Serious data integrity violations, including the backdating of records and failing to provide pertinent data to regulators, were included in warning letters for five manufacturing facilities from both Sandoz and Dr. Reddy’s in India, according to the US Food and Drug Administration (FDA).
Both companies previously disclosed receiving the FDA warning letters in October and November, though the contents of the violations were not released until now. And like a number of other warning letters issued to manufacturing sites in India, and Form 483s issued, both letters detail the companies’ lack of regard for ensuring that the data released from the sites is credible.
FDA officials inspecting two of the generic drug manufacturer’s sites in Maharashtra, India in August 2014 noted some peculiar handling of batch documentation by Sandoz employees.
For instance, investigators uncovered two “uncontrolled Excel spreadsheets” that were used to “record discrepancies and certain in-process drug quality data. This data was initially missing in the batch manufacturing record. Your firm later entered this data into batch records and backdated them,” FDA alleges.
Sandoz later admitted to the discrepancies, noting that batch records were backdated when missing data was added, which FDA says "is unacceptable.” FDA also says the company “failed to demonstrate how widespread this practice is, and whether data recorded and reported for CGMP [current good manufacturing practice] or other purposes in the past is reliable.”
Later on at the same site, FDA investigators found original preventive equipment maintenance work orders in trash bags.
“A partially-completed document retrieved from the waste receptacle included handwritten notes about the condition of equipment observed during preventive maintenance. However, the corresponding official record did not include the same information. Your response did not sufficiently identify the scope of these practices at your facility,” FDA said.
Sandoz also failed to inform FDA of an out-of-specification impurity result until that product was approved.
“Your decision to withhold information from the agency raises serious concerns,” FDA says.
In addition, FDA found that a Sandoz contract employee who trains other contract employees on good documentation practices was unable to explain the material he was required to present during training. The agency also notes that “a significant number of your contract employees” do not speak English, though the company only provided English training materials to these employees.
At the other site, Sandoz failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination, and also failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas.
The warning letter for Dr. Reddy’s Laboratories -- for three sites in Telangana and Andhra Pradesh, India – notes several violations that are recurrent or represent “long-standing failures to adequately resolve significant manufacturing quality problems.”
And unlike the Sandoz letter, FDA tells Dr. Reddy’s in its concluding statement: “It is apparent that you have not implemented a robust quality system at your sites.”
As for the specifics, one FDA investigator found that active pharmaceutical ingredient (API) batch samples were routinely re-tested following failing or atypical results until acceptable results were obtained, although those failures or atypical results were not investigated or included in the official laboratory control records.
In addition, FDA said none of Dr. Reddy’s explanations “justify your failure to maintain complete records, nor do they support your practice of substituting repeat tests after failing results.”
The company was also cited for failing to control access to some of its computer systems with passwords, and failing to explain discrepancies between the release of APIs and deviations that occurred, among other inconsistencies with media-fill records and batch records for drums used to hold intermediates during manufacturing.
Dr. Reddy’s Warning Letter
Sandoz Warning Letter