The Silvasa facility of Ipca Laboratories, which received a Form 483 on December 19, citing five deficiencies...
The Silvasa facility of Ipca Laboratories, which received a Form 483 on December 19, citing five deficiencies, is not the facility’s first run-in with the US Food and Drug Administration. It follows a 10-point Form 483 issued in July 2012 and an establishment inspection report (EIR) issued in January 2014, which said the unit has “significant problems”, and recommended a warning letter to be issued against the unit, according to USFDA documents reviewed by FE.
The December 19 report largely revolves around incompleteness of record keeping and incomplete data submission, according to Ambit Capital Research, which issued a report on Tuesday disclosing about the latest Form 483. Analysts said the Form 483 is not significant.
However, the January 2014 EIR says the investigators recommended a warning letter due to “significant problems in investigations, corrective and preventive actions (CAPA), numerous analyst errors and glassware contamination incidents”.
Unusually, the USFDA issued a letter dated April 5, 2013, saying it reviewed the company’s responses dated August 20, 2012, with supportive documentation, based on which the facility was classified as “acceptable”.
However, the EIR, issued almost nine months after the letter, insists on stringent action to be taken against the facility. The document, dated January 11, 2014, lists eight products manufactured at the site, including the anti-hypertensive drug, metoprolol tartrate and propranolol Hcl. Remaining names were redacted.
“Drug products were marketed in the US prior to full assessment of the product to assure that the product meets the quality, purity and potency through the shelf life of the product,” the EIR said. The investigator proceeds to provide the example of three validation batches of a drug (tablets), whose name was redacted in the document, were deemed validated and marketed in the US before establishing the stability of the product. The batches were later recalled, after it failed stability tests.
The next observation then points out that “apparent trends in the stability data were not investigated”.
The investigator said that tests and laboratory incident investigations were “not thorough”. The root cause of certain problems, “were not based on objective evidence”, and “systemic nature of problems, if any, were not investigated”.
The document added that the preventive actions were inadequate and not reviewed for the effectiveness of the corrective actions. “This deficiency is very significant and 11 examples were provided in the 483,” the EIR said.
“During the investigation of several out-of-specification (OOS tests) and laboratory incidents, analyst error and glassware contamination was identified as the ‘root cause’, evidencing that the laboratory controls were inadequate,” the investigator said. “This deficiency was very significant and 35 cases were included in the 483 presented to the firm.”
The investigator has pointed out that the Silvasa facility was inspected in May 2010 with the inspection classified as an “official action indicated (OAI)”, a term used by the USFDA when significant objectionable conditions or practices are detected in an investigation and regulatory action is warranted to address the establishment’s lack of compliance with regulations.