The utilization of near-infrared (NIR) spectroscopy for the quality control (QC) of pharmaceutical tablets has become increasingly widespread over the past decade. This is due in part to stricter regulatory control of QC in the pharmaceutical manufacturing environment, but also the increasing realization that it may no longer be practical to use a wide range of testing methods within one manufacturing plant.
Chapter 5.30 of the Good Manufacturing Practice (GMP) guidelines specifies that a pharmaceutical company must provide suitable procedures or measures to guarantee the identification of the material contained in each recipient. Traditionally, companies used a number of different analysis methods for the testing of individual raw materials as suggested in early versions of Pharmacopeia methods. However, a number of new regulatory guidelines now advocate that near-infrared (NIR) spectroscopy is the best universal method for raw material testing.
By adopting NIR spectroscopy for QC purposes, pharmaceutical companies can now make significant time and cost savings in raw materials characterization. This article will explore how and provide a review of Abiogen Pharma S.p.A and its use of NIR spectroscopy for raw material analysis.
Characterization of Raw Materials
Raw material analysis is an essential process in any pharmaceutical manufacturing laboratory. According to Annex 8, EU GMP:
In compliance with GMP guidelines the identification of the starting raw materials must be executed on each API and excipient. As most pharmaceutical manufacturing laboratories often receive a huge amount of raw materials, this can be a difficult job in terms of time and cost. Scientists are often required to spend time away from the laboratory in order to carry out raw material analysis, resulting in decreased productivity, and the administrative burdens of carrying out several tests on each batch of raw material can significantly increase laboratory workloads.
Pharmaceutical companies have the option to comply with traditional Pharmacopoeia methods for raw material identification. Prior to the European Pharmacopoeia 5th edition (2002), there was no universal method recommended by pharmaceutical guidelines relating to the analysis of raw materials. Different methods were specified for each raw material to be identified, meaning that a number of different analyses were conducted using different identification methods. Analysis times differ significantly between methods and can cause the characterization of the raw materials to be extremely time-consuming (see Table 1).
Table 1: Individual methods of raw material analysis, with time typically taken for each analysis.
Individual methods of raw material analysis with time typically taken for each analysis. Using individual methods for each raw material analysis can also incur significant costs, including the cost of different instruments, reagents and other chemicals resulting in decreased productivity of laboratory instruments and personnel. This is further amplified by the overall increase in the amount of raw materials containers received by many pharmaceutical manufacturing laboratories. Pharmaceutical companies often have a huge range of raw materials to identify, and therefore it is difficult to standardize the method used for analysis, as the type of raw materials entering the laboratory is often subject to change.
Traditionally, raw material identification was performed on a statistical basis, where only a certain percentage of each batch of raw materials would be analyzed. Although this method was advised by certain guidelines, many pharmaceutical companies have begun to identify all of the containers of the actives but not of the excipients, in order to carry out a more in-depth analysis. However, there is now a requirement to identify every single container of each batch of raw materials, and to analyze containers of both the actives and the excipients. The only exceptions to this requirement are sucrose, talc and sodium chloride, all of which are produced in mono production; therefore it would not be possible for a manufacturer to supply an incorrect raw material.
Additionally, when using traditional Pharmacopoeia methods for raw material analysis, often more than one test is mandated, for example when analyzing lactose it may be necessary to use three different methods: IR spectroscopy testing, thin layer chromatography tests and analysis using melting point.
It is evident that where there are a large number of raw materials that need to be analyzed, the use of multiple analysis methods isnt practical. There are three possible solutions to this challenge, for example mandating that suppliers provide larger size containers, validating suppliers, or finding an alternative method of analysis.
A number of recent sets of guidelines now advise the use of NIR spectroscopy as a universal method suitable for the identification of raw materials:
- European Pharmacopoeia 5 (2005), page 59;
- EMEA CPMP/QWP/3309/01 and EMEA/CVMP/961/ 01 Note for Guidance on the use of Near infrared spectroscopy by the pharmaceutical industry and the data requirements for new submissions and variations, EMEA, London, 2003;
- USP 29 (2006), page 2979.