Regulatory Focus™ > News Articles > FDA Issues Stern Warning Letter to Hospira Over Manufacturing Lapses in Italy

FDA Issues Stern Warning Letter to Hospira Over Manufacturing Lapses in Italy

Posted 07 April 2015 | By Alexander Gaffney, RAC

FDA Issues Stern Warning Letter to Hospira Over Manufacturing Lapses in Italy

The US Food and Drug Administration (FDA) has just issued biopharmaceutical manufacturer Hospira a new Warning Letter—the company's seventh in the last seven years—regarding alleged deficiencies found at the company's Liscate, Italy manufacturing facility.

Background

The letter, issued 31 March 2015, references a May 2014 inspection of Hospira's Liscate facility where the company manufactures finished pharmaceutical products.

During the seven-day inspection, FDA said its investigators found several "significant violations of current good manufacturing practice (CGMP)," which collectively caused the company's drug to be adulterated under federal law.

Under federal law, a drug is adulterated if, among other things, it:

  • has been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth, or whereby it may have been rendered injurious to health
  • is a drug and the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this chapter as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess

Major Deficiencies

Hospira's manufacturing operation had several deficiencies which caused FDA regulators to conclude that drugs produced at the facility were adulterated, the Warning Letter explains. For example, FDA said it found that Hospira never conducted "dynamic airflow studies"—also known as smoke studies—to ensure the sterility of drugs manufactured using certain equipment. Outside air can expose finished drugs and unfinished pharmaceuticals to microbiological contaminants, especially when drugs are packaged in vials, FDA noted.

In another instance, Hospira employees were observed to be "reaching over" vials on the production line, which FDA said "could compromise product sterility by introducing microbiological contaminants."

FDA investigators also said Hospira "failed to thoroughly investigate" a product which outside complaints claimed was discolored relative to its normal appearance. While Hospira investigated the event, its investigation was not sufficiently thorough, FDA claimed, and failed to evaluate how the change in color might affect the quality of the product. The company also failed to assess "vulnerabilities in [its] manufacturing process," FDA added.

Data Integrity

Another major deficiency identified by FDA relates to its control over computerized systems which ensure the integrity of data collected and made available to regulators. FDA said Hospira's high performance liquid chromatography (HPLC) software "did not have sufficient controls to prevent the deletion or alteration of raw data files."

Data saved to Hospira's server by the program could have been deleted by analysts, FDA found. Some files had been deleted, while other backup files had been "overwritten," FDA found. Investigators also chided the company for not having an "audit trail function" which would have allowed the company to determine which changes were made, when the changes were made and by whom.

Similar deficiencies have resulted in Warning Letters to more than a dozen Indian pharmaceutical companies.

Recommended Steps

FDA's Warning Letter concludes by calling Hospira's alleged deficiencies "serious," and advising the company to work with an outside consultant to assess its compliance with manufacturing, laboratory and quality regulations. FDA also asked Hospira to provide it with a "management strategy" detailing the company's "global corrective action and preventive action plan."

 

FDA Warning Letter to Hospira


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