by Robert J. Janetschek, Company Director, Verichem Laboratories
Those working in the clinical laboratory environment agree there is a recognized trend in the shift away from traditional lyophilized and dry-fill product platforms—as commonly seen with such products as diagnostic reagents, quality control products, calibration materials, etc.—to entirely liquid-stable formats. One product group that benefits from such a product design is those categorized as clinical reference materials.
For purposes here, clinical reference materials are those products explicitly designated for the calibration and the calibration verification of diagnostic testing systems, as well as for the required validation testing of both new diagnostic assays and instrumentation. Testing such as this is vital for the determination of a clinical system’s overall accuracy, sensitivity, linearity, and reportable range as currently required under the current CLIA directives.
The fundamental reason for the shift to a liquid-stable product format is to eliminate the inherent drawbacks related to lyophilized and dry-fill products. All lyophilized and dry-fill products require some type of reconstitution procedure, typically accomplished by using deionized water or accompanying diluents. This not only results in increased labor, but there is also the additional chance of potential procedural error and resulting product waste. Additionally, if a product might require serial dilution, or any other product manipulations to achieve desired target concentration levels, which is common with lyophilized reference materials, the potential for procedural errors and product waste would apply again.
Third, if deionized water is used for reconstitution and dilution procedures, the quality of the overall water system plays a major role, as a sub-standard system is surefire way to cause product problems. Finally, lyophilized and dry fill products are big time consumers—they take time to prepare; they take time to fully dissolve; and they take time to equilibrate and stabilize—all of which can take anywhere from 15 minutes to a full hour, depending on the product. Simply put, a liquid-stable product format improves laboratory productivity and efficiencies.
However, despite the obvious advantages that a liquid-stable clinical reference materials can offer a laboratory, there are still challenging and problematic issues that need to be addressed and overcome by manufacturers of in-vitro diagnostic (IVD) products. One must keep in mind that not all liquid-stable clinical reference materials are manufactured the same, and that there are significant differences in product from one vendor to the next. As such, the laboratorian responsible for the acquisition of such materials not only needs to be cognizant of these issues, but as these products are only utilized on an “as needed” basis, there are other product attributes to consider ensuring the laboratory receives as much “bang for the buck” as possible. That said, a few of the most important and key facets to consider include:
- Accuracy/Traceability Claims: From a quality management and inspection/audit perspective, it is certainly advantageous to obtain reference materials with certified accuracy claims traceable to Standard Reference Materials (SRM’s) available from recognized organizations (i.e., NIST, USP, ACS, etc.).
- Documentation: In today’s regulatory environment, it is important to select a vendor whose product(s) have the necessary FDA 510(k) clearance, when applicable, but is also able to supply various product support documentation (i.e., Certificate of Analysis, MSDS, Value Assignment Sheets, etc.) quickly upon request.
- Instrument Applications: When relevant, it is highly desirable to obtain clinical reference materials which offer universal product compatibility and feature multiple applications for use across many diagnostic testing systems.
- Packaging: With laboratory storage space at a premium, another point to consider are products packaged within ergonomically designed kits for convenient storage. Also, consider if materials are filled within vials—which not only facilitate ease of use, but also minimize product deterioration. Lastly, the product should contain fill volumes ample enough to cover multiple testing events, any unexpected system trouble-shooting necessities, or any additional calibration verification testing.
- Product Design Specifications: For clinical reference materials, it is vital that product formulations incorporate critical blends of specific biologicals, along with highly purified raw material components, to produce bio-based materials that minimize matrix variations. In addition, they should incorporate the necessary set point designs and equidistant target concentrations to address current CLIA requirements for calibration verification materials.
- Stability Claims: As these are not used routinely, it is important to select products that not only have extended shelf-life and open vial stability claims, but also feature multiple freeze/thaw events, as well.
- Support Services: Aside from just product, investigate what ancillary services are available from vendors to further support product and assist the laboratory in meeting all CLIA and CAP requirements. Support includes data reduction services, test report generation and printing, online and phone support, and other customer success services.
To assist clinical laboratorians in meeting their obligations with the employment of such products, Verichem Laboratories, Inc., offers liquid-stable and ready-to-use biosynthetic clinical reference materials. The products address the needs and requirements of a wide variety of medical laboratory professionals, including those involved in routine diagnostic testing, clinical research applications, and in the development, manufacturing, and support of IVD products.
Robert Janetschek is a seasoned veteran of the clinical laboratory and IVD industry with over 40 years of experience. He has held numerous Technical and Business leadership positions with such organizations as Olympus America, Pall Corporation, Diagnostic Chemicals Ltd., and The Binding Site, among others. He is now affiliated with Verichem Laboratories Inc. (Providence, RI) as one of their Company Directors. Inquiries can be sent directly to his attention at [email protected]. The author wishes to thank Liz A. Pasini of Harborside Press LLC (Huntington, NY) for her assistance in the editing and formatting of this article.