| Public Health Service Food and Drug Administration |
| 466 Fernandez Juncos Avenue San Juan, Puerto Rico, 00901 Compliance Branch Telephone: 787-474-9500 FAX: 787-729-6658 |
Department of Health and Human ServicesFEB 7 2011
WARNING LETTER
VIA United Parcel Service
Mr. Graham Blackbeard
Managing Director
Southern Implants (Pty.) Ltd.
One Albert Road
Irene, Gauteng
South Africa
Dear Mr. Blackbeard:
During an inspection of your firm located in Irene, Gauteng, South Africa on October 4-7, 2010, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures Dental Implant Devices and Accessories. 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 manufacture, 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 (C.F.R.), Part 820. We received a response from Graham Blackbeard, Managing Director dated October 20, 2010, concerning our investigator’s observations noted on the Form FDA 483, List of Inspectional Observations that was issued to you. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:
1. Failure to establish and maintain adequate procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example:
Not all quality data sources are being monitored as described in your firm’s Customer Complaint/Input Work Instruction (QAP-14) to identify sources of nonconformance for corrective actions. Specifically, customer complaints are to be (b)(4) and (b)(4) analyses prepared each (b)(4); however, these analyses are performed (b)(4). In addition, the (b)(4) analyses categorizations lack specificity of the identified complaints to identify corrective actions. Nonconformances are not being monitored to identify potential areas requiring corrective actions even though your firm’s Procedure for Quality Management System Improvement (QAP-14-13) requires that nonconformance information is a (b)(4). Nor does QAP-14-13 identify internal complaints (nonconformance not related to suppliers) as a (b)(4).
Internal complaint (b)(4) refers to the incorrect product description appearing on the label. The product was a transfer coping, two part product, but was labeled as an impression coping, two part product. The internal complaint includes the comment “Unfortunately after the revision the same error was not corrected and the incorrect description remained on the label”. The internal complaint also includes the comment “(b)(4) of complaint not severe enough to require corrective action”. An investigation of the root cause and label control procedures was not documented; in addition, actions needed to correct or prevent the recurrence of nonconforming product due to incorrect product description were not identified.
Customer Complaint (b)(4) reported that item code (b)(4) labeled as a length (b)(4)mm Healing Abutment was in fact a (b)(4)mm Healing Abutment. The complaint was confirmed and the staff involved was retrained but there was no documented investigation to determine the root cause.
CAPA (b)(4) was opened in July 2010 as a preventive action regarding the lack of consistent procedures for applying laser marking on devices. The CAPA included categorizing laser marked products with information pertaining to the location of information for laser markings. The interim corrective action included using (b)(4) as guidance for the laser marking operators yet no documentation of the use of the (b)(4) or training of the operators on these revised procedures was made.
We have reviewed your response and have concluded that it is inadequate because your firm did not provide documentation of correction for internal complaint (b)(4), customer complaint (b)(4), and CAPA (b)(4). In addition, your firm only provided trend analyses of complaints and nonconformities per (b)(4) for 2009 and 2010. Your firm did not provide documentation of analysis conducted for each (b)(4) as indicated by their procedures. Your firm did not provide documentation which includes a description and evidence of implementation of the correction and corrective action (including consideration of systemic corrective action) to ensure that corrective and preventive action are implemented as required
2. Failure to establish and maintain adequate procedures to ensure that the design requirements relating to a device are appropriate and address the intended use of the device, including the needs of the user and patient. The design input requirements shall be documented and shall be reviewed and approved by a designated individual, as required by 21 CFR 820.30(c). For example:
The design input for the Zygomatic implants does not describe the rationale for the establishment of the design requirements. The design input requirement for the restorative angle of the implant is (b)(4) relative to (b)(4) but there was no documentation or reference to the basis for this angle to ensure that this design requirement is appropriate. The predicate device from Branemark has an angle of (b)(4) but your firm indicated this angle was causing problems with speech. There is no determination of how the (b)(4) design input was established.
The design input for the head diameter is not explicitly identified and the procedure does not specify how to address this ambiguous requirement. It is indicated to be “large enough such that an internal (b)(4) thread can reach a depth of (b)(4)mm”.
There are no specified design requirements for the dimension or characteristic of the input identified as (b)(4) and the procedure does not specify how to address this incomplete and ambiguous requirement. The flute is part of the Zygomatic implant that provides the bone cutting and location for the cut bone residue to pass away from the cutting surface. The design input does not describe the dimensions or sharpness of the cutting surface. The design for the flutes changed twice since the initial design implementation.
We have reviewed your response and have concluded that it is inadequate because your firm did not provide documentation of completing all the applicable design requirements required when implementing corrections and corrective action for not implementing appropriate design inputs for the Zygomatic implants. Your firm did not provide documentation which includes a description and evidence of implementation of the correction and corrective action (including consideration of systemic corrective action) to ensure that design requirements are appropriate for the Zygomatic implants. Your firm revised their Requirement Specifications/Design Input – Zygomatic Implant (Rev. 2) to address additional design requirements such as the flutes. Your firm also provided a justification for the head diameter input and angle of the zygomatic implant. Evidence of the appropriate employees being retrained was provided.
3. Failure to establish and maintain adequate procedures for the identification, documentation, validation, or where appropriate verification, review, and approval of design changes before their implementation, as required by 21 CFR 820.30(i). For example, the design change for the Zygomatic implant includes changes made to the flute. The design for the flute was changed in revision 3 and 6 yet neither of these changes included a reason for the change or validation or where appropriate verification, of the change.
We have reviewed your response and have concluded that it is inadequate because your firm did not provide validation or verification of the design changes made to the flute but instead provided the requirement specifications for the Zygomatic implant and justification for the specifications of the Zygomatic implant head diameter. Your firm did not provide documentation which includes a description and evidence of implementation of the correction and corrective action (including consideration of systemic corrective action) to ensure that design changes are performed as required for the Zygomatic implants
4. Failure to establish and maintain procedures to ensure that formal documented reviews of the design results are planned and conducted at appropriate stages of the device’s design development. The results of the design review, including identification of the design, the date, and the individuals performing the reviews, shall be documented in the design history file, as required by 21 CFR 820.30(e). For example, your firm’s Procedure for Design Control (QAP-04-13) for the Zygomatic implant was retrospectively compiled. The original version of the design drawing was made in 2000 but the design history file was compiled in September 2010. The design history file does not show that a design plan and design reviews were made.
We have reviewed your response and have concluded that it is inadequate because your firm did not provide documentation that design reviews were conducted and placed in the design history file. Your firm did not provide documentation which includes a description and evidence of implementation of the correction and corrective action (including consideration of systemic corrective action) needed to ensure that design reviews would be performed as required for the Zygomatic implants.
5. Failure to establish and maintain adequate procedures to control labeling activities, as required by 21 CFR 820.120. For example:
Your firm’s Work Instruction: Packaging and Labeling (PRO-6003-06) is the procedure for the labeling operations of the implants and accessories.
The procedure does not clearly describe who will verify the accuracy of generated labeling. Checks are made and documented on the label order form but the details of how the check is to be made are not identified in the procedure.
We have reviewed your response and have concluded that it is inadequate because your firm did not provide documentation that the all labeling previously released had been controlled as required using the revised procedures. Your firm did not provide documentation which includes a description and evidence of implementation of the correction and corrective action (including consideration of systemic corrective action) as needed to ensure appropriate packaging and labeling checks are conducted as required for the implants and accessories. Your firm provided the CAPA that was generated addressing the root cause of these issues. Your firm revised their Master Label template to include a verification process to eliminate errors such as the same revision number on two revisions of labels. A revised Work Instruction: Preparation of Labels (PRO-6037) addresses more stringent verification procedures and final label approval by the Design Engineer, Sales Manager, Regulatory Officer, and MRQ. Your firm revised their Work Instruction: Packaging & Labeling (PRO-6003) procedure to state that the ordered labels will be verified by a second Packaging and Labeling Officer. A flow diagram for both work instructions (PRO-6037 and PRO-6003) accompanies the procedures. An amended Work Instruction: Secondary Processing Logistic Officers (PRO-6032) addresses streamlining the controls of labeling.
Our inspection also revealed that your Dental Implant Devices and Accessories devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. 352(t)92), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. 360i and 21 C.F.R. Part 806- reports of Corrections and Removals regulation. Significat deviations include, but are not limited to the following:
Failure to provide justification for not reporting a correction or removal action to FDA as required by 21 CFR 806.20(b)(4). For example, your firm initiated a recall of Converter/I-WI-C-S due to the possibility of breakage of the piece when it was subject to excessive torque. Your firm had at least two complaints that described breakage of the part yet there was no documentation justifying the decision for not notifying FDA of the correction and removal.
Your response to this observation appears to be adequate in that your actions were reviewed and it was determined that your firm’s modifications to the converter did not pose a risk to health; however, your firm failed to make available the documentation supporting this decision during the inspection.
You should take prompt action to correct the violations addresses in this letter. Failure to promptly correct these violations may result in regulatory action, which may include detaining your devices without physical examination upon entry into the United States until the corrections are completed. Section 801 (a) of the Act 921 U.S.C.§ 381(a)). .Also, U.S. 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 approval 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 in writing 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 action 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, state the reason for the delay and the time within which the corrections will be completed. If the documentation is not in English, please provide a translation to facilitate our review.
Your response should be sent to: Field Operations Branch, Office of Compliance, CDRH, Food and Drug Administration, 10903 New Hampshire Avenue, Building 66, Silver Spring, Maryland, 20993, USA. If you have any questions about the content of this letter please contact: Damia Jackson at (301) 796-6671 or (301) 796-8137.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your facility. 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 (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 and to bring your products into compliance.
Sincerely yours,
/s/
Steven D. Silverman
Director
Office of Compliance
Center for Devices and
Radiological Health
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