Indian pharmaceutical industry, which has been facing the heat from the US Food and Drug Administration (US FDA) over the last few years in the form of warning letters and import bans, is finally showing gradual progress in regulatory compliance. Though the industry is still not out of the woods from the US FDA regulatory standpoint, data shows there has been an improvement in inspection outcomes and are now more in line with the global trend. In 2018, India had 174 inspections by US FDA or 14 percent of the total inspection conducted by the US drug regulator around the globe. According to US FDA data, out of 174 inspections in 2018 only 4 percent inspections have been classified as Official Action Indicated (OAI), attracting agency’s regulatory and administrative action such as withholding new approvals, warning letters and import alerts, in contrast to 15 percent in 2017. Around 91 fell under Voluntary Action Indicated (VAI), and the rest were No Action Indicated (NAI). For all US FDA inspections, the OAI stood at 4.31 percent.
US FDA classifies its inspection based on the observations noted during the inspection into three baskets, OAI for plants found in an unacceptable state of compliance with regard to current good manufacturing practice (CGMP), Voluntary Action Indicated (VAI) wherein US FDA finds objectionable conditions, but these issues are not considered to be of regulatory significance and NAI means the agency hasn’t found any objectionable conditions that warrant further action. Out of 68 warning letters issued by USFDA in 2018, 10 warning letters were related to India. In 2017, India’s share of warning letters was 17 out of 79 handed out by the agency. Some big examples of company’s resolving USFDA warning letters include Sun Pharma’s Halol plant in Gujarat, Cadila Healthcare’s Moraiya site (Gujarat), Dr Reddy’s Duvvada (Andhra Pradesh) and Miryalaguda (Telangana) plants and Divis Labs Visakhapatnam unit (Andhra Pradesh). Lupin is in the process of resolving its warning letter on Goa and Pithampur-Indore plant (Madhya Pradesh).
EU, a different case
But things aren’t that rosy with European Union drug regulator. Around 43 percent of the Europe Medicines Agency’s GMP non-compliance reports or equivalent of a US warning letter were issued to Indian manufacturers. EMA issued 16 GMP non-compliance reports in 2018. India exported about USD 17.3 billion worth of medicines in FY18, of which US alone accounted USD 5.1 billion or 30 percent. But exports to US are declining due to regulatory issues at India plants and pricing pressure in that market. Europe constituted about 20 percent of Indian exports.
Areas of concern
McKinsey & Company, which is supporting the Indian Pharmaceutical Alliance (IPA) that represents large domestic drug makers to drive industry wide quality improvement, points to a significant reduction in data reliability, and investigation and root cause assessment related errors that plagued industry. But most concerns of non-compliance are now related to gap in manufacturing systems and lab controls. Out of the all the Form 483 observations made by US FDA in 2018, 35 percent were due to failure to establish laboratory controls and failure to ensure that test procedures are scientifically sound. Around 21 percent were related to gaps in good shop floor practices or standard operating procedures and gaps in manufacturing, packaging and process equipment reliability. Data integrity or data reliability issues now constitute 17 percent, from 46 percent in 2016. The significant drop in data integrity issues could be attributed to stringent crackdown by US FDA through import bans and warning letters against manufacturers who manipulated and falsified data. Investigations and root cause assessment now reduced to 9 percent in 2018. It was 28 percent in 2017. – Money Control