| Direct answer USP Class VI is the strictest of six plastics classifications defined under General Chapter <88> of the US Pharmacopeia. It confirms that a material passes three in vivo tests — systemic injection, intracutaneous, and implantation — using four different extraction solvents. All three tests must pass. It is a material-level standard, not a device-level approval. |
Imagine a tiny seal inside a syringe or a flexible tube delivering medicine into your body. If these parts leak harmful chemicals, they could cause serious health risks. That’s where USP Class VI steps in—a safety standard to ensure materials in medical devices won’t poison you.
When a medical device specification calls for ‘USP Class VI’ materials, it is asking for something specific: proof that the plastic or elastomer does not release harmful substances into the body under a defined set of test conditions.It is not the same as FDA approval.
USP Class VI is not the same as ISO 10993 device compliance. Understanding what it actually covers — and what it does not — matters for material selection, regulatory submissions, and supplier qualification.
What Is the US Pharmacopeia, and What Is USP <88>?
The United States Pharmacopeial Convention (USP) is a private, non-governmental scientific organisation that publishes quality standards for medicines, pharmaceutical ingredients, food additives, and medical device materials. [1]
Its standards are published in the US Pharmacopeia and National Formulary (USP-NF). The FDA recognises USP standards as authoritative, which is why USP compliance appears in so many medical device and pharmaceutical manufacturing specifications.
General Chapter <88> of the USP-NF covers Biological Reactivity Tests, In Vivo — the formal framework under which plastics are classified from Class I through Class VI.
Class VI is the most stringent classification. It requires all three available in vivo test types, run with all four extraction media. Classes I through V require fewer tests or fewer extraction fluids.
The Three Tests Required for USP Class VI
All three in vivo tests must be passed. This is a pass/fail standard — there is no partial Class VI. [2]
Before testing begins, material extracts are prepared using four solvents at specific temperatures and durations:
- 0.9% sodium chloride (saline) — simulates aqueous physiological fluids
- 1:20 alcohol in saline — simulates fluids with solvent content
- Polyethylene glycol 400 (PEG-400) — simulates polar non-aqueous contact
- Vegetable oil (sesame oil) — simulates non-polar lipid contact
These solvents cover the range of fluids a medical material might realistically encounter — from saline in an IV line to oil-based drug formulations. Each of the three tests below is run with each extraction fluid.
Test 1 — Systemic Injection (Acute Systemic Toxicity)
Material extracts are injected intravenously into mice. The animals are observed for 72 hours and monitored for signs of systemic toxic reaction: abnormal breathing, movement, or gastrointestinal distress.
The result is compared against a control group injected with the same solvent but no material extract. If the test group shows significantly greater adverse reactions, the material fails.
Test 2 — Intracutaneous Test (Localised Skin Reaction)
Extracts are injected just beneath the skin of rabbits. Over 72 hours, researchers score redness (erythema) and swelling (edema) on a standardised scale.
The average reaction score must remain within defined acceptable limits compared to the control. This test is particularly important for materials used in catheters, IV lines, and any device with prolonged skin or tissue contact.
Test 3 — Implantation Test (Tissue Response)
Small samples of the material are surgically implanted into muscle or subcutaneous tissue and monitored for at least 120 hours (five days). [3]
At the end of the observation period, the surrounding tissue is examined for inflammation, fibrous capsule formation, and any other sign of adverse reaction. Minimal response — comparable to the control — constitutes a pass.
| Testing timeline — what to plan for A full USP Class VI test programme typically takes 6–12 weeks from sample submission to final report:• Sample preparation and submission: 1–2 weeks• In vivo testing and observation periods: 4–8 weeks• Final report and documentation: 1–2 weeksAny change in material formulation, curing method, or processing may require re-testing. This is especially relevant for LSR manufacturers who run different platinum-to-base ratios or cure temperatures across product families. |
USP Class VI vs. ISO 10993: Understanding the Difference
These two standards are often mentioned together — and they are complementary. But they are not interchangeable, and passing one does not automatically satisfy the other.
The key distinction: USP Class VI tests the material. ISO 10993 tests the finished device.
| Dimension | USP Class VI | ISO 10993 |
| Governing body | U.S. Pharmacopeial Convention (USP) — private, non-governmental, US-focused | International Organization for Standardization (ISO) — international, device-focused |
| Scope | Plastics and polymeric materials. Covers drug containers, packaging, and device components. | All medical device materials — polymers, metals, ceramics. Evaluates the finished device, not just the material. |
| What is tested | Material-level: extracts from the raw or processed material are tested. | Device-level: the complete device in its final form, accounting for all materials, processes, and patient contact conditions. |
| Testing approach | Fixed three-test protocol: systemic injection, intracutaneous, implantation. Pass/fail. | Risk-based matrix: tests selected according to contact type (surface / external / implant) and duration (limited / prolonged / permanent). |
| FDA recognition | Widely recognised by FDA for pharmaceutical packaging. Adopted by FDA in 1995 for device review, ISO 10993 superseded USP Class VI as primary device standard. | FDA’s current primary biocompatibility standard for medical devices (FDA guidance G95-1). Required for device 510(k) and PMA submissions. |
| Long-term endpoints | Does not cover genotoxicity, carcinogenicity, or reproductive toxicity. | Covers genotoxicity (ISO 10993-3), carcinogenicity, reproductive toxicity, and implant degradation for long-contact devices. |
| Practical use today | Material-level qualification. Provides baseline confidence that a raw material will not introduce obvious toxicity. Valuable at supplier qualification stage. | Required for FDA device submissions. Demonstrates the device’s overall biocompatibility in its actual use conditions. |
In 1995, the FDA adopted ISO 10993 as its primary biocompatibility framework for medical devices, effectively superseding USP Class VI as the sole standard for device submissions. [4] Since then, ISO 10993 has been the required framework for 510(k) and PMA biocompatibility packages.
A material that passes USP Class VI testing provides a strong starting point. But it does not automatically satisfy ISO 10993, which adds risk-based requirements based on the device’s actual contact duration, contact type, and patient population.
For implantable devices — anything with contact exceeding 30 days — ISO 10993 requires additional testing for genotoxicity, carcinogenicity, and reproductive toxicity. USP Class VI has no equivalent requirements.
| Practical guidance for procurement teams When evaluating a material supplier’s certification:• USP Class VI data alone is sufficient for pharmaceutical packaging and short-contact drug-delivery components.• For regulated medical devices requiring FDA submission, ISO 10993 testing is required in addition to — not instead of — USP Class VI.• Most reputable medical polymer suppliers provide both USP Class VI test reports and ISO 10993 biocompatibility data as part of their material certification package. |
Which Materials Qualify for USP Class VI?
Many engineering polymers and elastomers can achieve USP Class VI certification, but the result is specific to the exact formulation, curing system, and processing conditions tested.
A grade change, a new additive, a different cure catalyst, or a different processing temperature can alter the extractables profile enough to require re-testing. The certification follows the specific compound — not the polymer family in general.
| Material | Key Properties | Typical Medical Applications | USP Class VI Notes |
| LSR / Silicone | Platinum-cured, no extractable byproducts, autoclave-stable | Seals, valve membranes, catheters, respiratory components, infant care | Most common medical-grade elastomer; USP Class VI + ISO 10993 available from major suppliers |
| Polycarbonate (PC) | High optical clarity, impact-resistant, autoclave-compatible grades | IV connectors, diagnostic housings, fluid-path components, instrument windows | USP Class VI medical-grade (e.g., Makrolon 2458, Lexan 940) |
| Polypropylene (PP) | Chemical-resistant, lightweight, gamma/EtO sterilisation compatible | Disposable syringes, IV connectors, pipette tips, pill trays | Economical choice for high-volume disposables; leachable profile well characterised |
| PEEK | High mechanical strength, radiolucent, withstands 1,000+ autoclave cycles | Spinal implants, orthopedic screws, surgical guides, reusable instrument handles | Often combined with ISO 10993 implant testing for long-term contact applications |
| PTFE | Chemically inert, very low friction, non-stick surface | Heart surgery tubing, valve seats, catheter liners, stopcock bodies | Resistant to virtually all solvents; standard in fluid-path pharmaceutical equipment |
| PPSU | Superior impact resistance, withstands 1,000+ autoclave cycles | Reusable surgical instrument trays, sterilisation containers, endoscope components | Better hydrolysis resistance than polysulfone; preferred for reprocessed devices |
| TPU / TPE | Flexible, biocompatible, overmoldable onto rigid substrates | Catheter shafts, wearable device skins, ergonomic grip components | Shore hardness from 35A to 80D; medical grades require USP Class VI verification |
| PVC (medical grade) | Flexible, transparent grades, historically dominant in IV tubing | Blood bags, IV tubing, oxygen masks, nasal cannulas | DEHP-free medical-grade PVC required for patient contact; alternatives gaining share |
Note: Contact duration and sterilisation method affect material selection independently of USP Class VI status. A material may be Class VI certified but incompatible with the required sterilisation method. Always verify sterilisation compatibility alongside biocompatibility data.
USP Class VI and LSR Injection Molding
Liquid Silicone Rubber (LSR) is the material most commonly associated with USP Class VI certification in injection molding applications.
This is not coincidence. Platinum-cured LSR releases no acidic byproducts during curing — unlike tin-catalysed condensation systems — and its extractables profile under the four USP test solvents is characteristically low.
But certification does not survive manufacturing errors. The testing confirms the raw compound. What the compound actually leaches after injection molding depends on the complete production process.
Variables that can affect extractables in molded LSR parts include:
- Barrel temperature and cure conditions — incomplete cure leaves unreacted siloxane oligomers
- Post-cure step — a 200°C/4-hour post-cure drives off residual volatiles; skipping it increases extractables
- Mold release agents — any contamination introduced during demolding may not be covered by the material’s original USP test
- Cleanroom environment — particulate contamination does not affect USP Class VI test results directly, but affects the bioburden reaching sterilisation
At Fecision, our medical-grade LSR cell operates in a Class 1000 (ISO 7) cleanroom. Before any medical program begins production, we verify the specific lot’s material certification against the USP Class VI test report — not just the grade name. Post-cure at 200°C for four hours is standard on all medical LSR runs.
Frequently Asked Questions
Is USP Class VI required by the FDA?
Not directly. The FDA does not mandate USP Class VI certification as a legal requirement for medical devices. However, it is widely expected by FDA reviewers for materials used in drug contact, pharmaceutical packaging, and short-contact medical device components.
For medical device biocompatibility submissions, the FDA requires ISO 10993 testing — not USP Class VI alone. USP Class VI data can support an ISO 10993 programme, but it does not replace it.
How long does USP Class VI testing take?
Typically 6–12 weeks from sample submission to final report. The in vivo observation periods drive the timeline: both the systemic injection and intracutaneous tests require 72-hour observation windows, and the implantation test requires at least 120 hours of tissue contact.
Third-party laboratories such as Pacific BioLabs, Nelson Labs, and NAMSA run these tests on a contract basis. Most have scheduled test batches that start on fixed days of the week, so submission timing relative to the next batch start affects total turnaround.
Does USP Class VI certification cover the manufactured part, or just the raw material?
Strictly speaking, USP <88> tests the material — raw compound or processed sample — not the finished part in its end-use condition.
In practice, manufacturers typically test the compound in a form representative of production: cured, processed, and post-cured (if applicable). A change in formulation, curing method, or processing conditions may invalidate the original test results and require re-testing.
Can a material be USP Class VI certified and still fail ISO 10993?
Yes. USP Class VI and ISO 10993 use different test matrices and different risk logic.
USP Class VI does not test for genotoxicity, carcinogenicity, or reproductive toxicity — all of which are required under ISO 10993 for long-contact and implantable devices. A material can pass all three USP Class VI tests and still require additional ISO 10993 testing for regulatory submission.
What is the difference between USP Class VI and FDA food grade?
These are entirely separate designations. FDA food grade (21 CFR) confirms a material is safe for contact with food under defined conditions. USP Class VI confirms a material does not cause adverse in vivo biological responses under the three test conditions.
A material can be food grade but not USP Class VI certified, and vice versa. For medical device applications where patient contact is involved, USP Class VI is the relevant standard — not food grade.
Conclusion
USP Class VI is a material-level biocompatibility classification — not a finished-device approval, not an FDA clearance, and not interchangeable with ISO 10993.
What it confirms is specific and valuable: that a plastic or elastomeric material, tested in its processed form, does not produce adverse systemic, local, or implant-related biological reactions under the three standard in vivo tests and four extraction solvents.
For procurement teams and design engineers, this makes it a useful first checkpoint in material qualification. For medical device regulatory submissions, it supports but does not replace an ISO 10993 biocompatibility programme.
For manufacturers working with LSR and other medical-grade polymers, the certification is only as good as the production process that follows. Material lot verification, controlled post-cure, cleanroom environmental controls, and full traceability are what translate a material’s test data into a part that actually behaves the same way in the field.
References & Authoritative Sources
All sources publicly available. Accessed April 2026.
[1] US Pharmacopeial Convention (USP). ‘USP-NF General Chapter <88> Biological Reactivity Tests, In Vivo.’ (Official source for USP Class I–VI classification and test requirements.) https://www.usp.org
[2] TBL Plastics. ‘What is USP Class VI Testing.’ (Covers three test types, four extraction solvents, 72-hour observation windows, pass/fail criteria under USP <88>.) https://tblplastics.com/usp-class-vi-testing/
[3] Pacific BioLabs. ‘USP Class Plastics Tests (USP Class VI).’ (Biocompatibility laboratory context: Class IV and Class VI uniquely require implantation test; USP vs. ISO 10993 scope comparison.) https://pacificbiolabs.com/usp-class-plastics-tests/
[4] Holland Applied Technologies. ‘What is ISO 10993? How is it Different from USP Class VI?’ (FDA adoption of ISO 10993 in 1995 via G95-1; superseding of USP Class VI as primary device standard.) https://hollandapt.com/what-is-iso-10993-how-is-it-different-from-usp-class-vi/
