Inspections, Compliance, Enforcement, and Criminal Investigations
Therics, LLC 15-May-06
Department of Health and Human Services
Public Health Service
New Jersey District
Telephone (973) 526-6010
May 15, 2006
RETURN RECEIPT REQUESTED
Mr. Randall Theken
Theken Spine, LLC
283 E. Waterloo Road
Akron, OH 44319
Dear Mr. Theken:
During an inspection between March 3 and 16, 2006, at Therics, LLC, located at 115 Campus Drive, Princeton, NJ 08540 (hereafter, "your firm"), an investigator from the Food and Drug Administration (FDA) determined that your firm manufactures sterile bone void fillers. These bone void fillers are devices as defined by Section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S. C. § 321(h).
The March 2006 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 manufacture, packing, storage, or installation are not in conformance with the Quality System (QS) Regulation for medical devices, as specified in Title 21, Code of Federal Regulations (21 C.F.R.), Part 820, as follows:
1. Your firm failed to establish adequate procedures for quality audits, to conduct such audits to assure that the quality system is in compliance with the established QS requirements, and to determine the effectiveness of the quality system as required by 21 C.F.R. § 820.22. For example:
a. Your firm did not conduct quality audits at least annually even though your firm's procedure requires a complete quality audit "at least once every year." (FDA-483 Item 1).
b. Your firm's procedures for conducting quality audits are incomplete because they do not include provisions for examining areas such as Management Controls, Design Controls, Corrective and Preventive Actions, Production and Process Controls, etc. (FDA-483 Item 2).
2. Your firm failed to establish and maintain procedures for verifying the device design and confirming that the design output meets the design input requirements as required by 21 C.F.R. § 820.30(f). Your firm does not have a design verification protocol for the TheriLok II device. As such, specific test parameters and acceptance criteria were not outlined. (FDA-483 Item 4).
3. Your firm failed to review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency, according to the established procedures, to ensure that the quality system satisfies the requirements of the QS Regulation as required by 21 C.F.R. § 820.20(c). Your firm's procedures for management review were not implemented even though this procedure was approved in May 2005. The last management review was conducted in June 2005, yet it did not document coverage of appropriate quality inputs as outlined in the procedure. (FDA-483 Item 3).
4. Your firm failed to document activities related to corrective and preventive actions (CAPA), including investigations of nonconformities, as required by 21 C.F.R. § 820:100(b). Your firm has not documented any investigations or other CAPA activities regarding the following nonconformities:
a. Batch B030716003A was [redacted] during the verification study of [redacted] flow control for the TheriLok II device. There was no data to support the acceptability of the [redacted] process for the device, yet your firm considered the study to be acceptable. (FDA- 483 Item 6).
b. The qualification report for Kiln [redacted] was accepted by your firm even though it documented that the kiln did not meet specified temperature requirements. (FDA-483 Item 6).
5. Your firm failed to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit as required by 21 C.F.R. § 820.198(a). Your firm has not implemented or approved a draft complaint handling procedure dated August 2005 . (FDA-483 Item 7).
6. Your firm failed to maintain procedures for implementing CAPA as required by 21 C.F.R. § 820.100(a). Your firm has no documentation to show that it is reviewing and analyzing appropriate sources of quality data in order to identify existing and potential causes of nonconformance of products and other quality problems even though your CAPA procedure requires this. (FDA-483 Item 5).
7. Your firm failed to validate with a high degree of assurance, and to approve according to established procedures, a process that cannot be fully verified by subsequent inspection and test as required by 21 C.F.R. § 820.75(a). Your firm has not validated and approved the packaging process, the results of which cannot be verified by subsequent inspection and testing. For example:
a. There is no documentation that the [redacted] packaging process validation was complete and acceptable; there were no specified acceptance criteria to assure that the sealing process would maintain the sterility of the TheriLok II finished products. (FDA-483 Item 9).
b. Neither the [redacted] Heat Sealer process verification protocol, nor the Pouch Peel test method, specify requirements for sealing parameters or acceptance criteria for the pouch seal testing. Additionally, two different types of [redacted] packaging material were used during the validation study. (FDA 83 Item 9).
9. Your firm failed to establish and maintain acceptance procedures to ensure that specified requirements for in-process product are met as required by 21 C.F.R. § 820.80(c). Your firm did not have sufficient data to support the expiration period of the [redacted] Binder, and there was no assurance that your firm performed a visual package integrity test on bulk-packaged products prior to sterilization. (FDA-483 Item 10).
10. Your firm failed to establish and maintain procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria as required by 21 C.F.R. § 820.80(d). Your firm has not established physical test methods to assure the pouch seal integrity of finished products. The pouch seal is necessary to maintain the sterility of the finished product; therefore, your firm must perform more than visual check of the seal before and after sterilization. (FDA-483 Item 11).
11. Your firm failed to use a sampling plan that is written and based on valid statistical rationale as required by 21 C.F.R. § 820.250(b). Your firm's sampling plan for in-process, finished product, and stability samples was not complete because no Acceptance Quality Limit (AQL) was specified as required by your procedure. (FDA-483 Item 12).
In addition to your violations of the QS Regulation, the March 2006 inspection revealed that your devices are misbranded within the meaning of section 502(t)(2) of the Act (21 U.S.C. § 352(t)(2)), because your firm failed to establish complete Medical Device Reporting (MDR) procedures as required under section 519 of the Act (21 U.S.C. § 360i) and the MDR Regulations, 21 C.F.R. Part 803.
Your firm failed to develop, maintain, and implement a written MDR procedure for internal systems that includes the timely transmission of complete medical device reports to FDA and/or manufacturers as required by 21 C.F.R. § 803.17(a)(3). Specifically, your firm's MDR procedures do not provide for timely transmission of complete medical device reports to FDA. (FDA-483 Item 8).
This letter is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure adherence to each requirement of the Act and regulations. The specific violations noted in this letter and on the Form FDA-483, issued at the conclusion of the inspection, may be symptomatic of serious underlying problems in your firm's quality system. We note that many of these deviations were brought to your attention during the previous inspection of February 2005, yet corrections have not been made or were incomplete. You are responsible for investigating and determining the causes of the violations found by the FDA. Moreover, you must promptly initiate permanent corrective and preventive action on your deviations from the quality system and medical device reporting procedures.
We have received your written response, dated March 28, 2006, to FDA's March 2006 inspection of your firm. This response, however, does not demonstrate that your firm has made all of the necessary corrections and has ensured future compliance with the Act and FDA regulations. For example:
The response addresses only the FDA-483 items. However, as discussed above, the deviations noted on the FDA-483 may be a result of underlying, systemic problems with your quality system and medical device reporting procedures. Therefore, you must investigate your quality system and medical device reporting procedures beyond the scope of the FDA-483 observations and correct all deviations from the QS and MDR Regulations.
The action plan you provided in your response included only a bullet-point summary of proposed corrective actions. Without providing more comprehensive details of your actions, including revised standard operating procedures, revised forms, etc., FDA cannot determine whether your firm has corrected its deviations from the QS and MDR Regulations. Indeed, after FDA's February 2005 inspection, you provided FDA with a similar response to the deviations that FDA observed during that inspection. However, the March 2006 inspection revealed many deviations that were similar to those observed in the February 2005 inspection.
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 pre-market approval applications (PMAs) for Class III devices to which the Quality System/GMP deficiencies are reasonably related will be approved until the violations have been corrected. Also, no requests for Certificates to Foreign Governments will be approved until the violations related to the subject devices have been corrected.
You should take prompt action to correct all of your violations. 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 penalties.
Please notify this office within 15 working days of receipt of this letter of the specific steps you have taken to correct the noted violations, including an explanation of each step being taken to identify and make corrections to any underlying systems problems necessary to assure that similar violations will not recur. 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 implemented.
Please send your response to Sarah A. Della Fave, Compliance Officer, U .S. Food and Drug Administration, New Jersey District, 10 Waterview Boulevard, 3rd Floor, Parsippany, New Jersey 07054.
Dodglas I . Ellsworth
New Jersey District