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.
