A USP Class VI gasket is one whose compound has passed the most demanding of the six biological reactivity classes in USP chapter 88, tested in living animals. That rating says the material did not provoke a toxic or irritant response when its extracts were injected and implanted. It says nothing about whether the gasket will survive steam, caustic or a year of clamp load. Choosing a sanitary gasket material for a hygienic process system means reading the Class VI line and then reading everything else, because the failures that stop a plant come from the everything else.
What USP Class VI means
USP chapter 88, Biological Reactivity Tests, In Vivo, sorts plastics and elastomers into Classes I through VI according to which tests the material passed and under which extraction conditions. The tests are a systemic injection test, an intracutaneous test and an implantation test. Extracts of the material are prepared in four media (sodium chloride injection, alcohol in saline, polyethylene glycol 400 and vegetable oil) and the extraction can be run at 50 °C, 70 °C or 121 °C. Class VI calls for all three tests across the extraction media, and elastomer suppliers normally test at the 121 °C condition so the rating covers steam-sterilized service. Chapter 87 covers the in vitro cytotoxicity screen that often precedes it. USP has published proposals to revise chapter 88 and its class designations, so a specification should cite the edition in force at the time.
Two limits matter. Class VI is granted to a compound, not a finished part, so a molder can change the cure or the release agent and the rating may no longer describe what ships. And Class VI is biocompatibility, not an extractables profile; a Class VI EPDM can still shed compounds into a product stream.
USP Class VI vs 21 CFR 177 vs ASME BPE Part SG
These three are cited together on datasheets and mean different things. USP Class VI is a biological safety test. FDA 21 CFR 177 is a list of permitted ingredients and extraction limits for polymers in food contact: section 177.2600 covers rubber articles intended for repeated use, and section 177.1550 covers perfluorocarbon resins such as PTFE. A gasket “complies with 21 CFR 177.2600” when it is compounded from listed ingredients and meets the water and hexane extraction limits; no animal testing is involved. ASME BPE Part SG covers sealing components: seal designs for hygienic clamp unions, performance testing under thermal cycling, and the classification of how far a seal intrudes into or recesses from the bore. BPE Part PM covers the polymeric materials themselves and points to USP chapter 88 Class VI or ISO 10993 for biocompatibility and to 21 CFR 177 for food contact. A pharmaceutical gasket typically carries all three; a dairy gasket under 3-A may carry only the CFR compliance and the 3-A material requirements.
Sanitary gasket material families and where each fits
Five compounds cover almost every hygienic clamp joint. The ranges below are typical continuous-service figures; the gasket manufacturer’s datasheet for the exact compound governs, and steam and chemical exposure narrow them.
| Material | Approximate temperature range | CIP caustic and acid | SIP steam | Typical use |
|---|---|---|---|---|
| EPDM, peroxide cured | About -40 °C to 150 °C | Good in both; the default for hot water and CIP | Good, with cycle-count aging | WFI, purified water, buffers, CIP loops, most pharmaceutical process lines |
| PTFE, virgin or modified | About -200 °C to 260 °C | Inert to almost all chemistry | Good, but creeps under clamp load | Solvents, oxidizers, high temperature, chemistries that attack elastomers |
| Silicone, platinum cured | About -60 °C to 200 °C | Poor in strong caustic; fair in dilute acid | Limited; hydrolyzes with repeated wet steam | Low-chemical duty, tubing, single-use interfaces, temperature extremes |
| FKM fluoroelastomer | About -20 °C to 200 °C | Good in acids; standard grades poor in hot caustic | Standard grades poor in hot steam | Fats, oils, flavors, solvents, aggressive acids |
| NBR, Buna-N | About -30 °C to 100 °C | Fair in dilute caustic; poor in oxidizing acid | Not suitable | Food and dairy oil and fat lines only; not a pharmaceutical material |
EPDM is the workhorse because water, steam and CIP chemistry are exactly what it resists, and it fails only where oils, fats and hydrocarbon solvents swell it. PTFE resists everything but is not an elastomer; it has no memory, cold-flows under load and loosens joints as it creeps. Silicone has the widest temperature window and the weakest tear strength and steam life. FKM is the oil and solvent compound, with a caustic and steam weakness in general grades that specialty grades reduce. NBR belongs in food plants under 21 CFR 177.2600 and nowhere near a pharmaceutical line. Beyond these, perfluoroelastomer (FFKM) covers the small number of duties where nothing else survives, at a cost that keeps it out of general service.
EPDM vs PTFE gasket
The comparison that comes up on nearly every hygienic piping project is an EPDM vs PTFE gasket for the same clamp joint. EPDM seals at low clamp load, recovers after thermal cycling, and can be inspected for compression set by eye. It fails in oils, aromatic solvents and some cleaning agents, and it ages with each steam cycle. PTFE survives all of that chemistry and higher temperatures, but it creeps: the joint that was tight at installation loosens after the first SIP cycle and needs retightening, and repeated tightening increases intrusion. PTFE-enveloped gaskets with an EPDM or silicone core try to combine the two, giving PTFE contact with elastomer recovery, at the price of a seam that can trap product if the envelope splits. The practical rule: EPDM unless the product or the cleaning chemistry attacks it, PTFE where it does, and a documented retorque step wherever PTFE is used.
Steam, CIP chemistry and replacement intervals
Steam-in-place is what ages elastomers. Each cycle at sterilization temperature advances the cure, hardens the compound and reduces its recovery; the gasket that seals perfectly at 20 cycles may leak at 200. CIP adds chemical stress: hot caustic swells or hardens some compounds, acid attacks others, and oxidizing sanitizers embrittle most of them. No standard sets a fixed replacement interval, and a plant that copies a number from a datasheet is guessing. The interval comes from the plant’s own history: the SIP cycle count, the CIP chemistry and temperature, and what the gaskets look like when the joints are opened. A sound program inspects every gasket at every opening, records the material, lot and cycle count, replaces on evidence of set, cracking, discoloration or intrusion, and converts that history into a scheduled replacement count per service class. Our CIP vs SIP guide covers the cycles that do the damage.
Extractables, leachables and gasket intrusion
Extractables are compounds that can be pulled out of a material under exaggerated conditions of solvent, temperature and time. Leachables are what actually migrates into the product under process conditions. USP chapters 1663 and 1664 describe the assessment of each for drug product contact. A Class VI rating covers neither; it is a toxicity screen on extracts, not an identification of what those extracts contain. For product-contact gaskets in biologics and sterile injectables, the manufacturer’s extractables data per BPE Part PM is the document to ask for, and the plant’s own leachables study is what closes the question.
Intrusion is the mechanical failure mode. When a hygienic clamp union is tightened, the gasket compresses and its inner edge moves toward the bore. Too much clamp load or a gasket that is too soft pushes the edge into the flow path, where it forms a dam and a crevice on either side. Too little load or a hard gasket leaves a recess where product pools. ASME BPE Part SG classifies seals by measured intrusion after thermal cycling, and gasket makers publish that class. The installer controls the rest: correct gasket size for the tube, one gasket per joint, clamps tightened by hand or to the maker’s torque, never with a wrench on a wing nut. Details of the joint itself are in our guide to sanitary pipe connections.
How to specify a sanitary gasket
A gasket callout on a line list or a P&ID should carry six items: the joint standard and size (for example a hygienic clamp union to ASME BPE, 1.5 inch); the compound family and cure (EPDM, peroxide cured); the compliance set required (USP Class VI, 21 CFR 177.2600, BPE Part SG intrusion class where relevant); the service temperature and the CIP and SIP conditions the gasket must survive; traceability (lot marking and a certificate per lot); and the replacement basis the plant intends to use. A callout that says only “EPDM” leaves cure system, compliance and traceability to whoever places the purchase order.
What to require from a gasket supplier
Ask for the USP chapter 88 test report for the exact compound number, not a letter that says “Class VI available”. Ask for the 21 CFR 177 statement of compliance and, for BPE joints, the Part SG intrusion class with the test data. Require lot marking on every gasket and a certificate that ties the lot to the compound and the test reports. Ask whether the compound has changed in the last several years and what notification is given when it does. For biologics and injectables, ask for extractables data. From the installer, require a gasket log per joint with material, lot and installation date, so that a later leak or a leachables question can be traced to a specific part.
What Paul Industries does
Paul Industries installs hygienic tubing and components across pharmaceutical, biotech, food, dairy and beverage plants, and the gaskets go in under the same documentation as the welds. Our crews install the compound the specification names, size it to the tube, seat it to the manufacturer’s torque and record material, lot and joint on the turnover package. Where a specification leaves the gasket undefined, we recommend a compound from the service conditions above and state the reasoning in writing before installation. Gasket replacement is part of our preventive maintenance scope, using the plant’s own inspection history to set the count. Component selection is covered on our sanitary components and instrumentation page.
Standards referenced: ASME BPE · 21 CFR 211 · 21 CFR 117 · 3-A · ISO 10993 · 21 CFR 820
Frequently asked questions
What does USP Class VI mean on a sanitary gasket?
It means the gasket compound passed the most demanding class of USP chapter 88 in vivo biological reactivity testing: a systemic injection test, an intracutaneous test and an implantation test on extracts prepared in four media, usually at the 121 °C extraction condition. It is a biocompatibility rating for the compound. It does not describe chemical resistance, steam life, extractables or how the gasket seals.
Is a USP Class VI gasket automatically FDA compliant?
No. FDA compliance for a gasket normally refers to 21 CFR 177, which lists permitted ingredients and extraction limits for polymers in food contact. USP Class VI is an animal toxicity test on extracts. A compound can pass one and not the other. Pharmaceutical gaskets generally carry both, and the datasheet should cite the specific CFR section, such as 177.2600 for rubber articles.
Which sanitary gasket material holds up best in hot caustic CIP?
Peroxide-cured EPDM. It resists hot water, steam, sodium hydroxide and most acid cleaners, and it recovers after compression. PTFE also resists caustic but creeps under clamp load. Silicone and standard FKM grades soften or harden in hot caustic and are usually avoided in CIP loops. The compound datasheet for the specific caustic concentration and temperature should be checked before final selection.
When is an EPDM vs PTFE gasket decision settled in favor of PTFE?
When the product or the cleaning chemistry attacks EPDM: oils, fats, aromatic or chlorinated solvents, strong oxidizers, or temperatures above the EPDM limit. PTFE survives all of these. The cost is creep, so the specification should add a retorque step after the first thermal cycle and a check on intrusion. Where neither chemistry nor temperature rules EPDM out, EPDM is the simpler and more reliable seal.
Do food and dairy plants need USP Class VI gaskets?
Not as a rule. Food and dairy joints are governed by 21 CFR 177 for the compound and by 3-A Sanitary Standards for the joint and material, and the Pasteurized Milk Ordinance for dairy. USP Class VI is a pharmaceutical expectation. Some food plants specify it anyway to simplify purchasing across sites, which is harmless, but it is not what the inspector will ask for.
Can a PTFE gasket be used in a standard hygienic clamp union?
Yes, in the same clamp and ferrules, but PTFE behaves differently. It needs more clamp load to seal, it cold-flows so the joint loosens after thermal cycling, and repeated tightening pushes the inner edge into the bore. PTFE-enveloped gaskets with an elastomer core reduce these problems. Whatever the choice, the retorque and the intrusion class belong in the installation procedure.
Why does a gasket intrude into the tube bore, and why does it matter?
Clamp load compresses the gasket and its inner edge has nowhere to go but inward. A soft compound, an oversize gasket or an overtightened clamp pushes that edge into the flow path, where it creates a dam and a crevice on each side that CIP cannot reach. ASME BPE Part SG classifies seals by intrusion after thermal cycling, and the installer controls the rest through size and torque.
How many SIP cycles can an EPDM gasket take before replacement?
There is no fixed number in any standard, and datasheet figures are for laboratory conditions. Each steam cycle hardens the compound and reduces recovery; the useful life depends on the temperature, the cycle length, the CIP chemistry between cycles and the clamp load. Plants set the interval from inspection history: log the cycle count, inspect at every opening, and replace when set, cracking or discoloration appears.
What is the difference between extractables and leachables for a gasket?
Extractables are the compounds that can be drawn out of the gasket under exaggerated conditions, using solvents, heat and time well beyond the process. Leachables are what actually migrates into the product under real process conditions. USP chapters 1663 and 1664 describe assessing each. A Class VI rating is a toxicity screen on extracts and identifies neither; the manufacturer's extractables data and a product-specific leachables study do.
Does USP Class VI testing apply to the finished gasket or the compound?
To the compound as tested, under the conditions the supplier chose. A molder can change cure, release agent or filler and the finished gasket may no longer match the tested material. That is why the specification should name the compound number and require lot traceability to it, and why suppliers should be asked what notification they give when a compound changes.
Is silicone a suitable sanitary gasket material for steam-in-place service?
Silicone has the widest temperature range of the common elastomers but the weakest steam life. Repeated wet steam hydrolyzes it, and it has low tear strength, so it fails at the clamp edge. Platinum-cured silicone is common where the duty is low in chemistry and steam exposure is occasional, and in tubing and single-use interfaces. For routine SIP on a process line, EPDM is the usual choice.
Where does FKM fluoroelastomer fit among sanitary gasket materials?
In fats, oils, flavors, hydrocarbons and aggressive acids, where EPDM swells. Standard FKM grades are weak in hot caustic, amines and hot steam, so they are unusual in CIP-heavy pharmaceutical water and buffer lines. Specialty grades close some of that gap. FKM is common in flavor and fat lines in food plants and in solvent-bearing lines in extraction and chemical synthesis.
Should Buna-N gaskets be used in a pharmaceutical plant?
No. NBR is an oil-resistant food and dairy compound available in 21 CFR 177.2600 grades, and it is unsuitable for steam, oxidizing sanitizers and most pharmaceutical duties. It is rarely offered with a USP Class VI rating. In pharmaceutical and biotech systems the elastomer choice is between EPDM, PTFE, silicone and FKM, selected on the chemistry and temperature of the service.
What should a gasket callout on a line list say?
The joint standard and size, the compound family and cure system, the compliance set required (USP Class VI, 21 CFR 177 section, BPE Part SG intrusion class where relevant), the service temperature with CIP and SIP conditions, lot traceability and a certificate per lot, and the replacement basis. A callout that says only the material family leaves everything else to the purchasing department.
Does ISO 10993 replace USP Class VI for process gaskets?
ISO 10993 is the biological evaluation series for medical devices and is the reference in device work under 21 CFR 820. ASME BPE Part PM accepts USP chapter 88 Class VI or an ISO 10993 evaluation for polymeric product-contact materials. Most process gasket suppliers test to USP chapter 88 because it is what pharmaceutical purchasers ask for; device manufacturers may require ISO 10993 instead.
Related: Types of Sanitary Pipe Connections · Sanitary Components & Process Instrumentation · What Is Sanitary Piping & ASME BPE? · Sanitary Piping Standards & Types of Sanitary Pipe · CIP vs SIP: What’s the Difference? · Sanitary Process Piping Installation (ASME BPE) · Request a quote