessitate that FDA personnel preparing such instructions have complete understanding of API and formulation processes. Once such instructions are prepared they will have to be internally tested by FDA reviewers to make the application perfect. This would be equivalent to operators at a manufacturing site testing the operations instructions to see if they are able to produce expected quality product. If not, the processes would need to be repeated till they produce perfect quality product.
FDA’s filing instructions (operating instructions) that would be detailed but general enough to apply to every API and formulations application (5,6) . It will necessitate that FDA personnel preparing such instructions have complete understanding of API and formulation processes. Once such instructions are prepared they will have to be internally tested by FDA reviewers to make the application perfect. This would be equivalent to operators at a manufacturing site testing the operations instructions to see if they are able to produce expected quality product. If not, the processes would need to be repeated till they produce perfect quality product.
Following time table would be followed for ANDA submissions and their grant/denial.
Plant in USA
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Plant outside USA
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Day 1
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Application arrives at FDA
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Day 1
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Application arrives at FDA
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Day 7 from the filing date
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FDA informs the applicant company for completeness or asks for missing information or clarifications. If no additional information is needed the review process continues.
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Day 15 from the filing date
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FDA informs the applicant company for completeness or asks for missing information or clarifications. If no additional information is needed the review process continues.
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Day 15 from the filing date
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Company submits the needed information. Review process continues. Plant inspection is scheduled.
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Day 45 from the filing date
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Company submits the information. Review process continues. Plant inspection is scheduled.
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Day 30
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Company is granted or denied the ANDA application
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Day 90
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Company is granted or denied the ANDA application
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Girish Malhotra, PE
President
EPCOT International
2. 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 Accessed March 15, 2020
3. Malhotra, Girish: What Is Needed for a Regulatory Approval of NDA/ANDA Filings in 90 Days? Profitability through Simplicity,October 24, 2018 Accessed March 15, 2020
4. Coronavirus shows US needs to restore pharmaceutical production — in Puerto Rico, New York Post, March 7, 2020 Accessed March 16, 2020
5. Malhotra, Girish: What Is Needed for a Regulatory Approval of NDA/ANDA Filings in 90 Days?, Profitability through Simplicity, October 24, 2018
6. Malhotra, Girish: ONE PAGE Road Map to Reduce Drug Shortages, Assure Quality and Improve Affordability, Profitability through Simplicity, December 6, 2019
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