Pharmaceutical production is an incredibly complex and costly task that requires the management of volatile and potentially potent materials. Widely distributed therapeutics must be produced quickly, efficiently and at scale. Manufacturers must also comply with the US Food and Drug Administration regulations, which are in place to ensure products are safe for consumers.
Tackling the above and achieving targeted time-to-market is no small task. To do so, quality control laboratories and process optimizers must identify ways to accelerate time to production and market that ensure quality and compliance with safety regulations. Key regulatory mandates that manufacturers must account for include in-process materials testing to determine identity, strength, quality and purity. Developing a well-controlled, validated and vigorous pharmaceutical manufacturing process is critical to any reputable biopharmaceutical or “traditional” pharmaceutical drug manufacturer. This must be balanced with reducing costs, which is a challenge for both brand name and generic drug producers.
The procedures that manufacturers must follow can be incredibly lengthy and require several steps, which include material identification, in-process control and measurement and on-line/in-line/at-line product inspection. Employing the right applications and technologies throughout each step of the process may be the difference between having a trusted product portfolio the brand name can stand behind, or utter disaster with product quality and patient quality of life.
Material identification with handheld devices
Effectively managing the pharmaceutical production process begins when pharmaceutical raw materials enter the facility doors. Raw material analysis helps ensure manufacturers correctly and efficiently identify and quantify raw materials prior to entering the production line. For decades, this process required sending raw material samples to an on-site or off-site lab for materials identification. While critically necessary, this process is a significant bottleneck. It takes time and capacity resources away from both the laboratory and production suite, with potential to halt or deprioritize future innovations.
Fortunately, just as biopharmaceutical and traditional pharmaceutical discovery have advanced, so have the tools and practices needed for production. The introduction of handheld analyzers speeds up the materials identification workflow and moves raw material identification from the laboratory to the warehouse, resulting in fewer costly lab sample tests, faster release of raw materials to the production line, improved inventory management and a welcomed boost in laboratory capacity to tackle analytically intensive testing and investigations. In most instances, it also eliminates the risk of cross-contamination by enabling the identification and quantification of materials through the primary packaging.
Handheld analyzers must generate trustworthy and actionable information to empower quick decision making in critical situations. Furthermore, handheld analyzers must generate easy to interpret results when placed in the hands of non-technical operators. When these analyzers are equipped with in-depth chemometric software, the process of identification is significantly enhanced without the need for specialized training by the end-operator. This software can support the quantification of up to 10 chemicals, discriminate between materials with similar compounds, replace slower lab testing and run qualitative and quantitative methods at-line. Handheld analyzers provide accurate and reliable material identification, process quality checks, quantitative and qualitative analysis and offer both intermediate and final product inspection capabilities. They enable users to bring rugged, analytical instrumentation to the pharmaceutical/biopharmaceutical manufacturing floor to quickly release in-process materials.
Using spectrometers to understand raw materials
Once the materials have been identified correctly, manufacturers may proceed to the production process according to their supplier quality risk assessment. Production capabilities vary among sites and companies; however, there is a growing need for rapid and real-time process information to ensure production batch quality. These process control and measurement stages involve monitoring and adapting the manufacturing processes to ensure that the product conforms to specification repeatedly. Mass spectrometers can perform accurate and reliable material identification, real-time process and quality checks, quantitative and qualitative analysis and intermediate and final product inspection. This technology is ideal for streamlining the manufacturing process and may be used on the pharmaceutical and biopharmaceutical manufacturing floor.
On-line mass spectrometers deliver faster, more complete, lab-quality online gas composition analysis. They are ideal for the continuous analysis of respiratory gases, including oxygen uptake rate, CO2 evolution rate and respiratory quotient. The mass spectrometers conduct analysis quickly and offer improved precision, accuracy, long intervals between calibration and resistance to contamination.
Mass spectrometers can also generate reliable quantitative solvent drying process data. Solvent drying is the complete or partial removal of a solvent or solvents from an active pharmaceutical ingredient or intermediate. It is an incredibly complex and sensitive process where even a minor misstep can mean significant product losses. Mass spectrometers can monitor and improve drying stages, improve consistency and quality of the final product, reduce drying times, increase throughput and maximize profitability and avoid over-drying, ensuring that this step is not only completed correctly but efficiently.
Varying technologies identify raw materials
Pharmaceutical manufacturers must develop a trusted quality equilibrium between understanding and following regulatory compliance, and safely identifying materials efficiently and cost-effectively. New technologies, such as handheld Raman analyzers and spectrometers, are enabling pharmaceutical companies to become more compliant, safer and more productive during numerous stages of pharmaceutical development – from raw material delivery to solvent drying and final production.
About the author:
O. Dean Stuart is a product manager at Thermo Fisher Scientific.