Sarah, David and Martin

We have finally received the long awaited letter from FDA regarding the ASR PMA. It is a non-approvable letter. A copy of the letter is attached.

The FDA took issue with several aspects of the pooled clinical data and subsequent data analysis and have essential asked us for a new clinical data set and analysis, which are cited for the major cause of the non-approvable classification (the 5 major deficiencies on page 1 and 2). There are also several other deficiencies associated with the clinical data noted in Items 1-3. FDA has also requested additional information related to fatigue testing (item 4), sterilization (item 5 and 6) packaging validation (item 7) Porocoat characterization (Item 8) and HA coating (item 9).

The clinical data deficiencies are the major concern. There are a few issues.

1. There have been a significant number of revisions within the ASR group (both in the IDE and in the OUS study) as opposed to very few in the control group.

2. The demographics of the control group are significantly different than the ASR group, which seriously complicates the analysis.

3. There are insufficient numbers of subjects in the original IDE cohort to demonstrate non-inferiority and even when the data is pooled with data from OUS, we are unable to demonstrate non-inferiority unless we exclude one site with one site with very poor results which was attributed to failure to use ASR specific instruments. FDA took major issue with this and believes that we have not demonstrated the required non-inferiority.

We are currently evaluating the data that is available to address FDA concerns and recommendation to provide a new data set. One possibility, especially to address issue 2 above is to determine if we can identify a demographically matched data set by pooling data from the ASR data sets and the other IDE control datasets. The team’s concern is that given the revision rate in the ASR group that we will still not be able to demonstrate non-inferiority with additional downside risk. Any need to enroll new ASR cases will significantly delay the PMA submission and approval by years.

We will provide you with a more detailed evaluation in the coming weeks, but we did want you to be aware of the significant risk associated with the FDA approval of this product. This comes at a time when ASR data from national registries (Australia and UK) is being closely scrutinized because of higher revision rates.

Please let me know if you have any comments or questions.

Pam

DePuy Statement on Tuesday

The ASR Hip Resurfacing System was not “rejected” by the U.S. Food and Drug Administration (FDA), nor did the company inappropriately sell it in other countries.

In the U.S., the ASR™ XL total hip replacement system was first cleared by the FDA for marketing in 2005 via the 510k process.  DePuy filed a submission containing clinical data for pre-market approval (PMA) for the hip resurfacing version of the ASR device with the FDA in July 2007.  In August 2009, DePuy received a letter from the FDA stating that based on the data submitted, the FDA was unable to assess safety and effectiveness for the ASR Hip Resurfacing System.  The FDA recommended that DePuy provide a new clinical data set to support the potential determination of a reasonable assurance of safety and effectiveness.  The letter concluded with the various options available to the company under FDA regulations, including the right to decide not to submit a new dataset and withdraw the application.

At the same time that the company received this FDA letter, market demand for hip resurfacing was declining rapidly.  DePuy chose not to move forward with gathering additional data based on the declining demand for hip resurfacing. This was purely a business decision for the U.S. market. The decision not to pursue the ASR Resurfacing PMA application in the U.S. did not impact the use of the ASR Hip System in other countries.

Medical device registration requirements are defined by a country’s legislation.  The legislation specifies the data required for the submission and approval process.  DePuy properly complied with the regulatory process for each separate country where the ASR Hip System was available.  At the time of the PMA submission in the U.S., the ASR Resurfacing System had already been approved for marketing by regulatory authorities in other countries. For example, in Europe, the ASR™ XL Acetabular System and DePuy ASR™ Hip Resurfacing System met the requirements of the Directives specified by the European Union for all medical devices and received CE mark approval.

It is common to receive letters, such as the FDA’s request for more data for evaluation, from a regulatory authority reviewing the product for marketing. Correspondence dealing with requests specific to one country’s regulatory authority are not necessarily relevant to another country’s regulatory authority, so they are typically not communicated and there is no requirement to do so.  Significant safety information regarding a product, however, is communicated to each country where DePuy markets a product, and this was done for the ASR Hip System.