Streamline material inspection in regulated industries with new Raman USP library
2023. 9. 4.
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Raman spectroscopy is a fast, easy, and specific method that simplifies material identification. This blog article explains how Metrohm’s Raman systems and Comprehensive USP Raman Library support regulated industries like pharmaceutical manufacturing. This support takes the form of streamlining inspection of deliveries, reducing inspection resources, facilitating delivery of raw materials to production, and ultimately getting the final product to the market faster.
Click below to learn more about each topic.
Identification with Raman
Raman spectroscopy is classified as an identification test by the United States Pharmacopeia – USP <1225>. Identification tests are intended to ensure the identity of an analyte [1].
For Raman, this is achieved by comparing a sample spectrum to either:
- the spectrum of a reference standard (identification)
or
- a spectral reference library acquired from a suitable number of similar materials which exhibit typical variation (manufacturer, batch, particle size, impurity profile, etc.) and comply with established specifications (verification) [2]
The basic difference between identification and verification can be demonstrated with the following questions:
For the pharma sector, inspection of incoming raw materials requires both types of tests, and Raman can be used for each of them. This article will focus on identification of substances using a large spectral library of reference standards, with verification references at the end.
Read our related blog article here to learn more about how Metrohm’s Raman solutions comply with other pharmaceutical standards.
Ph. Eur. 2.2.48 Raman Spectroscopy: How Raman instruments from Metrohm comply with the 2022 update
Confident identification with almost 1,000 USP-traceable standards—our library does the work for you!
That’s the benefit of the new Comprehensive USP Raman Library—prepared by Metrohm’s Raman experts, created for Metrohm’s compliant Raman instruments. The use of this spectral collection of >900 reference standards, built according to US drug compendial standards, ensures that safe, high-quality medicines make their way to consumers [3].
The Comprehensive USP Library is our largest collection of chemicals and substances that are traceable to a USP-compliant certificate of analysis (COA). An in-house library can be made specific to either 785 or 1064 nm excitation and is tailored to the exact spectral range and y-calibration of Raman instruments from Metrohm. This results in the highest-quality data that provide the ease of identification with the accuracy of verification. Keep this in mind during the following discussion of specificity.
The specificity of Raman
The accepted validation characteristics used to establish official analytical procedures for raw material identification (RMID) testing are [1]:
- Accuracy
- Precision
- Specificity
- Detection Limit
- Quantitation Limit
- Linearity
- Range
The most important characteristic for identification methods is specificity, and Raman is a highly specific analytical technique [4]. Specificity is the successful identification of an analyte in the presence of, but unaffected by, substances that are expected to be present, including impurities, degradants, matrix, etc.
An extreme example of this is mixture analysis, where all three components in a compound formulation of acetaminophen, urea, and sucrose can be identified from a single complex Raman spectrum in under 30 seconds (Figure 1). Identity tests, no matter how specific, do not test for impurities—their presence, identity, or quantity—nor are they a quantitative measure. That is a different, and essential, form of testing.
The United States Pharmacopeia defines testing categories with specific validation criteria that represent minimum expectations for a technology. The most exacting analytical methods, «primary» testing methods, require more validation data/characteristics. A summary of Category I, II, and IV Assays [1] follows in Table 1.
Table 1. USP testing categories and their specific validation criteria.
| Category | Definition | Required Characteristics |
|---|---|---|
| I | Analytical methods for quantitation of major components in finished pharmaceutical products | Accuracy Precision Specificity Linearity Range |
| II | Analytical methods, to include quantitative assays and limit tests, for determination of impurities in raw materials or degradation compounds in finished pharmaceutical products | Accuracy Precision Specificity Detection Limit Quantitation Limit Linearity Range |
| IV | Identification tests | Specificity |
For most regulated materials (i.e., products that are used in or on the body) a combination of two or more analytical procedures is recommended to achieve the necessary level of discrimination [5]. Raman spectroscopy is identified as a Category IV identification test – a test that supplements the primary methods that accomplish qualification of impurities and quantification, such as HPLC, ATR (attenuated total reflectance), or GC/MS. It is used as a preliminary test that is then verified or supported by a second, well-characterized analytical procedure. Raman, ultimately, is the very best possible preliminary test, and it is a powerful way to simplify RMID.
How does Raman simplify material ID?
Raman spectroscopy is ideal for moving food, pharmaceutical, and nutraceutical producers toward 100% testing. In classic RMID scenarios, each received container is opened, sampled, and quarantined until confirmation with primary methods (e.g., ATR, GC/MS, or HPLC). The resources required for 100% lab testing are considerable.
Raman achieves 100% testing as follows: √(N)+1 samples (11 out of 100) are lab tested, while the remainder are tested right at the receiving dock. This means that 89 containers can easily be sampled within 2 hours, and the reduced workload leads to faster turnarounds for the lab samples. It is estimated that 100% testing of 100 containers can be accomplished in less than 4 hours this way. Raman makes RMID fast and easy (Figure 2).
Find out more about Raman spectroscopy and RMID in our related blog post below.
Real World Raman: Simplifying Incoming Raw Material Inspection
Fast and easy material ID
Speed and convenience only count if quality remains high. Here is where these individual parts come together to show the bigger picture. Metrohm offers the ideal preliminary method for raw materials testing in regulated industries. Compliant Raman systems, whether laboratory (i-Raman) or handheld (MIRA P/NanoRam-1064) spectrometers, outfitted with the Comprehensive USP Library are a powerful combination.
- Raman is well known as a fast and easy but robust through-container or direct-contact testing method that requires no sample preparation or technical training, delivering accurate results in seconds.
- Raman is an ideal preliminary identification method that can recognize materials, even in the presence of adulterants or in mixtures with high specificity.
- Raman simplifies testing with a large, traceable USP library that maintains all the standards of US drug compendial standards and ensures that safe, high-quality medicines, supplements, and body- and beauty care products make their way to consumers.
Summary
In regulated industries, identification of incoming materials with Raman can begin directly at the loading dock, very quickly and with great success, by nontechnical professionals. This article should provide a better understanding of how instruments, standards, and libraries help to streamline this process while safeguarding quality.
References
[1] General Chapters: <1225> VALIDATION OF COMPENDIAL METHODS. http://www.uspbpep.com/usp29/v29240/usp29nf24s0_c1225.html (accessed 2023-08-01).
[2] Lynch, I. R.; Schuh, W.; Kessler, W. Rationale for the Update of the European Pharmacopoeia General Chapter 2.2.48. Raman Spectroscopy. Pharmeur Bio Sci Notes 2015, 2015, 166–180.
[3] Compendium, compendia, compendial: Clearing up the mystery of these terms | Quality Matters | U.S. Pharmacopeia Blog. https://qualitymatters.usp.org/compendium-compendia-compendial-clearing-mystery-these-terms (accessed 2023-08-02).
[4] Meek, C.; Hoe, J.; Evans, J.; et al. Raman Spectroscopy: A Sensitive and Specific Technique for Determining the Accuracy of Compounded Pharmaceutical Formulations. J Pediatr Pharmacol Ther 2016, 21 (5), 413–418. DOI:10.5863/1551-6776-21.5.413
[5] 〈858〉 Raman Spectroscopy; General Chapter; United States Pharmacopeia, 2023. DOI:10.31003/USPNF_M8188_02_01
Your knowledge take-aways
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Handheld Raman for RMID in pharma and other regulated industries
These tutorials cover the basic applications of handheld Raman, including sampling considerations and types of evaluation, the development of methods for RMID with handheld Raman, from specific recommendations for collecting best quality spectra to Training and Validation Set building, more about method implementation in non-traditional sampling scenarios, and how RMID with MIRA P can streamline your process and benefit your bottom line.
