For Indian pharmaceutical manufacturers, 2019 has so far been a difficult year as many are finding it tough to comply with US Food and Drug Administration (USFDA) norms. At the last count, there are at least four listed companies that have received warning letters in the span of five months.

It started with a warning letter issued to Jubiliant Life’s Roorkee facility in March this year. The key charge against Jubiliant Life was inadequate investigations into consumer complaints and deviations. Following the warning letter to Jubiliant Life, Strides' Puducherry facility, Aurobindo’s Unit XI and Indoco’s Goa Unit 1 also came under the FDA scanner. For Aurobindo, the warning letter was centred on issues related to the manufacturing of Valsartan bulk drug. The letter also noted discrepencies in two of Aurobindo’s other facilities, Unit I and Unit IX, which were slapped with an Official Action Indicated Status, along with Unit XI in May 2019. While details are still awaited on Indoco’s Goa formulation plant inspection, the street is currently concerned over the contents of the warning letter issued to Strides' Puducherry plant.

Strides' Puducherry facility manufactures formulations. It was previously a Shasun Pharma facility that Strides inherited with a merger in 2014. The facility had undergone three successful audits prior to the January-February 2019 inspection that led to the warning letter. The warning letter was issued on July 1. The facility currently manufacturers six drugs which won’t be affected by the warning letter. However, the 10 drugs filed for approval from the plant, which is almost 30 percent of the company’s total drug pipeline, will get delayed till the site gets an all-clear.

The key issue is that the warning letter to Strides’ Puducherry plant points to data integrity. Lack of data integrity at a pharma plant means the USFDA is concerned that the company officials have fudged records to ensure a favourable or suitable outcome. Data integrity issues are always tougher to solve and can make future inspections of other company facilities tougher. For Strides’ Puducherry plant, the USFDA pointed to a quality system that does not ensure accuracy and integrity of data. For example, observations included discarding and uncontrolled shredding of documents. In one instance, the investigator found a blue binder with compliance records discarded along with other data in a 55-gallon drum at a scrapyard. Some of the documents found in the drum were as recent as a week before the USFDA inspection. Besides those data integrity issues, the warning letter also highlighted test results that failed to meet criteria. According to the USFDA, the responses by the company to the observations are inadequate.

The data integrity issues in the Strides warning letter came as a disappointment for the industry, as such issues were non-existent for most of the large Indian generic manufacturers in the past few years. Of late, the focus had moved from data integrity to failed test results, inadequacies in the manufacture of Valsartan API and poor investigation of consumer complaints. However, the fear is whether the trend is re-emerging. For instance, US-based pharma company Hospira’s Tamil Nadu plant was issued a warning letter in March 2019 citing data integrity over inaccurate reporting of microbiological data. Inaccurate microbiological data can eventually impact the quality of the drug and can be a risk to patients. The analysts at the Hospira plant reported ‘nil’ growth of microbes whereas the USFDA investigator had observed microbial growth. Similarly, the plant personnel ‘significantly under-reported' microbial results for three samples.

The street also seems to be worried about Torrent’s Dahej plant. The facility, during an inspection in March 2019, was issued five observations, of which one was a repeat observation from 2017. But the more worrisome bit for Torrent was observation number two that pointed to shredding of quality control documents. It highlighted that shredded pages of documents from quality control and warehouse were found in a polybag. The management’s justification was that a contract employee had misinterpreted instructions and shredded documents by mistake. The street fears that the observations are enough to qualify it as data integrity and may lead to a warning letter.

First Published:Jul 17, 2019 2:17 PM IST