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U.S. Department of Health and Human Services

522 Postmarket Surveillance Studies

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Metal Ion Levels

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522 Number / Requirement Number PS110005 / PSS001
Current Plan Approved 06/14/2013
Study Name Metal Ion Levels
Root Document Number K052888  K061423  K062994  K062995  K063002  K063514  K070274  K073637  K062998  K993438  K002379  K011110  K042037  K042774  K042841  K050124  K043547  K082446  K090757  K050251  K050441  K093235  K852351 
General Study Protocol Parameters
Study Design Cross-Sectional Study
Data Source New Data Collection
Comparison Group No Control
Analysis Type Analytical
Study Population Transit. Adolescent B (as adults) : 18-21 yrs, Adult: >21
Detailed Study Protocol Parameters
Study Design Description A cross-sectional study to evaluate metal ions and ALTR among cohorts of patients established for each year post implant for metal ion level evaluation. Patients from each cohort, defined by the number of years post implant, will have a one-time assessment on metal ion levels. The objectives of the Metal Ion Levels studies focus on determining whether the presence of high blood and serum cobalt and chromium ion concentrations generally increase over time and if those concentrations are related to increased pain, adverse local tissue reactions (ALTRs), or revision; they also include analyses of explanted devices and the adverse events collected on study subjects.

Study Population Description Patients who have received one of two Biomet implant types; a MOP primary THA or Biomet MOM primary THA devices (M2a Ringloc, M2a Taper, M2a 38 or the M2a Magnum) and who are not contraindicated for MRI.

Sample Size Approximately 308 to 436 patients at five centers

Data Collection For Postoperative Group patients only, the data listed below will be collected: Patient-reported outcomes. Harris Hip Score and hip physical exam. Patient questionnaire to collect contact information for follow-up. Patient questionnaire to collect occupational and/or environmental exposures to metal ions, general medical and physical history and description of any problems or pain. For Postoperative Group patients only, the following tests will also be performed: MRI - Magnetic Resonance Imaging will be utilized to determine the presence of soft tissue changes. Radiographic evaluation: cross-table lateral and AP films will be taken to assess component position and determine the presence of any radiographic changes. Metal Ion Testing: levels of both cobalt and chromium in whole blood and chromium in serum

Follow-up Visits and Length of Follow-up Not applicable.

Final Study Results
Interim Safety Information According to this 522 study results, device safety for the following Biomet Metal-on-Metal Hip Arthroplasty devices: M2a 38mm, M2a Magnum, M2a Ringloc, and M2a Taper, is consistent with the expected safety of MoM hip arthroplasty devices in general. No unexpected adverse events were identified in association the devices under review. However, some Musculoskeletal and Neurological AEs appeared to occur earlier in the MoM vs. MoP; the rate of Allergy/ Immunological AEs was higher in the MoM group.

Both Cr and Co levels were significantly associated with revision. The Implant type (MoM vs. MoP) was shown to affect the metal ion levels; the MoM (but not MoP) patients with an ALTR had higher metal ion levels. A number of variables (e.g., gender, bilateral status) were shown to correlate with metal ion levels. While no significant predictors were identified in the analysis based on a conventional threshold of >7 ppb, in the >2.5 ppb based regression model, “high” ion levels were predicted by the MoM implants, bilateral implants, younger age, longer post- implantation time (year since surgery), and occurrence of pain or functional symptoms. Although the latter analysis should be viewed as exploratory, these results suggest that lowering the currently accepted cut-off of 7ppb may benefit the risk assessment of possible metal debris related complications. In addition to the correlation between taper wear and development of pseudotumors, as identified in the Biomet explant analysis, the current clinical study emphasized the role of MRI in the assessment of pseudotumors. These findings are particularly important for the management of asymptomatic patients with MoM THR.

Metal Ion Levels Schedule

Report Schedule
Date Due
FDA Receipt
Applicant's Reporting Status
6 Month Report 08/20/2012 08/20/2012 On Time
12 month Report 03/29/2013 02/13/2013 On Time
18 month report 08/13/2013 08/14/2013 Overdue/Received
2 yr report 02/12/2014 02/19/2014 Overdue/Received
3 yr report 02/12/2015 02/13/2015 Overdue/Received
Final Report 12/31/2015 12/23/2015 On Time

  • The 522 Postmarket Surveillance Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated under section 522 of the Federal Food, Drug and Cosmetic Act. The program helps ensure that well-designed 522 postmarket surveillance (PS) studies are conducted effectively and efficiently and in the least burdensome manner.
  • In May 2008, the oversight responsibility of the 522 Postmarket Surveillance Studies Program was transferred to the Division of Epidemiology (DEPI) of the Office of Surveillance and Biometrics (OSB)/Center for Devices and Radiological Health (CDRH). DEPI continues to build the 522 program.
  • CDRH has established an automated internal tracking system that efficiently identifies the reporting status of active 522 PS studies based on study timelines incorporated in study protocols and agreed upon by the CDRH and applicants. This system represents CDRH's effort to ensure that all 522 PS commitments are fulfilled in a timely manner.
  • In addition, CDRH launched this publicly available webpage to keep all stakeholders informed of the progress of each 522 PS study. The webpage displays general information regarding each study, as well as the overall study status (based on protocol-driven timelines and adequacy of the data) and the applicant's reporting status for each submission due.


Contact Information

Cheryl Reynolds
Project Manager, 522 Postmarket Surveillance (PS) Studies Program
Food and Drug Administration
10903 New Hampshire Ave
Silver Spring, MD 20993-0002

Phone: (301) 796-7033
Fax: (301) 847-8140