Pain Pump Law Blog : Medical Device and Malpractice Lawyer & Attorney for Local Anesthetic Infusion Pump & Post-Operative Infection Cases

For most of the pain pumps on the market in 1999 (referred to in Part One of this post), scant information remains available online from the FDA.  However, the Summary of Safety Effectiveness for I-Flow's PainBuster under K980558 is still accessible.  In this document, I-Flow stated that the PainBuster was substantially equivalent in intended use to the Pain Control Infusion Pump (PCIP) (K896422) distributed by Sgarlato Laboratories and to the Homepump C-Series (K944692) and Homepump Eclipse (K932740) marketed by I-Flow. 

There are several interesting things about these statements of equivalence.  It was actually the Burron Ambulatory Drug Delivery System approved as K896422 and not the Sgarlato PCIP, which was K990101.  I-Flow's document did accurately state that the PCIP was produced by Burron/B. Braun.  And, K990101 does show that Sgarlato claimed equivalence to the Burron device and that Burron would manufacture the PCIP for Sgarlato.   The strange thing is that I-Flow's submission to the FDA was made in February 1998 and Sgarlato's was not made until January 1999.  On its face, therefore, I-Flow claimed substantial equivalence to a device that had not yet been submitted to the FDA for approval.  

Sgarlato's summary stated that its PCIP would be used for the same intended purpose as the Burron device.  Sgarlato's intended use was for continuous infusion of local anesthetics directly into the intraoperative site for management of postop surgical pain.  The Burron device was submitted to the FDA in 1989, however.  I am quite skeptical that it could have been approved for use as a pain pump at that time.  Unfortunately, all information about the 510(k) for the Burron device has been purged from FDA's 510(k) database. 

The other devices I-Flow claimed in 1998 as predicates were its own Homepumps.  However, both the C-Series and Eclipse pumps had much higher flow rates (up to several hundred ml/hr) and other routes of administration, including intravenous.  I-Flow claimed that the design of the PainBuster would be identical to that of the Homepump. 

In short, I-Flow claimed substantial equivalence to the Sgarlato PCIP for intended use and to its own Homepump for the components of the device.  The I-Flow PainBuster (which would be used by I-Flow as a predicate device for all of its later pain pumps and by numerous competitors for their devices in years to come) is premised upon what is known as a "split predicate."

A few weeks ago, the Center for Devices and Radiological Health at the FDA, issued extensive Preliminary Internal Evaluations of the 510(k) process.   This document contains a very useful history of the 510(k) program and a number of findings and recommendations by a working group charged with reviewing the existing process, including this finding:

"The term 'split predicate' refers to a situation in which a 510(k) submitter is attempting to 'split' the 510(k) decision-making process by demonstrating that the new device has the same 'intended use' as one predicate and the same 'technological characteristics' as another.  This practice is akin the combining different attributes of two or more devices into a single, nonexistent predicate device that may bear little resemblance to the device under review or to any marketed device.  Concerns have been raised that the use of a 'split predicate' may not allow for a valid comparison of safety and effectiveness because not such device exists, either in part or whole, and there is therefore no real world information about its risks and benefits." (p. 59)

In Part One of this post, I wrote that at some point there had to have been a step from an infusion pump intended to be used for other purposes to a pump intended to infuse local anesthetics.  It appears that I-Flow's PainBuster was one of the earliest (if not the first) of these steps.  Much of the current pain pump market has developed by making claims of substantial equivalence to I-Flow devices.  If there are serious questions about the basis of FDA approval for a threshold device like the PainBuster, those questions necessarily spread through the chains of substantial equivalence to numerous devices that have followed. 

 

 

 

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The FDA's guiding principle for approval of 510(k) submissions for new medical devices is "substantial equivalence."  An applicant is directed to use at least one previously-approved predicate device as the foundation for its application and show how the new device has the same intended use as the predicate device.  To find that a device is substantially equivalent, the FDA must determine that the new device has the same technological characteristics as the predicate device, or has different characteristics but the applicant has demonstrated that the device is safe and effective and does not raise different questions of safety and effectiveness as the predicate device. 

Once a device has been approved, it may become a predicate device for later versions of the same product or for a competitor's product.  And, each new applicant may rely on just the most recently approved devices and not the earlier generations.   For pain pumps, as an example of this process, take the Alpha Infusion Pump, manufactured by Advanced Infusion, Inc.  The most recent version of this device was approved by the FDA in 2008 under 510(k)071532.  The predicate devices listed are a prior version of the Alpha Infusion Pump, approved in 2002 under K021964, and the Help Technologies (later McKinley) Accufuser under K003915.  (The links are not to the complete 510(k)s; only summaries are available from the FDA's online database.  Earlier than 10-12 years and typically even the summaries have been purged and only the clearance letter and a brief statement of the indications for use remain).  The 2002 510(k), in turn, relies upon the initial Alpha Pump approved in October 1999 under K992551. 

What's interesting in the 1999 510(k) summary is the number of predicate devices to which the Alpha Infusion Pump claims equivalence:

"The proposed device, the Alpha Infusion Pump, claims substantial equivalence in intended use and operation to the Baxter Intermate LV Elastomeric Infusion Device (K922382) and the I-Flow PainBuster Infusion System (K980558). Both are elastomeric chamber infusion pump intended to deliver medications or fluids to a patient by an intravenous, intra-arterial, subcutaneous, or epidural route. These pumps are ambulatory, external disposable infusion pumps which deliver medication or fluids percutaneously to the patient via a catheter. They control flow rate using a flow restrictor.

The proposed device, the Alpha Infusion Pump, claims substantial equivalence in intended use to the Burron Ambulatory Drug Delivery System (K896422), the Sgarlato Laboratories Pain Control Infusion Pump (K990101), and the McKinley Medical OutBound Disposable Syringe Infusor (K982256). These infusion pumps differ from the Alpha Infusion Pump only in the method used to pressurize the medication or fluid contained within the pump.

The proposed device, the Alpha Infusion Pump, claims substantial equivalence in intended use to the McKinley Medical OutBound PCA Pain Management System (K982256) and the Breg Pain Care 2000 (K983454). These infusion systems provide for the delivery of a bolus of medication on patient demand through a percutaneous catheter."

In 1999, the pain pump market was already beginning to expand quickly and, as far as I can gather, the predicate devices listed in this 510(k) comprise most of the then existing devices.   What I'm interested in is that at some point, there had to have been a step from an infusion pump intended to be used for other purposes to a pump intended to infuse local anesthetics.   How sound was the information the FDA was relying on when it found the first pain pump to have been substantially equivalent to an infusion pump used for other purposes? How stable is the foundation of predicate devices upon which the pain pump market has been built?

 

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I have been reviewing the FDA's regulatory scheme over pain pumps and believe I've identified several  weaknesses which are likely to adversely affect patient safety.

Pursuant to 21 United States Code 360c, medical devices are divided into three classes for purposes of regulation: Class I, General Controls; Class II, Special Controls; and Class III, Pre-Market Approval.

The pre-market approval process is rigorous and the FDA requires a device manufacturer to submit considerable documentation regarding a device’s safety and effectiveness in order to obtain approval. Understandably, device manufacturers prefer to attempt to have their devices approved as Class I or II devices.

I was surprised to find that Class III is actually the default classification. Subsection (f) of 21 USC 360c provides:

Any device intended for human use which was not introduced or delivered for introduction into interstate commerce or commercial distribution before May 28, 1976, is classified in Class III unless—

(A) The device—

(i) is within a type of device (I) which was introduced or delivered for introduction into interstate commerce for commercial distribution before such date and which is to be classified pursuant to subsection (b) of this section or (II) which was not so introduced or delivered before such date and has been classified in Class I or II, and

(ii) is substantially equivalent to another device within such type…(emphasis added)

Pain pumps are classified as Class II devices pursuant to federal regulation 21 CFR 880.5725, which covers infusion pumps and is part of the overall regulation of general hospital and personal use devices.  Class II devices are subject to special controls and for pain pumps this concerns performance standards.  A pain pump manufacturer is required to certify in its application materials to the FDA that its device meets an industry standard relating to infusion pumps.  These standards include:  1) AAMI (Association for the Advancement of Medical Instrumentation),  Draft Infusion Device Standard; 2) UL (Underwriters Laboratory) 544 Standards for safety, medical and dental equipment; and 3) IEC (International Electrotechnical Commission) 601-1/ANSI (American National Standards Institute) ES1-1985 Safe Current Limits for Electromedical Apparatus. 

I'm sure these standards are important and applicable to the safe-functioning of many types of infusion pumps. I'm also sure they're relevant to the types of adverse events in infusion pumps the FDA recently announced it was seeking to combat through tighter regulation.  (My post on this is here ).  However, most pain pumps are much less mechanically-complicated than the infusion pumps used to deliver insulin or chemotherapy drugs (to name a few types).  So, these standards really don't get at the main safety concerns with pain pumps which involve the basic threshold question of whether they are reasonably safe for their intended use of continuous infusion of local anesthetics.  As a result, I don't see the FDA's classification of pain pumps as Class II devices conferring any benefits for patient safety.

To my knowledge, all pain pump manufacturers have received approval from the FDA by utilizing the substantial equivalence provision mentioned above.  In this process, the FDA requires device manufacturers to submit a Section 510(k) Pre-Market Notification of intent to market the device. If approved, the FDA issues a letter (see example here) with the following operative language: “The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.”

In March 1993, the FDA issued Guidance on the content of Pre-Market Notification [510(k)] Submissions for external infusion pumps. Section II D is on device description. The description is required to provide a clear statement of the intended use(s) of the infusion pump, including specifying the route(s) of administration and if the infusion pump is labeled for use with a specific drug/biologic the applicant must supply information demonstrating that use of the drug/biologic with the device is consistent with the approved drug/biologic labeling.

Pain pumps are clearly labeled for use with local anesthetics. However, as I have argued in a previous post, the continuous infusion provided by pain pumps is not an approved use of local anesthetics, especially the most commonly used—Marcaine.

For example, in its 1998 510(k) submission for its PainBuster pump, I-Flow reported that there are no specific drugs referenced in the labeling for the PainBuster infusion system, but that it is intended for use with general local anesthetics. I suspect that most, if not all, 510(k) submissions for pain pumps list only a similar general statement.

The FDA could insist that pain pump manufacturers provide evidence in their 510(k) submissions demonstrating how these devices are consistent with the uses approved in local anesthetic labeling. Manufacturers would then be forced into attempting to characterize the use of local anesthetics in their devices--continuous infusion--as akin either to local infiltration or a peripheral nerve block (PNB), which are approved uses. 

Local infiltration involves the injection of a small amount of local anesthetic, typically near a surgical site. Far too much anesthetic is delivered by a pain pump for a manufacturer to claim it is similar to local infiltration.

A PNB likely utilizes a larger amount of anesthetic than in local infiltration, but typically does not approach the volume used in a pain pump. Also, a PNB involves the insertion of a catheter at some distance from an incision site, while a pain pump catheter is intended to be inserted close to an incision. Traditionally, PNBs were accomplished with a single dose of local anesthetic. However, in recent years continuous PNBs have begun to be used by anesthesiologists. Dr. Brian Ilfeld is one of the leading researchers on this technique; here's an article by him on PNBs

It is unclear to me whether continuous PNBs are really an approved use of local anesthetics, per the manufacturers' labeling. However, the articles I’ve seen indicate a greater degree of safety than with pain pumps. I would think this has much to do with continuous PNBs being performed by anesthesiologists as opposed to pain pumps which are typically placed by surgeons. A catheter which will deliver a local anesthetic at a greater distance from a surgical site is less likely to produce wound healing problems. Also, an anesthesiologist is likely to pay closer attention to the volume of local anesthetic used in a continuous PNB than a surgeon utilizing a pain pump.

The incidence of adverse events involving pain pumps has certainly been such that much greater regulatory scrutiny is warranted. These events extend far beyond chondrolysis in shoulder surgeries.  (See my prior post).  The FDA's recently announced requirements that pain pump manufacturers and local anesthetic manufacturers must revise their product labels to highlight the risk of chondrolysis in shoulder surgeries leaves unaddressed the more basic question of whether continuous infusion is a safe use.  The FDA should require pain pump manufacturers to provide detailed evidence about why their devices are consistent with the uses approved by local anesthetic manufacturers. 
 

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I am still a bit confused as to whether the new oversight regime the FDA announced yesterday applies to the disposable local anesthetic infusion surgically-implanted pumps that are my focus in this blog.

Reading the New York Times article on the announcement led me to think these devices might be excluded, as it focuses on IV-implanted, programmable devices used to provide insulin, chemotherapy, and pain medications (but patient-controlled).  There have been over 56,000 adverse events and 710 deaths involving these devices in the past 5 years.  These are truly staggering numbers.  Regarding the types of problems reported, the FDA Press Release indicates: The most common types of reported problems have been related to:

* software defects, including failures of built-in safety alarms;
* user interface issues, such as ambiguous on-screen instructions that lead to dosing errors; and
* mechanical or electrical failures, including components that break under routine use, premature battery failures, and sparks or pump fires.

Failures of infusion pumps have been observed across multiple manufacturers and pump types. The FDA says that many of the reported problems appear to be related to deficiencies in device design and engineering.

I saw nothing about shoulder chondrolysis or other injuries from local anesthetics. So far, all of this sure seemed outside the scope of pain pumps. 

The next step up in document complexity is the FDA's White Paper on its Infusion Pump Improvement Initiative.   I read  "In general, an infusion pump is operated by a trained user, who programs the rate and duration of fluid delivery through a built-in software interface" and it confirms my initial belief.   However, then among the pump mechanisms elastomeric is listed and this is one of the most common types for disposable pain pumps.  Finally, at the end of the paper I see among the footnotes:  1 This document does not pertain to implanted infusion pumps, which are surgically placed in the body.  Okay, now I'm pretty sure this significant announcement doesn't apply to the devices with which I'm familiar.  However, there are several additional documents the FDA has included and, for completeness sake, I read on.

The letter to infusion pump manufacturers from Jeffrey E. Shuren, Director of the FDA's Center for Devices and Radiological Health (CDRH) also focuses on software, design, human factors, and manufacturing problems. 

There's detailed information about CDRH's software research on infusion pumps.  I had no idea the FDA has a software engineering laboratory. 

Ultimately, there's the agency's Guidance for Industry and Staff regarding 510(k) Pre-Market Notification Submissions.  This is a draft document (34 pages in PDF form) which will be entering a 90-day comment period.  When complete it will replace the Guidance on the Content of Premarket Notification [510(k)] Submissions for External Infusion Pumps, issued March, 1993.  

My confusion was finally resolved (I think) by reading the Scope section of this document.  It makes clear that all infusion pumps addressed by 21 C.F.R. 880.5725 will be covered by the new guidelines. This includes numerous types of devices including all Elastomeric Infusion Pumps (products coded MEB), and excludes only the following: gallstone dissolution pumps (MHD), opthalmic infusion pumps (MRH), and analytical sampling infusion pumps (LZF).   Just to be sure, I double-checked the most recent 510(k) Submission for the On-Q Painbuster, which confirms the same regulation (880.5725) and product code (MEB). 

So, it does indeed look like I-Flow, Stryker and company will have to learn how to comply with considerable new requirements and provide alot of additional information in future premarket submissions to the FDA.   This is certainly good news, but I have lingering confusion because of the lack of mention in any of these new documents from the FDA of the adverse events involving these devices with which I'm familiar.   An Appendix to the Guidance document lists the following categories of "Risks to Health" with infusion pumps:  Overdose, Underdose, Delay in Therapy, Incorrect Therapy (wrong medication or correct medication but wrong dosage or infusion rate), Air Embolism, Trauma (burns, cuts, abrasions, bruising), Electric Shock, Infection, Allergic Response, and Exsanguanation.  Perhaps the numerous cases of chondroylsis and tissue necrosis are intended to be included in one of these categories (Infection? Allergic Response?). 

When I think again about the number of adverse events--56,000--reported involving all types of infusion pumps over just the last 5 years, I realize that the number involving local anesthetics, even if it's 500 or more, is likely to be less than 1% of the overall events.  Where do local anesthetic infusion pumps and the injuries they appear to cause fit into the broader regulatory and safety scheme involving this class of devices?  My initial reaction is that the problems with pain pumps don't have much to do with design, human factors, or manufacturing issues (and certainly not software).    I will certainly reserve judgment and keep an eye on how the new oversight regime takes shape.  Of course, it will also be interesting to see how these developments may affect litigation involving injuries and deaths from PCA and other programmable pumps.  I can envision claims which were initially viewed as malpractice expanded to also (or instead) focus on the liability of the pump manufacturer. 

 

 

 

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