Using NIR Spectroscopy for Raw Materials Characterization
Italian drug company Abiogen Pharma has significantly boosted productivity, saved time on analysis and reduced instrument and chemical costs by implementing NIR spectroscopy to characterize incoming raw materials.
By Nicola Cecconi, Chemical QC Manager, Abiogen, and Emiliano Genorini, European NIR Product Manager, Thermo Fisher Scientific
ó EMEA, Note for Guidance
The identification of a substance with NIR spectroscopy is based on a comparison between the spectral data of the substance being analyzed and the spectral data of multiple samples of batches in a reference library. To compare the data and come to conclusions, chemometrics should be used.
For the characterization of raw materials, the technique has been found to have some unique benefits. NIR spectroscopy enables analysis of the starting material in the original packaging, without the need to open the main container, thus reducing the risk of cross-contamination and abolishing the need to conduct the analysis within a designated sampling area. This leads to a significant decrease in the time involved for each analysis. For example, the time required for identification of one container of raw material using IR spectroscopy is approximately 15 minutes, using color reaction and viscosity is approximately 45 minutes, while identification of the same amount using NIR spectroscopy takes approximately two minutes.
NIR spectroscopy can be used to collect high-quality reflectance spectra of both the active ingredient and excipients, and is sensitive to both the chemical and physical properties of the powder blend. It can also be beneficial within pharmaceutical manufacturing as it is non-contact and non-destructive, highly reproducible, rapid and does not require any sample preparation. Online blend monitoring has placed certain demands on NIR instrumentation including wireless communication, battery operation, rapid data collection, appropriate hazard and cleaning rating and software/hardware validation and qualification. It is also important that the NIR instrumentation can be used from pilot to production scale blenders in order to follow the development of a pharmaceutical product.
Within a pharmaceutical manufacturing plant, NIR spectroscopy can be carried out at multiple stages in the manufacturing process: in the raw materials warehouse, in the dispensing area or in the QC laboratory. Considerations need to be given to the individual company and its requirements. If the analysis is carried out in the warehouse, no sampling is required by GMP guidelines and therefore the time for analysis is reduced.
There are also practical advantages, as raw materials can be analyzed as they arrive in the warehouse, and do not have to be transported for analysis, ensuring improved workflow. However, placing the analyzer in the raw materials warehouse means that the analysis may not be carried out by specialized personnel. This can be remedied by using correct training for staff, and by appointing an instrument manager to oversee the raw material identification.
Figure 1: NIR spectroscopy can be conducted at multiple stages in the manufacturing process, including in the raw materials warehouse (shown: Abiogen).
If the analysis takes place in the dispensing area, there is again no need for sampling, which results in a reduction in analysis time. There are also cost savings on reagents and other chemicals, however the analysis is again carried out by non-specialized personnel and the flow of raw materials through the manufacturing plant is interrupted. A further option is to place the analyzer in the QC laboratory, where specialized personnel can carry out NIR spectroscopy analysis. Although time per analysis would be reduced, in order to comply with GMP guidelines, it would be necessary to sample, also again interrupt the flow of raw materials. When choosing to use NIR spectroscopy, each individual company must decide where best to place the analyzer.
Abiogen Pharma S.p.A is a pharmaceutical manufacturer based in Pisa, Italy. Abiogen manufactures its own products and carries out contract manufacturing for the pharmaceutical sector, including products such as granules, filmed tablets, pills, capsules, ointment, lyophilized products, syrups, drops, suppositories and aseptic ampoules. The main areas of Abiogenís business are R&D and manufacturing of pharmaceutical products, and the company has laboratories dealing with QC (chemical and microbiological), pharmaceutical development (analytical development, QC of medicinal products and formulation) and research laboratories. Abiogen develops pharmaceutical products mainly for the musculoskeletal, respiratory, diabetology and dermatology areas.
Prior to using NIR spectroscopy for raw material analysis, Abiogen used individual methods for each raw material container in accordance with the European Pharmacopoeia guidelines, including UV-Vis spectroscopy, infrared spectroscopy and gas chromatography (GC). Conducting raw material identification with these methods proved to be extremely time consuming. Additionally, the amount of incoming raw materials doubled from 2001 to 2006 (see Table 2), while the number of differing types of raw materials arriving at Abiogen tripled in this period (see Table 3).
Table 2: Amount of incoming raw materials to Abiogen, 2001-2006
Table 3: Number of different incoming raw materials to Abiogen, 2001-2006
To continue sampling each different raw material individually, it would have been necessary to engage a second sampler to cope with the workload. This would cause an increase in cost, in addition to the increase in time consumed by the growing number of samples to analyze. Carrying out separate analyses for each raw material also takes a huge amount of planning and organization, taking scientists away from the laboratory and increasing their workload.