Leaning on NIR in Pisa

Neither is there a need for sampling if the analysis is done in the dispensing area. In addition, there are cost savings on reagents and other chemicals. However, analysis must be carried out by non-specialized personnel in both the warehouse and dispensing areas. Further, the flow of raw materials through the manufacturing plant is interrupted if done in the dispensing area.

Another option is to place the analyzer in the QC laboratory. Although time per analysis would be reduced, GMP guidelines require sampling, which would interrupt the flow of raw materials through the plant.

NIR at Abiogen

Abiogen Pharma S.p.A. (Pisa, Italy) manufactures its own products and carries out contract manufacturing for the pharmaceutical sector. The main areas of Abiogen’s business are R&D and manufacturing of pharmaceutical products, and the company has laboratories dealing with QC (chemical and microbiological), pharmaceutical develop-ment (analytical development, QC of medicinal products and formulation) and research.

Figure 1: Metfonorm, Abiogen’s diabetology product (metformine hydrochloride active ingredient).

Prior to adopting 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, IR spectroscopy and gas chromatography. Conducting raw material identification with these methods proved to be extremely time-consuming. Additionally, the total amount of incoming raw materials doubled from 2001 to 2006, while the number of different types of raw materials arriving at Abiogen tripled in this period.

To continue sampling each different raw material individually, it would have been necessary to engage a second sampler to cope with the workload. Besides a cost outlay, it would also require a great deal of planning and organization, taking scientists away from the laboratory and increasing their workload.

In particular, metformine hydrochloride was entering the plant in ever-increasing quantities. At a standard weight of 25 kg per container, this material was originally analyzed using IR spectroscopy. This no longer proved viable when the number of incoming containers and the time required for material analysis continued to rise.

While examining alternative methods of analysis, increasing the container sizes was ruled out, since that can only be done for low-cost raw materials, and would have had a significant impact on transport and weighing systems. Although GMPs allow for fewer tests on raw materials that are supplied by qualified vendors, this was not a suitable alternative for Abiogen, because the qualification process takes a considerable amount of time. Also, GMPs require periodic vendor re-qualification, which could result in a future need to change suppliers.

Having considered these alternatives, Abiogen chose to implement NIR spectroscopy with an FT-NIR analyzer. Abiogen engineers decided to place the analyzer in the raw materials warehouse, in order to comply with GMP guidelines while minimizing the time per analysis and analyzer operating costs. Since the implementation, Abiogen has significantly increased productivity due to no longer having to sample each container of raw material, and has reduced its instrument and chemical costs.

Conclusion

NIR spectroscopy can be an extremely accurate and beneficial method for the analysis and QC of raw materials in pharmaceutical manufacturing plants. Using NIR can help laboratory and manufacturing workers improve productivity productivity by reducing analysis time, and can support regulatory compliance as well.

Figure 2: Thermo Scientific Antaris FT-NIR analyzer in Abiogen’s raw materials warehouse.

In recent years, NIR spectroscopy has been recommended as a valuable tool for raw material analysis by a range of pharmaceutical guidelines, including the Pharmaceutical Analytics Science Group’s guidelines for the development and validation of NIR spectroscopic methods, as well as the European Agency for the Evaluation of Medical Products’ note for guidance on the use of NIR spectroscopy by the pharmaceutical industry. The practical example of Abiogen’s experience shows that using NIR spectroscopy for raw material analysis can save a significant amount of time in the laboratory, improve productivity and reduce operating costs.

References

1. Chapter 5.30, GMP guidelines
2. Annex 8, EU.GMP
3. EMEA, Note for Guidance on the Use of NIR Spectroscopy by the
   Pharmaceutical Industry and the Data Requirements for New
   Submissions and Variations.

About the Authors

Nicola Cecconi is the Chemical QC Manager for Abiogen Pharma
S.p.A, and Emiliano Genorini is European NIR Product Manager,
Thermo Fisher Scientific.