Tag: CDRH

FDA Internal Surgical Staples and Absorbable Collagen-Based Hemostatic Device Hearings: Consumer Representative Perspective

Disclaimer: Views in this post are my own and does not represent the views of the FDA.

On May 30, 2019, the FDA Advisory Panel committee discussed and made recommendations regarding the reclassification of surgical stapler devices for internal use from Class I (general controls) to Class II (special controls).

On May 31, 2019, the committee discussed and made recommendations regarding the reclassification of certain Absorbable Hemostatic Agents from Class III to Class II (special controls).

I served as Consumer Representative for both hearings.

Internal Surgical Staples

The advisory committee met to discuss the April 2019 proposed reclassification order after the following risks to health were discovered:

  • Complications associated with device failure/malfunction. Device failures or malfunctions may result in prolonged surgical procedures, unplanned surgical interventions, and other complications such as bleeding, sepsis, fistula formation, tearing of internal tissues and organs, increased risk of cancer recurrence, and death.
  • Complications associated with use error/improper device selection and use. Use error may result from a device design that is difficult to operate and/or labeling that is difficult to understand. For example, user difficulty in firing the stapler may result in staples not being fully deployed, and misfiring may result in staples being applied to the wrong tissue. Inadequate instructions for use may result in selection of incorrectly sized staples for the target tissue. When staples are applied to the wrong tissue or when incorrectly sized staples are applied, staples are unable to properly approximate the underlying tissue, resulting in tissue damage, anastomic leakage, and bleeding. This in turn may lead to more severe complications, such as abscess, sepsis, peritonitis, hemorrhage, or death.
  • Adverse tissue reaction. If the patient-contacting materials of the device are not biocompatible, local tissue irritation and sensitization, cytotoxicity, or systemic toxicity may occur when the device contacts sterile tissue.
  • Infection. If the device is not adequately reprocessed or sterilized, the device may introduce pathogenic organisms into sterile tissue and may cause an infection in a patient.

Surgical staplers are currently classified as Class I devices. Class I are “low risk” devices. Low risk devices are not tested. These include items such as band-aids, tongue depressors, crutches, and are subject to General Controls. The proposal would reclassify surgical staplers to Class II. Class II devices are considered “moderate risk”, and subject to Special Controls.

In the proposed reclassification order, FDA proposed that the following special controls would mitigate the risks to health and provide reasonable assurance of safety and effectiveness for surgical staplers for internal use:

  • Performance testing must demonstrate that the stapler, when use with compatible staples, performed as intended under anticipated conditions for use. Performance testing must include evaluation of staple formation characteristics in the maximum and minimum tissue thickness for each staple type; measurement of the worst-case deployment pressures on stapler firing force; measurement of staple line strength; confirmation of staple line integrity; and in vivo confirmation of staple line hemostasis.
  • Usability testing and labeling comprehension study must demonstrate that the clinician can correctly select and use the device, as identified in the labeling, based on reading the directions for use.
  • The elements of the device that may contact the patient must be demonstrated to be biocompatible.
  • Performance data must demonstrate the sterility of the device.
  • Validation of cleaning and sterilization instructions must demonstrate that any reusable device components can be safely and effectively reprocessed per the recommended cleaning and sterilization protocol in the labeling.
  • Performance data must support the shelf life of the device by demonstrating continued device functionality, sterility, and package integrity over the identified shelf life.

Labeling the device must include that unless data demonstrates the safety of doing so, contraindications must be identified regarding use of the device on tissues for which the risk of stapling outweighs any reasonably foreseeable benefit due to known complications, including the stapling of necrotic or ischemic tissues and tissues outside of the labeled limits of tissue thickness; unless available information indicates that the specific warnings do not apply, the labeling must provide appropriate warnings regarding how to avoid known hazrads associated with the device including:

  • Avoidance of obstructions to the creation of the staple line and the unintended stapling of other anatomic structures
  • Avoidance of clamping and unclamping of delicate tissue structures to prevent tissue damage
  • Avoidance of use of the stapler on large blood vessels, such as the aorta
  • Establishing and maintaining proximal control of the blood vessels prior to stapling
  • Appropriate measures to take if a stapler malfunction occurs while applying staples across a blood vessel, such as clamping or ligating the vessel before releasing the the stapler, while the stapler is still closed on the tissue
  • Ensuring stapler compatibility with staples

Reported adverse events are 412 deaths and 11,000+ injuries. Seventy-two percent are from linear stapler and 17% were from circular stapler. Thirty percent was during the procedure and 52 occurred post operative.

Madris Tomes, CEO of Device Events and former FDA employee, reported even higher numbers. She also presented information regarding materials in staples- most specificially nickel- which can cause allergy and autoimmune issues.

Immediately following, the Panel Chairman ruled that we as a panel cannot discuss the staples; only the staplers. My opinion, and that of other panel members, is that you cannot discuss staplers without also discussing staples but the Chairman harshly shut down the discussion. It still makes no sense to me since Medtronic, a maker of surgical staplers (and the only surgical stapler manufacturer to show up for the hearing) wanted to discuss biocompatibility and the FDA themselves proposed biocompatibility testing of the staples in the special controls.

Both Medtronic and the FDA admit that adverse events are underreported. When I attemped to ask the FDA what they plan to do to improve their reporting system and be transparent about adverse events,  I was cut off by the Chairman. This highlights the concern about whether FDA truly values the patient and consumer perspective when all other panel members were permitted to ask multiple questions, but the Consumer Representative was not.

At the end of that hearing, the advisory panel voted unanimously to up-class internal surgical staplers from Class I to Class II with special controls.

The staples themselves, unfortunately, will have to be a separate discussion due to the subject being shot down at this one. I encourage all readers to do research about surgical staples prior to sugery. It is a discussion that needs to be had and patients have the right to know what is going into their bodies.

 

Absorbable Collagen-Based Hemostatic Agents

On Day 2, the panel discussed reclassifying absorbable collagen-based hemostatic agents from the current Class III classification to Class II with Special Controls. We were instructed to not consider added biologics.

FDA identified several risks to health for absorbable collagen based hemostatic devices:

  • Uncontrolled bleeding. Failure to completely control bleeding can lead to death or severe injury.
  • Hematoma. If small amounts of bleeding persists following application of an absorbable collagen-based hemostatic device, the accumulation of blood behind the device will form a hematoma. A hematoma may press on soft tissue and cause soft tissue or nerve damage. It also has a high mortality rate.
  • Infection. An absorbable collagen-based hemostatic device may serve as a nidus for infection and abscess formation. They are manufactured from materials derived from animal sources such as collagen and gelatin and bacteria can grow on device materials.
  • Wound dehiscence. Devices near the sites of incision closures has interfered with the healing of the incision. This interference is due to mechanical interposition of the device and is not due to intrinisic interference with the wound healing process.
  • Foreign body reactions. These devices have been associated with foreign body reactions involving fluid accumulation due to encapsulation of the device. This has resulted in granuloma formation, inflammation, and edema, which may require surgical removal. Encapsulated devices can also present as an image artifact mimicking residual or recurrent tumor or abscess resulting in additional diagnostic studies and surgical procedures.
  • Immunological reactions. These devices are made of products rerived from porcine and bovine gelatin or collagen. Some patients are allergic (emphasis is mine) to these animal-derived materials.
  • Adhesion formation. These devices, in the presence of coagulated blood and tissue fluid, can often lead to scarring and adhesion formation in the weeks and months (emphasis is mine) following the surgical procedure. The procedure itself can result in additional scarring and adhesion formation.
  • Failure to be absorbed. These devices are readily degraded by emzymatic and hydrolytic action. They may be implanted in an area with low emzymatic and hydrolytic activity. In such instances, it may not be efficiently absorbed. Subsequently, it may become incapsulated and exert pressure or create a chronic granulomatus inflammatory reaction on surrounding soft tissue to cause necrosis or injury, requiring surgical intervention.
  • Interference with Methylmethacrylate Adhesives. Some types of these devices have been reported to reduce the strength of methylmethacrylate adhesives used to fixate orthopedic prosthetic devices to bone.
  • Aspiration into Blood Salvage System Filters. Fragments of these devices may pass through blood salvage system filters and occlude the systems or patient’s vasculature.
  • Embolization. These devices used near moderate to large blood vessels may result in embolization of the blood vessel (which has a high mortality rate).Embolization has been associated with severe adverse effects, including fever, duodenal and pancreatic infarc, embolization of lower extremity vessels, pulmonary embolization, splenic abscess, necrosis, asterixis, and death.
  • Paralysis/Nerve Damage/ Tissue Necrosis.These devices absorb fluids and swell to varying degrees, up to 40 times their weight in volume. The device swelling can encroach on surrounding nervous tissue to cause paralysis or tissue necrosis.
  • Disease Transmission. These devices are composed of animal-derived collagen-based materials, which may carry a risk of transmitting infectious disease when improperly collected, stored, or manufactured.
  • Adverse Tissue Reaction. These devices may result in local or systemic adverse tissue reaction due to material composition or interaction of the material with the body.
  • Toxicity. These devices may contain materials or ingredients that result in local or systemic toxicity.

FDA claims that the following Special Controls would mitigate the risks to health and provide reasonable assurance of safety and effectiveness for absorbable collagen-based hemostatic devices.

  • Material source information must be sufficient to demonstrate that the likelihood of the risk that the device is transmitting infectious diseases is minimized.
  • Material processing information must detail all reagents used in the manufactur of the device, and residual amounts must be quantified.
  • For crosslinked devices, the density of crosslinks must be provided.
  • Device related particulates must be characterized.
  • Collagen characterization information, including elemental analysis and decellularization efficiency determination, must demonstrate the identity, purity, and quality of the collagen.

FDA was unable to provide any evidence or science in the Executive Summary- or when pressed by the panel- on why they proposed down-classing absorbable collagen-based hemostatic agents from Class III High Risk classification, down to Class II with Special Controls. Class III devices are considered “life sustaining” or “life saving” and have the highest amount of FDA oversight. The panel was not provided any evidence as to their reasoning and when the panel questioned this, we were told that information is “confidential”. FDA put us in a bad position because we can’t make a recommendation on something we were not shown and essentially, FDA was asking us to just take their word for it. The discussion got heated about that. We as a panel cannot- and neither should the FDA- use anecdotal evidence over scientific evidence. The only evidence provided to us were two premarket approvals which stated that there is no difference between the device and the control. It should also be noted that absorbable hemostatic agents have remained in Class III for 42 years.

FDA also stumbled on their answers to panel questions and were visibly uncomfortable that they couldn’t.

Absorbable collagen-based hemostatic devices come in powder, paste, sheets, and sponges and are made from porcine or bovine byproducts. This raised a concern from another panel member about those who cannot consume those products due to religious or cultural reasons, as well as for diabetics who often switch from porcine to bovine insulin (and vice versa). It was suggested by the panel member to include the ingredients on the labeling as part of the Special Controls.

Because FDA provided no evidence and no reasoning for down-classing the devices, we adjourned 4 1/2 hours earlier than planned. Most of the morning was spent discussing the lack of evidence and that we are put in a bad position by making a decision on so little information.

Points we could unanimously agree  upon is:

  1. Whether FDA should consider a validated bleeding scale to be used to demonstrate effectiveness of hemostasis. We felt that there needs to be some objectivity and standardization and we unanimously voted yes.
  2. Whether the panel agreed with FDA that absorbable collagen-based devices are not life supporting or life sustaining. We unanimously voted no– that the panel disagrees with FDA on that question.

That said, in a surprising vote about whether to keep these devices at Class III (life saving or life sustaining) or whether to down-class them to Class II following a heated discussion, I was the only panel member to vote no on down-classifying the devices and remaining firm that these devices should remain Class III.  The patient representative abstained from the vote stating that he will deflect to “the experts on this”. All other panel members voted to down-class to Class II. I was shocked considering that we unanimously agreed that these device are, in fact, life saving and life sustaining, that the vote was markedly different than the discussions leading up to it.

In a nutshell, the rest of the panel decided to just take the word of the FDA that they’ll do the right thing with the information that was not presented to us by reason that it’s “confidential” or that FDA “just didn’t think to bring that information and in hindsight, should have”

I’m extremely uncomfortable with that.