WARNING LETTER
Steiner Biotechnology, LLC
MARCS-CMS 651802 —
May 19, 2023
Delivery Method:
VIA UNITED PARCEL SERVICE
Product:
Medical Devices
Recipient:
Recipient Name
Gregory G. Steiner, DDS
Recipient Title
CEO
Steiner Biotechnology, LLC
1051 Olsen Street, Suite 3611
Henderson
,
NV
89011
United States
Issuing Office:
Center for Devices and Radiological Health
United States
WARNING LETTER
CMS #651802
May 19, 2023
Dear Dr. Steiner:
During inspections of your firm located at 1051 Olsen Street, Suite 3611, Henderson, NV 89011 on August 15–19, 2022 and November 3-8, 2022, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures bone grafting materials including, the Socket Graft, Socket Graft Plus, Socket Graft Injectable, OsseoConduct, OsseoConduct Micron, Ridge Graft Kit, Immediate Graft, and Oral Bond. 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 to affect the structure or any function of the body.
Observations Pertaining to Quality System Regulation Provisions and Regulations
The inspections 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 requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820. We received a response from you dated November 21, 2022, concerning our investigators’ observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that was issued to your firm. 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 to control the design of the device in order to ensure that specified design requirements are met, as required by 21 CFR 820.30(a). For example,
Your firm manufactures various implantable bone grafting materials, including the OsseoConduct, Socket Graft, Immediate Graft, and Socket Graft Injectable, which require design controls and you have not established design control procedures.
a. Your firm’s “Quality Management Systems Manual,” dated June 1, 2017, includes high level requirements indicating design activities will be conducted and meet the requirements outlined in 21 CFR 820.30; however, this manual does not include procedures on describing how these activities will be conducted or documented.
b. You verbally confirmed your firm’s only design control procedures were your “Design Input Requirements,” SOP 010-02, dated June 1, 2017. However, these procedures do not include procedures for design output, design reviews, design verification, design validation, design transfer, or changes, as required by 21 CFR 820.30(d) through (i).
c. Your firm’s “Design Input Requirements,” SOP 010-02, dated June 1, 2017, does not include a mechanism for addressing ambiguous, incomplete, or conflicting requirements, as required by 21 CFR 820.30(c).
d. Your firm has not established and maintained procedures for design verification, as required by 21 CFR 820.30(f). For example, your firm’s “Quality Management Systems Manual,” dated June 1, 2017, states design verification will be conducted to ensure design outputs have satisfied design input requirements. The product labeling for your OsseoConduct device identifies the following design inputs:
(b)(4)
However, you did not provide procedures for confirming that design output meets the design input requirements. You also did not provide documentation showing these design inputs have been verified. This is a repeat observation from the previous December 10-13, 2018, FDA inspection and a violation listed on the Untitled Letter issued to your firm on April 3, 2019. Your November 21, 2022 response is inadequate because, although you provided images of histological results, you did not provide supporting data or records, including pyrogen testing, to support what the test methods and records are purported to be.
e. Your firm has not established and maintained adequate design validation procedures to ensure that devices conform to defined user needs and intended uses and shall include testing of production units under actual or simulated use conditions, as required by 21 CFR 820.30(g).
i. Your firm’s “Quality Management Systems Manual,” dated June 1, 2017, requires design validation to ensure that the resulting product is capable of fulfilling the requirements for the specified or known intended use or application. The labeling for your OsseoConduct bone grafting material states that this product was developed to meet the following criteria:
1. Does not elicit an inflammatory response
2. Produce bone with normal form and function
3. Be significantly resorbed in 3 months
4. Be able to handle reasonable load in order to resist deformation during the remodeling phase
5. Allow ease of application
6. Be designed to prevent bacterial colonization
However, your firm did not provide procedures to ensure that devices conform to defined user needs and intended uses that include testing of production units under actual or simulated use conditions. You also did not provide documentation to demonstrate the OsseoConduct device was validated to ensure it conforms to these user needs. Your November 21, 2022 response is inadequate because, although you provided images of histological results, you did not provide supporting data or records, including pyrogen testing, to support what the test methods and records are purported to be.
ii. Your firm has not established adequate procedures for risk analysis, as required by 21 CFR 820.30(g). Specifically, your firm manufactures the OsseoConduct bone graft material which is labeled to be an implantable, sterile, biocompatible, and pyrogen free device. However, the risk analysis documented in your Design History File dated June 1, 2017, does not identify any foreseeable hazards associated with the use of this device. Your November 21, 2022 response is inadequate because the “Risk Management Plan” you provided does not identify reasonably foreseeable hazards with your implantable sterile device.
We reviewed your firm’s response dated November 21, 2022, and conclude it is not adequate. Your firm’s response states your firm has conducted histology and biocompatibility studies which support the validation and verification of your OsseoConduct device. However, the records you provided to support this assertion do not show these studies were conducted using the OsseoConduct device. Additionally, the histology data provided does not include the study protocol or methods used to generate the data. Further, your response does not address the lack of adequate design control procedures or how you plan to correct this deficiency.
2. Failure to adequately ensure that when the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedure, as required by 21 CFR 820.75(a). For example,
a. Your firm’s “Process Validation,” SOP 018, revision 2, dated June 1, 2017, establishes high level requirements for process validation; however, these procedures do not establish any specific requirements for the sterilization process validation for each of your devices.
b. Your firm uses a
(b)(4)
process to sterilize your Oral Bond and Socket Graft devices. Your firm does not have records demonstrating these processes were validated as set forth in your firm’s “Process Validation,” SOP 018 and as required by 21 CFR 820.75(b)(1).
c. Your firm uses a
(b)(4)
sterilization process to sterilize your OsseoConduct device. Your firm does not have records demonstrating this process has been validated as set forth in your firm’s “Process Validation,” SOP 018 and as required by 21 CFR 820.75(b)(1).
This is a repeat observation from the FDA inspection conducted December 10-13, 2018, and a violation listed on the Untitled Letter issued to your firm on April 3, 2019. We reviewed your firm’s response dated November 21, 2022, and conclude it is not adequate. Your response is limited to a description of
(b)(4)
activities purportedly conducted; however, it does not describe the specific processes used or include a protocol indicating critical process parameters to support the process is validated. Additionally, your response does not include a systemic evaluation of your firm’s manufacturing processes to ensure all processes requiring validation have been validated. Finally, your response did not include procedures establishing any specific requirements for the sterilization process validation for each of your devices.
3. Failure to establish and maintain adequate 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’s “Purchasing & Suppliers,” SOP 410, Version 0, dated June 1, 2017, requires suppliers to be evaluated and reviewed as part of a continuous and iterative process. However, your firm did not provide any records to support that these activities have been conducted.
We reviewed your firm’s response dated November 21, 2022, and conclude it is not adequate. Your response states all suppliers have been evaluated to meet standards and be in compliance with “SOP 140 00.” Your response also provided a supplier evaluation form, stating it will be used moving forward. However, your response does not include your revised procedures describing how this form will be used or records of training for the new process as required by 21 CFR 820.25. Additionally, your response is unclear if the supplier evaluation form is a requirement of your revised procedures and if so, whether the form has been completed for all suppliers or if this corrective action is ongoing. In response to this letter, we request you provided the most current purchasing control procedures showing compliance with 21 CFR 820.50, which addresses the use of the supplier evaluation form.
4. Failure to establish and maintain adequate procedures for acceptance activities, which include inspections, tests, or other verification activities, as required by 21 CFR 820.80(a). For example,
Section 9 of your device history records (DHR) identifies specific acceptance criteria for each device. However, you do not have records required by 21 CFR 820.80(e) demonstrating these acceptance activities were conducted or documented for eight out of nine DHRs reviewed, as follows:
a. Socket Graft Plus lot 061422
b. OsseoConduct lot 060822
c. BioDensification lot 072622
d. Ridge Graft lot 060922
e. Immediate Graft lot 100322
f. Sinus Graft lot 072622
g. Socket Graft lot 061322
h. Socket Graft Injectable lot 090722
We reviewed your firm’s response dated November 21, 2022, and conclude it is not adequate. Your response states you will analyze the criteria for acceptability for each device prior to the time of release and ensure appropriate documentation has been generated. However, your response does not include a retrospective review of previous lots to evaluate if previously release lots were deficient. Additionally, your response does not address any procedural corrective actions or revisions you are taking to ensure appropriate acceptance activities are conducted.
5. Failure to establish and maintain adequate procedures to ensure that equipment is routinely calibrated, inspected, checked, and maintained, and to include provisions for handling, preservation, and storage of equipment, so that its accuracy and fitness for use are maintained, as required by 21 CFR 820.72(a). For example,
Your firm uses a
(b)(4)
for
(b)(4)
sterilizion of your OsseoConduct device; however, your firm’s Laboratory Manager verbally confirmed this
(b)(4)
has not been calibrated and there are no records for calibration.
We reviewed your firm’s response dated November 21, 2022, and conclude it is not adequate. Your response states you have established an equipment list that identifies all production equipment requiring calibration. However, your response did not provide evidence the referenced
(b)(4)
has been calibrated.
6. Failure to establish and maintain procedures to adequately control environmental conditions that could reasonably be expected to have an adverse effect on product quality and failure to periodically inspect environmental control systems to verify that the system is adequate and functioning properly, as required by 21 CFR 820.70(c). For example,
Your firm conducts manufacturing and packaging operations in ISO 7 certified cleanrooms both
(b)(4)
of your dental graft material devices. Your firm does not have established written procedures for the environmental monitoring of these cleanrooms. Additionally, our investigators observed a box fan inside cleanroom
(b)(4)
which may disrupt unidirectional airflow. Further, our investigators observed the area surrounding the cleanrooms to be dusty and contain miscellaneous items such as exercise equipment and a motorcycle. Your firm’s Laboratory Manager stated she gowns in this area prior to entering the ISO 7 cleanroom. Lastly, our review of the certification report for cleanroom
(b)(4)
dated
(b)(4)
, documented the cleanroom failed the high average particle count specification. Your firm did not have a justification or investigation into this failed result.
We have reviewed your firm’s response dated November 21, 2022, and conclude it is not adequate. Your response states the box fan has been removed from cleanroom
(b)(4)
. However, your response does not address the other aspects of the observation or describe the corrective actions you have taken to address the lack of adequate environmental monitoring procedures.
7. Failure to establish and maintain adequate procedures for quality audits and 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.
These quality audits shall be conducted by individuals who do not have direct responsibility for the matters being audited, as required by 21 CFR 820.22. For example,
Your firm’s “Audit,” SOP 023, revision 2, dated June 1, 2017, states general audits will be conducted
(b)(4)
. However, your firm has not conducted audits which meet the requirements of 21 CFR 820.22. Your firm’s Vice President of Marketing provided MDSAP task audit form templates for 2020, 2021, and 2022; however, these templates were limited to design control coverage and did not include coverage of other quality system requirements.
This is a repeat observation from the previous December 10-13, 2018, FDA inspection and a violation listed on the Untitled Letter issued to your firm on April 3, 2019. We have reviewed your firm’s response dated November 21, 2022 and cannot determine the adequacy at this time. Your response states you have purchased auditing tools which will assist in generating and conducting the
(b)(4)
audits. However, your response does not include a timeframe of the implementation of these tools or procedures describing their use for compliance with 21 CFR 820.22. Additionally, we remind you that any software used as part of the quality system shall be validated for its intended use, as required by 21 CFR 820.70(i).
Observations Pertaining to Premarket Submission Requirements
Our inspection also revealed that the Socket Graft, Socket Graft Plus, OsseoConduct, OsseoConduct Micron, Ridge Graft Kit, and Immediate Graft devices are adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because your firm does not have an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. § 360e(a), or an approved application for an investigational device exemption under section 520(g) of the Act, 21 U.S.C. § 360j(g). The device is also misbranded under section 502(o) the Act, 21 U.S.C. § 352(o), because your firm did not notify the agency of its intent to introduce the device into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C. § 360(k). For a device requiring premarket approval, the notification required by section 510(k) is deemed satisfied when a PMA is pending before the agency. [21 CFR 807.81(b)] The kind of information that your firm needs to submit in order to obtain approval or clearance for the device is described on the Internet at
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/default.htm. The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed.
1. Specifically, Socket Graft was cleared under K052493 and K113049 for use in dental extraction sockets that have all walls remaining. The earliest time point for implant placement in sockets grafted with Socket Graft is at 8 weeks.
Based on evidence obtained from your firm’s website (https://www.steinerbio.com/for-professionals/regenerative-products/socket-graft/) as of May 10, 2023, your firm is marketing Socket Graft for a different intended use, namely for use at an earlier time point than 8 weeks for implant placement. For example, your firm’s website states the following:
“A faster and healthier bone regeneration sequence allows for an implant to be placed sooner than if other bone grafts were used. Implant placement at 4 weeks, 6 weeks, 12 weeks or more can now be achieved with predictable results.”
However, there is no information in K052493 or K113049 to support an indication for placement at 4 or 6 weeks. This change in Indications for Use constitutes a significant change requiring a new premarket submission to modify the proposed indications for this device. Furthermore, promoting Socket Graft for use with implants earlier than what the data supported could significantly affect the safety or effectiveness of the device for implant to abutment compatibility, resulting in potential osseointegration complications of the dental implant bodies for patients. If you have data to support these indications, please submit that data to FDA for review.
2. Additionally, based on evidence obtained from your website (https://www.steinerbio.com/regenerative-products/socket-graft/) as of May 10, 2023, several performance statements related to the use of Socket Graft appear to be unsupported. We have conducted a review of our files and are unable to identify an additional FDA clearance or approval supporting these performance statements. For example, your website includes the following:
“This innovative delivery system allows for ease of application, but most importantly, produces superior bone quality with bone to implant integration due to its osteogenic properties.” There is no information in K052493 or K113049 demonstrating that Socket Graft is superior to other bone graft material.
“Socket Graft is a dual phase calcium phosphate based synthetic bone graft material designed to quickly treat the extraction socket, retain alveolar bone, stimulate bone formation, reduce post-operative complications, and resorb quickly and completely.” There is no information in K052493 or K113049 demonstrating that use of Socket Graft results in an accelerated healing response.
“No allergic reaction” and “No inflammatory response.” There is no information in K052493 or K113049 demonstrating that use of Socket Graft results in no possibility of these adverse reactions occurring. In your June 14, 2022, response to our May 27, 2022, letter, you referenced external vendor
(b)(4)
, wherein testing per ISO 10993-1 evaluated safety and performance of the device; however, the testing results do not substantiate these performance statements. Your written response dated November 22, 2022, to our FDA 483, Inspectional Observations, included a biocompatibility study, which you also included in your June 14, 2022, response. You purport that this study supports the above performance statements. However, the biocompatibility study does not support these performance statements because the study data shows that an inflammatory response occurred.
We are not aware of any new data supporting such statements. These statements were communicated to you in our letter dated May 27, 2022. In your response to this letter dated June 14, 2022, you committed to removing or modifying some of these statements; however, to date, they have not been revised. Marketing the Socket Graft with these performance statements represent significant changes to the cleared device that require a new premarket submission. These assertions of performance characteristics identify new risk in affecting the timeline of patient treatment, treatment considerations, and effectiveness of the received treatment, that require additional performance testing and/or clinical testing in a new premarket submission. If you have data demonstrating these performance characteristics, please provide that information to the agency.
3. Further, the OsseoConduct device was cleared under K101718 and intended to fill, augment or reconstruct periodontal or bony defects of the oral and maxillofacial region. Specifically, for the augmentation of deficient maxillary and mandibular alveolar ridges and the treatment of oral, maxillofacial, and dental intraosseous defects including ridge augmentation, sinus lifts, craniofacial augmentation, filling of defects of endodontic origin, filling of cystic defects, filling of extraction sites, filling of lesions of periodontal origin, repair of traumatic defects of the alveolar ridge, filling of resection defects from bone tumors, cysts or other osseous defects, and a substitute for autogenous or allogenic bone grafts. The device is fully resorbed in 6 months.
However, based on evidence obtained on your firm’s website (https://www.steinerbio.com/regenerative-products/osseoconduct/) as of May 10, 2023, several performance statements related to the use of OsseoConduct appear to be unsupported. We have conducted a review of our files and are unable to identify an additional FDA clearance or approval supporting these performance statements. For example, your website includes the following:
“Be designed to prevent bacterial colonization.” There is no information in K101718 demonstrating that OsseoConduct prevents bacterial colonization.
During our inspection conducted November 3-8, 2022, our investigators requested any data or studies that were conducted to support this statement, as would be required under 21 CFR 820.30. You stated that an external vendor
(b)(4)
conducted extensive biocompatibility studies for the
(b)(4)
used in the manufacture of OsseoConduct. However, the the
(b)(4)
reports did not include adequate data, such as a prospective, long-term, statistically relevant clinical study to support this claim. Further, in your June 14, 2022, response to FDA’s May 27, 2022, letter, you agreed that the statement is not supported by the clearance and would remove the statement from your website; however as of May 10, 2023, the statement has not been removed.
“Be significantly resorbed in 3 months.” There is no information in K101718 demonstrating that OsseoConduct is significantly resorbed in 3 months. The data show that full resorption occurs in
(b)(4)
months. Your June 14, 2022, response to FDA’s May 27, 2022, letter, asserts that the clearance establishes this statement. Your June 14, 2022, response also agreed to modify or remove this statement from your website; however as of May 10, 2023, the statement has not been modified or removed.
We are not aware of any new data supporting the above statements. Promoting this device with these performance statements constitute major changes or modifications to its intended use, for which your firm lacks clearance or approval. These assertions of performance characteristics identify new risks in affecting the timeline of patient treatment, treatment considerations, and effectiveness of the received treatment, which may lead to a need for additional surgical procedures, increased healing time, and unnecessary cost to patients. As such, these statements impact the intended use and performance of the device and require additional performance testing and/or clinical testing in a new premarket submission. If you have data demonstrating these performance characteristics, please provide that information to the agency.
4. Your firm is currently marketing the Ridge Graft Kit, which appears to be a combination of the Socket Graft and OsseoConduct devices. Based on evidence obtained from your website (https://www.steinerbio.com/for-professionals/regenerative-products/ridge-graft-kit/) as of May 10, 2023, the Ridge Graft Kit is packaged in syringes. However, this form of packaging was not previously cleared in K101718, which describes OsseoConduct as being distributed in single-use pouch packaging. Evaluation of a product’s packaging and shelf-life for devices provided sterile is necessary to ensure the sterilization methods used in manufacturing settings adhere to FDA’s Quality System (QS) regulation requirements, 21 CFR part 820. Assurance of sterility is important to prevent a serious risk to human health because of the risk of infection. Additionally, packaging and sterility assurance, including delivery mechanisms such as syringes, are considered part of the finished device that must be assessed for safety (e.g., biocompatibility testing per ISO 10993-1). The interactions of packaging and the effects of sterilization can have direct and potentially negative impacts on a product’s biocompatibility; this may lead to a need for additional surgical procedures, increased healing time, and unnecessary cost to patients. As such, use of different packaging and materials require additional performance testing and/or clinical testing as these changes could affect the safety and effectiveness of the devices and require submission of a new premarket submission. If you have data to support the new packaging, please submit that data to FDA for review.
5. In addition, your firm is marketing the Socket Graft Plus, which appears to be a combination of your firm’s Socket Graft and OsseoConduct devices. Based on evidence obtained from your website (https://www.steinerbio.com/regenerative-products/socket-graft-plus/) as of May 10, 2023, the Socket Graft Plus is intended for use as “a bone graft material appropriate for all socket grafting situations” and is used to “integrate immediate implants.” We have reviewed our files and are unable to identify FDA clearance or approval for a product with this indication.
In your response dated June 14, 2022 to our letter dated May 27, 2022, you state the Socket Graft Plus is cleared under K113049 and K101718 due to references being made to Socket Graft being used in conjunction with OsseoConduct in your 510(k) submissions. However, these 510(k) clearances do not include clearance for use as a single formulation without socket walls remaining, and for immediate implantation. Specifically, there is no information demonstrating the sterilization validation methods performed for the combined materials. In addition, the indications for use in these 510(k)s do not support the combination of these two devices, which is limited to use in dental extraction sockets that have all walls remaining; whereas the Socket Graft Plus indicates the device may be used for defects with missing walls. Further, grafts for immediate implants were not cleared in either of the Socket Graft or OsseoConduct submissions. The use of the product as described creates the risk of ineffective bone formation, infection, or non-biocompatible responses, which may lead to a need for additional surgical procedures, increased healing time, and unnecessary cost to patients. As such, these changes impact the intended use, sterilization, and performance of the device and require additional performance testing and/or clinical testing in a new premarket submission. If you have data to support the sterilization validation method performed and additional indication, please submit that data to FDA for review.
6. Further, your firm is currently marketing the Immediate Graft, which appears to be a
(b)(4)
. Based on evidence obtained from your website (https://www.steinerbio.com/for-professionals/regenerative-products/immediate-graft/) as of May 10, 2023, Immediate Graft is a dental bone grafting material intended to fill defects and achieve implant integration. Your firm’s website indicates this product is “proven to produce integration to immediate implants.” We have reviewed our files and are unable to identify FDA clearance or approval for a product with this indication.
In your response dated June 14, 2022, to our letter dated May 27, 2022, you state the Immediate Graft is cleared under K113049 and K101718 due to references being made to Socket Graft being used in conjunction with OsseoConduct in your 510(k) submissions. However, these 510(k) clearances do not include clearance for use as a single formulation and as grafts for immediate implants. The use of the product as described creates the risk of ineffective bone formation, infection, or non-biocompatible responses, which may lead to a need for additional surgical procedures, increased healing time, and unnecessary cost to patients. As such, these changes impact the intended use and performance of the device and require additional performance testing and/or clinical testing in a new premarket submission. Specifically, there is no information demonstrating the performance of your device (i.e., sterilization validation, biocompatibility, resorption/new bone formation) for the combined materials. If you have data to support the indication, please submit that data to FDA for review.
7. Additionally, based on evidence obtained during our November 3-8, 2022 inspection and evidence on your firm’s website (https://www.steinerbio.com/for-professionals/regenerative-products/osseoconduct/) as of May 10, 2023, you are marketing the OsseoConduct Micron device for “Treating Peri-Implantitis with βTCP Air Abrasion.” There is no information in K101718 demonstrating that OsseoConduct is cleared for this intended treatment.
Your June 14, 2022 response to FDA’s May 27, 2022 letter, states you are only marketing the device for the abrasive cleaning of dental appliances; however, as identified above, your firm’s website markets the device for the treatment of disease. This change in Indications for Use constitutes a significant change requiring a new premarket submission to modify the proposed indications for this device. Furthermore, promoting OsseoConduct for treatment of a new disease creates the risk of ineffective bone formation, infection, or non-biocompatible responses. If you have data to support this indication, please submit that data to FDA for review.
8. Additionally, based on evidence obtained on your firm’s website (https://www.steinerbio.com/for-professionals/regenerative-products/socket-graft-plus/) as of May 10, 2023, you are marketing the Socket Graft in a new ‘petal’ form with silicone trays. This form and packaging were not previously cleared in K052439 and K113049, which describe Socket Graft as being distributed in single use syringes or in a pouch with single use packets in powder form. Evaluation of a product’s packaging for devices provided sterile is necessary to ensure the sterilization methods used in manufacturing settings adhere to FDA’s Quality System (QS) regulation requirements, 21 CFR part 820. Assurance of sterility is important to prevent a serious risk to human health because of the risk of infection. Additionally, packaging and sterility assurance, including delivery mechanisms such as syringes or trays, are considered part of the finished device that must be assessed for safety (e.g., biocompatibility testing per ISO 10993-1). The interactions of packaging and the effects of sterilization can have direct and potentially negative impacts on a product’s biocompatibility. As such, use of different packaging and materials require additional performance testing and/or clinical testing as these changes could affect the safety and effectiveness of the devices and require submission of a new premarket submission. If you have data to support the new form and packaging, please submit that data to FDA for review.
9. Further, based on evidence obtained on your firm’s website (https://www.steinerbio.com/for-professionals/regenerative-products/socket-graft-plus/) as of May 10, 2023, you are marketing the Socket Graft for use with a drug. For example, the instructions for use document (https://www.steinerbio.com/wp-content/uploads/2022/08/DFU-Socket-Graft-2022.pdf) for the Socket Graft in a new ‘petal’ form states “Add moisture by applying a few drops of local anesthesia to the petals of graft for a manageable putty.” This new indication was not previously cleared in K052439 or K113049. We have reviewed our files and are unable to identify FDA clearance or approval of a product for use in combining anesthetics with the device. Additional data is required to assess if the combination of the two products can influence effectiveness of one or the other material components. These changes could significantly affect the safety and effectiveness of these devices requiring a new premarket submission because the previous clearances have not provided data that show this preparation and use of Socket Graft does not negatively impact bone formation, healing, or biocompatibility of the product.
10. Additionally, based on evidence obtained on your firm’s website (https://www.steinerbio.com/for-professionals/regenerative-products/ridge-graft-kit/) as of May 10, 2023, you are marketing OsseoConduct βTCP 3D-Printed Grafts device for “Custom 3D-printed beta tricalcium bone grafts designed to be used for lateral and vertical ridge augmentation with implant placement ridge augmentation”. There is no information in K101718 demonstrating that OsseoConduct is cleared for this intended treatment which is manufactured using a new additive manufacturing process that is outside the scope of the manufacturing process that was cleared in K101718. This major manufacturing change is a modification that could significantly affect the safety or effectiveness of the device and requires the submission of a new premarket submission. The use of the product as described creates the risk of ineffective bone formation, infection, or non-biocompatible responses, which may lead to the need for additional surgical procedures, increased healing time, and unnecessary cost to patients. As such, these changes impact the performance of the device and require additional performance testing and/or clinical testing in a new premarket submission.
If you have data to support the new manufacturing method, please submit that data to FDA for review.
The OsseoConduct is further misbranded under § 502(a) of the Act, 21 U.S.C. § 352(a), because there are statements on your firm’s website (https://www.steinerbio.com/regenerative-products/osseoconduct/) as of May 10, 2023, that, under 21 CFR § 801.6, constitute false or misleading representations with respect to another device. Specifically, the information makes misleading comparisons between your device and competing devices. For example, your website states: “Unlike allografts and xenografts, OsseoConduct produces bone with normal physiology and architecture.”
We are not aware of any new data supporting this statement. This statement is false or misleading because allograft bone, which is human derived, represents normal physiology and architecture, and data do not demonstrate that the OsseoConduct is superior to other bone grafting materials such as allograft or xenograft. This comparison may mislead consumers about the effectiveness of OsseoConduct by implying less effectiveness of other bone grafting materials that may be equally advantageous. Misleading information may lead clinicians to overestimate the performance of the device and minimize the importance of other risk mitigating factors, which may lead to patient harm. These claims therefore constitute misleading representations with respect to another device. If you have data demonstrating that OsseoConduct is more effective than other bone grafting materials, please provide that information to the agency.
Observations Pertaining to Other Regulations
In addition to being a manufacturer of devices including the Socket Graft, Socket Graft Plus, OsseoConduct, OsseoConduct Micron, Ridge Graft Kit, Immediate Graft, and Oral Bond, the inspection of November 3-8, 2022, revealed your firm is a “labeler” of these devices as defined in 21 CFR 801.3 and 21 CFR 830.3. The inspection revealed that your devices are misbranded within the meaning of section 502(c) of the Act, 21 U.S.C. § 352(c), in that your firm failed to have on the label or labeling of the device information that is required by or under the authority of this Act. In particular, 21 CFR 801.20(a), which was promulgated under authority of section 519 of the Act, among other provisions, requires, with exceptions not relevant here, that the label of every medical device bear a unique device identifier (UDI) that meets the requirements of 21 CFR part 801, subpart B, and 21 CFR part 830. The labels of these devices do not bear such a UDI. In addition, your devices are misbranded within the meaning of section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that there was a failure to furnish material or information required by or under section 519 of the Act, 21 U.S.C. § 360i, respecting these devices. In particular, 21 CFR 830.300(a) and 830.320(b), both of which were promulgated under section 519 of the Act, among other provisions, require, with exceptions not relevant here, that the labeler of a device submit electronically to FDA’s Global Unique Device Identification Database (GUDID) the information required by 21 CFR part 830, subpart E, for each version or model required to bear a UDI. Your firm has not submitted to GUDID any information required by 21 CFR part 830, subpart E, respecting these devices. Furthermore, it is a prohibited act under section 301(q)(1)(B) of the Act, 21 U.S.C. § 331(q)(1)(B), to fail to furnish any notification or other material or information required by or under section 519 of the Act, 21 U.S.C. § 360i.
These violations include the following:
1. Failure to ensure that the label of every medical device shall bear a UDI that meets the requirements of 21 CFR part 801, subpart B, and 21 CFR part 830, as required by 21 CFR 801.20(a). For example,
The labels for the Socket Graft, Socket Graft Plus, OsseoConduct, OsseoConduct Micron, Immediate Bond, and Oral Bond do not include a UDI. Class II devices manufactured and labeled after September 24, 2016, must bear a UDI, unless an exception or alternative applies.
1
No exception or alternative to the requirements of 21 CFR part 801, subpart B, and 21 CFR part 830 applies to the Socket Graft, Socket Graft Plus, OsseoConduct, OsseoConduct Micron, Immediate Graft, and Oral Bond manufactured and labeled after September 24, 2016.
This is a repeat observation from the previous FDA inspection of December 10-13, 2018. During our inspection conducted November 3-8, 2022, your Director of Marketing committed to generating a UDI and updating your labels accordingly. However, you have not provided any additional updates to this proposed corrective action. In response to this letter, please provide evidence of implementation of the following documents: records to verify identification and traceability controls, a copy of the revised labeling to verify that requirements have been met, training records, updated SOP which includes the requirements for developing and assigning UDIs to your devices, the requirements for printing labels that contain the UDI for all devices, label verification procedures, and recordkeeping.
2. Failure to provide required information to GUDID as required by 21 CFR 830.300(a). For example:
Labelers of devices required to bear a UDI are required to submit specific data pertaining to these devices to FDA’s GUDID on or before September 24, 2016. Your firm has failed to submit the information required under 21 CFR part 830, subpart E, for each version or model required to bear a UDI, as specified by 21 CFR 830.300(a).
This is a repeat observation from the previous FDA inspection of December 10-13, 2018. During our inspection conducted November 3-8, 2022, your Director of Marketing committed to registering UDIs to the GUDID. However, you have not provided any updates to this corrective action and to date there are no records pertaining to your Socket Graft, Socket Graft Plus, OsseoConduct, OsseoConduct Micron, Immediate Graft, and Oral Bond devices that have been submitted.
Your firm should take prompt action to address any violations identified in this letter. Failure to adequately address this matter may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties.
Other federal agencies may take your compliance with the FD&C Act and its implementing regulations into account when considering the award of federal contracts. Additionally, should FDA determine that you have Quality System regulation violations that are reasonably related to premarket approval applications for Class III devices, such devices will not be approved until the violations have been addressed. Should FDA determine that your devices or facilities do not meet the requirements of the Act, requests for Certificates to Foreign Governments (CFG) may not be granted.
Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to address the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (which must address systemic problems) that your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm’s response should be comprehensive and address any violations included in this Warning Letter. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration as part of your response.
Your firm’s response should be sent to: Jessica Mu, Director of Compliance Branch, at oradevices3firmresponse@fda.hhs.gov. Refer to CMS # 651802 when replying. If you have any questions about the contents of this letter, please contact: Jeff Wooley, Compliance Officer at 214-253-5251 or jeffrey.wooley@fda.hhs.gov.
Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility. It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems. Your firm should investigate and determine the causes of any violations and take prompt actions to address any violations and bring the products into compliance.
Sincerely,
/S/
Shari J. Shambaugh Program Division Director
Office of Medical Devices and Radiological
Health, Division III
/S/
Malvina Eydelman
Director
OHT 1: Office of Ophthalmic, Anesthesia,
Respiratory, ENT & Dental Devices
Office of Product Evaluation and Quality
Center for Devices and Radiological Health
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1
See the UDI Final Rule, 78 FR 58786 (September 24, 2013) at 58815-58816. More information about compliance dates for UDI requirements can be found at FDA’s website (https://www.fda.gov/medical-devices/unique-device-identification-system-udi-system/udi-compliance-policies-and-udi-rule-compliance-dates).
Content current as of:
06/06/2023
Regulated Product(s)
Medical Devices