The FDA has inspected 160 drug plants in India since July 2012, when the US passed the Food and Drug Administration Safety and Innovation Act. These inspections have revealed that some manufacturing facilities in India have produced medications that were adulterated or contaminated, and manufacturing facilities were often filthy or invested with bugs. The FDA investigators also caught some of the Executives at these manufacturing facilities lying to them, which has led to felony charges.
On May 7, 2014, the FDA released a warning letter to Sun Pharmaceutical Industries Limited, a pharmaceutical manufacturer in India. Investigators from the US Food and Drug Administration (FDA) identified manufacturing violations and deviations from good practices when manufacturing active pharmaceutical ingredients, causing Sun Pharma's affected products to be adulterated under the US Federal Food, Drug, and Cosmetic Act.
FDA inspectors found that Sun Pharma violated FDA regulations by missing fundamental raw data and information necessary to document its analyses. Two major findings from the FDA investigation were that Sun Pharma had serious data integrity problems and physical records were discarded.
Data Integrity Problems
According to the FDA warning letter, Sun Pharma's analyses failed to provide critical data on:
- Identification of the samples tested - including name, source, batch number or other distinctive code, and date of sample,
- Complete record of all raw data generated during each test - including graphs and electronic files from laboratory instrumentation,
- Test methods used,
- Sample preparation as prescribed by methods, preparation and testing of solutions,
- Records of all calculations performed in connection with the test,
- Test results,
- The signature of the person who performed each test,
- Date(s) when the tests were performed, and
- Date and signature of a second person showing that original records had been reviewed for accuracy, completeness, and compliance with required criteria.
Unlabeled and unidentifiable raw materials were found by FDA investigators in three partially filled bags in Sun Pharma's raw material warehouse and its employees were unable to determine the identity or status of the materials. Numerous unidentified partially filled bags were also observed by FDA investigators.
Furthermore, Sun Pharma was found to have unacceptable and flawed data handling practices, including using, what employees appeared to call data from "unofficial" injections as "official". Additionally, Sun Pharma was found by FDA investigators to frequently perform "unofficial testing" of samples, disregarding results, and reporting results from additional tests. For example, Sun Pharma employees tested a batch sample six times and subsequently deleted the data. In addition to the finding that actual testing results differed from reported results, the finding that Sun Pharma deleted testing results was common the FDA's report. Sun Pharma's general lack of reliability and accuracy of generated data is further supported by 47 instances of apparent trial injections of samples which tested out-of-specification and some of these batches were distributed to the US market.
Discarding Physical Data Records
The FDA's investigation of Sun Pharma revealed that there were many examples of deleted electronic raw data files on computers which controlled testing instruments. Some deleted files were replaced with identically named files that were used as "official" data files. Sun Pharma also failed to consistently archive data to its central server. Other files were deleted with no audit trail or other adequate form of traceability to document deletion activity in the operating system. These actions allow the data to be manipulated, while appearing to be in sequence, regardless of whether the files were created sequentially.
The FDA investigators also found approximately 10 trash bags containing torn or partially destroyed raw data and manufacturing product records. The waste bags included the following documents:
- Calibration check records,
- Six corrective action and preventive action records, without official documentation that the corrective action described in the torn documents was necessary,
- Five torn completed preventive maintenance forms, which an employee said that he had mistakenly torn them and, therefore, destroyed the forms,
Sun Pharma failed to detect and correct the manipulation, alteration, and premature destruction of records.
Here is a list of pharmaceutical products that Sun Pharma manufactures: http://www.sunpharma.com/indiaproducts.
Other cases of hidden and discarded data
This is not the only case in which pharmaceutical companies have discarded or hidden data. Discarding or hiding data to control and manipulate the evidence base, on which prescribers base their prescribing choices, occurs internationally. The following are other examples in which pharmaceutical companies have hidden or destroyed data to manipulate the evidence base. This is not a complete list of drug companies that have hidden data.
- Takeda (Japan) and Eli Lilly (US partner): US$9 billion in punitive damages for concealing cancer risks associated with its Actos diabetes drug,
- GlaxoSmithKline (United States): US$3 billion total, $1 billion criminal for off-label promotion and hiding/failure to disclose safety data, $2 billion civil for making false and misleading statements re: safety of Avandia, misbranding of Wellbutrin and Paxil,
- Roche (United States): refused to release 8 of the 10 clinical trial results conducted on Tamiflu.
*This is Part 2 of a 2-part post. See Part 1: India manufacturer, Ranbaxy, pleads guilty, pays $500 million
FDA Warning Letter to Sun Pharma
FDA Warning Letter to Sun Pharma Finds Trash Bags of Data and Secret Studies
Drug Companies Are Hiding Research
GlaxoSmithKline pleads guilty in $3B US drug fraud case
US Jury Orders Takeda To Pay $6 Billion Over Actos Claims
Higher penalties for big pharma: Data destruction alleged