March 6, Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane, Room 1061 Rockville, MD 20852

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1 701 Pennsylvania Avenue, NW Suite 800 Washington, D.C Tel: Fax: March 6, 2017 Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane, Room 1061 Rockville, MD Re: Docket No. FDA 2016 D 4436: Premarket Notification (510(k)) Submissions for Bone Anchors; Draft Guidance for Industry and Food and Drug ; Availability Dear Sir/Madam: On behalf of AdvaMed, the Advanced Medical Technology Association, we are pleased to submit these comments in response to the Food and Drug Administration s (FDA s or the Agency s) request for comments on the draft guidance entitled: Premarket Notification (510(k)) Submissions for Administration Staff. AdvaMed represents manufacturers of medical devices, diagnostic products, and health information systems that are transforming health care through earlier disease detection, less invasive procedures, and more effective treatments. Our members produce nearly 90 percent of the health care technology purchased annually in the United States and more than 50 percent of such technology purchased annually around the world. These members range from the smallest to the largest medical technology innovators and companies. Nearly 70 percent of our members have less than $30 million in sales annually. AdvaMed supports FDA s efforts to provide updated guidance to sponsors regarding FDA s recommended content for 510(k) submissions and testing associated with bone anchor devices and has general and specific comments (included in table format) below. General Comments AdvaMed recommends a number of changes that are intended to synchronize the draft guidance on 510(k) submissions for bone anchors with a least burdensome approach and to ensure consistency with existing final guidance or guidance currently in draft but that will be finalized in the future. These include the following: The Class II Special Controls Guidance Document: Surgical Sutures for data submission requirements associated with sutures; Bringing innovation to patient care worldwide

2 Division of Dockets Management (HFA-305) March 6, 2017 Page 2 of 11 The guidances entitled Submission and Review of Sterility Information in Premarket Notification (510(k) Submissions for Devices Labeled as Sterile and Use of International Standard ISO , Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process with respect to materialmediated pyrogenicity; and The draft guidance Deciding When to Submit a 510(k) for a Change to an Existing Device with respect to when 510(k) submissions for bone anchor device modifications are required. Specific Comments AdvaMed s specific comments on the guidance are presented below in tabular form. In closing, thank you for the opportunity to comment on the draft guidance Premarket Notification (510(k)) Submissions for Bone Anchors. Please don t hesitate to contact me if you have any questions. Sincerely, /s/ Tara Federici Vice President Technology and Regulatory Affairs

3 Several suture anchor products currently bear cleared indications for both repair and reconstruction utilizing artificial graft materials. It is inappropriate to exclude these from this guidance. Clarify that other product codes (HWC) may still be used as predicates. Requiring fully dimensioned drawings for all device components exceeds the concept and mandate of the 510(k) which requires a summary device description. This also leads to risks that minor changes to drawings, which would not otherwise trigger a new 510(k) may be deemed changes requiring re-submission. This section should clarify that there is no need to repeat all the materials information if referencing a cleared 510(k). When using a marketed suture, manufacturers may not have access to the proprietary information from the suture manufacturer. If a manufacturer is utilizing a previously cleared suture as a component of a suture anchor device, they should not need to restate all detailed specifications related to USP conformity. This does not represent a least burdensome approach. address anchors used to attach bone to bone, or interference screw components., nor does it address anchors intended for use with artificial ligaments or tendons. future submissions be submitted and cleared under the product codes MAI or MBI as noted above. Older product codes may still be used as predicates. Delete the following: We recommend you provide fully dimensioned engineering drawings for all device components to capture this information. Add the following at the end: Manufacturers may reference the supplier s master file to access this information. If a suture is included with the anchor construct (e.g., preloaded with the anchor on an inserter), you should provide the identity and percentages of all materials (including coatings and additives) and the sizes of sutures using the size system identified in the currently recognized United States Pharmacopoeia (USP). For more information of details of the data to be included with a suture component, please refer to the FDA guidance document, Class II Special Controls Guidance Document: Surgical Sutures. ( 3/6/2017 Page 3 of 11

4 vices/deviceregulationandguidanc e/guidancedocuments/ucm pdf) If the suture has been previously cleared by the Agency, you should identify the submission number (e.g., 510(k) number) and provide a statement that the suture is the same as the previous 510(k) or confirm that the suture remains compliant with USP requirements as defined in the reference 510(k). For more information on appropriate information to be included with a suture component, please refer to the FDA guidance document, Class II Special Controls Guidance Document: Surgical Sutures ( es/deviceregulationandguidanc e/guidancedocuments/ucm pdf) To clarify what is meant by compatible component. Please clarify the intent of this (i.e., what does the Agency define as the degradation timeframe ) and confirm that providing this information would not be required if the proposed device s material of construction is identical to that of the predicate device. It is unclear why specifications for raw materials would be required in a 510(k) when using a risk assessment to assess biocompatibility but not when testing is completed. Additionally, specifications for raw materials seem to exceed the intended scope of the 510(k). All compatible components intended by the sponsor to be used with of the fixation system should be provided. Strike and insert the following: a. Specifications Description of the incoming raw material. 3/6/2017 Page 4 of 11

5 This text is redundant to the existing FDA Guidance document on biocompatibility and provides an opportunity for divergence of requirements and confusion regarding the source guidance document to reference for FDA s current thoughts on the topic. We believe the reference to the current guidance is adequate instruction and is more consistent with FDA s approach in subsequent sections of this guidance (i.e., s D, F, H et al.). The guidance for biocompatibility testing within this document should only focus in detail on biocompatibility considerations which are unique to bone anchor devices. To clarify it is acceptable to conduct testing on finished coated suture rather than treating the coating and suture as separate entities and conducting testing on both respectively. Per ISO and Attachment A of FDA s guidance, bone anchors are considered implant devices in contact with tissue/bone for a permanent contact duration. Devicespecific, patient-contacting instrumentation (e.g., inserter shafts) in contact with tissue/bone are considered a temporary contact duration. Therefore, the following endpoints should be addressed in your biocompatibility evaluation: Material-Mediated Pyrogenicity If the suture component includes a coating, this coating should be evaluated as part of the finished good per for biocompatibility in addition to the bulk suture material And This language is redundant to the reference to the guidance on line 242 to 247 and the guidance provides more detail regarding pyrogenicity. These lines are unnecessary when considering the Sterility and Biocompatibility Guidance, which is also referenced in this section. Removing these lines will eliminate the possibility of conflicting information between the documents. Strike the following: Significance: Pyrogenicity testing is used to help protect patients from the risk of febrile reaction due to gram-negative bacterial endotoxins and/or chemicals that can leach from a medical device (e.g., materialmediated pyrogens). Strike the following: For devices intended to be labeled as nonpyrogenic, we recommend that both bacterial endotoxin and rabbit material-mediated pyrogen testing be conducted. 3/6/2017 Page 5 of 11

6 Use of past tense suggests that all packaging testing is complete prior to the 510(k) being submitted. Clarify to ensure that routine packaging/distribution validation can be done during or after the 510(k) review process when appropriate. Use of past tense suggests that all routine shelf life testing has been completed prior to the 510(k) being submitted. Clarify to ensure routine shelf life validation can be completed during or after the review 510(k) process when appropriate. The wording this testing may be conducted in parallel with 510(k) review and clearance could imply that all real-time aging must be completed at the time of FDA clearance. It is common practice that the real-time aging testing runs well beyond FDA clearance and the device is initially labeled based on the results of accelerated aging data. To clarify that bench testing should, where possible, mimic surgical and clinical use. Examples of what the Agency deems as acceptable for clinically based justification would be helpful, especially for small companies. Insert the following: test methods used and/or planned. Add the following: specify the way in which the devices plan to be or were aged Strike and add the following: This testing may be conducted initiated in parallel with 510(k) review and clearance. with rresults of testing completed after 510(k) clearance may be documented to file in the design history file (i.e., the test reports do not need to be submitted to FDA unless the results raise new questions of safety and effectiveness). Strike and replace the sentence on lines 305 to 308: Bench testing should assess implantation of the device using the surgical technique identified in the labeling, including any device specific instrumentation. Bench testing should, where possible, mimic surgical and clinical use, for instance in assessing the directionality of forces placed on the components. 3/6/2017 Page 6 of 11

7 A complete test report is only provided for Traditional 510(k)s. This information is summarized in Special 510(k)s. Some anchor designs can make it very difficult to quantify and show that the anchor itself is or is not damaged. Clarifies that showing adequate anchor fixation strength and no (or acceptable levels of) damage to inserter is acceptable. The example referenced contradicts a recent reviewer recommendation on foam bone. Companies have received recent direct guidance from FDA that 40 pcf foam bone is appropriate for bone anchor static insertion testing. In addition, ASTM only covers foam bone up to 40 pcf. We believe this should be left to sponsor discretion based on clinical justification. Add the following: When submitting a Traditional 510(k), you should ensure that a complete test report is provided for each test, including all relevant Add the following: The worst-case for insertion should evaluate the ability of the anchor to be deployed correctly and without damage to the device. It is acceptable to show that the device has been deployed undamaged by evaluating fixation/pullout strength. Strike the following: the Agency recommends testing in a dense bone substitute (e.g., 50 pound per cubic foot (PCF) foam per ASTM F1839) Under clinical circumstances, load is transferred through the healing period and thus, the relevance of pull out is that even if there is a drop over time, the anchor would not be required to carry full load through the healing period. Add the following: We recommend that you conduct cyclic testing with a clinically justified load and cycle number. We further recommend you conduct pullout testing following cyclic loading to demonstrate that clinically relevant pullout strength is retained Ensure that fatigue testing can be a direct comparison to the predicate or clinical literature. Insert at the end the following: Fatigue testing acceptance criteria can be supported either by clinical literature or the performance of a predicate device. 3/6/2017 Page 7 of 11

8 AdvaMed Comments on Premarket Notification (510(k)) Submissions for To clarify that this section is for Nitinol specifically, edits are suggested. To clarify that methods outlined in the following standards are acceptable to the Agency: ISO Poly(L-lactide) resins and fabricated forms for surgical implants -- In vitro degradation testing ISO Biological evaluation of medical devices -- Part 9: Framework for identification and quantification of potential degradation products, ISO Implants for surgery -- Copolymers and blends based on polylactide -- In vitro degradation testing Remove the following: or other metallic bone anchor materials Add references to the following standards: ISO Poly(L-lactide) resins and fabricated forms for surgical implants -- In vitro degradation testing ISO Biological evaluation of medical devices -- Part 9: Framework for identification and quantification of potential degradation products, ISO Implants for surgery -- Copolymers and blends based on polylactide -- In vitro degradation testing The recommendation to perform degradation testing in foam bone contradicts standard F1635 as follows: Excerpt from F1635, section Note 3 Caution must be taken to ensure that fixturing does not introduce artifactual performance and/or degradation issues. An example is the use of rigid foam block, which restricts swelling and expansion and can elevate pull out strength test results from sample compression within the block. Additionally, restricted perfusion due to the closed cell nature of the foam can result in concentration of acidic byproducts that result in accelerated degradation when compared to a normally perfused and buffered in vivo condition. Strike and add the following: Furthermore, it is recommended that degradation testing be performed in an appropriate worst-case bone substitute consistent with the setup described in the pullout testing section above in accordance with the test setups described in ASTM F1635 and ASTM F /6/2017 Page 8 of 11

9 FDA is requesting head-to-head degradation testing with the predicate device. This is a restrictive and burdensome requirement and can be demonstrated by conformance to clinically relevant, pre-specified performance criteria over time. FDA has allowed clinically relevant justified acceptance criteria in Sec.5 lines This makes the various requirements consistent. Add the following: During testing, the peak pullout force should be compared to a legally marketed predicate with equivalent indications for use and technological characteristics or to prespecified and clinically relevant justified acceptance criteria. We recommend you compare the performance at time zero (0) and at multiple time points beyond (e.g., 3, 6, 12, 26 weeks). To clarify that testing needs to be conducted on the finished device. Add language to Sec. 7 to clarify that all degradation testing must be performed on devices packaged and sterilized in a manner consistent with that of the final device In addition to the mechanical characterization, it is recommended that you characterize device material degradation (e.g., mass loss, molecular weight changes (number and weight average)) over the course of testing to more fully characterize the degradation process To clarify expectations with respect to clinical studies. Add an example along the following lines: A device has the same intended use but a new indication in different anatomical area is being pursued and clinical literature is not yet available Clinical testing should not generally be required in cases where a difference in technology does not raise different questions of safety or effectiveness. As per the FDA Guidance The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)], Strike the following: different technology (e.g., materials) from that used in legally marketed devices of the same type, yet does not raise different questions of safety or effectiveness, 3/6/2017 Page 9 of 11

10 it is only in limited situations where clinical data may be needed to evaluate the safety and effectiveness of the new device as compared to the predicate device. The guidance document states that clinical data should only be required if the differences in technology raise different questions of safety or effectiveness Please note that not all bone anchors are intended for use by orthopedic surgeons. For instance, anchors are used by gynecologists doing sacrocolpoplexy. familiarize users trained in the target specialty (e.g., orthopedic surgery surgeons, gynecologists) with the features The recommended changes make this draft guidance on Premarket Notification (510(k)) Submissions for Bone Anchors consistent with the draft guidance entitled Deciding When to Submit a 510(k) for a Change to an Existing Device guidance. These two guidances should be consistent when they are finalized. FDA has determined recommends that manufacturers use Deciding When to Submit a 510(k) for a Change to an Existing Device to analyze that any one of the modifications listed below. If it is determined the change significantly affects safety and effectiveness of the device, it would generally require a new 510(k). Please note that this list is not exhaustive, but provides examples of modifications FDA believes that will generally lead to significant changes in safety and effectiveness thereby requiring require a new 510(k). The addition of a smaller or larger anchor diameter than what was previously cleared or the addition of a smaller suture size FDA considers these changes to be a significant change in design. FDA has determined that these For example, the changes could significantly affect the safety and effectiveness of the device by introducing a new potential worst-case scenario for some failure modes. A modification to the insertion technique (e.g., change from pre-drilled to 3/6/2017 Page 10 of 11

11 self- punching) FDA considers this change to be a significant change in design of the anchor or the instrumentation. FDA has determined that this For example, the change could significantly affect the safety and effectiveness of the device by altering the risk of adequate fixation. The modification of the material formulation of a bone anchor or a change to a new material such as from a non-absorbable to absorbable suture FDA considers these changes to be a significant modification in material, chemical composition, or material processing. FDA has determined that For example, these changes could significantly affect the safety and effectiveness of the device by introducing new or increased biocompatibility concerns or a change in the risks associated with device failure. 3/6/2017 Page 11 of 11