Avoiding warning letters in pharmaceutical industry: A qualitative study in the Indian context

Abstract

The purpose of this paper is to identify the cause and effect of increased number of warning letters (www.fda.gov) issued by the Food and Drug Administration (FDA) of United States year after year in spite of clarity in the guidance published by the agency. Increased number of warning letters is matter of concern for the drug product / drug substance manufacturer, drug authority and end consumers (patients). Author identified six pharma professionals through their personal contacts and interviewed each of them. Poor quality management systems and lack of management oversight were found to be the key reasons for issuance of warning letters. Issuance of warning letters had adverse financial impact on business, delay in approvals thus loss of business opportunity and negative image of the organization among regulators, customers. Quality culture in the organization plays an important role to ensure regulatory compliance and building up the right quality culture in the organization is vital. Involvement of top management and participation in the management review meetings is essential for monitoring the compliance level in the organization. 1. Introduction FDA is USA based health regulatory agency (hereafter referred to as FDA) and is responsible for healthcare of the US citizens. As a part of verification of cGMP compliance, investigators from the agency perform inspections of the drug substance and drug product manufacturing sites. FDA Inspections are conducted for four reasons: (1) Pre-approval inspection (PAI) before approval of the drug product (2) Regular cGMP inspection and (3) Post approval & Surveillance and (4) Cause Audit. During inspection, if any non-compliance is observed, the investigator issues the non-compliance observation on form-483 (Objectionable conditions cited by FDA on the Form No 483) and that is why the observations are popularly known as 483 observations. The manufacturer shall submit the response within 15 business days explaining the reason for existence of non-compliance, impact of the product quality and appropriate corrective action taken to avoid the recurrence. If the response is not satisfactory; non-compliance observations are critical in nature having direct impact on product quality, patient safety and data integrity, the FDA issues warning letters to the manufacturers. Number of warning letters issued by the FDA is increasing year after year in spite of clarity in the guidance issued by the agency. Increased number of warning letters is matter of concern for the manufacturer, drug authority and consumers. To study the reasons for issuance of the warning letters to Indian pharmaceutical manufacturers, authors interviewed six pharma professionals through their personal contacts with an objectives that how did they remediated the warning letters to satisfy FDA and what is their advice to industry friends.