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Posted 28 January 2014 | By Alexander Gaffney, RAC,
Indian generic pharmaceutical manufacturer Ranbaxy may be just the latest company to see its products banned from entry into the US, but it's also the latest company to join far more dubious company: the list of Indian manufacturers accused of fabricating and falsifying data in an attempt to fool US regulators.
Regulatory Focus covered the start of FDA's crackdown on Indian companies in 2013, when we noted that regulators had sent a series of seriously-worded Warning Letters.
Agila Specialties Private Limited
Posh Chemicals Private Limited
Aarti Drugs Limited
Fresenius Kabi Oncology Ltd
RPG Life Sciences Limited
However, unlike many Warning Letters, which usually cite basic current good manufacturing practice (CGMP) issues, these letters have been altogether far more serious in nature.
In fact, FDA has accused all of these companies with either actually or potentially tampering with their data.
RPG Life Sciences, for example, was said to have "selectively reported" data when re-testing out-of-specification results. Fresenius was accused of keeping data outside of its quality systems, allowing it to selectively report and change results. FDA said the company's practices raised "serious concerns regarding the integrity and reliability of the data generated" at its manufacturing plant.
Wockhardt, which received two Warning Letters in 2013, was accused of data falsification and even attempting to hide data from inspectors while they were in the respective facilities.
Aarti, Posh Chemicals and Agila were all sent letters citing similar alleged infractions or a lack of data integrity.
Now Ranbaxy-a company that pleaded guilty to falsifying data in May 2013, resulting in the largest false claims case ever recovered by FDA-is back in the news again for reportedly failing to ensure the integrity of its data.
In a FDA Form 483 released by regulators this week, FDA inspectors reportedly found evidence that the company was "over-writing electronic raw data files for ongoing sample sequences until acceptable results [were] achieved."
"We identified numerous such examples during our review of archived data drawn from approximately five months of data," FDA continued. "The number of such examples of over-writing raw data files until acceptable results are achieved could not be quantified during our inspection due to the large amount of data," it added.
FDA also noted that Ranbaxy's computerized systems did not have appropriate controls to prevent unauthorized access, changes, omissions or deletions. "We found that raw data files related to standard and sample injections can be deleted and all evidence of testing removed, as demonstrated by the lack of raw data files present in the electronic Chemstore data archives," FDA wrote. Regulators found evidence of employees taking steps to allow for back-filling and back-dating quality testing records.
All products manufactured at the facility are now subject to an FDA import alert.
That Ranbaxy-a company already subject to a consent decree covering many of its manufacturing facility, several import restrictions covering its factories, and still reeling from a 2013 fraud conviction-could still be charged with violating such basic regulatory standards is by itself troubling.
But when taken together as a whole, the violations exhibited by Indian manufacturers in 2013 presents a far more troubling picture, and raises a disturbing question: If large, established manufacturing operations in India can't even manage to meet basic standards of regulatory quality, what does that say about the entire industry? Could lapses by smaller manufacturers be even worse?
Data falsification and fabrication claims aren't something to scoff at. Falsified data can make a drug seem more bioequivalent than it really is; more pure; more potent; more sterile; more bioavailable.
For US consumers, who are increasingly turning to generic drugs as their pricier branded equivalents lose patent protection, this could conceivably present huge safety problems. If an antibiotic doesn't work as intended, a patient could needlessly suffer. If a sterile injectable drug is manufactured under non-sterile conditions, a patient could die.
But for the Indian pharmaceutical industry, and in particular its regulators, the cases may very well-and should very well-serve as a call to arms.
Already, Fresneius Kabi, one of the recipients of the Warning Letters, has announced that it will overhaul its entire management staff at its Indian facilities.
But the impact of those efforts may well depend on how much emphasis Indian regulators place on the same standards. After all, US regulators are thousands of miles away. It is India's own regulators that should have the most contact and impact on its regulated manufacturing sector.
So when G.N. Singh, the drug controller general of India (DCGI), told Indian media that "we cannot judge Ranbaxy by standards set up by the American drug regulator," it's not exactly comforting.
Data integrity, after all, is not an advanced regulatory concept; it's a basic regulatory competency, one without which no regulatory system can reliably function.
US regulators, then, may have two battles ahead of them: Convincing Indian companies that US standards are worth following, and convincing Indian regulators that basic US regulations are worth adopting and enforcing. Even with new regulatory authorities thanks to new legislation, failure to accomplish either may well ensure that the troubles unearthed in 2013 continue for the foreseeable future.
Tags: Crackdown, warning letter, data
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