An Open Letter to the Dental Profession
FDA BANS IMPORT OF NOBELPHARMA IMPLANTS
Reprint of FDA Letter to Nobelpharma AB [now Nobel Biocare] from
Carol Shirk, U.S. Food and Drug Administration, with Preface by Dr. Niznick
The FDA, in its February 21 1992 Warning Letter to Nobelpharma AB, Sweden, ruled that, due to serious violations in Good Manufacturing Practices (GMP), Nobelpharma’s endosseous implants shall be banned from importation into the United States. The FDA Warning Letter states that this ban will remain in effect until Nobelpharma provides an adequate written response to the charges and the FDA has an opportunity to conduct another inspection of the Swedish facilities to verify the implementation of the corrections. Due to Nobelpharma USA’s lack of candor with its customers, the full text of the FDA Warning Letter is being sent to you. Nobelpharma’s response letter to its customers failed to even mention that it is banned from shipping endosseous implants to the United States for an indeterminate period of time.
Nobelpharma’s response letter characterizes their 11 serious violations to GMPs as "suggestions by the FDA." It acknowledges the FDA’s criticism of "the Company’s sterilization procedures," but attempts to explain this away by stating that this is because Nobelpharma’s procedures "are generally unfamiliar to the FDA, but widely used in Europe." In 1989, Nobelpharma’s Swedish manufacturing plant and corporate headquarters received its first inspection by the FDA. Nobelpharma’s corporate management at Gothenburg was issued a control of the dry heat sterilization process." At that time, it was noted that "management promised corrective action" and that "product may have to be refused entrance into the U.S." Nobelpharma apparently failed to undertake the required corrective action regarding sterility controls. Nobelpharma’s letter to its customers further asserts that "none of the FDA inspectional observations in any way called into serious question the safety or efficacy of the FDA to protect the public from unsafe products." Now that the profession is aware of Nobelpharma’s serious violations of GMPs and the resulting ban on importation of its implants, the profession should consider the potential medical/legal liability from use of Nobelpharma’s implants in the absence of full disclosure and proper informed consent from their patients. A partial list of Nobelpharma’s GMP violations is listed below:
FAILURE #2: –– "Failure to establish adequate written procedures describing any processing controls...there are no procedures for, nor documentation of, the ampoule inspection prior to any of the sterilization processes, and after the dry heat sterilization."
FAILURE #5 –– "Failure to investigate, after a device has been released for distribution, any failure of that device or any of its components to meet performance specifications."
FAILURE #7 –– "Failure to immediately review, evaluate, investigate, and to maintain in a separate portion of the complaint pertaining to injury, death, or any other hazard to safety."
FAILURE #10 –– "Failure to establish adequate written procedures for warehouse control and distribution of finished devices to assure that only those devices approved for release are distributed."
FAILURE #11 –– "Failure to provide device packaging and shipping containers that are designed and constructed to protect the device from alteration or damage during customary conditions of distribution...709 complaints were received during the past year."
In light of the FDA’s Warning Letter, all dentists using implant devices might question the quality control standards that exist in the industry. Core-Vent Bio-Engineering manufactures the Spectra System® and Swede-Vent® Implant in full GMP compliance including conducting the stringent testing requirements for obtaining 510(k) authorization to market abutments. Nobelpharma USA was sent an FDA Warning Letter in August 22, 1991 for selling an implant device without 510(k) authorization and for failure to report implant fractures to the FDA. In the most recent Warning Letter to Nobelpharma Sweden, reference is also made to restriction of sale of certain products in the US that do not have 510(k) market authorization.
Re-print of FDA Letter to Nobelpharma AB [now Nobel Biocare]:
REGISTERED MAIL –– RETURN RECEIPT REQUESTED
February 21, 1992
Mr. Mats Pettersson
Gothenburg, S-40226 Sweden
Dear Mr. Petterson:
During an inspection of your manufacturing facilities located at Dimbovagen 2, Karlskoga, Sweden, and Bohusgatan 15, Gothenburg, Sweden, on November 11 through 13, 1991, our investigator observed conditions which may contribute to serious violations of the Federal Food, Drug, and Cosmetic Act (the Act) and deviations from implementing regulations as follows:
1. Failure to establish adequate procedures for specification control measures to assure that the design basis for the device is correctly translated into approved specifications, as required by 21 CFR 820.100(a)(1). For example, the dry heat sterilization process has not been adequately validated and documented to support the use of parametric release.
2. Failure to establish adequate written procedures describing any processing controls necessary to assure conformance to applicable specifications, and conduct all process control operations in a manner designed to assure that the device conforms to applicable specifications, as required by 21 CFR 820.100(b) (1) and (2). For example, there are no procedures for, nor documentation of, the ampoule inspection prior to any of the sterilization processes, and after the dry heat sterilization. About 309 complaints regarding ampoule breakage were received in the past year.
3. Failure to maintain a device history record which demonstrates that the device is manufactured in accordance with the device master record, as required by CFR 820.184. For example, sterilizer loads in the dry heat oven have exceeded the maximum load defined in the established procedures, i.e., batch 506132 and 504572, and time/temperature for each cycle is not recorded in the sterilization control log as required.
4. Failure to maintain a critical device history record which contains or refers to the location of the inspection checks performed, the methods and equipment used, results, the date and signature of the inspecting individual, as required by 21 CFR 820.185(c). For example:
a. Product received under work order numbers 580483, 520091 and 520093 from the contract sterilizer were released without the required documentation of inspection and review.
b. The device history records for work order numbers 502737, and 502981 fail to document the performance of critical device inspections and the signature of the inspecting individual(s).
5. Failure to investigate, after a device has been released for distribution, any failure of that device or any of its components to meet performance specifications, and maintain a written record of any failure investigation, including conclusions and follow-up, as required by 21 CFR 820.162. For example:
a. The procedure for returned goods does not provide for review and evaluation to determine if a failure investigation should be conducted.
b. There are no records to demonstrate that failure investigations have been performed.
c. "Quality Messages" issued to Nobelpharma subsidiaries identify product defects for distributed products, but there is no record of the investigation, to include conclusions and follow-up.
6. Failure to establish written procedures for any reprocessing associated with the production of a critical device or component that provides for equipment to be used, any special quality assurance methods or tests, determination and documentation of the effect of constant reprocessing on a device or a component, and written testing and sampling procedures for any critical device or component subject to reprocessing to assure conformity to the original, or subsequently modified, and approved specifications, as required by 21 CFR 820.116. For example, there are no procedures for, nor documentation of, the rework/resterilization of the ampoules, no retesting is performed, and there is no documentation to demonstrate that the rework does not adversely affect the product.
7. Failure to immediately review, evaluate, investigate, and to maintain in a separate portion of the complaint pertaining to injury, death, or any other hazard to safety, as required by 21 CFR 820.198(b). For example, complaints pertaining to injury are not reviewed and evaluated in a timely manner, and are not maintained in a separate portion of the complaint file.
8. Failure to maintain a record of the reason and the name of the individual responsible for the decision not to investigate written and oral complaints, as required by 21 CFR 820.198(a). For example, when an investigation is not performed, the reason and person responsible for making the decision not to investigate are not documented.
9. Failure to subject specification changes to controls as stringent as those applied to the original design specifications of the device, have such changes approved and documented by a designated individual(s), and include approval date and the date the change becomes effective, as required by 21 CFR 820.100(a)(2). For example, the recent change in specifications for the endosseous implant [INFORMATION CENSORED] packaging, due to the change to steam sterilization, has not been validated, and there is no documentation of the approval of this change.
10. Failure to establish adequate written procedures for warehouse control and distribution of finished devices to assure that only those devices approved for release are distributed, as required by 21 CFR 820.150. For example, accepted product was stored in process/unaccepted product.
11. Failure to provide device packaging and shipping containers that are designed and constructed to protect the device from alteration or damage during customary conditions of distribution, as required by 21 CFR 820.130. For example, 709 complaints were received during the past year, the majority of which were for receipt of broken ampoules which contain the sterile endosseous devices.
Review of our records indicates that you have not submitted any premarket notification 510(k) for the [INFORMATION CENSORED]. Promotion and distribution of this device without submission of a premarket notification may result in the device being misbranded in accordance with Section 502(o) of the Act.
Therefore, you are hereby notified to discontinue any further distribution of the subject device in the United States. The [INFORMATION CENSORED] will be refused entry into the United States until your firm has received a 510(k) clearance from the FDA.
Questions regarding the submission of a premarket notification 510(k) should be directed to the Food and Drug Administration (FDA), Center for Devices and Radiological Health (HFZ-403), 1390 Piccard Drive, Rockville, Maryland 20850, phone (301) 427-1190.
The above identification of violations is not intended to be an all-inclusive list of deficiencies at your facility. It is your responsibility to ensure that all products manufactured, distributed, held, and labeled by your firm are in compliance with the provisions of the Act.
Given the serious nature of these violations of the Act, all endosseous implants manufactured by Nobelpharma AB, Bohusgatan 15, Gothenburg, Sweden, and Nobelpharma Produktion AB, Dimbovagen 2, Karlskoga, Sweden, will be refused entry into the United States until these violations are corrected. Until these violations are corrected, Federal agencies will be informed that the FDA recommends against the award of contracts for affected products.
In order to remove the devices from this detention, it will be necessary for you to provide written response to the charges in this Warning Letter for our review. After we notify you that the response is adequate, it will be your responsibility to schedule another inspection of your facility. As soon as this inspection has taken place, and the implementation of your corrections has been verified, your products may resume entry into this country.
Please advise us in writing as to the specific actions taken, or intended to be taken, to correct these deficiencies. We acknowledge receipt of your January 21, 1992, letter in response to the inspection, and you may refer to it in your response to this letter. Please include any and all documentation to show that adequate correction has been achieved. In the case of future corrections, an estimated date of completion, and documentation showing plans for correction, should be included with your response to this letter. To expedite our review, please include an English translation of the supporting documentation with your response. Please address any questions to:
Ms. Carol Shirk
U.S. Food and Drug Administration
CDRH, Office of Compliance and Surveillance (HPZ-331)
1390 Piccard Drive
Rockville, Maryland 20850 U.S.A.