Hospira’s Device Shortage Response Draws FDA Warning Letter For Product Release

FDA isn’t convinced by Hospira’s explanation for why it released non-GMP compliant product from its Rocky Mount plant, which also manufactures sterile injectables.

The potential for a negative impact on a shortage situation may not be enough to give Hospira Inc. a pass at releasing a Sterile Empty PCA injector and vial that did not conform with current good manufacturing practice (cGMP) requirements, an FDA warning letter to the company indicates.

FDA cited the company’s Rocky Mount, N.C., facility for numerous GMP violations related to devices that are used with drug products after a seven-week inspection last fall. The warning letter, issued March 7 and posted online April 8, reflects the agency’s dissatisfaction with Hospira’s December response to the Form 483 issued after the inspection ended Nov. 15, 2013.

The warning letter asks Hospira to provide FDA with additional justification for its release of a lot of PCA injector and vials even though a unit failed air leak testing. At least one malfunction for this lot occurred in the field, FDA noted.

Citing an Oct. 18, 2012 memo on the subject, Hospira’s Form 483 response said the rationale for release of the lot was based on data from a water leak test of the sample that failed the enhanced sampling plan, mitigation provided as part of the Field Action Letter issued Aug. 2, 2012 and “the commitment to prevent risks to the field by maintaining supply continuity during critical product shortage.”

The warning letter says FDA needs a full copy of the October 2012 memo as well as data from the water leak test to evaluate the adequacy of this response. Hospira claims the water leak test it used to evaluate the unit that failed the air leak test simulated the actual worse case of the product.

Hospira wouldn’t name the product whose shortage would have been affected by its failure to release this lot of PC injector and vials. The company makes sterile generic injectables, the most common type of product in shortage, and has a number of drugs on FDA’s shortage list.

Manufactured Device With Materials That Caused Recall

Hospira was also cited for manufacturing a Sterile Empty Vial lot from the same parent lot that was found to contain embedded particulates that resulted in a product recall. Prior to the inspection FDA said Hospira had not reviewed the lot to determine if there was any quality impact to the distributed Sterile Empty Vials.

The Form 483 response “fails to address the use of a component (which resulted in a recall in your drug product) in your Sterile Empty Vial lot,” the warning letter says.

The warning letter also cited the company for not adequately establishing procedures for corrective and preventative action, and not adequately establishing procedures for receiving, reviewing and evaluating complaints by a formally designated unit. And the warning letter cited the firm for not having controls in place to monitor the product bioburden of the devices that are included in the EO sterilization process.

Hospira declined to comment on the warning letter and any impacts on its production and availability of products, including any impact the letter might have on shortage situations.

In a Securities and Exchange Commission Form 8-K submitted March 10, the company said the warning letter does not restrict production or shipment of devices from Rocky Mount. It also said it is still in the process of evaluating what corrective actions and associated costs may be required to address the warning letter.

Many Manufacturing Woes

The Rocky Mount plant has been subject to multiple enforcement actions in recent years. A 2010 warning letter cited the facility for failure to adequately validate the processes used to manufacture products as well as other inadequacies including procedures related to the quality control unit, investigations and medical reporting obligations, according to Hospira’s 2013 annual report, which was released February 2014.

Subject to multiple follow-up inspections since the 2010 letter, Rocky Mount also received a Form 483 with observations after an inspection of the plant as a sterile pharmaceutical manufacturer in March 2013. The inspection identified further areas for remediation and improvement (Also see "Manufacturers Provide SEC GMP Enforcement Updates" - Pink Sheet, 28 Mar, 2013.).

In February 2014, FDA verbally informed the company that based on information submitted and ongoing commitments, the plant had been upgraded to Voluntary Action Indicated status, meaning Hospira is free to pursue new product approvals and export certifications for products manufactured at the site, the company’s 2013 annual report said.

Hospira’s 2013 annual report also noted that its facilities have been subject to warning letters and inspection observations as a result of quality issues cited by FDA and other regulatory authorities, which have interrupted the release of products at certain manufacturing facilities, adversely impacting the company’s ability to manufacture and sell its products.

For instance, in May 2013, the company received a warning letter for sterility problems at its plant in Irungattukottai, India (Also see "Contamination and Raw Material Testing Issues Raised in FDA Warning Letters" - Pink Sheet, 27 Sep, 2013.).

If Hospira experiences further interruption of manufacturing at its facilities, “such an interruption could further materially and adversely affect Hospira’s ability to manufacture and sell its products,” the annual report noted.

Besides a string of warning letters since 2010, the company has been hit with a number of recalls, including a Dec. 23 recall for one lot of lidocaine HCL injection, USP, 2%, 5mL single-dose vials due to particulates (Also see "In Brief: Merck, Hospira, Baxter particulates, EU GMP deficiencies, gelatin imports, aseptic deficiencies, UK labeling recalls" - Pink Sheet, 15 Jan, 2014.).

[Editor’s note: This article has been modified to emphasize that the warning letter dealt with device issues, not sterile injectables. The original headline was “Hospira’s Shortage Solution Draws FDA Warning Letter For Product Release.”]