The USP General Information Chapter <1078> entitled "Good Manufacturing Practices for Bulk Pharmaceutical Excipients" has been subject to a thorough revision. The revised version is based on the GMP Guidelines for Excipients issued by the WHO, the Joint IPEC-PQG Good Manufacturing Practices Guide for Pharmaceutical Excipients of 2006, the IQA PQG PS 9100:2002 Pharmaceutical Excipients Guide and the ISO Standards for Quality Management Systems. The content of USP <1078> is identical to the Joint IPEC PQG Guide.
 
Compared to the hitherto valid Chapter <1078> of USP, the requirements in the revised document are much more detailed and strict. Appendix A, for example, requires the excipients manufacturer to demonstrate by means of risk analyses which are the critical process steps and starting from which point GMP has to be applied. The text gives examples for quality-critical steps, like phase changes in the manufacturing process (dissolving, crystallising, sublimating, distilling etc.), phase separations, critical chemical reactions, the mixing of several components. The excipients manufacturer has to identify and control such critical process steps. Another example: It is mandatory for the top executives to conduct periodic reviews of the quality management system. The text also gives examples for the review input.
 
This information chapter refers to excipients used to manufacture medicinal products. Excipients for specific pharmaceutical applications for which special requirements are in place are not included, like e.g. excipients for parenterals, inhalants, ophthalmics and medicinal products for the treatment of open lesions as well as generally for medicinal products that have to be sterile and/or pyrogen-free.
 
One of the reasons why this subject is extremely controversial is the fact that the greatest part of incidents with medicinal products is caused by defective or contaminated excipients manufactured in Far Eastern countries (China, India, and Korea).
 
The final version of USP Chapter <1078> is expected to be published in the Pharmacopoeial Forum PF 34(2) with the March/April issue.
 
The interest group of the European fine chemicals manufacturers, EFCG, published a position paper with proposals for a harmonised European GMP standard for excipients already in September last year. The position paper can be found here:
http://www.efcg.cefic.org/isoFILES/publications/items/DOWNLOAD_128.pdf
 
Author
Dr Gerhard Becker
On behalf of the European Compliance Academy (ECA)

 
The GMP-compliant manufacture of excipients and active pharmaceutical ingredients is a focus topic at the 3rd EFCG Conference - Strategies for Compliant Pharma Sourcing in Lisbon, Portugal, on 29-30 May 2008. Representatives from supervisory authorities and industry, from EMEA, the FDA as well as associations present the latest global developments and tendencies in the sourcing of GMP-compliant excipients and active pharmaceutical ingredients.