Vibrational Spectroscopy for Pharmaceutical Analysis

1. Vibrational Spectroscopy for Pharmaceutical Analysis Part III. Introduction to Process Analytical Chemistry Rodolfo J. Romañach, Ph.D.

2. Sampling • Pharmaceutical processes are often evaluated through samples that are obtained from a process and taken to a remote lab where they wait for analysis. • This type of sampling is called “grab” sampling.

3. Process Analytical Chemistry • In 2001, FDA started a new initiative called Process Analytical Technology (PAT), issued a new Draft Guidance in September 2003, and the final guidance a year later. • PAT is the name given by FDA to Process Analytical Chemistry. • FDA did not invent PAT, but it has encouraged industry to use this alternative.

4. PAT Definition • “The Agency considers PAT to be a system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes, with the goal of ensuring final product quality.” • “It is important to note that the term analytical in PAT is viewed broadly to include chemical, physical, microbiological, mathematical, and risk analysis conducted in an integrated manner. ” PAT Guidance, page 4.

5. Process Analytical Technology vs. Process Analytical Chemistry “The Agency considers PAT to be a system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes, with the goal of ensuring final product quality.” The goal of process analytical chemistry is to supply quantitative and qualitative information about a chemical process. Such information can be used not only to monitor and control a process, but also to optimize its efficient use of energy, time, and raw materials. J.B. Callis, D.L. Illman, and B.R. Kowalski, “Process Analytical Chemistry”, Anal. Chem., 1987, 59, 624A.

6. Design, Analysis & Control of Mfg with measurements obtained during processing for critical quality and In-line performance attributes of raw and in process materials to ensure final product quality On-line Off-line At-line

7. PAC - Sampling Terms • At line (also called near line) means manual sampling with transport to an analyzer located in the manufacturing area. • On line analysis means automated sampling and transport to an automated analyzer. • In line analysis means that the process to analyzer interface is located within the process itself, in-situ (sees the process as it occurs), by means of a probe. • In line analysis can be performed non-invasively with no physical contact between the analytical system and the sample analyzed is not altered in the system. R. Reshadat, S. Desa, S. Joseph, M. Mehra, N. Stoev, S.T. Balke, “In-Line Near Infrared Monitoring of Polymer Processing”, Part I: Process Monitor Interface Development”, Appl. Spectrosc., 1999, 53(11), 1412 – 1418.

8. In-Line vs. On-Line • Some publications do not make a distinction between in-line and on-line, and use the term on-line to refer to both in-line and on-line.

9. Recommended Reading • Guidance for Industry PAT — A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation (CDER), and Research (CDER),Center for Veterinary Medicine (CVM), Office of Regulatory Affairs (ORA), September 2004.