Raw material identification (RMID) is a critical stage in the pharmaceutical manufacturing process. The globalization of the pharmaceutical industry has led to the implementation of regulations that require 100% inspection of incoming raw materials in some countries, meaning that efficient RMID is more important than ever before for ensuring quality control and compliance. The RMID process can be time consuming, inefficient and costly and in an industry trying to achieve lean manufacturing processes. This creates a need for a quick, reliable, and robust solution. The capabilities of handheld Raman enable pharmaceutical companies to increase productivity, comply with Good Manufacturing Practices (GMP) and achieve cost savings whilst offering enhanced material analysis.

This article will outline the capabilities of handheld Raman for RMID and showcase how one company, who were looking to improve the efficiency of their manufacturing processes, successfully implemented handheld Raman into their material identification process and saw significant cost savings in the manufacturing of their patient hygiene products.

THE RMID CHALLENGE

Manufacturers face a number of challenges associated with RMID in order to ensure stringent industry regulations and quality goals are met. Incorrect formulation, contamination, mislabeled containers and counterfeiting of materials can result in products being “out of specification”. Ultimately, if these materials are not promptly identified and rejected, this can lead to additional costs due to waste, re-processed work, delays or recalls.

The increasing pressure to analyze a higher volume of materials compounds time delays that can be encountered in the traditional RMID workflow. Internal laboratory analysis can often take between three and five days. Waiting for results from external laboratories can take anywhere between three and five weeks, causing unnecessary delays in the production process. Materials must be held in a quarantine area before receiving a confirmation of results. Additional floor space is occupied by materials awaiting clearance. By reducing the time and space required for RMID, pharmaceutical manufacturers can move closer to achieving leaner manufacturing processes.

CAPABILITIES OF HANDHELD RAMAN

Raman spectroscopy is a recognized technique in the USP and the European Pharmacopoeia (EP) and for RMID purposes. Handheld Raman devices are as analytically effective as conventional lab based methods. With increasingly stringent regulations and the push towards lean manufacturing, handheld Raman enhances the RMID workflow in a number of ways.

By enabling analysis performed at the point of need, handheld Raman devices deliver accurate identification and results in seconds. This eliminates time delays, optimizes material movement potentially removes the need for quarantine. Recent advancements in Raman technology support the detection of substances through packing and bags, reducing the risk of compromising the integrity of the contained materials. Unlike most other sample analysis techniques, handheld Raman does not require sample preparation, saving valuable time.

All of these factors demonstrate the capabilities of handheld Raman in the pharmaceutical manufacturing process. Implementation of this technology is uncomplicated, resulting in workflow improvements that saves time and money.

SAVING TIME AND COSTS WITH HANDHELD RAMAN

Implementing handheld Raman into the manufacturing process enables manufacturers to revolutionize their RMID workflow and achieve accurate rapid results for confident material identification.

Ease of use is a key factor for handheld Raman, the ergonomic and rugged design has been engineered to be quick and easily implemented into RMID workflows, with a large easily readable angled display and single button operation. Users of handheld Raman can perform ‘point and shoot’ materials analysis through some types of containers while monitoring the measurement progress on the screen.

Handheld Raman enables technicians to screen samples on the spot, delivering a high speed analysis on a broad range of materials. This helps to dramatically reduce time delays and minimizes the cost of outsourcing RMID.

A wider range of materials can be analyzed using the latest handheld Raman technology. Users of handheld Raman devices with 785nm or 532nm visible range extraction lasers may experience material identify match issues when analyzing colored substances, materials through colored containers or samples with high fluorescence interference. However, the introduction of handheld Raman analyzers with 1064nm excitation lasers enable users to measure colored solids and liquids, a capability that has proven challenging to conventional handheld Raman instruments. The power of 1064nm lasers also means that substances can be measured through containers, overcoming issues of fluorescence interference.

The technique complies with the USP’s and the EP’s so that users can have complete confidence that they are meeting the highest standards for patient hygiene products.

REVOLUTIONIZED RMID FOR SAGE PRODUCTS

Sage Products a manufacturer and distributor of health and personal care products for the hospital and retail markets was looking to improve the efficiency of its manufacturing process. Their primary objectives were to reduce the time and costs associated with RMID analysis which was being carried out by internal and external laboratories. In addition, as all of Sage’s products are manufactured under current GMPas required by the FDA the chosen solution would need to enable them to comply with these requirements.

 Sage created an SOP for use by QA technicians to deliver the levels of accuracy and reliability required and streamline their RMID workflow. The qualification process, which involved tests to establish the

suitability of the device for the specific needs of the QA technicians, took around three months to complete. Due to the ease of use, the training process took just five days and within a month the process was fully implemented into the RMID workflow.

The effectiveness of the Raman measurement was demonstrated graphically through the use of a specificity matrix diagram of the various materials potentially received by Sage (Figure 1), which demonstrates the selectivity of their required qualitative chemical ID’s.

Sage set up different methods on the instrument for each material their technicians would be analyzing. When completing this process, they ensured that materials could be correctly identified with any method and this meant that technicians could use any method and still produce the correct results, delivering the levels of accuracy and reliability required within the application. This is clearly demonstrated in Figure 2, which shows Butylparaben can be correctly identified by two different methods. Figure 3 shows that 2 closely related materials Butylparaben, Propylparaban and Methylparaben can be distinguished by Raman.

Handheld Raman enabled Sage to meet their own internal requirements for RMID faster and more cost effectively than ever before. For example Sage has saved close to $500,000 per year excluding overhead with the existing methods of analysis in place. Sage also saw significant reductions in analysis time meaning that valuable QC resources could be freed up. Being able to add materials to the library was a key benefit for Sage and this is now being used to support new product development and product engineering projects.

CONCLUSION

With the stringent regulations within the pharmaceutical industry for RMID, handheld Raman optimizes the RMID workflow. New generation analyzers utilizing 1064nm excitation lasers overcome the limitations of existing devices and enable manufacturers to analyze a wider range of materials than ever before with confidence. The benefits of handheld Raman are demonstrated by the results seen by Sage who successfully achieved leaner manufacturing processes and lower costs per analysis without comprising on quality.