(195 days)
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No
The summary describes a biological implant for ACL repair and clinical study results. There is no mention of AI, ML, or any computational analysis of data for diagnosis, treatment planning, or device function.
Yes.
The device is indicated for the treatment of anterior cruciate ligament (ACL) injuries and helps to stabilize blood between torn ligament ends, which is then replaced by fibrovascular repair tissue.
No
Explanation: The device is an implant designed for the treatment of ACL injuries, not for diagnosing them. Its purpose is to repair the ligament, not to provide diagnostic information.
No
The device description clearly states it is a physical implant made of collagen and extracellular matrix, intended for surgical implantation. It is a hardware device, not software.
No, this device is not an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use is for the treatment of ACL injuries by providing a scaffold for repair. IVDs are used to diagnose diseases or conditions by examining samples from the body (like blood, urine, or tissue).
- Device Description: The device is an implant designed to be surgically placed within the body. IVDs are typically reagents, instruments, or systems used to perform tests outside the body.
- Function: The BEAR® Implant's function is to stabilize blood and facilitate tissue repair in vivo. IVDs analyze samples in vitro to provide diagnostic information.
- Performance Metrics: The performance metrics provided (IKDC score, knee laxity, hamstring strength, KOOS domains) are clinical outcome measures related to the success of the surgical treatment, not diagnostic performance metrics like sensitivity, specificity, or AUC.
The BEAR® Implant is a medical device used for surgical repair, not for diagnosing a condition.
N/A
Intended Use / Indications for Use
The BEAR® (Bridge Enhanced ACL Repair) Implant is a bovine extracellular matrix collagen-based implant for treatment of anterior cruciate ligament (ACL) injuries. The BEAR® Implant is indicated for skeletally-mature patients at least 14 years of age with a complete rupture of the ACL, as confirmed by MRI. Patients must have an ACL stump attached to the tibia to construct the repair.
The BEAR® Implant is intended to protect the biological healing process from the surrounding intraarticular environment and not to replace biomechanical fixation via suturing. This can include devices that bridge or surround the torn ends of a ruptured ACL.
Product codes
QNI
Device Description
The BEAR® Implant (22 mm in diameter and 45mm in length) is cylindrical in shape and comprised of collagen and extracellular matrix derived from bovine connective tissue, which has been cleaned, disinfected and processed by a proprietary manufacturing method. The implant has been terminally sterilized by electron-beam irradiation and is intended to be used with up to 10 ml of autologous blood drawn during the surgical implantation procedure. The BEAR® Implant stabilizes the blood in the gap between the torn ligament ends. The BEAR® Implant is resorbed within 8 weeks and replaced with a fibrovascular repair tissue.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
magnetic resonance imaging [MRI]
Anatomical Site
anterior cruciate ligament (ACL), knee joint
Indicated Patient Age Range
skeletally-mature patients at least 14 years of age
Intended User / Care Setting
prescription use in accordance with 21 CFR 801.109.
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
SUMMARY OF NONCLINICAL/BENCH STUDIES
BIOCOMPATIBILITY/MATERIALS
The BEAR® Implant is manufactured from the following materials: Implant, Bovine collagen and extracellular matrix. Direct Patient Contact: Yes. Contact Duration: Permanent (>30 d).
Biocompatibility evaluation has been completed according to FDA Guidance, Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process".
SHELF LIFE/STERILITY
The subject implant is provided sterile to the end user. The sterilization method is e-beam radiation at a dose of "(b)(4)" kGy. Sterilization was validated using the VDmax method as per ISO 11137-1:2006(R/2018) Sterilization of health care products – Radiation Requirements for development, validation, and routine control of a sterilization process for medical devices to ensure that a Sterility Assurance Level (SAL) of 10th is achieved.
Representative sterilized samples real-time aged to "kGy" years were used to determine the shelf life of the device. Seal width, seal strength, and package integrity (bubble test) were used on accelerated aged samples to determine the sterile barrier packaging shelf life. Non-clinical performance testing of the representative devices was used to assess the performance shelf life.
Viral Inactivation and Titer Testing
The Viral Inactivation properties of the BEAR® Implant manufacturing process have model viruses and at least (b) (4) been validated to at least (b) (4) reduction for (b) (4) reduction for the (b) (4) model virus, following the guidance in ISO 22442-3:2007 Medical devices utilizing animal tissues and their derivatives- Part 3: Validation of the elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE), as well as the FDA guidance document "Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices, March 2019)".
Viral safety was confirmed via titer testing of representative product lots and incorporation of viral titer testing into the lot release criteria.
Reprocessing
There are no reusable or reprocessed components in this device.
MAGNETIC RESONANCE (MR) COMPATIBILITY
The BEAR® Implant is a non-ferromagnetic, collagen-based material. The subject device is considered MR Safe.
PERFORMANCE TESTING - BENCH
The sponsor provided both biochemical characterization and bench performance testing to demonstrate the device's ability to absorb blood and be sutured.
Biochemical Characterization (Lot release criteria):
- Collagen content: Mean (b) (4) (Acceptance Criteria: >(b) (4))
- DNA content: Mean: (b) (4) (Acceptance Criteria: (b) (4))
- SDS-PAGE: All samples show α, β, and γ protein banding typical of Type I Collagen (Acceptance Criteria: Presence of (b) (4)(b) (4)typical of Type I Collagen)
- DSC: Mean: (b) (4) °C (Acceptance Criteria: (b) (4) °C average peak temperature)
- Endotoxin content: Mean: =0.35kU/L: Positive in 3.1% (2/64) of BEAR subjects vs. 0% (0/33) control (p=0.546). These were low positive and resolved.
- For BEAR subjects with repair failure, 5 were non-compliant with postoperative requirements (physical therapy and/or brace use), returned to sports prior to surgeon clearance, had an accident or had a very high BMI, and 3 returned to sports prior to 9 months post-surgery.
- All subjects who re-tore the ACL, in both groups, were age 18 years or younger.
- The rate of ACL re-tear with the BEAR® Implant was similar to a historical control and consistent with published literature.
- The BEAR® Implant had a similar safety profile to ACLR, and repair failure was more likely to occur in younger subjects, consistent with literature.
Primary Effectiveness Endpoints (BEAR II study at 24 months, mITT population with multiple imputation)
- IKDC Subjective Score:
- Mean ± SD: BEAR 88.6 ± 13.4; Control 84.6 ± 13.3.
- Difference in Means (BEAR - Control): 4.03 (95% CI: -1.55, 9.61).
- p-value: = 2.0 mm).
- Conclusion: Instrumented AP knee laxity for the BEAR group was non-inferior to control.
Both primary endpoints were confirmed by multiple sensitivity analyses, including a tipping point analysis.
Secondary Effectiveness Endpoints (BEAR II study, mITT population with multiple imputation, hierarchical testing)
All 12 endpoints were statistically significant, either for non-inferiority or superiority.
- Prone Hamstring Strength (100*(Injured Knee/Non-injured Knee)) at 6 Months (superiority):
- Mean ± SD: BEAR 93.3 ± 23.6; Control 59.1 ± 21.3.
- Difference in Means (BEAR - Control): 34.21 (95% CI: 24.70, 43.72).
- p-value:
§ 888.3044 Resorbable implant for anterior cruciate ligament (ACL) repair.
(a)
Identification. A resorbable implant for anterior cruciate ligament (ACL) repair is a degradable material that allows for healing of a torn ACL that is biomechanically stabilized by traditional suturing procedures. The device is intended to protect the biological healing process from the surrounding intraarticular environment and not intended to replace biomechanical fixation via suturing. This classification includes devices that bridge or surround the torn ends of a ruptured ACL.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use and include the following:
(i) Post-operative evaluation of knee pain and function; and
(ii) Durability as assessed by re-tear or re-operation rate.
(2) Animal performance testing must demonstrate that the device performs as intended under anticipated conditions of use and include the following:
(i) Device performance characteristics, including resorption and ligament healing at repair site; and
(ii) Adverse effects as assessed by gross necropsy and histopathology.
(3) Non-clinical testing must demonstrate that the device performs as intended under anticipated conditions of use and include the following:
(i) Characterization of materials, including chemical composition, resorption profile, and mechanical properties; and
(ii) Simulated use testing, including device preparation, device handling, compatibility with other ACL repair instrumentation, and user interface.
(4) The device must be demonstrated to be biocompatible.
(5) Performance data must demonstrate the device to be sterile and non-pyrogenic.
(6) Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the identified shelf life.
(7) Labeling must include the following:
(i) Identification of device materials and specifications;
(ii) A summary of the clinical performance testing conducted with the device;
(iii) Instructions for use, including compatibility with other ACL repair instrumentation or devices;
(iv) Warnings regarding post-operative rehabilitation requirements; and
(v) A shelf life.
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DE NOVO CLASSIFICATION REQUEST FOR BEAR® (BRIDGE-ENHANCED ACL REPAIR) IMPLANT
REGULATORY INFORMATION
FDA identifies this generic type of device as:
Resorbable implant for anterior cruciate ligament (ACL) repair. A resorbable implant for anterior cruciate ligament (ACL) repair is a degradable material that allows for healing of a torn ACL that is biomechanically stabilized by traditional suturing procedures. The device is intended to protect the biological healing process from the surrounding intraarticular environment and not to replace biomechanical fixation via suturing. This can include devices that bridge or surround the torn ends of a ruptured ACL.
NEW REGULATION NUMBER: 21 CFR 888.3044
CLASSIFICATION: Class II
PRODUCT CODE: QNI
BACKGROUND
DEVICE NAME: BEAR® (Bridge-Enhanced ACL Repair) Implant
SUBMISSION NUMBER: DEN200035
DATE DE NOVO RECEIVED: June 4, 2020
SPONSOR INFORMATION:
Miach Orthopaedics, Inc. 69 Milk Street, Suite 100 Westborough, Massachusetts 01581
INDICATIONS FOR USE
The BEAR® (Bridge-Enhanced ACL Repair) Implant is indicated as follows:
The BEAR® (Bridge Enhanced ACL Repair) Implant is a bovine extracellular matrix collagen-based implant for treatment of anterior cruciate ligament (ACL) injuries. The BEAR® Implant is indicated for skeletally-mature patients at least 14 years of age with a complete rupture of the ACL, as confirmed by MRI. Patients must have an ACL stump attached to the tibia to construct the repair.
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LIMITATIONS
The sale, distribution, and use of the BEAR® Implant are restricted to prescription use in accordance with 21 CFR 801.109.
PLEASE REFER TO THE LABELING FOR A COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.
DEVICE DESCRIPTION
The BEAR® Implant (22 mm in diameter and 45mm in length) is cylindrical in shape and comprised of collagen and extracellular matrix derived from bovine connective tissue, which has been cleaned, disinfected and processed by a proprietary manufacturing method. The implant has been terminally sterilized by electron-beam irradiation and is intended to be used with up to 10 ml of autologous blood drawn during the surgical implantation procedure. The BEAR® Implant stabilizes the blood in the gap between the torn ligament ends. The BEAR® Implant is resorbed within 8 weeks and replaced with a fibrovascular repair tissue.
Image /page/1/Picture/5 description: The image shows a series of five diagrams illustrating a medical procedure on a knee joint. The diagrams depict the progression of the procedure, starting with the initial state of the knee and ending with the final placement of a prosthetic component. The diagrams show the knee joint from a side view, with the femur and tibia bones clearly visible. The procedure involves the use of various medical instruments and materials, such as sutures, screws, and a prosthetic component, to repair or replace damaged tissue in the knee joint.
SUMMARY OF NONCLINICAL/BENCH STUDIES
BIOCOMPATIBILITY/MATERIALS
The BEAR® Implant is manufactured from the following materials:
| Description | Material | Direct Patient
Contact | Contact Duration |
|-------------|---------------------------------------------|---------------------------|-------------------|
| Implant | Bovine collagen and
extracellular matrix | Yes | Permanent (>30 d) |
Biocompatibility evaluation has been completed according to FDA Guidance, Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process"
SHELF LIFE/STERILITY
2
E-beam Sterilization:
The subject implant is provided sterile to the end user. The sterilization method is e-beam radiation at a dose of " kGy. Sterilization was validated using the VDmax method as per ISO 11137-1:2006(R/2018) Sterilization of health care products – Radiation Requirements for development, validation, and routine control of a sterilization process for medical devices to ensure that a Sterility Assurance Level (SAL) of 10th is achieved.
Representative sterilized samples real-time aged to " years were used to determine the shelf life of the device. Seal width, seal strength, and package integrity (bubble test) were used on accelerated aged samples to determine the sterile barrier packaging shelf life. Non-clinical performance testing of the representative devices was used to assess the performance shelf life.
Viral Inactivation and Titer Testing:
The Viral Inactivation properties of the BEAR® Implant manufacturing process have model viruses and at least (b) (4) been validated to at least (b) (4) reduction for (b) (4) reduction for the (b) (4) model virus, following the guidance in ISO 22442-3:2007 Medical devices utilizing animal tissues and their derivatives- Part 3: Validation of the elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE), as well as the FDA guidance document "Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices, March 2019)". This addresses the ability of the process to inactivate/eliminate viruses that might enter the process via the tissue used as a starting material. In addition, viral safety was confirmed via titer testing of representative product lots and incorporation of viral titer testing into the lot release criteria.
Reprocessing:
There are no reusable or reprocessed components in this device.
MAGNETIC RESONANCE (MR) COMPATIBILITY
The BEAR® Implant is a non-ferromagnetic, collagen-based material. The subject device is considered MR Safe.
PERFORMANCE TESTING - BENCH
The sponsor provided both biochemical characterization and bench performance testing to demonstrate the device's ability to absorb blood and be sutured.
| Test | Purpose | Method | Acceptance Criteria | Results |
|---|---|---|---|---|
| Collagen content | Lot release criteria | Biochemical | ||
| characterization | >(b) (4) | Mean (b) (4) | ||
| DNA content | Lot release criteria | Biochemical | ||
| characterization |
3
| Pepsin activity | Lot release criteria | Biochemical
characterization | (b) (4) | Mean: (b) (4) µg/g |
| SDS-PAGE | Lot release criteria | Biochemical
characterization | Presence of (b) (4)
(b) (4)
typical of Type I
Collagen | All samples show α,
β, and γ protein
banding typical of
Type I Collagen |
| DSC | Lot release criteria | Biochemical
characterization | (b) (4) °C average
peak
temperature | Mean: (b) (4) °C |
| Endotoxin content | Lot release criteria | LAL test per
ANSI/AAMI ST72 | =0.35kU/L [3] | 3.1% (2/64) | 0% (0/33) | 0.546 |
| Bovine Antibody Level (kU/L) | | | |
| Mean ± SD (N) | 0.39 $\pm$ 0.00 (2) | | |
| Median (Min, Max) | 0.39 (0.39,
0.39) | | |
| [1] p-value from a two-sided Fisher's Exact Test, testing the null hypothesis that the true proportions
are equal for the two treatments versus the alternative hypothesis that they are not equal.
[2] Not including subjects requiring a second ACL surgery.
[3] Subjects who tested positive resolved after 15 months and 2 years post procedure date. | | | |
Graft or repair failure was determined by positive pivot shift exam, Lachman exam with >6 mm side to side difference, absence of tissue in expected ACL location on MRI, evidence of graft or repair loss of continuity on MRI or symptomatic instability requiring revision ACL surgery. Of the nine BEAR subjects who experienced repair failure, five were non-compliant with postoperative requirements (physical therapy and/or brace use), returned to sports prior to surgeon clearance, had an accident or had a very high body mass index (BMI), and three returned to sports prior to 9 months post-surgery. All subjects who re-tore the ACL, in both groups, were age 18 years or younger. Results of the BEAR II study were compared to data from a historical control for which the manufacturer was able to access subject-level data and to data from a structured literature review. The analyses demonstrated that the rate of ACL re-tear with the BEAR® Implant was similar to the historical control and was consistent with the published literature. In conclusion, the BEAR® Implant had a similar safety profile to ACLR, and repair failure was more likely to occur in younger subjects, which is consistent with the experience of ACLR as documented in the literature.
Primary Effectiveness Endpoints
The BEAR II Study had two co-primary effectiveness endpoints. IKDC score and instrumented AP knee laxity, both at 24 months (two years) post-surgery (Table 3). In the primary analysis of the mITT population using multiple imputation for missing data, IKDC score for the BEAR group at 24 months was found to be non-inferior to control based on the null hypothesis that the true difference in the means between treatment groups was less than or equal to -11.5, which is considered a clinically significant difference and was the pre-specified non-inferiority delta.
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Mean IKDC score in the BEAR group was 88.6±13.4 and in the control group 84.6±13.3. The 95% confidence interval for the difference in the means was 4.03 (-1.55, 9.61) (p0.05) then testing will not continue.
For tests of superiority, the p-value is from a two-sided, two-sample t-test, testing the true means are equal versus the alternative hypothesis that they are not equal.
For tests of non-inferiority, the p-value is from a one-sided, two-sample t-test of the true difference in means is less than or equal to -10 versus the alternative hypothesis that it is greater than -10.
[4] Data for prone hamsting strength and hamsting to quadriceps ratio at 6 months was imputed for 1 (1.5%) patient in the BEAR group, and 1 (2.9%) patient in the control group.
[5] Median, minimum and maximum values are shown for the observed data only, and do not include imputed values.
[6] Data for prone hamstring strength and hamsting to quadriceps ratio at 12 morths was imputed for 3 (4.6%) patients in the BEAR group, and 3 (8.6%) patients in the control group.
[7] Data for ACL RSI Score at 6 months was imputed for 1 (1.5%) patient in the BEAR group, and 1 (2.9%) patient in the control group.
[8] Data for KOOS (all parts) at 12 months was imputed for 1 (1.5%) patient in the BEAR group, and 2 (5.7%) of patients in the control group.
LABELING
The labeling consists of the following: device description, indications for use, instructions for use including surgical steps, compatibility of device with other soft tissue repair devices, principles of device operation, identification of device materials, contraindications, warnings, precautions, MR compatibility, a list of potential adverse effects, importance of patient compliance with post-operative activity restrictions, and a summary of the clinical data. Furthermore, the sterile packaging includes a shelf life for the device. The labeling meets the requirements of 21 CFR 801.109 for prescription devices.
RISKS TO HEALTH
The table below identifies the risks to health that may be associated with use of the resorbable implant for ACL repair and the measures necessary to mitigate these risks.
| Identified Risks to Health | Mitigation Measures |
|---|---|
| Repaired ACL has inadequate durability, | |
| leading to re-tear | Animal testing |
| Clinical performance testing | |
| Labeling | |
| Repaired ACL is loose or functionally limited, | |
| leading to joint instability | Clinical performance testing |
| ACL does not heal due to inadequate | |
| resorption or migration of implant | Non-clinical performance testing |
| Animal testing | |
| Adverse tissue reaction | Biocompatibility evaluation |
| Labeling |
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| Infection | Sterilization validation |
|---|---|
| Shelf life testing | |
| Labeling | |
| Febrile response due to endotoxins | Pyrogenicity testing |
| Implant is incompatible with other ACL repair | |
| instrumentation and sutures, leading to | |
| inability to complete surgery | Non-clinical performance testing |
| Labeling |
SPECIAL CONTROLS
In combination with the general controls of the FD&C Act, the resorbable implant for ACL repair is subject to the following special controls:
- (1) Clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use and include the following:
- (i) Post-operative evaluation of knee pain and function; and
- (ii) Durability as assessed by re-tear or re-operation rate.
- (2) Animal performance testing must demonstrate that the device performs as intended under anticipated conditions of use and include the following:
- (i) Device performance characteristics, including resorption and ligament healing at repair site; and
- (ii) Adverse effects as assessed by gross necropsy and histopathology.
- (3) Non-clinical testing must demonstrate that the device performs as intended under anticipated conditions of use and include the following:
- Characterization of materials, including chemical composition, resorption profile, (i) and mechanical properties; and
- (ii) Simulated use testing, including device preparation, device handling, compatibility with other ACL repair instrumentation, and user interface.
- (4) The device must be demonstrated to be biocompatible.
- (5) Performance data must demonstrate the device to be sterile and non-pyrogenic.
- (6) Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the identified shelf life.
- (7) Labeling must include the following:
- (i) Identification of device materials and specifications;
- (ii) A summary of the clinical performance testing conducted with the device;
- (iii) Instructions for use, including compatibility with other ACL repair instrumentation or devices;
- (iv) Warnings regarding post-operative rehabilitation requirements; and
- (v) A shelf life.
BENEFIT-RISK DETERMINATION
The sponsor has collected adequate data to assess the safety profile of the subject device and has identified that there are benefits. Compared to the standard-of-care ACL reconstruction procedures, treatment with the subject device results in no donor site morbidity, which is confirmed via superiority in hamstring strength secondary endpoints at 6 and 12 months post
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operative. The KOOS pain and function subscales and RSI scores also demonstrated superiority at the 6- and 12-month post-operative time points. There is also a presumed benefit from a repair procedure preserving more native anatomy than a reconstruction, which requires wider bone tunnels. Device-related serious adverse events such as infection or rejection/immunogenic response were not observed in the clinical data and are mitigated by design controls and processing controls. Serious adverse events that necessitated reoperation (i.e., re-tear) were observed with similar frequency between ACL repairs with the subject device and ACL reconstructions. In conclusion, the benefits of using the subject device for its intended use/indications for use outweigh the risks to health.
PATIENT PERSPECTIVES
This submission did not include specific information on patient perspectives for this device.
BENEFIT/RISK CONCLUSION
In conclusion, given the available information above, for the following indication statement:
The BEAR® (Bridge Enhanced ACL Repair) Implant is a bovine extracellular matrix collagen-based implant for treatment of anterior cruciate ligament (ACL) injuries. The BEAR® Implant is indicated for skeletally-mature patients at least 14 years of age with a complete rupture of the ACL, as confirmed by MRI. Patients must have an ACL stump attached to the tibia to construct the repair.
The probable benefits outweigh the probable risks for the BEAR® Implant. The device provides benefits and the risks can be mitigated by the use of general and the identified special controls.
CONCLUSION
The De Novo request for the BEAR® (Bridge-Enhanced ACL Repair) Implant is granted and the device is classified as follows:
Product Code: QNI Device Type: Resorbable implant for anterior cruciate ligament (ACL) repair Regulation Number: 21 CFR 888.3044 Class: II