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USP Class VI, ADI-Free, What Does it All Mean for Your Bioprocess?


Regulatory Requirements for Biotech MFC

Mass Flow Controllers (MFCs) are critical instruments in the gas management subsystem for the bioreactor, responsible for maintaining precise gas control during the development of biologically active pharmaceutical grade cells and tissues. Key gasses including N2, O2, Air and CO2 flow through the MFC and into the bioreactor to control the cell growth and must not be contaminated by foreign materials in the gas supply. This is especially important for pharmaceutical products, such as insulin and other drugs, which are injected into the body.

Many MFCs use elastomer sealing materials, so they should be certified as safe for these critical applications.  The Brooks Instrument SLA Series Biotech mass flow controller, described in more detail below, can offer USP Class VI/ADI-free certification for all elastomeric material in the gas stream of the MFC (wetted path) including:

  • Valve seats
  • O-rings  

USP Class VI

USP stands for U.S. Pharmacopeia, a private (non-government) organization that "promotes the public health by establishing state-of-the-art standards to ensure the quality of medicines and other health care technologies". For plastics, they have six different classes based on duration and application. Class VI is the most stringent and requires three tests:
  • Systemic injection test
  • Intracutaneous test and
  • Implantation tests
In order to pass the Class VI standards, the product/material must exhibit a very low level of toxicity by passing all the tests requirements when tested according to ISO 10993. The FDA requires testing of finished devices, however, the demonstration of biocompatibility of materials according to USP Class VI standards is provided as an aid to device manufacturers in their material selection process.

Compliance to USP Class VI is often requested by users in the biopharmaceutical and medical industries.

What is ADI-Free / BSE-Free / TSE-Free?

ADI-free certifies that the raw materials used in production of the elastomer contain no Animal Derived Ingredients (ADI). When production of the elastomer contain no ADI with respect to source, manufacture and treatment, they cannot transmit Prion diseases such as Bovine Spongiform Encephalopathy (BSE)  and Transmissible Spongiform Encephalopathy (TSE) . The certification includes a statement from the elastomer manufacturer certifying that there no substance of animal origin used to manufacture the product. When you see ‘CFR 21 FDA 177.2600' on MFC elastomeric material, it means that it is on the FDA list of base elastomers that are recognized as inherently safe and classified as GRAS (Generally Recognized as Safe).

As mentioned above, many MFC’s have elastomeric O-rings and valve seats in the wetted path. So, when MFC’s are used in critical biopharmaceutical applications, system designers and operators will often require the ADI-free designation.

SLA Series Biotech MFC Offers Two Options Packages

To serve the unique requirements of biopharmaceutical bioreactors, Brooks Instrument has created two options packages, both built on the proven performance of the industry-leading SLA Series MFC:

  1. SLA Series Biotech Performance
  2. SLA Series Biotech Premium

The Performance Package Includes all the benefits of the standard SLA including: high stability and repeatability, extended turndown (up to 250:1); very low leak control valve; pre-calibrated gasses (N2, O2, Air & CO2) and a welded sensor.

The Premium Package includes all elastomers in the wetted path of the SLA Series Biotech, including O-rings and Valve Seats, are USP Class VI and ADI Free, and include a full package of certificates. Additionally, 2.2 Material Certifications – certifying the composition of all materials in the wetted path –and International Calibration Traceability – calibrations traceable to NIST or other international metrology standards, are included. With these certifications, you can be confident  that your Brooks Instrument gas mass flow controller will provide only the purest gas delivery within your bioreactor. For an additional fee, add Material Certification 3.1 for those processes which require full material traceability.

Currently, Class VI, ADI-free elastomers are not a regulatory or industry requirement for MFC’s used in bioreactors. But, biopharmaceutical system designers and operators are concerned enough about BSE and TSE to want these special elastomers in their MFC when manufacturing injectable proteins such insulin or vaccines. The SLA Series Biotech Premium fulfills these advanced requirements.

Learn more about the benefits and specifications of the SLA Series Biotech Mass Flow Controller

About The Author

Darren Weinhold
Global Product Manager

Darren is the global product manager for mass flow and pressure control products for industrial applications at Brooks Instrument.

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