Pfizer Must Correct Data Integrity Problems Seen At India Plant Globally, FDA Says

US FDA warning letter instructed Pfizer to implement a global corrective and preventive action plan to address widespread data integrity problems. While the impact of the warning letter on the site is expected to be minimal due to its closure, the global impact on the company’s sterile drug operations could be significant.

Pfizer Inc.’s sterile injectables operation was dealt another blow after receiving a US FDA warning letter telling the company to develop a global corrective and prevention plan to address the type of data integrity problems found at a site in India that the firm acquired from
Hospira Inc. in 2015.

The emphasis in the warning letter on a global corrective and preventive action system is rare. The warning letter, which also blasted the company for multiple GMP violations, resulted from FDA's inspection of a sterile injectables site in Tamil Nadu, India, from March 27 to April 3, 2018.

FDA said that Pfizer should develop a global corrective action and preventive action plan to address data integrity failings, which should describe:

• How the company intends to ensure the integrity of the data emanating from manufacturing sites, including analytical data and manufacturing records;

• The root causes of the data integrity lapses, including evidence that the scope and depth of the current action plan is commensurate with the findings of the investigation and risk assessment, and to indicate whether individuals responsible for data integrity lapses remain able to influence cGMP data at the firm;

• Interim measures describing the actions the firm has taken or will take to protect patients and to ensure the quality of the drugs, such as notifying customers and recalling product, and conducting additional testing;

• Long-term measures describing any remediation efforts and enhancements to processes, procedures, methods, controls, systems and management oversight designed to ensure data integrity; and

• A status report on the above listed activities and whether they are already underway or completed.

FDA also cited numerous GMP problems at the Tamil Nadu site, including inaccurate laboratory data. The letter said that “your microbiology laboratory did not accurately report test results.”

During a walk-through of the laboratory, the investigator observed microbial growth on media plates, while the company recorded a result of “nil” or no growth on the plates. Staff confirmed later that laboratory records did not accurately reflect the actual microbial growth observed on plates.

FDA said that “your failure to report accurate data compromised the sterility assurance of drug products released from the facility and may have increased risks to patients. The critical data integrity breaches identified in our inspection also raise serious concerns regarding the validity of all results reported by your quality control laboratory.”

Investigators also found that the firm failed to adequately investigate critical defects found in the manufacturing process. An inspector found that the firm initiated multiple investigations for batches that exceeded critical defect limits for visual inspection, and the defects were attributed to power outages. Yet a timely CAPA was not put into place.

FDA placed the firm on an import alert on Aug. 1, 2018.

The impact of the warning letter on the site is expected to be minimal. In early January, Pfizer announced that it would be ending production activity at two “unviable” facilities, including the troubled Irungattukottai (IKKT) plant in Tamil Nadu. The other site is located in Aurangabad, Maharashtra. (Also see "Pfizer Pulls Plug On Two Unviable Indian Sites, Over 1,500 Jobs At Risk" - Scrip, 9 Jan, 2019.) Pfizer decided to end production at the locations after an evaluation concluded that due to the “significant long-term loss of product demand,” manufacturing at the plants is not viable.

FDA noted that even though the site is closing, the GMP problems must be fixed anyway in case it is bought by a successor that decides to resume drug manufacturing operations.

The IKKT facility has been under regulatory fire over the past few years; last year Pfizer stopped production at the facility to remediate GMP issues identified by FDA in a Form 483 report. (Also see "Pfizer Pauses To Remedy Quality At Irungattukottai Plant" - Pink Sheet, 25 Jul, 2018.) The site also received a warning letter in May 2013.

The plant made generic injectable cephalosporin and penicillin antibiotics for the US, the EU and the rest of the world.