Viscosity measurements operate on one of two opposing but equivalent processes: 1) a material flows past an immovable sensor, or 2) a mobile sensor travels through a material; in either case, a viscometer’s measurement of resistance to flow is translated to viscosity in units of centipoise (cP) or millipascal-seconds (mPa-s). As reference, the viscosity of water is defined as 1 cP or 1 mPa-s. There are several types of viscometers that can perform this function, using principles that have not been varied for decades.
Capillary viscometers measure the back-pressure required to propel material at a constant rate, whereas rotational viscometers calculate the torque required to rotate a disc or cylinder. Other types include falling ball viscometers, which translate the drop rate or height gain of a weighted sensor in a filled tube, and vibrating viscometers, which convert damping of vibrations within liquid medium to viscosity. Another variation is the rheometer, which calculates viscosities of liquids that are subject to variable flow properties over time and temperature changes, and which can impart shear stress to non-Newtonian fluids.
In the example of rotational viscometers, the viscosities they can measure are dependent on the range of torque that can be delivered to the system. Instruments with low torque capabilities are best for measuring low viscosity fluids, including most pharmaceutical elixirs, such as cough medicine. Systems with high torque capabilities can more accurately and reproducibly measure viscosities of thicker substances such as creams and lotions. Systems with capacities for the highest torques are more suitable to measurements of industrial materials, such as pitch or asphalt, or foodstuffs that resemble industrial sludge, such as molasses.
Viscosity is relevant for any material that can be pumped or piped, dipped or coated. In the biomedical sciences, viscosity can be used as a surrogate measurement to make predictions about density, molecular weight, and structure, and even enzymatic activity, which has an inverse relationship with viscosity. In practical terms, viscosity is an extremely important factor in quality control considerations, to ensure that whatever fluid is packaged and distributed to end users has flow properties that are consistent and predictable. By extension, this is a necessary facet of pharmaceutical production, and viscometer instrumentation has accordingly been upgraded in recent years to streamline adherence to the regulatory framework that guides electronic data collection and storage.
For all FDA-regulated companies, part 11 of the Title 21 Code of Federal Regulations (CFR Part 11) went into effect in 1997, after regulators realized that the digital revolution would obviate a substantial amount of paper-based record keeping. They sought to mitigate the costs in time and resources associated with maintaining and delivering written records to regulatory offices, so they developed a framework under which companies and facilities would still remain compliant with antecedent Good Manufacturing Practice, Good Clinical Practice, and Good Laboratory Practice guidelines. Therefore, CFR Part 11 provides directives for compliance on the production end, and enforcement on the regulatory end, in the areas of validation, audit trails, record copying, and record retention:
1) Validation: production facilities must be able to verify that each electronic system can reliably perform the duty assigned to it, with documented installation, operational, and performance qualifications.
2) Audit trails: a requirement to establish physical, logical, and procedural security measures to ensure record reliability, with dedicated time stamps and user logins/IDs.
3) Record copying: a requirement to enable straightforward copying of records by investigating regulatory officials, with standard file formats, and limited access to only approved internal users.
4) Record retention: the required length of time records are maintained is bound by predicate Good Practices rules specific to each instance.
One leading manufacturer of viscometers and rheometers, Anton Paar, features instruments with precision thermoelectric temperature control via an integrated Peltier element, combined with small footprints and minimal reagent use as a design feature to streamline and standardize measurements. The company’s ViscoQC 300 rotational viscometer is therefore adaptable to laboratory applications, and is available with low, regular, and high torque capabilities, to measure viscosities up to 320 million cP. Additionally, it is compatible with various international measurement standards, and has optional integrated V-Comply software, which allows seamless compliance with CFR Part 11. The V-Comply package includes time-stamped audit trails, electronic signatures with password protection, and a pharma qualification package.
Analogously, Brookfield AMETEK offers the DV2T rotational series with available RheocalcT software to manage Part 11 compliance with tiered password-protected login and access, and digital signatures. Finally, for users with older viscometers, there are contract organizations that offer external upgrades to Part 11 compliance with their own proprietary software, which can ostensibly be adapted to any digital system under Part 11 scrutiny. One example is MasterControl, which provides software solutions customized to deal with Part 11 compliance issues. In all cases, users should realize that compliance software is an add-on that carries extra costs. However, its capability to enable compliance with regulatory guidelines should be well worth the higher price.