FDA responses to ICIJ questions regarding SynchroMed devices 
 
ICIJ Q43: The original SynchroMed pump was approved in 1988 after being tested in 14 dogs and 160 
human subjects. Just 27 of these human subjects kept their implants functioning for more than a year. Does 
FDA think this is an appropriate trial size and scope for a high-risk implantable device? 
FDA RESPONSE TO Q43: Yes, we believe the trial size was appropriate for this device given the patient 
population studied and the indications for use. The device was studied in, and intended for, patients with significant 
malignant disease who had not adequately responded to prior attempts at treatment. These patients have an 
extremely high level of morbidity and the median survival for these patients was about 5.5 months. For comparison, 
in similar patient populations when a drug is being evaluated as a treatment, clinical trial sizes can be well below 
100 patients in a single arm study. 
Moreover, the purpose of the study was to demonstrate that the device could adequately deliver the medications – 
not to assess whether the device itself had any direct impact on patient survival or other cancer outcomes since the 
drugs were already approved by the FDA for those malignancies and route of administration. The severity of the 
patients’ clinical conditions is reflected in the fact that the median survival of the patients in the initial study was 
only 5.6 months. Hence, one would not expect many patients to have been “on-pump” for one year or more. In fact, 
the average time per patient during which the pump was used closely matches the median survival (5.5 months). 
In total, the study provided data for the equivalent of 667 patient-months of use. This allowed for adequate 
assessment of the pump and its performance. For example, in the original study of 122 cancer patients, more than 
1,300 reservoir refills, more than 1,400 programming changes, and more than 5,600 telemetry transmissions were 
performed. This provided a significant amount of information related to pump (and accessory) performance and its 
ability to adequately deliver the drugs being indicated in the population for which it was intended. 
The data submitted in 1986 was appropriate and of sufficient quality and quantity to assess the performance of the 
device in the intended population. 
 
ICIJ Q44: As a condition of the pump’s release, the FDA required to Medtronic to a perform a trial on the 
pump after it was released onto the open market. The study included 80 patients, and the FDA would later 
conclude that its “data may not be clinically meaningful.” What happened with this trial? Was there any 
consequence for Medtronic producing data that may not be meaningful in a post-market study? 
FDA RESPONSE TO Q44: 
The premise of this question is inaccurate. The agency did not conclude that the data from the post- approval study 
(PAS) was not clinically meaningful. The statement quoted above was meant to capture the fact that the study was 
not designed to capture certain additional information – not that the data collected in the study was non-informative. 
In fact, the study did provide clinically meaningful results for questions it was designed to answer. The data that 
may not have been clinically meaningful was outside the study design. For example, the study was not designed to, 
and did not capture, outcomes stratified by a specific drug name and this may introduce a degree of uncertainty in 
generalizing the results to specific medications. We have updated our website to more accurately convey this point. 
At the time of approval of the PMA Supplement for the Synchromed II device in 2003, the FDA ordered Medtronic 
to conduct a PAS to further assess the pump’s drug dispensing accuracy through six months as well as to further 
characterize adverse events associated with the device. Medtronic was required to provide data on at least 61 
evaluable subjects. The study enrolled its first subject in December 2004 and the last patient follow-up was 
completed in November 2008. The study enrolled 82 subjects and implanted devices in 80 subjects. The study met 
its predefined success endpoint in that, for all subjects, the amount of drug delivered by the pump was within the 

 expected range based on how the device was programmed. 
The most common device-related adverse events were implant site effusion (14%), lumbar puncture headache 
(10%), catheter dislodgment (6%) and implant site inflammation (5%) or infection (4%). These are well-known 
events associated with these types of devices and their implantation/use, and were already described in the product 
labeling. Only three subjects (4%) required device explantation due to a device-related event. 
This information was meaningful in informing the agency’s and health care providers’ understanding of the device’s 
accuracy and potential serious adverse events. 
In January 2010, the FDA notified the applicant that they had fulfilled their PAS requirement. 
ICIJ Q45: Does the FDA believe that the PMA supplement pathway was appropriately used to approve the 
SynchroMed II? 
FDA RESPONSE TO Q45: Yes. It is important to note that a 180-day PMA Supplement undergoes a rigorous 
in-depth evaluation using the same standards as an “Original” (new) PMA and, like an Original PMA, the sponsor 
must await FDA approval before initiating the requested change(s). The PMA process typically must be supported 
by data from clinical studies, rigorous non-clinical testing, and other information specified in the statute and 
regulations. 
Federal regulation (21 CFR 814.39(a)) provides the situations in which a PMA Supplement may be an appropriate 
submission type for changes being proposed to a PMA-approved device that affects the safety or effectiveness of 
that device. The regulation specifically notes the types of changes which may be requested via a PMA Supplement, 
including but not limited to: 
• New indications for use of the device 
• Labeling changes 
• New/different manufacturing or packaging facilities/establishments 
• Changes in performance or design specifications, circuits, components, principle of operation, or physical layout of 
the device. 
The FDA takes several factors into account when deciding whether a PMA Supplement is an appropriate submission 
type for a given change, including the degree of the change to the design/mode of operation or the treated patient 
population. As the fundamental design and operating principles between the original SynchroMed and SynchroMed 
II were unchanged, a 180 Day PMA Supplement was appropriate. 
In addition, it’s important to note that when the agency became aware of safety problems with this device, we 
worked to address them and protect patients. The FDA’s proactive work to address concerns with this device has 
included imposing a consent decree that required Medtronic to stop routine manufacturing and distribution of new 
SynchroMed Pumps in the United States and for export to other countries. This limitation was subject to certain 
exemptions, such as a physician’s determination that the product was medically necessary for patient care. Under 
that exemption, physicians were required to complete a Certificate of Medical Necessity (CMN), and Medtronic 
provided the FDA with reports on the number of CMNs. The limitations on routine manufacturing and distribution 
remained in effect until Medtronic made appropriate corrections to comply with the consent decree; the Food, Drug 
and Cosmetic Act (FD&C Act); and the Quality System (QS) regulation. Further, the consent decree requires that 
Medtronic retain an independent expert consultant to conduct comprehensive audits of Medtronic Neuromodulation 
facilities that design, manufacture, process, pack, label, hold, store or distribute the SynchroMed Pump. If problems 
are found, Medtronic must submit a detailed action plan to address the independent expert’s observations and 
achieve compliance with the decree, FD&C Act, and the QS regulation. In addition, the FDA has monitored 
Medtronic’s activities through inspections conducted by the agency.