OCD FY2006: FDA Goal 3 - Improving Product Quality, Safety, and Availability through Better Manufacturing and Product Oversight
To ensure the safety and effectiveness of medical devices and radiation-emitting products, CDRH sets and enforces good manufacturing practice requirements; monitors compliance and surveillance programs for products on the market; and collects, analyzes, and acts on reports of adverse effects of products. The Center’s goal is to improve the prioritization, coordination, consistency, quality, and timeliness of inspections, reporting, and enforcement actions to ensure the continued safety and effectiveness of products on the market.
These accomplishments exemplify CDRH’s efforts during FY 2006 to advance patient safety by improving problem detection capabilities in marketed device products.
Post-approval Studies Program
CDRH continued to make great strides in its Post-approval Studies (PAS) Program. The Center issued a draft guidance - Procedures for Handling Post-approval Studies Imposed by PMA Order - to enhance the efficiency and effectiveness of studies conducted by manufacturers as a condition of device approval. The guidance presents suggested format and content for reports on these studies, mentions presentations to Advisory Panels (to enhance study transparency), and notes possible enforcement actions when there is failure to comply. In addition, CDRH conducted regular meetings with the Implementation Workgroup (providing CDRH management oversight) to assure the smooth transition of the program and develop best practices. The epidemiology staff thoroughly reviewed all submissions for new PMAs and led the identification of post-approval questions, the design of new PAS, and review of ongoing PAS.
CDRH continues to monitor postmarket product performance through the Center’s nationwide reporting system and by conducting applied epidemiologic research. For the last quarter of FY 2006, safety analysts identified over 100 new and ongoing medical device safety issues. They also responded to over 100 consult requests related to information in the reports database. Epidemiologists, in addition to the central role in PAS, participated in new and ongoing applied research projects, such as the accuracy of troponin assays (for myocardial infarction) and the safety and effectiveness of vertebroplasty.
Section 522 Studies
FDA may order a manufacturer to conduct postmarket surveillance of a medical device under section 522 of the Food, Drug, and Cosmetic Act. In FY 2006, CDRH staff collaborated with industry sponsors to design science-based Section 522 studies that answer important postmarket questions. The Center issued a consolidated guidance document for postmarket surveillance, ordered postmarket surveillance for two devices (overnight orthokeratology lenses and a coronary vascular anastomosis device), continued postmarket surveillance of three critical products, began development of an enforcement plan for postmarket surveillance, and issued the first Warning Letter citing postmarket surveillance violations under Section 522.
The Medical Product Surveillance Network (MedSun) plays an important role in post-market surveillance efforts by connecting CDRH to device users. Hospitals, nursing homes, and other healthcare facilities use this interactive Internet-based reporting program to report medical device problems. This information helps CDRH, device manufacturers, and medical facilities proactively address device safety concerns.
During the fiscal year, CDRH exceeded by 15 percent its 2006 goal of obtaining a 71 percent participation rate from the 350 participating user facilities. MedSun expanded to include interactive networks that address particular health issues, including LabNet (laboratory devices), KidNet (pediatric devices), TissueNet (human cells and tissues), and HeartNet (electrophysiology devices, such as pacemakers), and used surveys of network facilities to determine the effectiveness of recalls and the training needed to reduce adverse events.
Medical Device Reports
Medical device reporting is how FDA receives information on significant medical device adverse events from manufacturers, importers, and user facilities so that problems can be detected and corrected quickly. CDRH received 224,197 medical device reports during the fiscal year.
(FDA Form 3500A)
Alternative Summary Reporting
(FDA Form 3500)
Compliance and Enforcement
CDRH risk management actions aimed at preventing harm to the public from regulated products include public health notifications, warning letters, and recalls. The following actions were taken during FY 2006.
CDRH protects the American public by ensuring that manufacturers of medical devices comply with Current Good Manufacturing Practice (CGMP) requirements and the Quality System Regulation, taking enforcement actions if warranted. During the FY 2006, CDRH developed and implemented the Real Time Regulatory Review Process to help reduce timeframes so that enforcement actions are processed in a timely manner.
CDRH improved product quality and the safety of numerous medical devices by taking at least 55 enforcement actions during FY 2006 including a corporate warning letter, 4 seizures, and 1 injunction.
Warning letters are intended to alert a device manufacturer that their product is in violation of the laws that FDA enforces. In the letter, the manufacturer is advised to take appropriate and prompt corrective action to avoid administrative or regulatory action. In FY 2006, 154 of the 538 warning letters issued were related to medical devices and radiological health (29%).
Recalls are issued to remove or correct a medical device that violates FDA law. Though FDA can order a recall, manufacturers initiate most recalls voluntarily in collaboration with FDA. During FY 2006, CDRH initiated 651 recall actions involving 1,550 products. This represents approximately a 10 percent increase in recall actions from FY 2005 (571 actions involving 1598 products) and includes 143 in vitro diagnostic device recall actions.
|Class I||Likely that use of the product will cause serious health problems or death|
|Class II||Unlikely that use will cause serious health problems, or problems resulting from use will be temporary and reversible|
|Class III||Unlikely that use will cause health problems|
|FY 2000||FY 2001||FY 2002||FY 2003||FY 2004||FY 2005||FY 2006|
The use of experts who provide testimony and certification to the compliance status of firms is very important in cases in which the Agency takes regulatory actions. In FY 2006, three cases required the services of expert witnesses. Their testimonies were critical to the success of these cases processed by the CDRH Office of Compliance.
CDRH and the Office of Regulatory Affairs (ORA) exceeded the FY 2006 inspection goals by at least 20 percent for domestic, foreign, and bioresearch monitoring (BIMO) inspections in FY 2006:
- 122% (1,299 of 1066) for registered domestic Class II and Class III medical device manufacturers;
- 123% (207 of 168) for foreign Class II and Class III medical device manufacturers; and
- 120% (336 of 278) for BIMO inspections with an emphasis on scientific misconduct, data integrity, innovative products, and vulnerable populations.
Bioresearch Monitoring (BIMO) Audits and Enforcement Activities
In addition to compliance with Good Manufacturing Practices (GMP) requirements, industry must comply with bioresearch monitoring (BIMO) requirements. BIMO requirements include good laboratory practices (GLP) and regulations related to human subject protection and data integrity.
CDRH collaborates with the Office of Regulatory Affairs (ORA) to conduct data audits to determine if devices should be approved. FY 2006 BIMO audit-related accomplishments include the following:
- Issued 24 BIMO Warning Letters and 13 BIMO Untitled Letters to bring non-compliant firms and researchers into compliance with the regulations;
- Entered into a consent agreement to restrict a device clinical investigator from participating in device research;
- Entered into an agreement to restrict an Institutional Review Board’s ability to approve any new FDA-related research;
- Entered into formal agreements with 3 medical device companies to stop the substantive review of their research/marketing submissions until they develop and implement corrective and preventive action plans to ensure the integrity of data submitted to support their premarket submissions;
- Identified and analyzed all inspections from the past 6 years with serious violations and issued 44 follow-up inspections to confirm whether corrective and preventive actions were implemented as promised;
- Removed four firms from FDA’s Application Integrity Policy list as a result of their comprehensive development and implementation of corrective and preventative actions to assure human subject protection and data reliability in submissions;
- Conducted inspections and subsequent analysis that resulted in 2 firms withdrawing their pending 510(k)s submissions due to unreliable substantial equivalence data/information, and 1 pediatric device sponsor withdrawing its Investigational Device Exemption (IDE) for lack of proper oversight and subject safety issues;
- Conducted 105 data audit inspections, addressed data integrity concerns, and issued compliance actions related to 54 active PMAs or PMA supplements; and
- Received and evaluated 157 allegations of research misconduct that could compromise the safety of human research subjects or undermine the quality of research data. Evaluation of the allegations resulted in the issuance of 82 inspections or investigations.
Approximately 85% of FDA inspections of clinical research with medical devices reveal only minor problems with research conduct. To help improve the remaining device research that may be problematic, the Division of Bioresearch Monitoring has increased outreach activities with regulated industries including study sponsors, clinical investigators, study site staff, and Institutional Review Boards plus small businesses through pre-IDE meetings and the Office of Orphan Product Development. In addition, staff have published several articles in professional journals to improve awareness of proper clinical research practices. These outreach activities have resulted in improvements in non-compliance over the past few years.
Risk-Based Inspection Work-Plan
CDRH continued to refine a risk-based management program for inspection and enforcement actions to improve the regulation and monitoring of the medical device industry. In order to utilize resources efficiently, the cross-Center risk-based inspection work plan prioritization process was used to identify public health concerns and issued special emphasis inspection assignments in three areas:
- IV Administration Test Kits
- Internal Cardioverter Defibrillators (ICD)
- Automatic External Defibrillators (AED)
Infusion Pump Project
This project initiated during the fiscal year will transform the way CDRH does business by making available the most up-to-date analysis of market share information on the infusion pump industry. This project should improve CDRH capability to make informed decisions that impact public health and medical necessity. This project also looked at the industry as a whole in order to determine areas that need to be addressed. As a result, numerous firms came into compliance while others were subject to regulatory action. An initiative to better educate the community is planned.
Evaluation of Inspection Violations
CDRH conducted a simple analysis of the Turbo EIR (establishment inspection report) database and identified the top five reasons violations were issued during a medical device inspection. The information will enable CDRH to develop strategies to work with industry to address inadequacies and bring firms into compliance.
Mammography Quality Standards Act (MQSA)
Congress enacted the Mammography Quality Standards Act (MQSA) to ensure that all women have access to quality mammography for the detection of breast cancer in its earliest, most treatable stages. FDA was charged with developing and implementing MQSA regulations. Examples follow of CDRH accomplishments in advancing mammography quality standards during FY 2006.
MQSA Program Inspections
CDRH conducted annual inspections at over 8,800 mammography facilities and ensured that 98 percent of those facilities met inspection standards with less than 2 percent having Level I (serious) problems. CDRH has completed over 104,000 facility inspections nationwide since the MQSA program inception.
MQSA Enforcement Actions
An Additional Mammography Review (AMR) is performed in cases where FDA or the Certifying State has reason to believe that mammography quality has been compromised and may present a serious risk to human health. CDRH has performed 80 AMRs since the MQSA program began.
Although not a regulatory action, an AMR occasionally results in a regulatory action, such as a Patient and Physician Notification (PPN). A PPN explains the problem found to patients and referring physicians and outlines actions to take to reduce related health risks.
If an accreditation body revokes a facility’s accreditation, FDA may conduct an investigation to determine the reasons for the revocation and may determine that the facility’s certificate shall no longer be in effect. A facility whose certificate is no longer in effect because it has lost its accreditation may not legally practice mammography.
During the FY 2006, CDRH completed several regulatory actions against mammography facilities including one Patient and Physician Notification (PPN) and one instance where FDA declared a facility’s MQSA certificate no longer in effect.
Through increased collaboration with external partners, CDRH is enhancing its ability to identify, analyze, and act on postmarket information, and improve enforcement strategies and outcomes.
Software Forensics Laboratory
In consultation with other federal agencies involved with software integrity issues (e.g., Department of Defense, FBI, National Institute of Standards and Technology, NASA), the CDRH Software Forensic Laboratory leveraged the latest academic research to implement a state-of-the-art software forensic capability during 2006. This capability may be used in any phase of the product life cycle, but is particularly valuable in understanding the root causes of adverse events due to software failures. In 2006, this new capability was used to the great benefit of the Center in several high-profile compliance cases. Ultimately, such tools will increasingly be used by medical device manufacturers in their own product development phase, thereby reducing the frequency of software defects and the incidence of adverse events and product recalls.
Defibrillator Working Group
CDRH established the Defibrillator Working Group to coordinate pre- and post-market FDA activities for implantable and external defibrillators. The working group addressed specific processes related to the regulation of defibrillators and collaborated with the Heart Rhythm Society and AdvaMed to assure a full perspective on the issues. The working group piloted a model for effective communication across the entire device life cycle.
Agency for Healthcare Research and Quality
CDRH continued several collaborations with the Agency for Healthcare Research and Quality (AHRQ) which administers several datasets of interest, including the Healthcare Utilization Project Nationwide Inpatient Sample (NIS) of hospital discharge claims and the State Inpatient Databases (SID) of hospital discharge claims. Although similar studies have been done with smaller patient groups, this is the first to use a national dataset to make national estimates of the short-term outcomes of hip prosthesis surgery.
Interagency Registry for Mechanically-assisted Circulatory Supports (Intermacs)
This effort aims to capture detailed clinical data on all patients receiving ventricular-assist devices for destination therapy. The effort is funded by NIH, requires facilities to meet Centers for Medicare and Medicaid Services (CMS) standards to receive reimbursement, and accommodates FDA needs for active surveillance and post-approval studies of these devices.
e-Bay and the Federal Trade Commission (FTC)
CDRH continued grass root and collaborative efforts with e-Bay and the Federal Trade Commission (FTC) to ensure that unapproved products were removed and not offered for sale on the e-Bay website.
The market place for medical devices is global - 40 percent of approved device firms have manufacturing facilities abroad while 6,000 overseas establishments export devices to the United States. CDRH plays an important role supporting global harmonization activities including assisting foreign manufacturers to comply with U.S. medical device regulations. As part of the effort to minimize burden to industry, CDRH participates in the development of international as well as national product standards.
In September 2006, CDRH and Health Canada announced a pilot multi-purpose audit program (PMAP). The purpose of the pilot, slated to begin in 2007, is to evaluate the effectiveness of performing a single third party inspection/audit of medical device manufacturers' quality systems that would meet the needs and regulatory requirements of both countries.
International Organization for Standardization (ISO)
The International Organization for Standardization (ISO) is the world's largest developer of standards. ISO standards are designed for implementation worldwide and include requirements for medical devices.
During FY 2006, CDRH participated in the ISO Technical Committee 94, Workgroup 4 (WG4), meeting in Chicago, Illinois to discuss and revise the draft standard for Clinical Investigation of Medical Devices for Human Subjects. The Workgroup voted to advance the standard for further review within the ISO. CDRH collated the comments of FDA representatives and other U.S. participants for the WG4 Editing Committee in an 11-page document to ensure that the comments were included in the final work product.
Global Medical Device Nomenclature
The Global Medical Device Nomenclature (GMDN) is an international standard for naming, defining, and coding medical device groups to ease identification of products worldwide and reduce confusion when investigating device-related problems. CDRH has contributed considerably to administration and technical maintenance of the standard such as promoting improved nomenclature practices for better data management and efficient communication of data with international regulatory partners.
Global Harmonization Task Force (GHTF)
The Global Harmonization Task Force (GHTF) is an international member organization dedicated to fostering convergence of medical device regulatory practices worldwide while ensuring the quality, safety, and effectiveness of medical devices. GHTF members also work to promote technological innovation and facilitate international trade. In FY 2006, CDRH actively participated in the work of 5 GHTF Study Groups:
- Study Group 1 – Regulatory and Premarket Requirements
- Study Group 2 – Postmarket Vigilance
- Study Group 3 – Quality Systems
- Study Group 4 – Regulatory Auditing of Quality Systems
- Study Group 5 – Clinical Evidence