Present:

Members reviewed and approved the summation report from the October 2002 meeting of the Orthopaedic Device Forum. New members and guests were introduced to the Forum. All participants disclosed conflicts of interests.

Janet Trunzo, Advamed Vice President of Regulatory Affairs discussed the Medical Device User Fee Modernization Act (MDUFMA) of 2002 with Forum members. Advamed was very active in drafting the legislative portion of the Act pertaining to user fees. The major sections of MDUFMA are:

	Title I:	Fees Related to Medical Devices
	Title II:	Amendments Regarding Regulation of Devices
	Title III:	Additional Amendments- including single-use device reprocessing (SUDs)

Fees
FDA will apply fees to the following applications and submissions under MDUFMA:
Premarket Application (PMA, BLA)
Product Development Protocol
Premarket Report
180-day Supplements
Panel track Supplements
Efficacy Supplements
Real-time Supplements
Premarket Notification Submission [510(k)]

Exceptions to the new fees include Humanitarian Device Exemptions (HDE), 510(k) submissions by a third party, PMAs or 510 (k) for pediatric conditions, state or federal sponsors and further manufacturing use supplements.

Small businesses with $30,000,000 or less in gross sales are exempt from fees for their first original PMA or pre-market report (PMR). Subsequent PMAs, PMRs, and supplements are subject to 38% of the standard fee.

A Federal Register notice will be forthcoming about payment fees and timelines. Additionally, a worksheet for user fees will be provided.

The Federal government has estimated fee revenue amounts to total:

	FY 2003	$25,125,000
	FY 2004	$27,255,000
	FY 2005	$29,785,000
	FY 2006	$32,615,000
	FY 2007	$35,000,000

FDA currently receives over 4000 510(k) applications each year. It is unknown how many small businesses are sponsoring the 510(k)s.

The Forum discussed that combination products, particularly device/biologic combinations, could prove to be challenging in defining the mode of action. Biological License Applications (BLA) typically cost approximately $500,000. Since a PMA submission fee is $154,000, companies may attempt to address the structural capacity of the device/biologic product as the primary mode of action in an effort to pay a smaller application fees. However, biologics and drug fees have been instrumental in providing FDA with resources to hire additional reviewers and staff.

MDUFMA mandates that financial and performance reports must be delivered to Congress annually. Performance goals have been defined for each type of submission (PMA, 510(k), etc.), with greater efficiency in successive years and shortened review times. Advamed noted that expedited pre-market applications, in general, had longer review times than original PMAs. Additionally, 60% of companies receive deficiency letters on their submission of the initial application. Patient accountability is a major reason for PMA deficiencies. The FDA must be able to ascertain what happened to the patients enrolled in the study.

Title II Amendments

• Third party reviews
• Office of Combination Products within the FDA Commissioner’s Office
• Electronic labeling & electronic annual registration
• Pediatric guidance must be issued in 270 days
• Branding provision
• Labeling for reprocessors
• Internet list of Class II devices exempt from premarket notification

Title III- Additional Amendments Three provisions Title III are of interest to the orthopaedic community:

• Identification of Manufacturers of Medical Devices- The name of the manufacturer must be attached to or on the device. The effective date is 18 months post enactment.
• SUDs- Labeling is required on a reprocessed device. The effective date is 15 months post enactment.
• MedWatch- The MedWatch form will be revised to accommodate information on reprocessed devices. Therefore, the FDA will be collecting information on adverse events when a reprocessed single-use device is used.

Discussion
Forum members discussed that a brief course for clinical investigators would be beneficial for surgeons and industry. Since the FDA finds many deficiencies in patient accountability, Forum members cited that educational efforts to address how to become a good investigator and document patient accountability warrant further development. Additionally, some Forum members review journal submissions and reported similar deficiencies with patient protocols.

Combination Products
The American Academy of Orthopaedic Surgeons (AAOS/Academy) was the only medical specialty society to provide testimony at the FDA open public meeting on the regulation of combination products. The meeting was held on November 25, 2002. AAOS presented several suggestions and comments to the FDA advocating the following:

• Combination products will provide unique regulatory challenges for the FDA;
• The FDA should develop a team approach for the review of combination products consisting of a material scientist, biologist, clinician, and engineer;
• Global harmonization efforts should be considered during the regulatory framework development of combination products;
• FDA should consider creating an Advisory Panel for combination products;
• Adverse event definitions are too broad and inclusive; and
• FDA must present a consistent and predictable regulatory approach.

Standards
The American Society for Testing and Materials (ASTM) was previously a national standards organization. During the past year, ASTM has changed to an international standards society. Forum members contend that the ASTM standards development process is more robust than that of the International Standards Organization (ISO). Members requested that the FDA and the Orthopaedic Surgical Manufacturers Association support ASTM International and assess how standards are going to be used in the orthopaedic community.

ASTM Symposia
May 7-9, 2003- Kansas City- Workshop on cleanliness of implant
November 2003- Biocompatibility
September 2003- Metrology workshop sponsored by the National Institute of Standards and Technology (NIST)
Salt Lake City- May 2004- Bone cement & calcium salts

Unscheduled Future Symposia
Ceramics- zirconia & alumina
Robotics

Evidence Based Medicine
Outcome measurements typically ascertain the pain and functionality of the patient. Forum members discussed that outcomes for hips and knees are somewhat discernible; however measuring outcomes for bone graft substitutes is considerably more nebulous. Members of the Forum suggested using biological standards as measurement tools, as are currently being developed by the ASTM. Additionally, a tissue-engineering researcher videotaped a procedure and created a CD-ROM to recreate his protocol. This type of interactive tool will be helpful in advancing the field of tissue engineering but will also be useful for other applications. Nonetheless, small companies are typically unable and unwilling to share intellectual property. Different products may have a different expectation levels: for instance, the expectations of the outcomes for a mechanical heart will be decidedly different than those of a knee device. AAOS is very interested in evidence-based medicine, which is differentiated from outcomes collection.

Reimbursement for New Technologies
Payers must grapple with reimbursement for new technologies given that some new products may not significantly improve upon existing technologies. Members cited the need for scientific discipline and stated that new products must compare with the natural history of the device, biologic, or combination product.

Antibiotic Bone Cement
Since there is a significant problem with antibiotic resistance attributed to systemic usage, there is a strong interest in the local delivery of antibiotics. Additionally, fungal infections are continuing to become a dilemma. Many infections can be eradicated or minimized by local delivery. For example, tubercular infections are treated optimally by debridement and local antibiotic delivery. The AAOS Infections committee will develop recommendations for the use of bone cement products.

The FDA determination of product jurisdiction and lead review responsibility are based on the primary mode of action of the antibiotic preparation. Antibiotic beads are considered a drug delivery system and are not currently available for marketing in the U.S. Manufacturers must decide what the intended use of the product is prior to submitting a marketing application. A product that claimed to reduce colonization would have different expectations and requirements than a similar product that claimed to be used for an adjunctive treatment.

Hip Document
The Forum will review the draft hip document at the July 2003 meeting. A one-day workshop is proposed during the fall AAHKS meeting so that the community may reach consensus on the outcome measurement tools. The Harris Hip Score is still widely accepted. However, there is generally no consensus on the length of follow-up for a hip replacement.

Tissue Engineering
The AAOS/ NIH Tissue Engineering in Musculoskeletal Clinical Practice Workshop was held in Santa Fe in January 2003. Tissue engineered skin substitutes are marketed products while bone and cell engineered products are currently being developed.

AAOS will publish a summary of the workshop sessions in electronic format to provide updates to developing information. The orthopaedic community universally lauded this workshop and agreed it would be helpful to revisit this topic in two years. Industry may provide the bulk of funding for the next workshop on tissue engineering since it is not anticipated that the NIH would want to repeat a similar workshop in the next couple of years. Forum members noted that request for applications (RFA) usually develop from NIH conferences. Forum members suggested that regulatory information is essential and requested that the FDA participate in the next tissue-engineering workshop.

Forum members will contact the editors of the Journal of Bone and Joint Surgery (JBJS) and the Journal of the American Academy of Orthopaedic Surgeons (JAAOS) to ascertain the feasibility of including some of the written submissions from the tissue-engineering workshop into their publications.

NIH Update
The next NIH consensus conference on Primary Total Knee Replacement will be held in December 2003. E. Anthony Rankin, MD, will chair the non-Federal panel. They will address the following questions:

1. What are the current indications and outcomes for primary total knee replacement?
2. How do specific characteristics of the patient, material, design of the prosthesis and surgical factors affect the short-term and long-term outcomes of primary total knee replacement?
3. Are there important perioperative interventions that influence outcomes?
4. What are the indications, approaches, and outcomes for revision total knee replacement and salvage procedures?
5. What factors explain disparities in the utilization of total knee replacement in different populations?
6. What are the directions for future research?

CDRH Fellows Program
The Center for Devices and Radiological Health (CDRH) is seeking expertise in its review of emerging spinal technologies. The Center is currently formulating a fellows’ program for one to four senior scientists to evaluate products that would encompass the entire life cycle of the device from premarket through postmarket. Additionally, senior scientists would provide support to the FDA by reviewing test protocols and test results to support FDA device approvals or safety evaluations to initiate clinical studies. The Academy is assessing what types of individuals to target for these fellowships and how to publicize them.

Mobile Bearing Knees
The Orthopaedic Surgical Manufacturers Association (OSMA) is preparing a petition to reclassify mobile bearing knees from Class III to Class II. Forum members will review the draft petition prior to its submission to the FDA.

Metal on Metal
OSMA will resubmit a new petition to CDRH in an attempt to reclassify metal on metal hip devices from Class III to Class II. The new petition will differentiate between good vs. bad design and will separate the articulation from the design of the hip device. Information on wear testing and impact loading will be included in the new effort. Metal-metal hips have been researched fairly extensively and performance data is available in the literature.

Some members of the Forum contend that the Clinical Orthopaedics and Related Research (CORR) article “Metal-on-Metal Versus Polyethylene in Hip Arthroplasty: A Randomized Clinical Trial” by S. J. MacDonald, et. al. misinterprets the data. The MacDonald article concludes that patients with metal on metal articulations experienced an increase of metal ion levels in their urine. Additionally, some Forum members suggest that some concerns are theoretical and that metal devices have been implanted for over thirty-five years successfully.

The new petition should identify the special controls that will be used to reclassify the device. Declaration of conformity to standards, risks, labeling, testing, and data need to be articulated in the petition.

FDA Update
Vertebroplasty/Kyphoplasty
Complications Related to the Use of Bone Cement in Treating Compression Fractures of the Spine was posted on the CDRH website on October 31, 2002. http://www.fda.gov/cdrh/safety/bonecement.pdf

The notice provides information to patients while alerting orthopaedists, neurosurgeons, and interventional radiologists to problems associated with Class I (bone tamps) and Class II (bone cement) devices. Physicians typically add barium sulfate to the bone cement and it is unclear how that changes the viscosity of the cement and adverse event profile.

Some hypotensive events are also occurring to patients who undergo vertebroplasty and kyphoplasty. Many of these patients have significant co-morbidities and autopsies are not usually ordered. The notice has served to develop communications between the FDA and physician specialty societies.

Final Rule
Final rule on the Reclassification of the Knee Joint Patellofemorotibial Metal/Polymer Porous-Coated Uncemented Prosthesis and the Knee Joint Femorotibial (Uni-compartmental) Metal/Polymer Porous-Coated Uncemented Prosthesis: http://www.fda.gov/OHRMS/DOCKETS/98fr/03-6857.html or http://www.fda.gov/OHRMS/DOCKETS/98fr/03-6857.pdf

Ceramic Hips
CDRH recently approved the following two ceramic hip devices:
Wright Medical Ceramic TRANSCEND® Hip Articulation System Approval; http://www.fda.gov/cdrh/mda/docs/p010001.html Stryker Howmedica Osteonics Approval: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/PMA.cfm?ID=6014

Guidance Documents Update
The Forum will convene a subcommittee to review the following CDRH guidance documents:

1. Guidance Document for Industry and CDRH staff for the Preparation of Investigational Device Exemptions and Premarket Approval Applications for Bone Growth Stimulator Devices; Draft http://www.fda.gov/cdrh/ode/bgsguide.pdf
2. Reviewers Guidance Checklist for Intramedullary Rods http://www.fda.gov/cdrh/ode/956.pdf
3. Reviewers Guidance Checklist for Orthopedic External Fixation Devices http://www.fda.gov/cdrh/ode/829.pdf
4. Guidance Document for Testing Non-Articulating, 'Mechanically Locked', Modular Implant Components http://www.fda.gov/cdrh/ode/916.pdf
5. Guidance Document For The Preparation of Premarket Notification For Ceramic Ball Hip Systems http://www.fda.gov/cdrh/ode/355.pdf
6. Guidance Document for Testing Orthopedic Implants with Modified Metallic Surfaces Apposing Bone Or Bone Cement http://www.fda.gov/cdrh/ode/827.pdf
7. Guidance Document for the Preparation of IDE and PMA Applications for Intra-Articular Prosthetic Knee Ligament Devices http://www.fda.gov/cdrh/ode/233.pdf

Spine Guidance
A CDRH spine guidance is in the process of being developed from interactions with the public and the Orthopaedic and Rehabilitative Devices Panel. FDA officials are interested in information on mechanical testing.

Tissue Coalition
AAOS is forming a coalition of surgical specialty societies to promote research and advocate for a safe tissue supply. Some tissue processors label their tissue as sterile; the definition of sterility is currently open to interpretation. Additionally, adventitious agents continue to develop therefore, processors of biological products will need to develop assays for these new infectious agents.

The Forum will convene a biological subcommittee to assess emerging biological issues.

National Joint Registry
The AAOS is developing a pilot project to assess the feasibility of a national joint registry. Surgeons hope to reduce the revision rate in this country by studying data collected from this effort. AAOS is partnering with a commercial entity on this venture.

The clinical community is very interested in identifying implants in a national registry but industry may be opposed to the collection of such information. Regardless, as patient safety efforts move forward, bar codes on orthopaedic implants will be very useful in assisting revisions and retrievals. A member of the Forum will contact OSMA to address the issue of achieving consensus on uniform bar code labeling for orthopaedic implants. Clinicians must decide what information they want captured in the bar code.

CMS Update
The CMS will evaluate the scientific evidence to determine the indications for which arthroscopic lavage and/or debridement for the treatment of the osteoarthritic knee is reasonable and necessary following the publication of the Moseley article in the New England Journal of Medicine, Volume 347, No. 2, 2002. CMS may refer this issue to a federal advisory panel upon completion of their review.

Some orthopaedists remarked that they are concerned about the CMS setting a new precedent after calling for a review following the publication of one study. The CMS representative reminded the Forum that 90 % of decisions are made at the local level whereas only 10% are national decisions although national coverage supercedes local coverage.

2003 Priorities
The Orthpaedic Device Forum determined several priorities for 2003. They will concentrate efforts to:

• Clarifying jurisdiction on combination products
• Update CDRH guidance documents
• Provide guidance on bone cement
• Investigate a workshop focused on how to conduct clinical trials (not just for the PI)
• How to facilitate the commercialization of small volume products