FDA may withhold approval of Dr. Reddy’s new applications or supplements listing

The U.S. Food and Drug Administration (FDA) inspected three Dr. Reddy’s Laboratories Ltd. pharmaceutical manufacturing facilities in India in the last twelve months. Particularly, the unit V, VI and VII, first located in Telangana and the last two located in Andhra Pradesh.

The FDA in Units VI and V facilities had found certain, described in the warning letter dated November 5, and addressed to the Chairman Satish Reddy, as significant deviations from current good manufacturing practice (CGMP) for the manufacture of active pharmaceutical ingredients (APIs).

At Dr. Reddy’s Laboratories Limited Unit-VII facility, the FDA also found “significant violations of CGMP regulations” for finished pharmaceuticals, and has found that the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.

The FDA also said it reviewed Dr. Reddy’s responses of December 15, 2014, February 19, 2015, and March 27, 2015, and noted that they lack sufficient corrective actions, and also noted it had received the company’s additional correspondence of January 31, April 9, May 13, May 21, July 14, and September 14, 2015.

According to the warning letter to Dr. Reddy’s, the FDA’s investigators observed specific deviations and violations during the inspection, including, failure to maintain complete data derived from all laboratory tests conducted to ensure compliance with established specifications and standards.

Namely, Dr. Reddy’s laboratory records did not contain all raw data generated during each test for API batches manufactured at the firm, the FDA said.

Furthermore, as seen in the warning letter, the investigator found that batch samples were routinely re-tested following failing or atypical results until acceptable results were obtained, and that failing or atypical results were not investigated or included in the official laboratory control records.

Uncontrolled “Custom QC laboratory” the FDA didn’t know about

Just to give some examples, as outtakes from the FDA’s warning letter to Dr. Reddy’s, we’ll mention that the FDA said that during the inspection, its inspection team found the presence of an uncontrolled “Custom QC laboratory” (CQC) that the FDA says didn’t know about.

The FDA said that Dr. Reddy’s QC Associate Director had acknowledged that the CQC laboratory was involved in CGMP analysis of APIs intended for export to the United States through 2012.

According to the FDA, that discovery was made one day before the end of the inspection, but during FDA’s brief evaluation of the high performance liquid chromatography (HPLC) electronic records generated by the CQC, FDA’s investigators found several fails of specification limit for purity of assay/related substances by HPCL on January 23, 2012.

No reason for Dr. Reddy’s failure to maintain complete records

As the FDA further said, among Dr. Reddy’s explanations given to the FDA in December 2014, the pharmaceutical company said that certain tests were repeated because its analysts observed significant drifts in the base line, chromatograph peak shapes inconsistent with the usual peaks, delays between sample preparation and injection, an injection of a sample before the previous sample was fully eluted from the column, and incorrect vial numbers entered into the auto injector.

However, FDA said, that was not good enough to justify Dr. Reddy’s failure to maintain complete records, nor they support the company’s practice of substituting repeat test after failing results.

The FDA said that Dr. Reddy was responsible for determining the causes of the violations and deviations found by the FDA, for preventing their recurrence, and for preventing other violations and deviations.

FDA questions Dr. Reddy’s corporate quality to comply with CGMP

FDA concluded in the warning letter: “These items, as well as other deficiencies our investigators found, lead us to question the effectiveness of your current corporate quality system to achieve overall compliance with CGMP.

Several violations are recurrent or represent long-standing failures to adequately resolve significant manufacturing quality problems. It is apparent that you have not implemented a robust quality system at your sites.”

Also, the FDA strongly recommended Dr. Reddy to evaluate global manufacturing operations to ensure compliance with CGMP regulations and requirements, comprehensively and immediately.

FDA may withhold approval of new applications

The FDA said that, until Dr. Reddy’s complete all corrections and FDA confirms its compliance with CGMP, it may withhold approval of any new applications or supplements listing Dr. Reddy as a drug product or API manufacturer.

The FDA has given Dr. Reddy 15 working days upon receiving the warning letter to disclose its specific steps taken to correct and prevent repeating listed deviations and violations.

However, Dr. Reddy revealed Thursday that it has gotten an extension to submit the response.

Dr. Reddy said:

“The Company is in the process of preparing a response to FDA’s warning letter. The FDA has granted an extension until December 7, 2015 for the submission of the Company’s response to its warning letter.”

Note to readers:

Please, have in mind that this is just an excerpt from the warning letter. You can read the full document here: http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/2015/ucm473604.htm