Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

The new role of excipients: Developments in the framework of GMP and the impact for the pharmaceutical industry

Dr. Karin Schleisiek (Abschlußjahr: 2013)

Language: English

Due to quality-related scandals, requirements for Good Manufacturing Practices (GMP) are currently being established for pharmaceutical excipients in addition to the already existing regulation for active pharmaceutical ingredients and medicinal products. There are different approaches for the implementation.

In Europe, formalised risk assessment is introduced to pharmaceutical manufacturers to determine the appropriate GMP level for the used excipients. Contracts with the excipient manufacturers have to be made, including respective quality agreements. As a basis, currently developed guidance such as EXCiPACTTM read in addition to the widely used certification according to ISO 9001:2008, might be used for the definition of appropriate GMP.

In the United States ISO 9000 certifications are much less common than in Europe. Consequently, a joint committee organised by the National Sanitation Foundation is currently developing the NSF 363 standard with the title "Good Manufacturing Practices (GMP) for Pharmaceutical Excipients". Currently, the draft of the version 363i1r4 was balloted without a dissentient vote in November 2012. The complete NSF 363 draft was passed to the Council of Public Health Consultants (CPHC), the NSF International advisory body for standards development. Although the NSF 363 draft standard was recently approved by the Council of Public Health Consultants (CPHC), NSF has not yet filed paperwork with ANSI to move the standard forward. The next ballot, 363i1r5, will include all proposed changes resulting from review and discussions that took place during the teleconferences in November and December. The 363i1r5 ballot will be a 60-day ballot, which will close on Friday, March 8, 2013.

This thesis gives an overview on the GMP regulations for excipients in USA, Europe and includes a short overview of the corresponding regulations in China. Different standards for GMP for excipients and quality management systems are compared to each other. Furthermore the standards for excipients are compared to GMP for active pharmaceutical ingredients and medicinal products.

In can be concluded, that the new NSF and EXCiPACTTM standards are comparable in regard to their content. They are presenting quality management principles as defined in general by ISO 9001:2008, amended by requirements for pharmaceutical excipients. GMP is a part of the pharmaceutical quality assurance system in a company.

The integration of quality risk management has to be highlighted as a new principle. Up to now, quality risk management is defined separately in the tripartite harmonised ICH Guideline "Quality Risk Management". The GMP principles as outlined in the EU GMP guidelines for finished medicinal products are all integrated in the different quality management standards. However, there are some differences; major differences can be identified for the principles of validation of processes, transport and storage and the style of instructions and procedures. Compared to the ISO standard the GMP standards are more detailed concerning the qualification and training of the personnel including personnel hygiene, adequate premises and space, change control and the expected content of manufacturing instructions and records.

In total, in the world of pharmaceutical excipients the changes are expected to be the biggest changes for the implementation of a quality management system by the excipient manufacturers, for the introduction of quality risk assessment focussing on excipients by the pharmaceutical companies and for the upcoming audits. The innovations expected for the manufacturers of medicinal products, for the excipient manufacturers and the interaction between both are described and discussed for the different regions. For the manufacturers of medicinal products, the expected innovations are the risk assessment for pharmaceutical excipients and their quality standards, auditing, realisation of audits of the excipient manufacturers, 3rd party audits with subsequent costs and time in the EU. In the USA only audits according to the new requirements are necessary, no particular additional work. The topics adaption of the quality management system to more detailed requirements and management of the expected wave of audits, direction to 3rd party audits are highlighted for the excipient manufacturers. The interaction of both is required for an effective quality risk assessment, as well as the development of common control and risk mitigation strategies.

Pages: 73, Annexes: pages : 0