Purity grades are standards that indicate that a substance meets pre-determined chemical and biological purity specifications, denoting suitability for use in specific research or manufacturing applications. Regulations define the appropriate purity grades for the manufacture of food, drugs, and medicinal products. There are also separate purity grades for products intended for laboratory and analytical applications.
An understanding of different reagent purity grades is vital when designing products for diagnostic or therapeutic purposes, and using raw materials of the appropriate grade during an early research phase can eliminate lengthy re-validation at the commercialization stage.
In this article, we introduce the main reagent purity grades and highlight specialty grades offered for specific molecular biology applications. We also explore considerations for choosing purity grades, especially for projects that may progress past research toward commercial manufacturing.
Main Purity Grades and Associated Applications
A material or reagent of a specific purity grade must meet criteria set out in a monograph, which is a document released by the relevant regulatory agency containing requirements for the ingredients or preparation, handling, and specifications of the substance. The specifications define which tests should be performed, as well as the acceptance criteria that enable a substance to be labelled with a particular grade.
There are several international agencies that provide purity grade regulations for reagents used in the manufacture of food, drug, and medicinal products. In the ranking of chemical purity, the ACS (American Chemical Society) and Reagent grade chemicals are highest (Table 1, download PDF), with both having a similar purity of ≥95%. United States Pharmacopeia (USP) and National Formulary (NF) grade reagents are also suitable for manufacture of foods, drugs, and medicinal products (Table 1). Every year these organizations publish a joint compendium called USP-NF, which provides standards for drugs, dosages, chemicals, and preparations. With a few exceptions (e.g., HPLC-grade materials, which are used in analytical and preparative separations), materials used for manufacturing at Teknova are of one of these four high-purity grades.
Specialty Grades from Teknova
In addition to the general grades outlined above, we offer specialty grades for a range of reagents. Molecular biology grade reagents have equivalent purity to ultra-pure chemicals, and include reagents, enzymes, and buffers (e.g., agar, RNase A, and SSC/SSPE buffers for Southern and northern hybridization procedures) (Table 1). Our molecular biology–grade, PCR-certified water is tested for DNase, RNase, and protease activity, as well as PCR-verified for the absence of bacteria.
Our ultra-pure grade reagents include fundamental biochemistry reagents such as Tris base, sodium chloride, TEMED, and SDS. In addition, Teknova provides specialty grades as guidelines for specific applications, such as DNA sequencing grade reagents, electrophoresis grade reagents, and histology grade ethanol.
Table 1. Common Reagent Purity Grades. (download PDF)
|ACS||Meets or exceeds the purity standards set by the American Chemical Society (ACS). Considered the highest purity chemical grade (≥95% purity).||Can be used for food, drug, and medical uses and general procedures that require strict quality specifications.|
|Reagent||Describes high purity chemicals for which no established specifications exist. Usually considered equivalent to ACS grade.||Can be used for food, drug, and medical uses and general procedures that require strict quality specifications. Very often these are solutions or dilutions of ACS grade materials.|
|USP||Meets or exceeds requirements set by the United States Pharmacopeia (USP).||Can be used for food, drug, and medical purposes, and also, for most laboratory purposes.|
|NF||Meets or exceeds requirements of the National Formulary (NF). The USP-NF publishes a book with the standards for chemicals.|
|BP||Meets or exceeds requirements set by the British Pharmacopeia (BP).|
|JP||Meets or exceeds requirements set by the Japanese Pharmacopeia (JP).|
|PhEur||Meets or exceeds requirements set by the European Pharmacopeia (PhEur or EP).|
|Multi-compendial||Meets or exceeds requirements set by more than one pharmacopeia.|
|Molecular biology||Tested for DNase, RNase, and protease activity.||Can be used in molecular biology research applications.|
|HPLC||High purity chemicals for use in analytical and preparative separations that are tested at one or more UV wavelengths.||Used in high-performance liquid chromatography, gel-permeation chromatography, and UV-spectrophotometric analysis.|
* ACS, Reagent, USP, NF grades are often interchangeable but applicable regulatory requirements should be reviewed to confirm that appropriate standards are met for your application.
In contrast, the following three grades are not suitable for food, drug, or medicinal use: laboratory, purified, and technical grade. Substances of these grades are mainly used for industrial or educational purposes where high purity is not required.
How to Choose Reagent Grades
Ultimately, your application and end goal (i.e., research vs. therapeutic or diagnostic) determine what reagent grade you need. You can reference some of our specialty grade designations to help guide product selection. In addition, note that we only use high-purity raw materials that allow us to make consistently high-quality research use only (RUO) products. We manufacture all products using ISO 13485:2016 certified processes, which provides an advantage if you are pursuing clinical application of your products.
Good Manufacturing Practices for Clinical Products
RUO reagents are often used during the early stages of diagnostic or therapeutic product development, due to their widespread availability and low cost. These reagents can be manufactured in compliance with either ISO 13485—the standard for medical devices—or the more general ISO 9001. However, before diagnostic or therapeutic products can be commercialized, FDA and EMA regulations require manufacturers to switch from using RUO reagents to those produced according to good manufacturing practices (GMP). GMP reagent production is subject to more stringent requirements for material traceability, equipment maintenance, environmental control, and staff training, which ultimately ensure the safety of the end user.
As mentioned above, all Teknova manufacturing facilities are ISO 13485:2016 certified and integrate extensive raw material analysis, bioburden testing, and quality control processes into production of reagents, enabling seamless transition from RUO to GMP manufacturing. The high standards imposed by ISO 13485 align well with the requirements of GMP, making transitioning these reagents to GMP faster and more flexible than moving from ISO 9001. Using ISO 13485 certified processes from the outset also enables protocol modifications that mitigate costs, such as replacing enzymes with less expensive alternatives.
High-Quality Water for Use in Research and Pharmaceutical Development
Another important consideration for obtaining high-quality end products is to use high purity, sterile water to manufacture reagents intended for research and clinical applications. Standards for the purity and sterility of water are defined by different agencies, including the US Pharmacopeia (USP) and the American Society for Testing and Materials (ASTM).
USP standards for “purified water” and “water for injection” (WFI) are the most relevant for use in laboratories and manufacturing. Of the two, WFI is of higher purity and the standard for pharmaceutical and diagnostic development. ASTM purity standards are comprised of four categories, with I being the highest purity and IV the least. Categories I to III include standards for sterility, whereas type IV does not. Learn more about USP and ASTM water in this overview of water standards.
All Teknova water meets USP WFI and ASTM Type I standards. We also offer four specialty grades of water that have additional testing, depending on use—three for specific applications, such as cell and tissue culture, RNA work, and PCR applications, and one general reagent grade for various buffer and media applications. In addition, water products can be manufactured under GMP, eliminating the need for transitioning reagents upon product commercialization. You can learn more about Teknova’s rigorous two-stage manufacturing and quality control procedures for water.
Knowledge of different reagent grades and their applications is vital when conducting research and considering commercialization of a biotechnology product. As well as supplying a wide range of pre-qualified GMP reagents that meet the purity grades outlined above, we also provide services for GMP transition, which include capabilities in manufacturing, logistics and warehousing, analytical and QC procedures, and secure document control services.