U.S. Food and Drug Administration05.15.20
The U.S. Food and Drug Administration issued warning letters to two breast implant manufacturers for failure to comply with various regulatory requirements. The agency issued a warning letter to breast implant manufacturer Allergan of Irvine, California, for failing to comply with requirements—under two separate premarket approval orders—to conduct post-approval studies to assess the long-term safety and risks of two models of breast implants, both of which were voluntarily recalled from the market last year. The FDA also issued a warning letter to Ideal Implant Incorporated of Dallas, Texas, for failure to comply with current good manufacturing practice requirements and adverse event reporting requirements following an inspection conducted earlier this year.
Allergan Warning Letter
Every manufacturer of approved silicone gel-filled breast implants is required to conduct post-approval studies to further evaluate the safety and effectiveness of the products and to answer additional scientific questions about the long-term safety and potential risks of breast implants that their premarket clinical trials were not designed to answer. Generally, a manufacturer must still comply with post-approval requirements even if a breast implant has been voluntarily recalled from the market, in part, to continue assessing long-term outcomes in patients who are already implanted with these devices.
“The FDA imposes post-approval requirements because they are an important tool for ensuring the safety and effectiveness of the medical devices we regulate,” said Binita Ashar, M.D., director of the Office of Surgical and Infection Control Devices in the Center for Devices and Radiological Health. “The agency has been diligently tracking post-approval studies as part of our ongoing efforts to evaluate, understand and provide updates to the public on breast implant safety and risks. Post-approval studies are especially important to inform our understanding of the long-term potential risks associated with Allergan’s implants, including the models that have since been recalled from the market due to increased risk of breast implant associated anaplastic large cell lymphoma. The manufacturer’s low recruitment and low follow-up rates for these devices is unacceptable. The FDA will continue to hold manufacturers accountable if they fail to fulfill their obligations.”
The FDA’s warning letter to Allergan noted several serious deficiencies in the manufacturer’s post-approval study to evaluate its NATRELLE Silicone Gel-Filled Breast Implants (“Round Responsive implants”) and its NATRELLE 410 Highly Cohesive Anatomically Shaped Silicone-Filled Breast Implants (“Style 410 implants”). The post-approval study group of subjects with Round Responsive implants has shown poor recruitment and follow-up rates. Allergan’s failure to address these concerns and comply with its post-approval study requirements is a violation of the firm’s premarket approval order.
The FDA requested a response from Allergan within 15 working days of issuance of the warning letter and asked Allergan to provide details about how the company will correct the violations. Failure to promptly comply with post-approval requirements may result in additional action.
Ideal Implant Inc. Warning Letter
Manufacturers must also adhere to quality system regulations, which includes compliance with applicable current good manufacturing practice requirements. Further, under the Medical Device Reporting (MDR) regulation, manufacturers must report certain device-related adverse events and product problems to the FDA—one of the postmarket surveillance tools the FDA uses to monitor device performance, detect potential device-related safety issues, and contribute to benefit-risk assessments of these products.
"Quality system inspections are a way for the FDA to determine if a manufacturer’s activities and procedures, conducted during and after the manufacturing of a device, comply with applicable regulations. When these regulations are followed, it results in safer products for patients,” said Dr. Ashar. “While inspecting the Ideal Inc. facility in January and February, FDA inspectors observed potential violations of the Federal Food, Drug, and Cosmetic Act. Although Ideal Implant Inc. responded to the FDA Form 483-List of Inspectional observations provided to the company at the end of the inspection, most of the corrective actions they took were not adequate. To protect patients, the company should now take additional action to make sure these issues are properly addressed. Addressing quality system and medical device reporting violations helps ensure patient safety, which is our top priority.”
The warning letter issued to Ideal Implant Inc. revealed the Ideal saline-filled breast implants were adulterated due to a failure to maintain proper files for device complaints the manufacturer received from customers, failure to establish and maintain appropriate procedures for implementing corrective and preventive actions and failure to establish and maintain adequate criteria for testing finished devices. The FDA’s warning letter requests that, in a response to the agency, Ideal Implant Inc. more adequately describe and clarify details about device complaints, including what happens when a customer cancels a complaint. The FDA also requests that the firm clarify how it tests a finished product to ensure it meets specifications.
The FDA’s inspection also revealed the products were misbranded because the firm failed to provide timely reports of device malfunctions to the FDA that could result in death or serious injury.
The FDA requested a response from Ideal Implant Inc. within 15 working days of issuance of the warning letter with details about how the company will correct the violations. Failure to address the violations identified within the Warning Letter could result in enforcement action, such as seizure, injunction and civil money penalties.
The FDA’s actions today are part of the agency’s ongoing commitment to its public health mission of ensuring patient access to safe and effective medical devices. As part of the Medical Device Safety Action Plan, the FDA is committed to streamlining and modernizing how the agency implements postmarket actions to address device safety issues in a more timely and effective manner, including taking action against manufacturers when their postmarket studies are non-compliant with study requirements. The FDA has issued several warning letters in recent years to manufacturers who did not adequately fulfill certain postmarket study requirements. For example, the FDA issued warning letters to Mentor Worldwide LLC of Irvine, Calif., and Sientra Inc. of Santa Barbara, Calif. in March 2019. Those warning letters and the letters sent to Allergan and Ideal Implant Inc. today reflect the agency’s continued commitment to act against manufacturers who fail to comply with post-approval requirements.
In addition to the required post-approval studies, the FDA has taken additional steps in the last several years to ensure the agency is monitoring the safety and risks of breast implants. For instance, FDA staff have coordinated with the American Society of Plastic Surgeons and the Plastic Surgeons Foundation to develop the Patient Registry and Outcomes for Breast Implants and Anaplastic Large Cell Lymphoma (ALCL) Etiology and Epidemiology, or PROFILE, which collects real world data regarding patients who have a diagnosis of Breast Implant Associated ALCL (BIA-ALCL). The data collected from this registry have contributed to a better understanding of BIA-ALCL and FDA communication updates to the public regarding BIA-ALCL.
Additionally, the FDA worked with multiple stakeholders to facilitate the development of the National Breast Implant Registry to provide a platform for collecting additional real world data on the safety and performance of breast implants. This registry will add to the information the FDA collects in post-approval studies about the long-term safety of breast implants, and potentially enhance the understanding of the long-term safety and risks associated with breast implants.
The FDA remains committed to thoughtful, scientific, transparent, public dialogue concerning breast implant safety and effectiveness.
Healthcare professionals and consumers should report any adverse events related to breast implants to the FDA’s Adverse Event Reporting program. The FDA monitors these reports and takes appropriate action necessary to ensure the safety of medical products in the marketplace.
Allergan Warning Letter
Every manufacturer of approved silicone gel-filled breast implants is required to conduct post-approval studies to further evaluate the safety and effectiveness of the products and to answer additional scientific questions about the long-term safety and potential risks of breast implants that their premarket clinical trials were not designed to answer. Generally, a manufacturer must still comply with post-approval requirements even if a breast implant has been voluntarily recalled from the market, in part, to continue assessing long-term outcomes in patients who are already implanted with these devices.
“The FDA imposes post-approval requirements because they are an important tool for ensuring the safety and effectiveness of the medical devices we regulate,” said Binita Ashar, M.D., director of the Office of Surgical and Infection Control Devices in the Center for Devices and Radiological Health. “The agency has been diligently tracking post-approval studies as part of our ongoing efforts to evaluate, understand and provide updates to the public on breast implant safety and risks. Post-approval studies are especially important to inform our understanding of the long-term potential risks associated with Allergan’s implants, including the models that have since been recalled from the market due to increased risk of breast implant associated anaplastic large cell lymphoma. The manufacturer’s low recruitment and low follow-up rates for these devices is unacceptable. The FDA will continue to hold manufacturers accountable if they fail to fulfill their obligations.”
The FDA’s warning letter to Allergan noted several serious deficiencies in the manufacturer’s post-approval study to evaluate its NATRELLE Silicone Gel-Filled Breast Implants (“Round Responsive implants”) and its NATRELLE 410 Highly Cohesive Anatomically Shaped Silicone-Filled Breast Implants (“Style 410 implants”). The post-approval study group of subjects with Round Responsive implants has shown poor recruitment and follow-up rates. Allergan’s failure to address these concerns and comply with its post-approval study requirements is a violation of the firm’s premarket approval order.
The FDA requested a response from Allergan within 15 working days of issuance of the warning letter and asked Allergan to provide details about how the company will correct the violations. Failure to promptly comply with post-approval requirements may result in additional action.
Ideal Implant Inc. Warning Letter
Manufacturers must also adhere to quality system regulations, which includes compliance with applicable current good manufacturing practice requirements. Further, under the Medical Device Reporting (MDR) regulation, manufacturers must report certain device-related adverse events and product problems to the FDA—one of the postmarket surveillance tools the FDA uses to monitor device performance, detect potential device-related safety issues, and contribute to benefit-risk assessments of these products.
"Quality system inspections are a way for the FDA to determine if a manufacturer’s activities and procedures, conducted during and after the manufacturing of a device, comply with applicable regulations. When these regulations are followed, it results in safer products for patients,” said Dr. Ashar. “While inspecting the Ideal Inc. facility in January and February, FDA inspectors observed potential violations of the Federal Food, Drug, and Cosmetic Act. Although Ideal Implant Inc. responded to the FDA Form 483-List of Inspectional observations provided to the company at the end of the inspection, most of the corrective actions they took were not adequate. To protect patients, the company should now take additional action to make sure these issues are properly addressed. Addressing quality system and medical device reporting violations helps ensure patient safety, which is our top priority.”
The warning letter issued to Ideal Implant Inc. revealed the Ideal saline-filled breast implants were adulterated due to a failure to maintain proper files for device complaints the manufacturer received from customers, failure to establish and maintain appropriate procedures for implementing corrective and preventive actions and failure to establish and maintain adequate criteria for testing finished devices. The FDA’s warning letter requests that, in a response to the agency, Ideal Implant Inc. more adequately describe and clarify details about device complaints, including what happens when a customer cancels a complaint. The FDA also requests that the firm clarify how it tests a finished product to ensure it meets specifications.
The FDA’s inspection also revealed the products were misbranded because the firm failed to provide timely reports of device malfunctions to the FDA that could result in death or serious injury.
The FDA requested a response from Ideal Implant Inc. within 15 working days of issuance of the warning letter with details about how the company will correct the violations. Failure to address the violations identified within the Warning Letter could result in enforcement action, such as seizure, injunction and civil money penalties.
The FDA’s actions today are part of the agency’s ongoing commitment to its public health mission of ensuring patient access to safe and effective medical devices. As part of the Medical Device Safety Action Plan, the FDA is committed to streamlining and modernizing how the agency implements postmarket actions to address device safety issues in a more timely and effective manner, including taking action against manufacturers when their postmarket studies are non-compliant with study requirements. The FDA has issued several warning letters in recent years to manufacturers who did not adequately fulfill certain postmarket study requirements. For example, the FDA issued warning letters to Mentor Worldwide LLC of Irvine, Calif., and Sientra Inc. of Santa Barbara, Calif. in March 2019. Those warning letters and the letters sent to Allergan and Ideal Implant Inc. today reflect the agency’s continued commitment to act against manufacturers who fail to comply with post-approval requirements.
In addition to the required post-approval studies, the FDA has taken additional steps in the last several years to ensure the agency is monitoring the safety and risks of breast implants. For instance, FDA staff have coordinated with the American Society of Plastic Surgeons and the Plastic Surgeons Foundation to develop the Patient Registry and Outcomes for Breast Implants and Anaplastic Large Cell Lymphoma (ALCL) Etiology and Epidemiology, or PROFILE, which collects real world data regarding patients who have a diagnosis of Breast Implant Associated ALCL (BIA-ALCL). The data collected from this registry have contributed to a better understanding of BIA-ALCL and FDA communication updates to the public regarding BIA-ALCL.
Additionally, the FDA worked with multiple stakeholders to facilitate the development of the National Breast Implant Registry to provide a platform for collecting additional real world data on the safety and performance of breast implants. This registry will add to the information the FDA collects in post-approval studies about the long-term safety of breast implants, and potentially enhance the understanding of the long-term safety and risks associated with breast implants.
The FDA remains committed to thoughtful, scientific, transparent, public dialogue concerning breast implant safety and effectiveness.
Healthcare professionals and consumers should report any adverse events related to breast implants to the FDA’s Adverse Event Reporting program. The FDA monitors these reports and takes appropriate action necessary to ensure the safety of medical products in the marketplace.
