Masterstudiengang "Drug Regulatory Affairs"


Global regulatory requirements and how to reflect them in the process control system of pharmaceutical industry - Implementation of Process Analytical Technology

Dr. Monika Hitzl (Abschlußjahr: 2008)

Language: English

Pharmaceuticals are of major importance for health care. It is essential that manufacture of pharmaceuticals exerts innovation, cutting edge scientific and engineering knowledge, along with the best principles of quality management to guarantee the highest quality of the drug product.

Effective use of state of the art pharmaceutical science and engineering principles and manufacturing process understanding can improve both, the efficiency of a manufacturing process and the quality of drug products. Nevertheless, the pharmaceutical industry is very conservative in building innovation in the manufacturing process of a drug product based on the fact that regulations are a limiting factor. Authorities are aware of this situation and therefore, started initiatives to collaborate with industries to adopt the regulatory framework to innovative approaches.

Drug product manufacturing in pharmaceutical industries is generally controlled by testing products resulting from a process - finished product testing. Another innovative approach is process analytical technology (PAT) analytical testing is performed during the process. This approach allows adjusting product quality in time and final product testing can be avoided. Process understanding is the basis for this innovative process control system.
The principle of PAT is to control the quality of a drug product based on process understanding by in/on/at line process control.

There are many tools available that enable process understanding for scientific, risk-managed pharmaceutical development, manufacture, and quality assurance. Tools can be categorized according to the following:
  • Multivariate tools for design, data acquisition and analysis
  • Process analyzers
  • Process control tools
  • Continuous improvement and knowledge management tools
Using these tools PAT can be implemented for new drug development and excisting marketing authorisations. The Strategy for regulatory implemention of PAT can be the categorized by the following steps:
  1. Building a science-based knowledge space
  2. Design space
  3. Implement process monitoring and control
  4. Documentation and drug application procedures
In order to support the PAT activities authorities enhanced dialogue between working groups and started to adapt the regulatory framework. The regulatory framework is open to the implementation of PAT in marketing authorization applications. Revision of the variations regulation is an important ongoing process and EDQM is also assessing how to adapt specifications of CEPs to the new technologies. Guidelines are revised and introduced for in-line testing methods like the use of near infrared spectroscopy.

Summarizing, understanding of the manufacturing process for a drug product and the ability to predict consequences of variation of process parameters leads to higher drug product safety and therefore to higher safety of the patient. The innovative approach of PAT leads to continuous quality improvement of the drug product.

Pharmaceutical industry has fallen behind other industries in its use of advanced process control systems and on-line measurements techniques for continuous quality assurance due to high regulations of the manufacturing process by authorities. PAT is a chance to innovate the manufacturing process of drug products and therefore improve safety of patients. Pharmaceutical industries may also benefit by implementation of PAT by:
  • Reduction of manufacturing time
  • Reduction of the number of defective goods
  • Possibility of real-time release of the drug product
  • Reduction of manufacturing costs
  • Improving energy and material use and increasing capacity
  • Increasing automation to improve operator safety and reduce human errors
  • Facilitating continuous processing to improve efficiency and manage variability
  • Pragmatic regulation of the manufacturing process by agencies for continuous improvement of quality assurance which enables the manufacturer to be more competitive
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