By Angelo De Palma, Ph.D., Contributing EditorNow that pharmaceutical manufacturers have enthusiastically embraced Process Analytical Technologies (PAT), the real fun starts. With FDA’s encouragement, innovation is suddenly in fashion.Solids, particularly blends and processed powders, have always challenged analytical chemists. Traditional analysis of drying and solvent operations through loss-on-drying involves removing samples and measuring how much mass is driven off through combined heating and vacuum. One could hardly imagine a semiconductor manufacturer or even a candy maker employing such an antiquated technique. Loss-on-drying is so time-intensive, dryers must be powered down to avoid possibly overshooting the dryness mark. Too-dry batches may be rescued by adding water and repeating the blending/drying/analyzing cycle, but now a process that might take one shift takes two or three. Often such batches are simply thrown out.Because manufacturers have had difficulty controlling drying operations, specifications for drying have been defined so broadly as to be meaningless. “You can drive a bus through some of those specs,” notes Nancy Mathis, president of Mathis Instruments (Fredericton, New Brunswick).Drying has been a favorite target for PAT-happy manufacturers, who have snapped up the latest in PAT instruments, sensors, probes, samplers and automation-related equipment. Mathis Instruments, whose specialty is effusivity sensing, has placed evaluation instruments in and maintains evaluation projects at around a dozen pharmaceutical facilities.A nondestructive technique, effusivity supplies heat, then measures how rapidly heat flows out of a material. As an online method, effusivity requires that materials be diverted from a fluid bed dryer. Its speed (one measurement per minute) and resolution (about 0.25%) permits moisture determinations in near-real time.The goal is process understandingIncreasingly, says Mathis, manufacturers interpret the PAT guidance as covering only direct product measurements. “Although the guidance clearly does not discourage use of temperature, pressure drops, and even torque measurements, people believe these are secondary measurements. This point of view holds that FDA is looking instead for physical, chemical, or microbiological measurements of the product itself rather than the process stream, although one could make an argument for either side.”Fluid bed dryer vendors, whose instruments contain built-in exit gas analysis, will argue against retrofitting equipment with additional layers of analytics which provide only minimal benefit. “This is fine,” comments Mathis. “If it works, there’s no need to fix it. After all, the goal is not PAT itself or sensor technology, but process understanding, which exit gas analysis can certainly provide.”According to the PAT guidance in its new risk-based GMPs, FDA does not discourage companies from using any technology – including those that may not fall under a particular definition of PAT – as long as those techniques provide greater process understanding.