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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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Bracco Diagnostics Inc 1/31/12


Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration

Central Region
Waterview Corporate Center
10 Waterview Blvd., 3rd Floor
Parsippany, NJ 07054
Telephone (973) 331-4902

January 31, 2012



Mr. Carlo Medici
President and CEO
Bracco Diagnostics Inc.
107 College Road East
Princeton, NJ 08540

Dear Mr. Medici:

File No: 12-NWJ-09

During our June 23 through July 11, 2011 inspection of your firm, Bracco Diagnostics Inc., located at 107 College Road East, Princeton, NJ 08540, investigators from the Food and Drug Administration (FDA) identified significant violations of Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211. These violations cause your drug product(s) to be adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 351(a)(2)(B)) in that the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.

We have reviewed your firm's response to the FDA 483 dated July 29, 2011, and note that it lacks sufficient corrective actions. We have also reviewed additional reports you provided as a part of status meetings with the agency.

Specific violations observed during the inspection include, but are not limited, to the following:

Your firm failed to thoroughly investigate the failure of a batch or any of its components to meet its specifications whether or not the batch has already been distributed [21 C.F.R. § 211.192].

For example, your firm failed to investigate numerous customer complaints for several lots of Iopamidol Injection 76% (Isovue-370) concerning cracked vials. Container-closure integrity is essential to assure sterility of a drug. Cracks in vials, when not detected before shipment, can lead to microbial contamination and a serious patient hazard. We have reviewed your response and acknowledge that you have hired a third party consulting firm to continue the investigation into these complaints. However we are concerned that you have failed to identify a root cause.

In addition, your firm's response failed to include a risk assessment for the product currently on the market.

The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist at your facility. You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence and the occurrence of other violations. It is your responsibility to assure compliance with all requirements of federal law and FDA regulations.

This inspection was initiated as a result of reports of unexpected radiation exposure in two individuals who underwent cardiac positron emission tomography (PET) scans with CardioGen-82®(Rubidium Rb 82 generator). We acknowledge your commitment to implement corrective actions for the CardioGen-82®(Rubidium Rb 82 generator) based upon these inspectional findings. As an overall global matter for all your products, we are concerned about your firm's fundamental understanding of quality assurance and the regulatory expectations of your firm. It is essential that your firm establish and maintain an effective quality system. Your firm's management has the ultimate responsibility to demonstrate effective quality leadership by participating in the design, implementation, and monitoring for quality throughout the company and with contract manufacturers and imaging facilities. Although you have agreements with contract manufacturers and imaging facilities that may delineate specific responsibilities to each party (e.g., quality assurance responsibilities), you are ultimately responsible for the quality of all your products. Regardless of who manufactures your products or the agreements in place, you are required to ensure that these products meet predefined specifications prior to distribution and are manufactured in accordance with the Act and its implementing regulations.

You should take prompt action to correct the violations detailed in this letter. Failure to promptly correct these violations may result in legal action without further notice including, without limitation, seizure and injunction. Other federal agencies may take this Warning Letter into account when considering the award of contracts. Additionally, FDA may withhold approval of requests for export certificates, or approval of pending drug applications listing your facility, until the above violations are corrected. FDA may re-inspect to verity corrective actions have been completed.

Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct violations. Include an explanation of each step being taken to prevent the recurrence of violations and copies of supporting documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the date by which you will have completed the correction.

Your reply should be sent to the following address: Food and Drug Administration, Attention: Joseph F. McGinnis, R. PH, Director, Compliance Branch, 10 Waterview Blvd., Parsippany, New Jersey 07054.

Diana Amador-Toro
District Director
New Jersey District