Process analytical technologies

The recent FDA initiative on Process Analytical Technology (PAT) attempts to define a design space for unit operations such as compaction 

Average first-layer tablet weight (n — 20) Individual first-layer tablet weight (n = 20) Average bilayer-tablet weight (n — 20) Individual bilayer-tablet weight (n — 20) Eirst layer-tablet cylindrical height Action limit 1.1% Tolerance limit 1.7% Action limit 2.0% Tolerance limit 3.0% Action limit 1.1% Tolerance limit 1.7% Action limit 2.0% Tolerance limit 3.0% 2.45-3.00 mm 

More realistically, scale-up effects would have to be built into the model, or the model would have to be validated at a constant scale in production. 

The Tandem system (Bruker Optics) is available for use during tablet production to measure tablet weight, thickness, hardness, and diameter, as well as online NIR content uniformity. The system can provide online analysis for drug substance uniformity, moisture content, and excipients. The advantage of systems like this is that the necessary data are available immediately to make adjustments to the production parameters in order to improve product rmiformity. Therefore, adjustments can be made to tablet weight in real time in order to achieve 100% of the label claim. 

Hersey JA, Rees JE. Proceedings from the 2nd Particle Size Analysis Conference, Society for Analytical Chemistry, Bradford, UK, 1970 33-41. 

Evaluation and Research (CDER), Office of Regulatory Affairs (ORA) and the Center for Veterinary Medicine (CVM), which was titled the PAT initiative. 

FDA assessors and inspectors will all receive technical training that has been designed in collaboration with industry and academia. 

The FDA s own definition of PAT is a useful starting point for the discussion in later sections of this chapter  

Note that product in this context covers both API, which is the subject of this chapter, and the formulated drug product itself. It is likely that the major applications of the PAT approach will be in secondary manufacturing, and indeed successful examples have already been published [40 2]. The FDA is also careful to qualify that the word analytical is meant in its broadest sense and covers chemical, physical, microbiological, mathematical and risk analysis conducted in an integrated manner. Although this chapter is primarily concerned with the first 

The aim of the FDA, and of other regulatory authorities who have taken up this theme, is to move from an industry that relies heavily on validated and fixed processes where quahty is ensured by end-point testing to one whose process are well understood and controlled. In other words, quahty is to be built into a product by design since it cannot be built in merely by testing. This begs the question of what is meant by a well-understood process. The Agency s own interpretation [43] is that a process is well understood when 

Office of Pharmaceutical Science, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, U.S.A. 

The objectives of this chapter are to discuss the FDA s Process Analytical Technology (PAT) framework using selected literature examples on granulation 

Conventional pharmaceutical manufacturing is generally accomplished using batch processing with laboratory testing conducted on collected samples to ensure 

In August 2002, recognizing the need to free industry from its hesitant perspective, the FDA launched a new initiative entitled Pharmaceutical cGMPs for the 21st Century A Risk-Based Approach. This initiative has several important goals, which ultimately will help improve the American public s access to quality health care services. The goals are intended to ensure that  

Product quality and performance are ensured through the design of effective and efficient manufacturing processes. 

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Bakeev, K.A. Process Analytical Technology, Blackwell Publishing, 2005. 

Chemometrics became well established in chemical industry within process analytical technology, and is important in the fast growing area of biotechnology. 

The chemometric basic tools may be divided into the following typologies of study data exploration, modelling, prediction and validation, design of experiments (DOE), process analytical technology (PAT), quantitative structure-activity relationship (QSAR). Details and relevant literature are reported in the following paragraphs. 

A chemical process is a series of steps. Each steps may be a chemical synthesis or a chemical analysis. Each step is multivariate. Hence, the global evaluation of the process must be a multivariate study process analytical technology (PAT) is applied. 

The FDA also introduces the concept of process analytical technology (PAT). PAT refers to systems that are used to analyze, monitor, and control manufacturing processes on a continuous basis. The quality attributes and specifications of raw materials, in-process intermediates, and processes are measured in real time and compared with predetermined parameters so that deviations can be rectified in a proactive nature to assure that the end products conform to the level of quality as expected. It is believed that a system based on PAT being implemented in a real-time manner would improve manufacturing efficiency and simultaneously retain or improve the product quality through these interactive measurements and controls. 

Discuss the benefits or otherwise of process analytical technology (PAT). 

CE instrumentation is quite simple (see Chapter 3). A core instrument utilizes a high-voltage power supply (capable of voltages in excess of 30,000 V), capillaries (approximately 25—lOOpm I.D.), buffers to complete the circuit (e.g., citrate, phosphate, or acetate), and a detector (e.g., UV-visible). CE provides simplicity of method development, reliability, speed, and versatility. It is a valuable technique because it can separate compounds that have traditionally been difficult to handle by HPLC. Furthermore, it can be automated for quantitative analysis. CE can play an important role in process analytical technology (PAT). For example, an on-line CE system can completely automate the sampling, sample preparation, and analysis of proteins or other species that can be separated by CE. 

Process Analytical Technology 2e Edited by Katherine Bakeev 2010 John Wiley Sons, Ltd. 

Process Analytical Technology 1.5 Glossary of Acronyms and Terms... 

FDA [Online], Office of Pharmaceutical Science (OPS) Process Analytical Technology (PAT) Initiative, Available http //www.fda.gOv/AboutFDA/CentersOffices/CDER/ucm088828.htm, accessed 7 December 2008... 

Introduction to Implementation of Process Analytical Technologies (PAT) in the Industrial Setting... 

This wider definition can be summarized as the analysis of the process and had been developing in the pharmaceutical industry since around 2004-2006 to encourage better use of the information content of classical process analytical methods for the improvement of process development and connol. Particularly in the pharmaceutical industry, the acronym PAT for Process Analytical Technology was often being used to describe this newer definition of process analytics. 

With the onset of the QbD initiative (see Section 2.3.4), first codified in the ICH Q8 document in 2006, the above-mentioned broader definition of process analytical technology has somewhat evolved into parts of the key elements of the broad definition of QbD, resulting in a partial retraction of the term PAT back... 

Implementation of Process Analytical Technologies 21 Table 2.1 Differences in process analytics applications in R D and manufacturing... 

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