| Public Health Service Food and Drug Administration |
| Cincinnati District Office Central Region 6751 Steger Drive Cincinnati, OH 45237-3097 Telephone: (513) 679-2700 FAX: (513) 679-2771 |
Department of Health and Human ServicesAugust 2, 2010
WARNING LETTER
CIN-10-111649-18
VIA UNITED PARCEL SERVICES
Milan Panic
President and Chief Executive Officer
MP Biomedicals LLC
3 Hutton Centre Drive, Suite 100
Santa Ana, CA 92707
Dear Mr. Panic:
During an inspection of your firm, MP Biomedicals Diagnostic Division, 29525 Fountain Parkway, Solon, OH on March 29 through April 22, 2010, an investigator from the United States Food and Drug Administration ("FDA") determined that your firm is manufacturing in-vitro diagnostic (IVD) kits. Under section 201(h) of the Federal Food, Drug and Cosmetic Act (the "Act"), 21 U.S.C. § 321(h), these product are devices because they are intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, or are intended to affect the structure or function of the body.
This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for manufacturing, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System (QS) regulation found at Title 21, Code of Federal Regulations (CFR), Part 820. These violations include, but are not limited to, the following:
1. Failure to validate a process whose results cannot be fully verified by subsequent inspection and test, as required by 21 C.F.R. § 820.75(a). Specifically,
• Your firm has not validated the foil bag sealing process used to protect components of the IVD kits, such as T3 tubes, (b)(4) tubes, TSH plates and Blood spots from moisture.
• Your firm has not validated the mixing, filling, plate coating, tube coating and cleaning processes used to manufacture the components of the IVD kits.
• The lyophilization process, used on tracers and antibodies that are part of the ACTH, Glucagon, and Insulin IVD kits, has not been adequately validated in that the review of the validation report for the ACTH test kits had 70 out of specification results out of 142 total results. These out of specification results were not addressed by your firm.
2. Failure of your finished device acceptance procedures to ensure that each production run, lot or batch of finished devices meets acceptance criteria, as required by 21 CFR § 820.80(d).
Specifically, your "ELISA MATERIAL SPECIFICATION" procedures allow for the averaging of out-of-specification values and/or allow the removal of the out-of-specification value (OOS) for one replicate of the set if the "CV of the triplicates is > 10%" during finished device testing. A total of 17 of the 30 Phenylalanine Kits' finished device testing records reviewed by the FDA investigator had one of the three values as OOS. Some of these OOS values were outside 3 standard deviations. Your firm does not conduct a failure investigation to determine the cause of these OOS results, nor is there a written justification based on a statistical rationale for acceptance of the OOS results.
Additionally, when your firm establishes values for your calibrators, which are used to create a standard curve, you routinely remove data points without documenting and justifying the rationale for removing these values. For example, in the last 2 years, you have manufactured two lots of these calibrators. One lot had 11 data points removed and the other two data points removed from the data sets with no written justifications.
3. Failure to evaluate nonconforming product to determine the need for an investigation and notification of the persons or organizations responsible for the nonconformance as required by 21 CFR § 820.90(a). For example,
A total of 4 of the 17 device history records for the Phenylalanine kits reviewed by the FDA investigator had readings outside of specified tolerances or discrepancies in total yield values recorded. These nonconforming results were not evaluated to determine the need for an investigation and notification of the person or organizations responsible for the nonconformance.
The inspection also revealed that the devices are misbranded within the meaning of section 502(f)(1) of the Act, 21 U.S.C. § 352(f)(1), in that its labeling fails to bear adequate directions for use. The labeling of the in vitro diagnostic products includes defined expiration and storage conditions. The labeling storage requirements must be determined as specified in, 21 CFR§ 809.10(b)(5)(iv) by reliable meaningful, and specific test methods such as those described in 21 § CFR 211.166. Our inspection determined that no stability testing has been performed on the Phenylalanine, FSH, TSH (RIA) and TSH (EIA) to show the kits and their components are stable when stored at 2-8°C for their 9 month expiration date. Additionally, some of the individual components of the kits are labeled for storage at other temperatures than 2-8°C. For example, the box label for some components state to store at -15°C, while others state 18-25 °C. No stability testing has been performed for these components.
You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations may result in the initiation of regulatory action without further notice. This may include, but is not limited to, seizure, injunction, and/or civil money penalties. Also, federal agencies are advised of the issuance of all Warning Letters about devices so that they may take this information into account when considering the award of contracts. Additionally, premarket applications for Class III devices to which the Quality System regulation deviations are reasonably related will not be approved until the violations have been corrected. Requests for Certificates to Foreign Governments will not be granted until the violations related to the subject devices have been corrected.
Please notify this office within fifteen (15) working days from the date you receive this letter of the specific steps you have taken to correct the noted violations, including an explanation of how you plan to prevent these violations, or similar violations, from occurring again. Include documentation of the corrective actions you have taken. If your planned corrective actions will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within 15 working days, state the reason for the delay and the time within which the corrections will be completed.
Your response should be sent to Ms. Gina Brackett, Compliance Officer, Food and Drug Administration 6751 Steger Drive, Cincinnati, Ohio 45237. If you have any questions about this letter, you may contact Ms. Brackett at (513) 679-2700, ext. 167, or you may forward a facsimile to her at (513) 679-2773.
Finally, you should know that this letter is not intended to be an all-inclusive list of violations at your facility. It is your responsibility to ensure compliance with applicable laws and regulations administered by the FDA. The specific violations noted in the Inspectional Observations, Form FDA483 (FDA 483), issued at the closeout of the inspection may be symptomatic of serious problems in your firm's manufacturing and quality assurance systems. You should investigate and determine the causes of the violations, and take prompt action to correct the violations and to bring your products into compliance.
Sincerely,
/S/
Teresa C. Thompson
District Director
Cincinnati District
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