Technical reasons for delay and denial of regulatory approval of Initial applications for (Abbreviated) New Drugs filed by Indian Companies by USFDA, 2005-2022

Abstract

Indian pharmaceutical companies are one of the leading sources of generic medicine to the United States. The US Food and Drug Administration (US FDA) conduct regular inspections and assessments of manufacturing facilities in order to confer product quality and to ensure a firm's compliance with applicable laws and regulations, such as the Food, Drug and Cosmetic Act and related Acts. Identified regulatory violations and noncompliance are notified by US FDA to the manufacturer in the form of 483s and warning letter. Warning letters led to the unfavourable consequences to the company such as loss of trust, reputation and affects their financial stability.  A trend analysis of warning letters may help Indian pharmaceutical manufacturing companies to adopt cGMP practices as per the requirement of US FDA and thus will result in reduced number and frequency of warning letters. Therefore, a trend analysis of warning letters issued to Indian Pharmaceutical sector between 2005 till 2022 by US FDA was carried out by extracting the information from publicly available FDA archives and dashboard. There is an increasing trend in number of US FDA inspections in India post 2012 which could be due to the new regulations, updated laws, also the changed expectations and mindset of FDA inspectors. The FDA major findings included inadequate investigations systems, lack of authoritative quality units, product contamination and inadequate documentation practices. The study reported here enlists the expectations of US FDA from Indian Pharmaceutical sector. This will help Indian pharmaceutical manufacturers to adopt the strategies to minimize US FDA warning letters.