Pharmaceutical Grade O-Rings
USP Class VI certified sealing for bioreactors, sterile filling lines, WFI systems and chromatography equipment. Full regulatory documentation and extractables support.
Overview
Pharmaceutical and biotech manufacturing operate under the most stringent sealing requirements of any industry. Seals in bioreactors, sterile fluid transfer systems, chromatography skids, filling machines, and lyophilisation equipment must not only prevent leakage but also avoid contributing extractable or leachable compounds that could compromise drug purity, alter efficacy, or endanger patient safety. Every material must be supported by comprehensive biocompatibility data, full batch traceability, and lot-specific documentation. In this environment, an O-ring is not a commodity — it is a critical process component with direct impact on product quality, regulatory compliance, and ultimately patient outcomes.
Steam sterilisation in autoclaves at 121°C or 134°C and Steam-in-Place cycles place extraordinary thermal and oxidative stress on elastomeric seals. Repeated exposure to saturated steam causes many elastomers to harden, shrink, and develop compression set — the permanent deformation that occurs when a seal is compressed at elevated temperature over time. Once compression set exceeds approximately 30–40%, the seal can no longer recover sufficient sealing force to prevent leakage during cool-down or pressure cycling. Pharmaceutical-grade silicone and peroxide-cured EPDM compounds are specifically formulated with low-compression-set architectures, advanced curing systems, and antioxidant packages to maintain seal integrity across hundreds of sterilisation cycles without significant degradation.
Extractables and leachables validation has become a central focus of pharmaceutical regulatory submissions and quality risk assessments. Extractables are compounds that can be released from a seal material under aggressive laboratory conditions such as solvents, heat, and extended exposure time, while leachables are substances that actually migrate into the drug product under normal process conditions. USP Class VI testing provides an initial biocompatibility screen, but modern drug manufacturers increasingly require detailed E&L studies using analytical techniques such as GC-MS, LC-MS, and ICP-MS to characterise even trace-level compounds. Our pharmaceutical-grade compounds are selected specifically for low extractables profiles, and we can supply comprehensive E&L data packages to support your regulatory filing, risk assessment, and submission to the FDA or EMA.
Common failure modes in pharmaceutical seals include adhesive failure in single-use bioreactor bags where the O-ring interfaces with film materials, hydrothermal degradation in WFI systems that operate at elevated temperatures continuously, and chemical swelling in solvent-based chromatography processes using acetonitrile, methanol, or tetrahydrofuran. Another often-overlooked failure mode is particle generation — aged or incompatible seals can shed elastomeric particles that contaminate sterile filtrates, clog precision dispensing nozzles, or trigger false positives in particulate monitoring systems. Material selection must therefore consider not only chemical compatibility and temperature resistance but also abrasion resistance, surface finish, and the potential for particulate shedding under dynamic or cyclic conditions.
Material selection in pharmaceutical applications is dictated by process media, sterilisation method, operating temperature, and regulatory pathway. USP Class VI silicone remains the default choice for bioreactors, filling machines, and any application requiring repeated autoclaving or SIP cycles due to its wide temperature range and biocompatibility. EPDM is preferred for WFI and clean steam systems due to its superior hot water resistance and lower cost than silicone. PTFE is specified for the highest purity requirements or aggressive solvent handling where elastomeric seals would degrade or contribute extractables. FKM is used in non-aqueous solvent applications such as organic synthesis, API extraction, or solvent recovery processes. For the most aggressive combined chemical and thermal environments, FFKM provides both steam and chemical resistance at a premium cost that is justified by the criticality of the application.
Regulatory documentation requirements in pharmaceutical manufacturing extend well beyond a simple certificate of conformance. USP Class VI compliance demonstrates biocompatibility through systemic toxicity, intracutaneous reactivity, and implantation testing protocols. FDA 21 CFR 177.2600 provides the foundation for food and drug contact compliance in the United States. ISO 10993 biocompatibility testing is required for medical device applications and is increasingly accepted for pharmaceutical manufacturing equipment. For European markets, compliance with EU 10/2011 on plastic materials and Regulation EC No 1935/2004 may be necessary depending on the drug product and route of administration. We supply comprehensive documentation packages including Certificates of Analysis, material safety data sheets, batch-specific extractables summaries, and supplier change notification agreements.
Our pharmaceutical sealing programme is built around three pillars: advanced material science, comprehensive regulatory documentation, and expert application engineering. We offer material selection consultations based on your specific process conditions including media composition, temperature, sterilisation frequency, and regulatory jurisdiction. Custom compounding services are available for unique extractables profiles, colour-coding requirements, or specific hardness needs. All pharmaceutical-grade O-rings are manufactured in controlled environments with full batch traceability from raw material to finished part. We also support validation activities by providing sample lots for extractables screening, compatibility testing, and accelerated ageing studies prior to production scale-up and commercial manufacturing.
Recommended Materials
Silicone USP Class VI
Bioreactors, sterile fluid transfer, filling machines, autoclavable equipment, and lyophilisation systems requiring the widest temperature range and lowest extractables.
Temp: -60°C to +200°C
Note: Lowest compression set for repeated autoclaving and SIP cycles. Platinum-cured grades offer the highest purity for sensitive biologics.
EPDM USP Class VI
WFI systems, clean steam distribution, CIP/SIP-resistant static seals, and hot water applications where cost efficiency is important.
Temp: -40°C to +150°C
Note: Excellent hot water and steam resistance at lower cost than silicone. Specify peroxide-cured grade for SIP service.
PTFE Virgin
High-purity process seals, aggressive solvent handling, chromatography equipment, and applications with zero-extractables requirements.
Temp: -200°C to +260°C
Note: Static applications only. Virtually zero extractables and universal chemical resistance. Requires careful groove design.
FKM FDA Grade
Organic solvent handling, API processing, solvent recovery systems, and non-aqueous chemical applications in pharmaceutical synthesis.
Temp: -15°C to +200°C
Note: Not suitable for steam or aqueous service. Verify compatibility with specific solvents; resistant to most organic chemicals.
FFKM Kalrez
Aggressive chemicals combined with steam sterilisation, high-temperature solvent applications, and processes where both FKM and EPDM would fail.
Temp: -15°C to +260°C
Note: Premium material for extreme combined chemical and thermal environments. Justified for high-value batch processes where failure is catastrophic.
Typical Applications
- Bioreactor seals
- Sterile process seals
- Aseptic filling seals
- Autoclave door seals
- Freeze dryer seals
- HVAC cleanroom seals
- Fluid transfer system seals
- API manufacturing seals
Relevant Standards
Frequently Asked Questions — Pharmaceutical
What is USP Class VI testing for O-rings?
USP Class VI is a comprehensive biocompatibility test standard from the United States Pharmacopeia that evaluates materials for systemic toxicity, intracutaneous reactivity, and implantation response in living tissue. The testing involves three distinct biological assays: the systemic injection test evaluates whether extractables from the material cause toxic reactions when administered to mice; the intracutaneous test assesses local tissue reaction at the injection site; and the implantation test examines the material's effect on muscle tissue over seven days. Passing all three USP Class VI tests indicates that the material is biologically safe for pharmaceutical and medical device contact applications. It is important to note that USP Class VI is a material-level test, not a finished-product certification. The test is performed on the base compound under standardised extraction conditions. While USP Class VI provides a strong foundation for biocompatibility, many pharmaceutical manufacturers now require additional extractables and leachables data beyond this baseline testing.
Can silicone O-rings withstand SIP sterilisation?
Yes, USP Class VI silicone O-rings can withstand repeated SIP cycles at 121°C and 134°C when the correct compound grade is specified. However, compression set resistance is the critical property for maintaining sealing force after multiple sterilisation cycles. Standard silicone compounds may develop compression set exceeding 50% after 100 steam cycles, causing leakage during system cool-down or pressure transients. For SIP service, you should specify a low-compression-set silicone compound that has been specifically formulated and tested for saturated steam exposure. Platinum-cured silicone grades generally exhibit lower compression set and lower extractables than peroxide-cured alternatives, making them the preferred choice for high-purity pharmaceutical applications. Our pharmaceutical-grade VMQ compounds are tested for compression set after 168 hours at 150°C and maintain sealing performance through over 500 documented SIP cycles. We can provide steam-ageing data and compression set certificates for your validation documentation.
Do you provide extractables and leachables documentation?
Yes, we provide comprehensive extractables and leachables documentation for our pharmaceutical-grade VMQ, EPDM, PTFE, and FFKM compounds. Our standard E&L package includes extractables data generated under aggressive solvent conditions including water, ethanol, and isopropanol at elevated temperatures, analysed by GC-MS, LC-MS, and ICP-MS techniques. The data package includes identified compounds, semi-quantitative concentration estimates, and toxicological risk assessments where available. For leachables, we can work with your analytical team to design customised studies under your specific process conditions. All E&L data is supported by Certificates of Analysis, batch traceability, and material safety data sheets. For new drug applications or regulatory submissions, we can provide formal supplier declarations and participate in joint risk assessment meetings. Contact our regulatory affairs team with your specific requirements and we will confirm the available documentation package for your chosen compound.
What O-ring material is best for bioreactor applications?
USP Class VI platinum-cured silicone is the material of choice for most bioreactor applications, including stainless steel reusable vessels and single-use disposable systems. Bioreactors operate under conditions that demand exceptional purity, wide temperature tolerance, and resistance to repeated sterilisation. Platinum-cured silicone offers the lowest levels of extractable metals and organic compounds, making it ideal for cell culture media where trace contaminants can inhibit cell growth or alter protein expression. The material maintains flexibility from -60°C to +200°C, accommodating both cold media storage and steam sterilisation. For single-use bioreactor bags where the seal interfaces with multi-layer film materials, adhesive compatibility must also be verified. EPDM is sometimes used as a lower-cost alternative for WFI and buffer media systems, but silicone remains the gold standard for cell culture and final fill applications. Our bioreactor-grade silicone compounds are tested for cytotoxicity and meet USP Class VI, ISO 10993, and BSE/TSE free requirements.
How many autoclave cycles can a pharmaceutical O-ring withstand?
The number of autoclave cycles a pharmaceutical O-ring can withstand depends on the base material, compound formulation, sterilisation temperature, and whether the application is static or dynamic. Under standard autoclave conditions of 121°C for 30 minutes, a high-quality USP Class VI silicone compound can typically withstand 200 to 500 cycles before compression set reaches critical levels. At 134°C, the cycle count is reduced to approximately 100 to 250 cycles. EPDM compounds generally perform well in steam but may show higher compression set than silicone after extended cycling. PTFE does not suffer from compression set but is limited to static applications and may cold-flow under sustained load. Dynamic applications such as agitator seals or pump shafts experience additional mechanical wear and typically require replacement every 50 to 100 cycles regardless of material. We recommend establishing a replacement schedule based on compression set monitoring rather than visual inspection, as significant performance degradation can occur before visible cracking appears.
What is the difference between USP Class VI and ISO 10993?
USP Class VI and ISO 10993 are both biocompatibility testing frameworks, but they differ in scope, geographical acceptance, and test methodology. USP Class VI is a specific chapter of the United States Pharmacopeia that requires three biological tests: systemic toxicity, intracutaneous reactivity, and implantation. It is widely accepted in the United States and has been the traditional standard for pharmaceutical sealing materials for decades. ISO 10993 is a more comprehensive international standard series that covers a broader range of biological evaluation tests including cytotoxicity, sensitisation, irritation, systemic toxicity, genotoxicity, and haemocompatibility. ISO 10993 is the preferred standard in Europe and is increasingly required by the FDA for medical device applications. For pharmaceutical manufacturing equipment, USP Class VI remains the most commonly cited requirement, but many global manufacturers now specify both standards to satisfy multiple regulatory jurisdictions. Our pharmaceutical-grade compounds are tested to USP Class VI as standard, and ISO 10993 testing can be arranged for specific compounds upon request.
Can you supply O-rings for single-use bioprocessing systems?
Yes, we supply O-rings specifically for single-use bioprocessing systems including bioreactor bags, media bags, mixing vessels, and fluid transfer assemblies. Single-use systems present unique sealing challenges because the O-ring must interface with multi-layer polymer films rather than traditional metal grooves. The seal material must not only be biocompatible and low-extractables but also compatible with the film material to prevent adhesive failure or delamination. Our platinum-cured silicone compounds are the standard choice for single-use applications due to their ultra-low extractables profile and broad regulatory acceptance. We can supply O-rings in validated cleanroom packaging with certificates of conformance, BSE/TSE statements, and lot-specific test data. For high-volume single-use manufacturers, we offer supply agreements with scheduled deliveries, batch reservation, and change control notifications to support your validation lifecycle. Custom sizes, colours, and hardness grades are available to match your specific bag design and assembly requirements.
What causes O-ring compression set in steam sterilisation?
Compression set in steam-sterilised O-rings is caused by the combination of sustained compressive stress and elevated temperature, which together accelerate molecular relaxation within the elastomer. During steam sterilisation at 121°C or 134°C, the polymer chains in the elastomer gain thermal energy and begin to disentangle and rearrange. Cross-links between polymer chains break and reform in new positions that relieve internal stress. When the temperature returns to ambient and the compressive load is removed, the elastomer cannot fully return to its original shape because the cross-link network has been permanently altered. In steam service, this effect is compounded by oxidative degradation and hydrolysis reactions that attack the polymer backbone and cross-links. Silicone elastomers generally exhibit lower compression set than most organic rubbers in steam because their siloxane backbone is more thermally stable. However, even silicone will eventually fail if the compound is not optimised for steam resistance. Specifying a low-compression-set compound, maintaining proper compression percentage in the groove design, and avoiding over-tightening are all essential for maximising seal life in autoclave and SIP applications.
Do you offer custom compounds for specific drug contact applications?
Yes, we offer custom compounding services for pharmaceutical applications with unique chemical, thermal, or extractables requirements. Custom compounds can be developed to optimise properties such as compression set resistance for high-frequency sterilisation, low-extractables profiles for sensitive biologics, or specific hardness grades for high-pressure dynamic seals. We can also formulate compounds with custom colours to support line identification and assembly verification, or with specific surface treatments to reduce friction and sticking in automated assembly equipment. The custom compound development process typically begins with a technical consultation to define your process conditions, regulatory requirements, and target performance specifications. We then select base polymers, fillers, curing systems, and additives from our approved ingredient database to formulate candidate compounds. Prototype batches are produced for extractables screening, physical property testing, and compatibility evaluation. Full-scale production follows validation and approval, with all batches manufactured under controlled conditions with complete traceability.
How do I validate O-ring compatibility with my drug product?
Validating O-ring compatibility with your drug product requires a systematic approach that combines material data review, extractables testing, and stability studies. The first step is to obtain detailed material composition information, extractables data, and regulatory certificates from your seal supplier — we provide comprehensive documentation packages for this purpose. Next, perform extractables studies under exaggerated conditions using appropriate solvents and analytical techniques to identify potential leachable compounds. The extractables profile is then used to design targeted leachables studies under actual process conditions with your specific drug product. Leachables are monitored over the shelf life of the product using validated analytical methods. Simultaneously, stability studies should evaluate whether identified leachables affect drug potency, purity, or stability. For biologics and high-value drug products, we recommend beginning with a risk assessment that considers the drug's route of administration, dosage form, and patient population. Our regulatory affairs team can support your compatibility validation programme by providing material data, participating in risk assessments, and supplying sample lots for preliminary screening studies.