A Warning Letter sent by the US Food and Drug Administration (FDA) to an Indian pharmaceutical manufacturer alleges that the company routinely repeated tests when initial testing did not give it the desired results and, in at least one case, improperly back-dated results.
The 28 May 2013 Warning Letter references two inspections conducted by FDA, one in November 2012 of RPG Life Sciences' Ankleshwar, Mumbai facility and the other a January 2013 inspection of its Navi, Mumbai facility.
Both facilities failed to pass FDA muster, with investigators focusing heavily on deficient practices involving sample testing. For example, at the Ankleshwar facility, FDA said it found evidence that a number of active pharmaceutical ingredients (APIs) had failed to meet established specifications, but were still included in the finished product.
Curious as to why that happened, investigators found that the API had ultimately met specifications, but only after the company retested the products several times, selectively reporting "only the passing retest values in the final assay results," it wrote. The failing results were then reportedly discarded and the cause of the out-of specification results went uninvestigated. Investigators said they found evidence that this had occurred numerous times over several months, and in some instances the company had used different processing methods and tests to process data analyses.
In at least one other case, FDA said it found evidence that the company had back-dated its results. It was only able to prove this in the discovered case because the date had been back-dated to before the form had been released for use.
"When your analyst affixed the related substance and IR weight printouts to the [form], he signed and dated this worksheet as July 29, 2011. A second analyst, who reviewed this worksheet, also signed and dated it as July 29, 2011," FDA noted. "However, your QA department did not issue this worksheet until July 31, 2011. Your analyst acknowledged during the inspection that he backdated this worksheet on July 31, 2011."
An embarrassing finding for the company, to be sure, but FDA's letter goes on to state that the company's response seemed to contradict itself, saying that there was "no intention to deliberately backdate the document."
"However, your response contradicted your analyst's backdating admittance during the inspection. In addition, your response did not explain the reviewer's signature which was also dated July 29, 2011," FDA observed. "Backdating documents is an unacceptable practice and raises doubt about the validity of your firm's records."
"This practice is a clear breach in your quality system that raises serious concerns regarding the integrity and reliability of the laboratory data used to release drug products," FDA continued.
Investigators said they found similar deficiencies at the company's Navi facility, including discarded data. Again, the company provided conflicting answers for the deficiencies, FDA said, with one response indicating that the company claimed a contaminated syringe had corrupted the results, while a report provided to FDA during the inspection said it was due to vial or glassware contamination.
"Your investigation lacked scientific evidence to support your root cause hypothesis," FDA observed.
FDA said until deficiencies are corrected, it "may" withhold the approval of any products manufactured in whole or in part by RPG Life Sciences, and may similarly refuse to allow the products to be imported into the US.
Warning Letter to RPG Life Sciences