Inspections, Compliance, Enforcement, and Criminal Investigations
Larson Medical Products, Inc. 07-May-08
Department of Health and Human Services
Public Health Service
Cincinnati District Office
May 7, 2008
VIA FEDERAL EXPRESS
Peter M. Larson
Larson Medical Products, Inc.
2844 Banwick Road
Columbus, OH 43232-3805
Dear Mr. Larson:
During an inspection of your firm located in Columbus, Ohio on March 14, 2008 through March 21, 2008, an investigator from the United States Food and Drug Administration (FDA) determined that your firm is a manufacturer of low temperature thermoplastics that are indicated for use as splinting materials; and that your firm is the specification developer and initial distributor of devices intended to be used for positioning and stabilizing patients undergoing radiation therapy treatment. Under section 201(h) of the Federal Food, Drug and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products 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, their manufacturing, packing, storage, or installation are not in conformity with the Current Good Manufacturing Practice (CGMP) requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820. These violations include, but are not limited to, the following:
1. Failure by management with executive responsibility to ensure that an adequate and effective quality system is implemented and maintained at all levels of the organization, as required by 21 CFR § 820.20. For example:
-Your firm has not established quality system procedures, as required by 21 CFR § 820.20(e). Specifically, there are no written corrective and preventive action procedures, design control procedures, medical device reporting procedures, and written acceptance activities.
-Management with executive responsibility has not reviewed the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency, as required by 21 CFR § 820.20(c). Specifically, there is no documentation that management reviews were ever conducted.
2. Failure to establish procedures for quality audits and failure to conduct such audits to assure that the quality system is in compliance with the established quality system requirements and to determine the effectiveness of the quality system, as required by 21 CFR § 820.22.
3. Failure to establish and maintain procedures for implementing corrective and preventive actions and the failure to document corrective and preventive activities, as required by 21 CFR § 820.100. For example, none of your firm's corrective activities, including analysis of results, the investigation, or the verification and validation of changes to the manufacturing process, were documented.
4. Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR § 820.198. For example, your firm has received complaints; however, your firm did not document the complaints or document that any review or evaluation of the complaints had been conducted.
5. Failure to establish procedures that define the responsibility for review and the authority for the disposition of nonconforming product, and the failure to establish procedures that set forth the review and disposition process for nonconforming product, as required by 21 CFR § 820.90(b)(1). Specifically, your firm has not established procedures that define the review and disposition of nonconforming product. Disposition and acceptance of nonconforming product is occurring on a regular basis. For example, your firm received approximately 20 lots of thermoplastic material in 2007. None of these lots passed all acceptance level testing, yet your firm made the determination to accept the lots for distribution. There was no justification rationale documented for the use, release, and distribution of these lots.
6. Failure to establish and maintain procedures to control the design of a device, as required by 21 CFR § 820.30. For example, your firm failed to establish design controls that included adequate procedures for design inputs, design outputs, design verifications, design validations, design reviews, design transfers, and design changes.
7. Failure to demonstrate that the design was developed in accordance with the design control requirements of the QS regulation; and failure to establish a Design History File. [21 CFR § 820.30(a) through (j)]
Specifically, design controls were not used during the development of the design of the radiation stabilization devices in that (1) a design plan identifying and describing interfaces with different groups or activities was not developed; (2) the design inputs were not established; (3) the design outputs that are essential for proper functioning of the software are not identified; (4) the verification testing has not been performed to show that the design output meets the design input requirements; (5) a formal document review of the design results has not been conducted and the results have not been documented; (6) design validation has not been performed to ensure design specifications conform with user needs and intended use(s); and design transfer. See 21 CFR § 820.30(b), (c), (d), (e), (f), (g) and (h).
8. Failure to establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, as required by 21 CFR § 820.50. For example, your firm has not documented evaluations of product suppliers and contract manufacturers.
The inspection also revealed that your devices are misbranded within the meaning of section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refused to furnish any material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 803 (Medical Device Reporting regulation).
Specifically, your firm failed to develop, maintain, and implement written Medical Device Reporting procedures, as required by 21 CFR § 803.17.
You should take prompt action to correct the violations addressed in this letter. Failure to promptly correct these violations may result in regulatory action being initiated by FDA without further notice.
These actions include, but are 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, no premarket submission to which the Quality System regulation deficiencies are reasonably related will 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 in writing within fifteen (15) working days from the date you receive this letter as to 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 corrections will occur over time, please include a timetable for implementation of those corrections. If corrective action cannot be completed within 15 working days, please state the reason for the delay and the time within which the corrections will be completed.
Your written 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 concerning the contents of 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 firm. It is your responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, Form 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 actions to correct the violations to bring your products into compliance.
Carol A. Heppe