Requirements for 100% identification of raw materials coming into a pharmaceutical manufacturing plant can overwhelm the quality-control (QC) department. At the other end of the supply chain, halting the flow of counterfeit drugs can be quite challenging without the ability to conduct on-the-spot analyses. Handheld Raman instrumentation (TruScan, Thermo Fisher Scientific) is an example of how those problems may be addressed.
“With the need to sample and analyze every drum, container, and package of raw materials that comes into a pharmaceutical plant, QC departments are inundated with these requests, which while routine, can take hours to days to complete due to their sheer numbers,” notes Maggie Pax, senior director for pharma-chem, Thermo Fisher Scientific. In addition, opening all of those containers poses a contamination concern, and storage of sampled raw materials that are awaiting approval is yet another issue.
“Through our close relationships with customers in the pharma industry, it became apparent that another solution to raw-material analysis was needed, and preferably one that would enable direct analysis. We previously developed handheld instruments for the military and recognized that a similar approach would be effective in this application,” Pax says.
With miniaturization of the laser accomplished and robust, proprietary algorithms validated, the challenge in developing a handheld instrument specifically for the pharmaceutical industry lay in meeting all of GMP requirements for electronic devices, particularly electronic signatures, and creation of the extensive supporting documentation demanded by highly regulated pharmaceutical customers.
Using the handheld Raman instrumentation
Once the Thermo Scientific TruScan was available, the next hurdle was to develop an effective program designed to help pharmaceutical companies implement changes to their raw-materials identification and verification procedures, which included numerous document templates as well as training and validation-assistance programs. “While the adoption process is not complicated, it is cumbersome to meet all of the regulatory requirements involved in switching to a new raw-material verification technology. Providing support and helping to simplify the process has been critical to our successful implementation of this handheld analysis approach,” Pax observes.
The ease of use of the TruScan has made it attractive. No scientific training is required, and the analysis result is presented as a basic “pass/fail” reading. In addition, the instrument weighs only two pounds, has no moving parts, and was designed to withstand fairly harsh conditions. Furthermore, materials stored in clear packaging can be analyzed without opening the package. Therefore, not only do samples no longer need to be sent to QC, in many cases the potential for contamination can also be avoided.
The technology behind the TruScan instrument is Raman spectroscopy. The vibrational energy of atoms is unique to their specific bonding environment. When interrogated with light, the energy signatures emitted due to those vibrations create a spectrum that serves as a “ fingerprint” for each different molecule. The TruScan compares the obtained spectrum with that of the expected raw material and indicates whether the substance is the right compound. “The matching program is based on well-established algorithms that are very robust,” says Pax. She adds that the instrument comes with a basic spectral library, and users then build a customized version for their specific set of raw materials.
Raw-materials testing and anticounterfeiting uses
Pax believes that the instrument has real potential for use in raw-material analysis throughout the supply chain. “With outsourcing on the increase, there are growing numbers of places in the supply chain where the evaluation of raw materials/ingredients would be valuable,” she notes. There is also particular interest in emerging markets, where the pharmaceutical industry has been growing significantly and many companies are hoping to expand beyond their domestic markets. Before they can begin to export to more highly regulated regions, however, they have to make significant advances in their processes and procedures to meet international standards, according to Pax. Thermo Fisher Scientific was recently invited to work with the US Pharmacopeial Convention on the development of spectral libraries for GMP pharmaceutical use in the US and in emerging markets.
The handheld instrument also has been used successfully by regulators for authenticating drug products in the marketplace. Dangerous counterfeit drugs have been identified and seized based on TruScan analyses. In one notable example, the Nigerian National Agency for Food and Drug Administration and Control credits the instrument with a significant reduction in substandard and counterfeit antimalarial tablets in Nigeria. Counterfeit drugs are a serious problem in developing countries, where the World Health Organization estimates that, in some less developed regions, counterfeits are higher than 39% of the drug supply. Nigeria has been aggressive in addressing the problem, and has reduced levels from 42% to 16% of the drug supply, partly aided by the ability to carry out on-the-spot analyses. “The advantage of using the TruScan is that the results are immediate. The counterfeit product can be immediately confiscated, and the perpetrators have no time to hide the evidence, as would be the case if a sample had to be sent somewhere for analysis,” Pax remarks. Agencies in developed countries use the instrument as well because counterfeiting is a problem worldwide. Pharmaceutical manufacturers send people out in the field with TruScan instruments to look for counterfeit products. Doing so is a way to not only ensure the safety of the products, but also to protect their intellectual property and prevent adverse events, according to Pax.
She also notes that on-the-spot analyses would be useful at many different points in the pharmaceutical supply chain, whether during the manufacturing process or for raw-material identification and drug authentication. “We are collaborating with our pharma customers to understand where other problems exist that might be addressed with such rapid analysis systems. Just as cell phones have become ubiquitous, we imagine that someday handheld analytical instruments will become commonplace out in the field and in the process environment, helping to improve manufacturing quality, productivity, and efficiency,” Pax concludes. Thermo Fisher also offers a near-infrared handheld instrument that complements the TruScan Raman device.