Endotoxin Testing of Surgical and Cleanroom Gloves

Endotoxin Testing of Surgical and Cleanroom Gloves

Endotoxins are large molecules found in the outer membrane of Gram-negative bacteria. If enough of the molecules get into the bloodstream of humans or animals, they produce a variety of inflammatory responses. Symptoms range from fever and septic shock to low blood pressure and respiratory distress.

Gram-negative bacteria are ubiquitous – found in soil, water and living organisms – so avoiding them isn’t an option. Glove testing and manufacturing controls are employed to reduce the risk of transmission during surgery, whether from surgical gloves or other medical devices.

Endotoxin Testing

To lower the risk of infection and possible death, sterile medical gloves and some cleanroom gloves are tested for endotoxin contamination.

Horseshoe-CrabUSP Chapter <85> Bacterial Endotoxins Test. There are 3 methodologies to detect or quantify endotoxins in sterile medical and cleanroom gloves – Gel Clot, Turbidimetric and Chromogenic. All three methods utilize a reagent produced from the lysate of amoebocytes (white blood cells) of the horseshoe crab (Limulus polyphemus or Tachypleus tridentatus.) This test is often referred to as Limulus Amoebocyte Lysate or LAL.

The average contaminant concentration is reported in endotoxin units per device (glove pair.) The FDA has set a limit of 20 EU/device for medical devices that have direct or indirect contact with blood or lymph fluid. Devices that come into contact with cerebrospinal fluid have a much lower limit – 2.15 EU/device.

Contamination Control

To reduce the amount of contamination on their end product, medical device manufacturers need gloves with low endotoxin levels for their employees. Endotoxin contamination on gloves can vary.

In a 2007 study performed by the Malaysian Rubber Board, endotoxin contamination on latex surgical and examination gloves varied widely between brands. The non-sterile examination gloves tested ranged from <8.4 EU/glove pair to as high as 9,632 EU/glove pair. Most of the sterile surgical gloves in the study were generally clean, with most in the minor to moderate contamination range. A few, however, did test much higher than the FDA limit.

These potentially deadly, fragmented remains of bacteria are bioactive and difficult to kill. Endotoxins can adhere to medical implants and devices, even after sterilization.

Thus, endotoxin contamination control is an important part of medical device manufacturing. Glove manufacturers use a variety of technologies and environmental controls to reduce particulate and biological contamination. The most common approach is to package surgical and cleanroom gloves in a cleanroom environment or white room that is regularly cleaned and sanitized, and operated by workers that are gowned and gloved.

Although bacterial endotoxins are everywhere in our environment, thorough testing and diligent contamination control can result in safe medical devices that enhance our lives.

HandPRO9100_LowEndotoxin_post

Compounding Pharmacies – Sterile Gloves and Fingertip Sampling Required

The fungal meningitis outbreak caused by contaminated steroid medications made by New England Compounding Center in Framingham (NECC), Mass. has brought about a flurry of articles and blog posts calling for tighter regulations and direct FDA oversight of compounding pharmacies.  Some of the articles make it appear that compounding pharmacies are nothing more than renegade miniature drug companies making HRT medications and other controversial drugs.

While there appear to be some pharmacies that need to be reined in, most compounding pharmacies exist in hospitals.  These pharmacies normally prepare a medication to order, for a specific patient from a prescription.  Independent compounding pharmacies contract with hospitals and clinics to fill their compounded medication needs.  Many feel that NECC crossed the line from a traditional compounding pharmacy to a drug manufacturer with interstate commerce.

At the end of all of the debating and legal haranguing (which won’t end soon,) the primary issue is safety.  So what regulations are in place to help ensure that sterile medications from compounding pharmacies are safe?

USP 797

The U.S. Pharmacopoeia (USP) issued the first practice standards for compounding pharmacies in the U.S. back in 2004.  Chapter <797>, Pharmaceutical Compounding – Sterile Preparations, commonly referred to as USP 797, was updated in 2008, and is designed to cut down on infections transmitted to patients through “compounded sterile preparations” (CSPs).

Compliance

After eight years, how are compounding pharmacies doing on compliance?  A nationwide Compliance Study conducted in 2011 and updated in 2012 shows that although the chapter has done much to improve the quality of CSPs, there is also much room for improvement.

Here is one example, a test called Gloved Fingertip/Thumb Sampling, designed to demonstrate that the compounder can properly don PPE and sterile gloves, and prepare a medication without contamination:

“In 2011, only 30% of hospitals complied with the requirement for all compounding personnel (including supervising pharmacists) to successfully complete at least three gloved fingertip/thumb sampling procedures (success is 0 CFUs for both hands) before being allowed to compound CSPs. This requirement is designed to verify that compounding personnel can properly don sterile gloves without contaminating them . . . in 2012, compliance with this requirement has increased to 36%.” – 2012 USP <797> Compliance Survey

This is certainly a cause for concern.  Skin cells are shed from the human body at a rate of a million or more per hour and these skin particles are laden with microorganisms.  Gloved Fingertip/Thumb Sampling measures both the microorganisms and particles in the controlled compounding environment and on surfaces like gloves.  It reveals poor aseptic technique or improper disinfection of sterile gloves.

Sterile gloves are a requirement in preparing CSPs.  Non-sterile exam gloves treated with 70% IPA have not been proven adequate in preventing contamination.  Eric Kastango, MBA, RPh, FASHP, president and CEO of Clinical IQ, LLC, a health care consulting firm in Madison, N.J., and a member of the 2010-2015 USP Compounding Expert Committee, states “The decision the USP committee made in requiring sterile gloves over nonsterile gloves is that you start with a pair of gloves with zero microbial bioburden and that it’s a very inexpensive way to maintain a state of control and prevent the risk for contamination and infections. It’s critical to make sure we’re giving patients the safest, best opportunity to have the lowest risk for contamination from compounded sterile preparations.”

Enforcement

So who enforces USP 797?  While the FDA regulates the ingredients, it does not regulate practitioners.  Compounders are regulated by a patchwork of state oversight, including Joint Commission and state pharmacy boards.  In general, the FDA has deferred to states in regard to USP 797, but it can investigate allegations of contaminated drugs, as in the case of NECC.

Compounding pharmacies can be sure that they will be coming under increased scrutiny and regulation.  Compliance with USP 797, which requires sterile gloves and a host of other safety standards is imperative.   By doing so, they can ensure the highest quality compounding environment and deliver ever-safer medications to the public.

Resources:

Summary of USP 797 for Compounding Sterile Preparations

 

 

What do you think?  Are compounding pharmacies doing enough to comply with USP 797?  Share your comments below.

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