| Science at Work Discussion
Approximately two years ago, CDRH anticipated that medicine would change measurably over the next decade. FDA's challenge is to anticipate changes before they happen while maintaining their proper focus on providing public safety. FDA is a century old consumer protection agency.
The Director of CDRH introduced the concept of total product life cycle (TPLC) to follow a device from its inception to its obsolescence. TPLC is now an integral part of the CDRH's strategic planning.
Human Resource Issues FDA lost 15 % of its workers during the Clinton administration. Currently, many employees have worked for FDA in excess of twenty years; therefore it is inevitable that staff turnover will increase in the years to come. CDRH management insist that scientific discipline is the primary backbone of the Center.
Standards
600 new standards have been approved since 1997. CDRH relies on standards for development of guidance documents and device reclassifications. The Center for Devices and Radiological Health is the only center regulated on a risk-based scheme.
Combination Products While the law does not define or consider combination products, these products are regulated under the existing inter-center agreements; FDA must determine what the primary mode of action is for the product.
Legislative Options Legislation is pending that proposes an Office of Combination Products. However, it is not clear whether similar products are likely to remain at the same center at which these products are currently regulated.
A bill is currently pending to allow 3rd parties to inspect 510(k) product submissions. While legislative options have traditionally been the last option, legislation may be necessary for future development of innovative technologies.
Bioterrorism Research Efforts to combat bioterrorism will receive huge increases in funding from the NIH. Approximately half of the NIH budget for fiscal year 2003 will fund these initiatives. New diagnostic tests are currently being developed.
Recalls
According to FDA, approximately five devices are recalled every day and the trend is increasing. Small changes in manufacturing processes can have huge consequences in performance. The Agency continues its obligation to investigate recalled devices and take appropriate or necessary actions.
CDRH External Science Review - Recommendations
- CDRH needs to communicate, both internally and externally, a clear vision of the fundamental role of science in the regulatory process. This vision should define the role of science in developing relevant guidance documents and in developing, modifying, and approving appropriate standards. The vision should delineate the role of science in determining how effectively CDRH responds to new technologies and facilitates the introduction of those technologies to users in a safe and effective manner. Development of a system for summarizing the scientific and other factors leading to guidances or approvals (or rejections) would be useful both for FDA, as it reviews its decisions, and for the public.
- So that science can play this fundamental role, CDRH needs to rethink how it carries out its mission, prioritizes its activities, outsourcing those functions it can while still maintaining oversight, and reallocating its resources so as to expand its investment in science, in all Offices. As part of this rethinking, CDRH should examine its existing organizational structure as well as other regulatory models, with consideration for change to implement and support the TPLC concept. Given fixed budgetary constraints, one model would be for FDA to focus its in-house expertise on selected tasks, and delegate others to official notified bodies or similar entities that derive funding from non-governmental sources.
- As part of its restructuring of activities to enhance the fundamental role of science, CDRH should assess and reconsider the structure of OST to focus on emerging science and technology; this assessment likely will require a separate review of OST.
- CDRH should develop a plan for enhancing cross-office and inter-agency (e.g., FTC, FCC) communication and collaboration.
- CDRH should establish an electronic database for liaison functions and internal and external expertise inventory.
- CDRH should develop and implement a formal process for capturing institutional knowledge through more time spent on guidance documents, standards, other written publications, and archiving and retrieval systems, with written precedent files so that when a decision is reached it does not only remain in the "mind" of the reviewer. Professional credit should be given to the contributors, and the contributors should be rewarded.
- In recognition of the large staff turnover anticipated in the next 5 years and in order to fill gaps in scientific expertise, CDRH should expeditiously perform an assessment of the current level and breadth of expertise and use this to develop a long-term strategic staffing and recruitment plan. Major gaps in expertise should be identified and filled during recruiting for staff replacements due to attrition and turnover. For each position, the options of full-time, part-time, or contract (external) personnel should be considered.
- CDRH needs to develop procedures and implement staff development/training opportunities to ensure that reviewer mandates for such issues as sample size or randomized trials are shaped by realistic clinical perspectives and relevant ethical considerations.
- In recognition of its staff being its greatest resource, CDRH needs to streamline processes that encourage scientific growth within the staff and the maintenance of scientific expertise; these processes need to provide for a more inviting career path and a reward structure for scientific personnel, and will require a reallocation of budget resources so that stated goals of staff growth can occur.
- CDRH should encourage and facilitate the use of internal but non-ODE expertise and also external expertise, including the development of operational and budget policies that promote a more liberal use of external experts.
- CDRH should expand its outreach to and scientific interactions with industry and universities through visitor programs and the creation of appropriate forums for professional development and for information exchange between FDA staff, industry, and academia with particular emphasis on new scientific fields that may result in new medical devices within the next 5 years.
- CDRH should develop a plan in collaboration with other Centers for the evaluation of combination products; this plan may require changes in organizational structure and operational procedures. Whether it is a new structure or some amalgamation of existing structure, the regulation of these products requires an approach that is least burdensome and embodies the philosophy of CDRH.
- CDRH should develop and implement a quality evaluation and improvement program, and as part of this, the evaluation system should develop metrics for the assessment of quality as well as the timeliness of results. The focus of these activities should be to achieve high quality product reviews in a timely manner. Management should implement a system for recognizing, rewarding, and encouraging high quality product reviews and investigations.
- CDRH should implement a quality system with both continuous evaluation and improvement programs in accordance with ISO 9000 or other relevant standards. The focus should be on CDRH as an organization with a specific mission and on the development of activities that contribute to high quality decisions making the most productive use of resources and with a high degree of consistency.
Science at Work in CDRH: A Report on the Role of Science in the Regulatory Process; Final Report (PDF version) (HTML version)
Regulatory Reform
The scientific orthopaedic community and OSMA compiled a list of potential projects that may lead to less burden on regulatory reform efforts. In general, the Forum sought to identify issues where progress could be readily identifiable within a twelve-month period. The scientific orthopaedic community and OSMA has identified the following issues to concentrate its 2002 efforts. The issues are antibiotic bone cement, pre-market/post market balance, and mobile bearing knees.
HHS Regulatory Reform Comments
The Forum discussed the content for the AAOS comment to the HHS Regulatory Reform Committee. As stipulated in the Federal Register, the comment must be limited to a total of five pages. AAOS will include comments on the Health Insurance Portability and Accountability Act (HIPAA), the Emergency Medical Treatment and Active Labor Act (EMTALA), and FDA regulations on new product development.
Coalition
Members discussed that a coalition might be beneficial to elicit a united front on regulatory reform efforts. An AAOS representative suggested that the Academy contact the S2C2 group to define similar concerns within the surgical community.
Regulatory Burden
All agreed that efforts should be made to decrease the bureaucracy in national governmental agencies. While the focus at FDA is more on safety than efficacy, perhaps the issue of time frame variability of pre-market/post-market studies can be explored.
3rd Party Reviewers
FDA indicates that their experiences are fairly positive with 3rd party reviewers for devices. OSMA members suggested that devices with 510k applications with/without clinical data be assigned to a 3rd party reviewer. The issue of conflict of interest is significant for FDA as many experienced reviewers have connections with industry.
Office of Combination Products
Several organizations have suggested that an Office of Combination Products might be a solution for future product development. Forum members surmised that a legislative remedy would be necessary for the development of this office. FDA reminded the Forum that each office has and develops their own regulations. Members concluded that the consistent evaluation of products is of great benefit to industry and the FDA.
FDA considers what the primary mode of action is for combination products in determining regulatory jurisdictions and the lead FDA center. According to the Science at Work document, a product will be evaluated with valid scientific methods, no matter what center reviews it.
Representatives proposed interagency communication for instance; FDA might find it beneficial to communicate with CMS. Furthermore, the concepts of safety and efficacy and reasonable and necessary might be discussed together to provide continuity of care for patients. Regardless of efforts toward developing a new center, Forum members agreed that interagency communication between NIH, CDC, FDA and CMS is vital to a better health care system.
Guidance for Hips and Knees
Forum members proposed new projects to develop guidance documents, one for hips and the other for knees. Members could consider a specific product (device description) including new articulating surfaces, degree of constraint, or novel hip resurfacing technology.
FDA orthopaedic guidances traditionally address:
- Substrate materials
- Degree of constraint
- Type of articulating surface
- Means of Fixation (e.g., cement, biologic, or press-fit)
Forum members will need to identify what clinical outcomes are anticipated and whether short or long term outcomes are more advantageous. Additionally, a researcher explained that the definition of constraint is of some concern to the research community. FDA noted that this may require a separate effort because the regulatory definitions are defined in the classification regulations for orthopaedic devices.
Post approval studies address the following questions:
- Is the patient still alive?
- Is the implant still in place?
- Does the surgeon have any plans to remove it?
Antibiotic bone cement
FDA Chief Counsel and a FDA representative reviewed the history of antibiotic bone cement. Historically, the substance was classified a drug by the FDA. After May 1976, bone cements with or without antibiotics were considered to be class III devices requiring a pre-market approval application (PMA). Two PMAs were sent to the Orthopaedic and Rehabilitative Devices Panel. One petition recommended antibiotic bone cement for use in the prophylactic treatment in primary surgery and the latter petition recommended use of the substance in revision surgery. The Panel did not recommend either petition for approval. Subsequently, bone cements without antibiotics were reclassified on October 14, 1999. One company holds a PMA on bone cement without antibiotics for the treatment of pathologic fracture.
FDA will entertain 510(k) submissions for antibiotic bone cements if the manufacturers limit the claims to device claims instead of drug claims (e.g., reducing colonization on or in the device). The 510(k) submission for antibiotic bone cements should address the appropriateness of the antibiotic for the microbial organisms that may be present; antibiotic resistance of the proposed formulation; local toxicity and toxicology data; effectiveness data supporting the manufacturer's claim(s) from preclinical study data, and characterization of the properties of the bone cement including elution rates and preclinical data previously outlined in our bone cement guidance (for bone cements without antibiotics). If a manufacturer wants to make drug claims for their product (e.g., antibiotic bone cement in beads are intended to actively treated infected joints), the FDA would consider antibiotic bone cement beads to be a drug delivery system requiring a New Drug Application (NDA) approval.
FDA representatives stated that prophylactic vs. primary vs. revision are all different modes of action for antibiotic bone cement. The proposed mode of action or intended use will drive whether the product may be considered under 510(k) or require an NDA. A manufacturer suggested that patients might be adding to antibiotic resistance problems by taking only half of the antibiotics that are prescribed. Manufacturers wondered if 30-year data from European countries would be admissible in a marketing submission. FDA representatives indicated that the sponsors would need to link the data from other countries to the product for which the sponsor was seeking market clearance.
The recent Humanitarian Device Exemption (HDE) approval of the Prostalac Hip temporary prosthesis contains bone cement with a combination of two antibiotics. A link to the summary of the product approval for the Prostalac hip is provided: http://www.fda.gov/cdrh/mda/docs/h000004.html.
NIST
Representatives from the NIST Industrial liaison office gave a presentation to the Forum. NIST is attempting to develop an industry needs database and may coordinate a symposium on the cleanliness and processing of medical implants in the future. The 1994 workshop on polyethylene engaged industry and grant proposals from NIH were encouraged as a result.
ASTM
ASTM has renamed their organization ASTM International. They are positioning themselves to be a leading standards organization with worldwide acceptance and participation.
Future meetings and symposia at ASTM
- May 7-10, 2002 Pittsburgh, PA - stainless steel
- November 5-8, 2002 Miami, FL - cross-linked polyethylenes for joint replacements, tissue engineering
- May 6-9, 2003 Kansas City, MO- biocompatibility testing
- November 18-21, 2003 Tampa, FL - bone graft substitutes
TEMPS
ASTM F-04 has developed a draft standard: Standard Guide for the In Vivo Assessment of Implantable Devices Intended to Replace, Repair, or Regenerated Articular Cartilage. The draft is currently out for comment.
International efforts are also underway with the Tissue Engineered Medical Products (TEMPS) division. ASTM appealed for more input from the AAOS Biological Implants Committee on the development of tissue standards. Additionally, the spinal implants publication is currently being circulated for editorial comment.
Biomaterials Access Assurance Act of 1998
The Biomaterials Access Assurance Act of 1998 intended to establish a mechanism to protect some biomaterials suppliers of implanted medical devices from liability in civil law suits. However, in reality, this mechanism did not protect the larger companies from liability. Consequently, several large manufacturers of polyethylene are ceasing business operations. Supply of raw materials may be more limited in the future and in general, suppliers may not want to accept the liability risk. Smaller companies are covered under this act but would not be able to provide the services of a larger manufacturer.
Educational Initiatives
An AAOS representative talked with several members of CDRH and the Educational College at FDA prior to the January meeting. The Forum anticipates providing/facilitating educational opportunities for CDRH staff.
Proposed Educational Opportunities:
- Internship/fellowship program:
- Forum could identify candidates
- FDA has funding, senior people with skills wanted by FDA for 6 -18 months
- Full time or part time available
- Conflict issues are important- cannot have financial interest in a company
- Prime locations- full time faculty at musculoskeletal lab
- Educational seminars
- Held on topic of interest- ½ day morning format
- No budget from FDA available
- Use FDA Staff College mechanism
Preferred topics of interest:
- Mechanical testing- cover of testing methods, clinical outcomes, spine, hips
- Materials testing-
- Ways to correlate clinical failure modes with bench testing
One member reminded the Forum that educational symposia on biomedical technology are presented at ASTM meetings regularly and perhaps FDA could receive a remote transmission from the seminars. Funding possibilities include the Corporate Advisory Council budget, ORS special projects committee, or the new AAOS Academic Affairs Council budget. A Forum member suggested that other agencies might be interested in these opportunities; for instance, CMS might be interested in technology assessment areas.
Registry workshop
AAOS and AHRQ held workshop on the feasibility of a National Joint Registry for orthopaedic devices in December of 2001. Sections covered in the workshop included:
- Clinical Economics of Total Joint Replacement and Cost Savings Associated with Decreasing Revision Burden
- Patient Safety Issues: Medical Device Reporting System, AHRQ's role in promoting patient safety
- Dissemination of Information in Orthopaedic Surgery
- Registry as a Research Tool
- Confidentiality and Liability Issues
- Data Management and Access
- Governance Issues
The AAOS Board of Directors are very committed to implementing patient safety measures and initiatives. A pilot project will be decided upon in the very near future.
OSMA
A delegation from the Orthopaedic Surgical Manufacturers Association (OSMA) met with FDA to discuss the current status of the metal/metal hip petition. Data from three companies that have Investigational Device Exemption (IDE) studies with this type of device were included in the OSMA petition. During the meeting, FDA suggested a five-year follow-up on clinical data.
An OSMA representative stated that there does not appear to be a consistent response from the Orthopaedic and Rehabilitative Devices Panel, particularly with the recommendation not to approve this device type. A new petition will need to be submitted to the FDA for the metal/metal hip device.
Mobile Bearing Knees
Orthopaedic Surgical Manufacturers Association (OSMA) convened a meeting recently. Companies that have experience with mobile bearing knee data will assess the current data and determine what changes might be needed for the petition.
MTLF
The Medical Technology Leadership Forum (MTLF) studies emerging issues in medical technology from a public policy perspective. This group currently has a strong emphasis on cardiology. MTLF is publishing booklets distribute to the government.
Recent topics of interest include patient access to developing technologies, conditional coverage on investment technology, and Medicare coverage on emerging technologies. However, this group does not have a lobbying presence. The spring meeting on tissue engineering will be held at Georgia Tech University from April 21-22, 2002.
Cartilage Guidance
Progress continues on the repair of hyaline cartilage guidance document. The work group anticipates a submission to FDA in the near future.
NIH
President Bush will fulfill his commitment to doubling the NIH budget within a five-year time frame. The President's fiscal year 2003 budget is expected to be $27.03 billion with an increase of $3.7 billion. Approximately half of the budget increase will be devoted to bioterrorism research.
The National Institute for Biomedical Imaging and Engineering (NIBIB) will fund research grants for the first time this year. The Institute expects approximately $112 million in funding for fiscal year 2003. NIBIB is currently seeking an institute director.
The Bioengineering Consortium (BECON) supports a symposium every year. This year BECON will host a symposium on Sensors for Biological Research and Medicine on June 24-25, 2002 at the Natcher Conference Center in Bethesda, MD.
(http://www.becon1.nih.gov/becon.htm.)
CMS
There are not currently any orthopaedic issues being considered by the national coverage desk. CMS will provide a speaker for the Sunday evening portion of the next meeting.
BOD Report
AAOS leadership supports a leadership-mentoring program for young fellows in the Academy. The new AAOS President will also lend significant efforts toward increasing the diversity within orthopaedics.
The AAOS Washington office will create new list serve for the AAOS research community to provide them with the latest grant announcements.
FDA
FDA representatives announced that a second Deputy Director has been appointed in the Division of General, Restorative and Neurological Devices. Additionally, the division is attempting to compile a priority list of Pre-amendment Class III devices that are ripe for reclassification.
The Orthopaedic and Rehabilitative Devices Panel recommended approval of the InFuse Bone Graft cage with the following recommendations.
- Study anti-RhBMP 2 in systemic administration mouse model for antibodies at conception, implantation, limb bud formation time points.
- Study mouse model with equal doing multiple dosing of RhBMP 2 over a long time to complement the large dose at single time.
- Assess the potential for BMP 2 to promote growth of primary tumor isolates which have been analyzed for BMP 2 receptor expression.
- BMP only approved for use with tapered cages.
From all accounts, this panel meeting successfully coordinated efforts from both CBER and CDRH.
Members suggested that a Bulletin article on humanitarian use devices (HDE) might be helpful to educate surgeons on the provisions of this special category of device approval. The Chairman of the Biomedical Engineering committee will add this to the list of committee projects.
AAOS Committees
Biomedical Engineering
The Biomedical Engineering committee completed the position statement on single-use devices (SUD). The AAOS Board of Directors approved the statement at their December 2001 meeting. The implant device recall advisory statement will be sent to the Board in February 2002. Additionally, the committee is working on a point/counterpoint Bulletin article that will address cross-linked polyethylenes for knee components.
Biological Implants
The Biological Implants committee will offer a symposium, an instructional course lecture and a scientific exhibit on bone graft substitutes at the 69th AAOS Annual meeting in Dallas, TX.
The Academy is very concerned about the recent reports of infected allograft tissue. The Board of Directors will choose a panel of experts to assess the problems, work with the CDC and CBER, and provide patient safety recommendations on the use of allograft tissues by orthopaedic surgeons.
|
