Estimating the Return on Investment for Raw Materials Identification Testing of Pharmaceuticals using Handheld Raman Analysers

Transcription

1 Estimating the Return on Investment for Raw Materials Identification Testing of Pharmaceuticals using Handheld Raman Analysers Moving raw material ID testing out of the laboratory and into the warehouse can improve product quality and save time and money By Dr Heather Murray, Analytik Introduction Raw material ID is commonly performed in many industries to ensure end-product quality and safety. Within the pharmaceutical industry there is a great emphasis on designing quality into a product by monitoring and controlling manufacturing processes rather than relying on end-product testing. As part of this process the identity and quality of raw materials should be verified. Potentially this places a great strain on pharmaceutical manufacturers as their QA departments struggle to cope with the increased testing burden. However, by moving analysis out of the laboratory to the point of need - the warehouse - raw material testing costs can be greatly reduced, 100% inspection becomes possible and ultimately product quality assured. Current Practices in Raw Material Testing Traditional raw material testing requires extensive handling of material containers and lengthy delays as they are transported from loading bays to warehouses, receiving areas, quarantine storage, isolation rooms, laboratories, and finally into the manufacturing areas. Typically, materials are received at a loading bay where they are stored in a quarantine area until they are ready to be tested and released. In order to test the contents of the container they must first be moved from quarantine to a safe sampling area or containment room to avoid contamination of the material and to reduce risk associated with operator exposure. Once in the sampling area the container may be opened. In the case of materials arriving in drums, the inner bag liner is opened; some material is extracted, placed in a suitable container and logged into the information management system. Only then is it transported to the testing laboratory. Once received in the laboratory, the sub-samples are queued awaiting analysis. Meanwhile, the original containers are placed in a holding area, while their respective sub-samples await analysis. Once positive identification results are received, the containers are finally released to manufacturing. While this process is operational, it is not efficient. Handheld analysers for materials identification, used in the warehouse as the containers are received can greatly simplify sample handling and streamline the manufacturing process. Page 1 of 5

2 The Benefits of 100% Testing Depending on the relevant regulatory requirements for each active and excipient material; a company will follow their own protocol for analysis from incoming containers varying from statistical sampling of (N+1) to 100% of containers, or sub-sampling from multiple areas within a container. Although it is extremely difficult to estimate the total cost of a failed production batch caused by a limitation in raw materials testing if a re-call of shipped product is required, the final costs may easily run into millions of Euros. Pharmaceutical manufacturers are facing continual customer pressure to reduce the price of their products. Shareholders are demanding more efficient manufacturing, quality systems and initiatives for improving realtime control now abound. However, there have been multiple instances of non-compliant raw materials entering the pharmaceutical supply chain. Public safety is paramount and product quality cannot be compromised in efficiency savings. Faced with this daily demand for improved efficiency a new approach for raw material ID testing, the adoption of portable analysers used in the warehouse is required. Simply put - 100% testing is desirable, but not achievable via current practices. Raman Spectroscopy for Raw Materials Identification Raman Spectroscopy is a very well established technique in the pharmaceutical industry, it is used mainly for research and development applications such as rapid analysis of microplate arrays in discovery, tracking polymorphs through development and scale up or spatial distribution mapping; or in product manufacturing for monitoring of granulation, blending or drying processes. Raman instruments for these applications range from laboratory-based automated microscope systems to dedicated process analysers equipped with fiber probes. However, moving away from these more specialised applications and considering bulk materials identification only how suited is Raman spectroscopy to this task? Requirements and suitability are summarised in table A below. Requirements and suitability of Raman Spectroscopy for Raw Material Identification Raman has excellent chemical specificity - similar to mid-ir Operates in the visible region - does not require sample purging or specialised accessories simply point-andshoot, results available in seconds Non-destructive analysis technique - original packaging and bottles can often be used, no contamination or waste, no sampling induced errors Raman is sensitive to the sample chemistry not the physical properties a single spectrum is often all that is required for a representative library entry* (explained below) Water has a weak Raman spectrum - wet samples can be analysed without pre-drying, the presence of water will not obscure the sample spectrum Raman spectra are generally well defined (see Figure B); data is understandable and does not automatically require complicated pre-processing Raman is suitable for the analysis of the vast majority of pharmaceutical raw materials whether excipient or active, solid or liquid Table A Fig. B: Typical Raman Spectrum Page 2 of 5

3 *When building an NIR library, often a number of samples/spectra are required for each entry to fully represent allowable physical differences between lots (such as variation in particle size distribution). Advanced spectral pre-processing and chemometric techniques are generally required for NIR library building requiring considerable time and expertise. However, Raman spectroscopy is much less sensitive to the physical characteristics of a sample than NIR and as a consequence a single Raman sample is very likely to be all that is required for a Raman library in a similar way to FT-IR. This is evidenced by the widespread availability of commercial Raman and FT-IR libraries. Raman is however very sensitive to changes in chemical form; individual polymorphs, isomers and amorphous compounds and hydrates can all be differentiated. It is clear from table A above that the Raman technique is well matched to the requirements for building a materials identification library. The next step is to determine how suited the instrumentation is to the hostile environment of the warehouse. Streamlining Testing with the PHARMA ID TM Handheld Raman devices are now available due to recent advances in both laser and filter technology. An example is shown in figures C and D, the PHARMA ID TM from DeltaNu. Weighing just over 300g, with dimensions of 13.5 x 6.5 x 4 cm, with a ruggedised case, and no fibers the analyser is operated via a simple push button, with ID results displayed on an LED screen. Point and shoot analysis and identification are complete in a matter of seconds, all data is saved and downloadable via USB for backup at end of shift. Detailed IQ/OQ procedures are available, and the PHARMA ID TM complies with USP <1120> and EP Ch guidelines for Raman. Fig. C Replacing current laboratory based raw materials testing methods such as FTIR, Raman or NIR with handheld Raman analysis greatly simplifies sample handling many materials can be analysed directly through their packaging, samples are analysed as they are received and can be sent for immediate processing. A case study showing the return on investment (ROI) for the implementation of PHARMA ID TM is shown below. Fig. D: PHARMA ID TM Page 3 of 5

4 Understanding the Return on Investment There are many factors to consider when evaluating the benefits of changing from current lab-based materials testing protocols to a handheld Raman-based testing regime and calculating the potential ROI. In this first example we will estimate the cost of a single analysis using the PHARMA ID TM against an existing lab based method, differentiating only the sample transport and lab-based sample preparation and clean up time. Cost comparison of conventional lab based spectroscopic analysis and warehouse based analysis Sample transport and subsampling* 15 min 15 min 2 min Sample preparation/presentation 5 min 1 min 2 min Lab analysis time 2 min 1 min 0.5 min Clean up time 3 min 1 min 0.5 min Total 25 min 18 min 5 min Cost per sample Monthly labour cost for 500 samples *Typical time for sample transport to central lab from receipt in warehouse From this simple cost comparison laboratory based spectroscopic techniques show a cost per analysis of approximately to 14.57, whereas a warehouse based Raman analyser has a much reduced figure, at By expanding the calculation to consider low, medium and high sample analysis costs below, the potential cost savings of warehouse based analysers based on labour costs only is remarkable. Labour cost comparison Usage Samples per year Labour costs per year for analysis Low Medium High In the example below a comparison is made between the ongoing cost of continuing analysis with an existing FT-IR or existing lab based NIR and purchasing and commissioning a PHARMA ID TM to be used in the warehouse. This example also includes the development and comparability protocol costs associated with the creation of a new PHARMA ID TM Raman library containing 30 materials and the subsequent annual costs of analysing 6000 samples in the first year. Page 4 of 5

5 Initial purchase, development and analysis costs Library build and validation / days Already established Already established 15 Comparability protocol with FTIR / days Not required Already established 10 Annual library maintenance / days Total / days Combined labour cost Approx capital cost dependant on application Yearly analysis costs Total It is evident that the combined initial purchase cost and subsequent development cost of implementing the PHARMA ID TM are quickly outweighed by the labour costs of laboratory analysis be it FT-IR or NIR. Calculating the Return on Investment and Payback In this case the ROI is based on cost savings rather than income generated and it is possible to calculate a simple ROI for the PHARMA ID TM for the first year versus the same analysis by FTIR at medium usage levels as 130% with a payback of less than 6 months. Assumptions used in the above calculations A single averaged operator rate (fully loaded to include overheads) was calculated at p.a. Investment in PHARMA ID TM includes purchase and development costs of producing and validating a 30 component library then carrying out the comparability protocol Cost savings = difference in analysis and running costs between FT-IR and PHARMA ID TM for the first year at medium usage levels (600 samples per month) ROI = (Cost savings investment)/ investment * 100 Conclusion From the standpoint of sample analysis only there are remarkable efficiencies to be made by utilising the PHARMA ID TM for materials identification in the warehouse as the ROI of 130% and payback of less than 6 months shows. However, there are also operational benefits from employing PHARMA ID TM and removing the bottleneck at the QC laboratory - reducing inventory and increasing material turnover. Ultimately, the greatest benefit comes from the potential improvements in product quality possible from 100% inspection. To learn more about PHARMA ID TM please visit (UK and Ireland) or alternatively visit Page 5 of 5