In surveying the current publications and literature concerning PAT, it is apparent that the lions share of attention has been given to laboratory techniques, analytical procedures, sampling methods. The role of Process Automation in PAT is not often discussed, and in most cases, PAT applications are described mostly as an IT "automation" function

This paper shows some recently proposed model-based PAT tools for the process of lyophilization of pharmaceuticals. The salient feature of these tools is the use of mathematical models that allow improving both the design of the apparatus, by using a two-scales model that couples a detailed description of the fluid-dynamics of the vapour in the drying chamber with a model of the drying of the product, and the monitoring & control of the process, by coupling some measurements (pressure or temperature) with a model of the process. Results obtained in a pilot-scale apparatus evidences the effectiveness of the proposed tools

As the bio analytical analysis of proteins becomes evermore important, attention must be paid to the three-dimensional structure of these analytes. Protein function, viability and efficacy in the case of protein-based therapeutics are intricately connected to protein structure. Here we highlight mass spectrometry based approaches for studying protein conformation. By labelling proteins with hydrogen/deuterium exchange or covalent labelling methodology, many challenges associated with biophysical characterisation of protein structure and dynamics can be addressed. There are multiple advantages to using MS, not the least of which is the small amounts of material that are required

In this paper we use a crude sample of bradykinin to demonstrate that synthetic peptides can be purified using isocratic elution. As the peptide is readily soluble, the purification was carried out using mass overload and the purity and recovery of the peptide determined using high performance analytical HPLC. A second purification was carried out using volume overload with a step gradient to assess the viability of using isocratic elution for the purification of dilute solutions of crude peptides without the need for a pre-concentration step. The purity and recovery of the two methods is compared

Drug Substance (DS) process development and Drug Product (DP) formulation development are two major areas of the drug development process. Impurities/degradants can be generated in either of the processes, from DS degradation or DS-excipient interaction. These impurities may be non-genotoxic or genotoxic in nature. Regardless, they are regulated by Food and Drug Administration (FDA)/ International Conference on Harmonization (ICH) guidelines. Routine impurity analysis in pharmaceuticals requires identification at levels of 0.05 percent to 0.2 percent depending on the daily dose

Pharmaceutical, biotech, and food/beverage industries predominantly use traditional cultured-based assays to detect microbial contamination in their products. There are significant benefits to the availability of faster methods that will provide equivalent or better results. Here, we present an approach to couple membrane filtration-based concentration and capture of organisms from complex liquid samples with purification and detection of the organisms nucleic acid using Real-Time Transcription-Mediated Amplification (Real-Time TMA; Gen-Probe Incorporated)

Microwave assisted micellar extraction (MAME) has several advantages with respect to conventional methods, with the use of surfactants as extractants, reducing extraction times, cost and toxicity. However, in MAME extraction some interfering compounds can be extracted, for this reason, the coupling with clean-up and preconcentration steps represent an improvement of this methodology. Solid phase micro extraction (SPME) and solid phase extraction (SPE) can be applied for the clean-up and preconcentration of MAME extract, increasing the sensitivity and selectivity of the method, removing the interference and decreasing the detection limits (from 300 ngg-1 to 10-30 ngg-1) applying HPLC as determination method

The availability of HPLC columns with very small particles (typically <2 m) in combination with HPLC pumps with a high pumping capability (>400 bar) opens new possibilities to increase the speed of analysis as well as to improve the chromatographic separation. In this article practical aspects of high speed and high resolution HPLC are discussed and examples are presented that were derived from daily laboratory practice. It is shown that the speed of analysis can be increased by a factor of 5 -10. But also extremely high resolution can be obtained as is shown by a separation on a 2.25 m HPLC column with an apparent plate number as high as 1,000,000