14/15 April 2021
GMP-News No 345
8 September 2003
FDA has just passed the FDA DraftGuidance for Industry PAT - A Framework for Innovative PharmaceuticalManufacturing and Quality Assurance. This new guideline will be presentedby Ali Afnan (FDA) at the PAT Workshop of Heidelberg University to be heldin Heidelberg on September 19, 2003.
The purpose of the current PAT (ProcessAnalytical Technology) Draft Guidance is to define the regulatoryframework conditions which are to support the voluntary development andimplementation of innovative pharmaceutical manufacturing processes andquality assurance activities. The intention of the guideline is also todispel the fear among pharmaceutical manufacturers that they will sufferregulatory disadvantages as a result of the introduction of newmanufacturing methods. This document is not a typical FDA guideline sinceits focuses on presenting options and principles aimed at promotinginnovations.
The guideline was compiled by the Officeof Pharmaceutical Science of the Center for Drug Evaluation and Research(CDER) under the leadership of the Process Analytical Technology SteeringCommittee with members from the CDER, the CVM (Center for VeterinaryMedicine) and the Office of Regulatory Affairs (ORA). This guideline isexpressly not applicable for the CDER's Office of Biotechnology Products.
The guideline sees PAT as a system forthe design, analysis and monitoring of pharmaceutical manufacturing bymeans of real-time measurements of critical quality and performanceattributes of starting materials, in-process materials and processes withthe aim of ensuring the quality of the finished product. It is emphasizedthat the term analytical as it is used in PAT is to be understood in avery broad sense.
The guideline covers principles and toolsfor PAT in detail. An example of this is that time-defined endpoints ofmanufacturing processes (e.g. mixing for 10 min) can be replaced byprocess-controlled definitions. This means that FDA allows a certainflexibility in the definition of process conditions. It expresslyaddresses the real time release, i.e. parametric release, as we knew it upuntil now mainly for terminal-sterilized products, would be imaginable forall dosage forms!
In a section on "RegulatoryStrategies" the guideline describes how FDA seeks to support theindustry in the introduction of new PAT technologies. PAT is certainlyparticularly suitable for the development and introduction of new productsbut is also recommended for the manufacture of products which already havemarketing authorization. Data from PAT experiments on products withmarketing authorization could be declared as research data and FDA wouldin its inspections not ask for these research data but restrict itself tothe existing regulatory standards (e.g. the presently permitted methods).Various options as to what a "risk based" approach could looklike in the implementation of PAT are described at the end of theguideline. The FDA guideline presented here is a very important element ofthe FDA initiative "Pharmaceutical cGMPs for the 21st Century: ARisk-based Approach".
Author: Dr. Günter Brendelberger CONCEPTHEIDELBERG