FDA’s 510(k) Certification: New Rules for Portable Exchange Tank Regeneration
By Francis J. DeSilva
Summary: New rules released late last year from the Food and Drug Administration (FDA) on water purification for kidney dialysis patients will have a big impact on portable exchange deionization (PEDI) tank services. The quality control focus requires much documentation.
Water purification systems used to treat water for hemodialysis are classified as medical devices. Section 510(k) of the Food, Drug and Cosmetic Act requires device manufacturers to notify the U.S. Food and Drug Administration (FDA), at least 90 days in advance, of the intent to market a medical device.
The requirements of Section 510(k) are known as “pre-market notification” and allow the FDA to determine whether the water treatment system is a device that falls into existing categories.
Blood and kidneys
The FDA, in regulation 21 CFR 876.5665(a) describes a hemodialysis water purification system as a “device that is intended for use with a hemodialysis system and that is intended to remove organic and inorganic substances and microbial contaminants from water used to dilute dialysate concentrate to form dialysate. This generic type of device may include a water softener, sediment filter, carbon filter, and water distillation system.” The FDA goes on to classify this water treatment device as Class II as stated in 21 CFR 876.5820(b) and the product code is 78 FIP.
The hemodialysis patient is exposed to large quantities of water during dialysis treatment. Water purification is therefore necessary to prevent adverse reactions to the common contaminants found in many city waters. Incomplete water purification or running the system past exhaustion introduces these contaminants into the treated water and can cause patient anemia, bone disease, hemolysis, metabolic acidosis, nausea, vomiting, neurological deterioration, pyrogenic reactions (caused by fever) and even death.
The hemodialyis water treatment system must be designed to remove:
- Metals: aluminum, copper, zinc, magnesium
- Dissolved ions: calcium, sodium, fluoride, chloride, sulphate
- Pyrogens: substances that produce fever
Due to the great variation in feed water quality across the United States, the water purification needs of individual dialysis clinics may vary. Suppliers of water treatment or purification systems commonly customize a system for an individual clinic that takes into account the feed water quality and the required capacity.
A multi-pass or multiple treatment technology approach is necessary to meet the stringent treatment method required for the water quality needed. The basic water treatment configuration commonly in use today includes:
- Filtration—5 micron
- Activated carbon filter
- Water softener
- Filtration—5 micron
- Reverse osmosis (RO)
- RO water storage tank
- Portable exchange deionization (DI) tanks—as polishers to RO or as standby in event of RO failure
- Filtration—5 micron
- Bacteria filter—0.2 micron
The FDA website for updated information on 510k submittals and certification:
The FDA recommends that any pre-market notification contain the following information:
- The device name, including the trade or proprietary name and the classification name (water purification system for hemodialysis),
- The establishment registration number,
- The generic class (class II) in which the device has been placed on the appropriate panel (78 Gastroenterology/Urology).
- Provide a statement of the action taken by the registered manufacturer to comply with the requirements of the Act for special controls, (Note that special controls aren’t currently required for water purification systems).
- Include either: 1) a summary of the safety and effectiveness information in the pre-market notification submission upon which an equivalence determination could be based—510(k) summary, or 2) a statement that safety and effectiveness information will be made available to interested persons upon request—510(k) statement. The information could be descriptive information about the new device(s) or performance or clinical testing information.
- Copies of the proposed labels, labeling, advertisements and directions for use (including maintenance, operation, cleaning and troubleshooting).
- The water purification component or system should be compared to a legally marketed device, providing the 510(k) number if known.
- For a device or device labeling that has undergone changes, the 510(k) should include any additional supporting data to show that the manufacturer has considered the consequences and effects of the change.
- Descriptive information and test requirements for the components of the water purification device.
In addition, the descriptive information required for the deionization portion of the system must include:
- A description of the deionization system including a diagram that shows sizes, capacities, flowrates and water quality, and identity and quality of the resins being used.
- A description of the DI monitoring and alarm system. System should include an audible and visual temperature compensated conductivity/resistivity monitor to alarm upon exhaustion.
- Include data or calculations that show the DI system has sufficient capacity to meet the performance specifications.
- List all the materials that come in contact with the feed water and the treated water:
a) all materials in contact with the product water must be relatively inert for the intended use and not leach anything harmful into the treated water, and
b) results of leach tests should be provided.
- User’s manual, including:
a) Installation, operation and maintenance, troubleshooting
b) List expected life of the resin
c) List anticipated quality and volume of treated water
d) Recommended quality of replacement tanks or resins
e) How to respond to alarm conditions
f) Pretreatment requirements (carbon filtration, i.e., acid washed carbon is required to minimize the metals content)
Note that the above component requirements are only for the deionization portion of the 510(k) submittal. There are similar requirements for the other components of the water purification system, including: RO, water softeners, carbon filtration tanks, sediment and cartridge filters, ultrafilters, UV disinfection units, water storage tanks and auxiliary components.
The guidelines listed above are written in broad general terms. For more specific detail on the requirements, it’s imperative to obtain a full copy of the “Guidance for the Content of Premarket Notifications for Water Purification Components and Systems for Hemodialysis.” It can be obtained online at http://www.fda.gov/cdrh/ode/hemodial.html
It means the water treatment company must define, document and implement almost every facet of the operation. The FDA will perform audits at companies that are manufacturing medical devices, so accountability, traceability and retrieval of information makes accurate record keeping paramount.
The regeneration of the ion exchange resin tanks must be performed within the guidelines of good manufacturing processes (GMP) from ISO9000. It’s up to the individual water treating companies to establish the exact methods and procedures. The areas that will fall under the scrutiny of the FDA audit include:
- Tanks and component parts—Provide part numbers, cut sheets, materials of construction, and QC test data if available.
- Ion exchange resin—Provide manufacturer, product number, specification sheets and QC data.
- Regeneration logs—The plant operator must keep track of the individual batches of resin, what quality was attained, what batches of acid and caustic were used, and what the date of regeneration was. Provide the full regeneration procedure with flows, times and volumes.
- Labeling—All tanks must be clearly labeled with part numbers, batch numbers, date of regeneration and type of tank (cation, anion or mixed bed). Additionally, all areas of the plant that store exhausted or regenerated tanks must be clearly defined and labeled. All components must be clearly labeled as well.
- Resin maintenance—What is the resin testing schedule? When are the anion resins treated for organic fouling? After how many regenerations is this necessary? What resin cleaning procedures are used?
- Internal audits—The water treating company must conduct its own audit of the chemical supplier, resin supplier, and other component suppliers.
- Regeneration chemicals—What chemicals are used in the plant? Provide certificates of analysis for chemicals used.
- Disinfection—What steps are taken during the regeneration process and resin loading and unloading steps to minimize bacterial contamination? What is the shelf life of regenerated tanks?
- Leachables—What are the expected levels of leachables off of the regenerated tanks—total organic carbon (TOC)?
- Alarms—What condition will trigger an alarm? What’s the method of response to alarm conditions? Where does “off-spec” water get diverted?
As for the resin type, any high grade gel type or gel type macroporous resin can be used, since they both comply with FDA regulations for potable water (paragraph 21 CFR 173.25 of the Food Additives Regulations).
It’s evident from the introductory information presented above that the utmost care must be taken when submitting documentation for a water purification system to meet 510(k) requirements. Obviously, accountability is important to the FDA, as is protection of the dialysis patient. If an upset condition were to occur at the hemodialysis center, and the ion exchange tanks were producing low quality water, can the problem be traced back to the regeneration plant? Which batch of resin was involved? What batch of acid or caustic was used for that specific regeneration? Appropriate record keeping and quality checks will not only assist in attaining certification as a medical device, but will help to consistently produce safe, clean water in accordance with standards (see AAMI Standards), thereby ensuring patient health and safety.
About the author
Francis J. DeSilva is national sales manager at ResinTech Inc., of Cherry Hill, N.J. He can be reached at (561) 225-0763 or email: email@example.com
Additional information on the required elements for a pre-market notification submission is contained in the “DRAERD Premarket Notification [510(k)] Screening Checklist.” A copy may be obtained from the Center for Devices and Radiological Health’s Division of Small Manufacturers Assistance (DSMA) at (800) 638-2041 or (301) 443-6597 or on the Internet at: http://www.fda.gov\cdrh\dsmamain.html
1918—Early experiments with dialysis, with the use of Hirudin (from the heads of leeches) to prevent blood from clotting.
1945—First successful human dialysis by Dr. William Kolph.
1950s—Dialysis used extensively in the Korean War for short-term support of soldiers that had renal failure due to war wounds. Some individuals didn’t regain renal function and they were maintained by dialysis. However, after a year or so, they would run out of sites on the body to obtain blood for the dialysis machine and patients consequently died.
1960—Dr. Belding Scribner in Seattle, Wash., developed arteriovenous shunt for chronic access to blood. This device worked well initially, but then the shunt would clot and the patient would have to be operated on again to find another site. Eventually, the patient would run out of sites with longevity from 3-to-5 years.
1963—Introduction of the arteriovenous fistula, a shunt device that made long term dialysis possible.
1964-1970—With patients living longer, new problems occurred, namely a neurological disorder that caused twitching, convulsions and was followed by death. It became known as Denver syndrome (studied extensively by a medical group in Denver) or dialysis dementia. The problem was caused by absorption of aluminum from city water that was used to make up the dialysis solution (called dialysate).
After the cause of the problem was determined to be aluminum absorption from water, various methods were tried by the medical community to prevent it, from filtration to water softening. Ion exchange deionization (DI) was tried and quickly became popular. While it solved the dialysis dementia problem, other problems arose whenever exhausted DI systems were left in service. Alarms, therefore, came into use (early alarms were simply quality lights). The next major advancement was the inclusion of reverse osmosis (RO) in the water purification process.
Figure 2. Glossary
System—The complete assembly of components that make up the water purification scheme.
Auxiliary component—A piece of the assembly that doesn’t directly effect the quality of the treated water: pumps, tubing, valves, pressure gauges, etc.
Hemodialysis—The process of purifying a patient’s blood by means of a semipermeable dialysis membrane. Dialysis water on one side of the membrane removes metabolytes from the patient’s blood. As a consequence, the patient is exposed to large quantities of water.
AAMI—Association for the Advancement of Medical Instrumentation (see Table 1).
510(k)—Premarket notification required by FDA for systems or components intended for use in hemodialysis.
Hemolysis—The rupturing of red blood cells which sometimes occurs during hemodialysis and may be caused by the presence of chloramines in dialysis water. Also attributed to copper ions in the water. The hemolysis is literally an explosion of the red blood cells and causes a release of the main intracellular chemical—potassium—that in turn causes cardiac paralysis.