Multianalyte Controls Part 2: Raw Materials and Uses for Controls

We recently discussed multianalyte controls and the role they play in in vitro diagnostic (IVD) quality control. Medix Biochemica provides IVD suppliers with quality raw materials, empowering our customers to produce reliable, high-quality multianalyte controls. Having covered the importance of a quality base matrix in Part 1, in this Multianalyte Controls Part 2 blog, we’ll discuss the purification and product parameters of our raw materials, as well as the uses for these controls. Read more on Multianalyte Controls Part 1.

Preparation and Purification of Raw Materials for Multianalyte Controls

Below are highlighted techniques utilized while producing raw materials for addition in to multianalyte controls.

Chromatography 

Chromatography is a technique used to separate, identify and purify the components of a mixture for qualitative and quantitative analysis. It can be used to purify proteins based on characteristics such as size and shape, total charge and binding capacity.^1,2

The chromatography technique includes three components:¹

• Stationary phase: composed of a ‘solid’ phase
• Mobile phase: composed of a ‘liquid’ or ‘gaseous’ component
• Separated molecules

The molecules are separated by the interaction between the stationary and mobile phase.¹

There are several different chromatography methods, including gas chromatography, column chromatography, paper chromatography and size exclusion chromatography.¹

Centrifugation

Centrifugation is a method of separating molecules of different densities by spinning them in solution around an axis at high speed, in a centrifuge rotor. It can be used to collect cells or separate precipitants from supernatants, purify virus particles and detect subtle differences in the conformation of different molecules.^3,4

Lyophilization

Lyophilization, also called freeze-drying, is a method of preparing dry powder cakes by removing water (in the form of ice) from the material. This is done by freezing the material quickly and then submitting it to a vacuum which removes the ice.^5,6,7

Solvent extraction

Solvent extraction is used to separate a substance from a mixture by exposing it to an appropriate solvent. The solvent will dissolve the target substance, allowing separation from the other components of the mixture.⁸

Salt-induced precipitation

This is a purification method that takes advantage of the decreased solubility of specific molecules in a solution with exceptionally high ionic strength.⁹

Our Product Specifications for Multianalyte Control Raw Materials

At Medix Biochemica, we have a set of parameters (product specifications) that all our raw materials must meet, in order to ensure that no substandard materials reach the customer. These parameters mean that our customers know they can expect consistent quality from us, empowering them to choose the most suitable multianalyte control raw materials for their needs.⁹

These are some of the highlighted the parameters we list in our product specifications:⁹

Purity

Purity is the extent to which a substance is free from contamination or impurities. In some applications, high purity is required for a specific multianalyte control to be successful, but higher purity sometimes means a higher cost. Some of our customers therefore prefer to prioritize consistent performance over higher purity levels.

Source

The source is the material used to produce a product (e.g. body tissues that produce enzymes). Knowing the source allows our customers to make informed choices when deciding on the most suitable products to purchase. Deciding factors include scale needed, supply chain stability, purity requirements, product performance and cost.

Activity

Ezymatic activity, or simply activity, is a measure of the amount of functional material present in a sample. This is usually expressed in units/mg or units/mL.  Being able to rely on this measurement allows customers to formulate each of their analytes of interest in their multianalyte controls to clinically significant levels.

Unit definitions

Enzymes increase the rate of chemical reactions. An enzymatic unit is a measure used to quantify the activity of an enzyme. The more active the enzyme is, the more units there will be. Many enzyme unit definitions are standardized. However, it’s still important to list the unit definitions so that customers are “comparing apples to apples” when making their purchasing decisions. For example, if results of >100 units/mL of an enzyme could indicate disease, it’s essential to make sure you are talking about the same unit definitions.

Contact us if you have specific product specification requirements

Considerations for Multianalyte Control Materials: What Our Customers Need

What do our customers consider when choosing a raw material for a control?⁹

Good sensitivity and specificity

Raw materials must have both the ability to recognize clinically relevant levels of a substance (sensitivity) and the ability to perform with minimal interference effects (specificity).

Stability

It’s crucial for these materials to remain stable during transport, storage and especially for the intended application.

Consistency

The materials must offer consistent quality and performance from batch to batch, ensuring accurate and reproducible testing results.

Supply chain stability 

A stable supply chain means customers can expect consistent availability of the materials they need, preventing any disruptions in their multianalyte control production.

Traceability

A material’s origin and production process must be documented for proper regulatory compliance and quality control.

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Common Challenges Associated With IVD Raw Materials

What are some everyday challenges faced by IVD companies when selecting their raw materials?⁹

Compliance

All raw materials must meet regulatory standards. Navigating complex regulatory requirements can be a challenge, so working with a trusted supplier makes the process much simpler.

Cost

IVD companies must balance the need for high-quality materials with cost considerations.

Batch to batch variability

Inconsistencies in raw material quality and performance can lead to variability in reliable performance of a control.

Supply chain risks

Disruptions in the supply chain can seriously impact an IVD company’s production schedule.  Further, if a finished multianalyte control has a long lead time or limited availability, it will affect the lab’s ability to conduct the necessary control tests. Partnering with a reliable supplier helps to avoid unnecessary delays.

Uses for Multianalyte Controls

In clinical analysis and analytical testing settings, a multianalyte control with a known value must be used to establish the accuracy and precision of the testing equipment. This gives laboratories and medical professionals confidence that the results they get from their analyses are sound.⁹

Daily checks

Many customers use multianalyte controls for laboratory quality assurance. In testing laboratories, tests are typically run daily to check the accuracy of the lab equipment.⁹

Calibration

Ensuring that all instruments in a laboratory are properly calibrated is a crucial step in any clinical or scientific setting. This means determining, checking and/or rectifying the settings or compensation factors on an instrument to ensure its accuracy. Quality control materials can be used to calibrate sensitive precision equipment in a lab.⁹

Linearity verification

A multianalyte control can be used to test the linearity of a measuring instrument or system. Linearity is the ability to provide test results that are directly proportional to the concentration of the quantity to be measured in a test sample. Testing is done by analyzing the control solution at different concentrations, to check if the system’s calibration is correct and a testing method and instrument are providing linear results.⁹

References:

1. Coskun O. Separation techniques: Chromatography. North Clin Istanb. 2016;3(2):156-160. doi:10.14744/nci.2016.32757.
2. Chromatography. Collins English Dictionary. Accessed January 16, 2024. https://www.collinsdictionary.com/dictionary/english/chromatography.
3. Stephenson FH. Chapter 12 - Centrifugation. In: Stephenson FH, ed. Calculations for Molecular Biology and Biotechnology (Third Edition). Academic Press; 2016:431-438. doi:10.1016/B978-0-12-802211-5.00012-6.
4. Centrifugation. Collins English Dictionary. Accessed January 16, 2024. https://www.collinsdictionary.com/dictionary/english/centrifugation.
5. Wang W. Lyophilization and development of solid protein pharmaceuticals. International Journal of Pharmaceutics. 2000;203(1):1-60. doi:10.1016/S0378-5173(00)00423-3.
6. Lyophilization. Collins English Dictionary. Accessed January 16, 2024. https://www.collinsdictionary.com/dictionary/english/lyophilization.
7. Nowak D, Jakubczyk E. The freeze-drying of foods—the characteristic of the process course and the effect of its parameters on the physical properties of food materials. Foods. 2020;9(10):1488. doi:10.3390/foods9101488.
8. Solvent extraction. Collins English Dictionary. Accessed January 16, 2024. https://www.collinsdictionary.com/dictionary/english/solvent-extraction.
9. Expert opinion. Anthony Austin, Global Marketing Manager at Medix Biochemica. January 2024.