Risk assessment and the supply chain
Another IPEC Federation priority has been the development of guidance on risk-assessment principles for excipients, along
the lines of the recent European Directive on Falsified Medicines, which was issued earlier this year. The aim is to develop a set of guidelines that can be used by users and suppliers of
excipients to determine how GMP principles should be applied for a specific excipient. Excipient risks can come from both
the intended uses of an excipient as well as the way the excipient is manufactured and distributed.
The federation responded quickly to extraordinary events affecting the excipient supply chain around the world in 2011, notably
the earthquake and subsequent nuclear incident in Fukushima, Japan, and adulteration of clouding agents with phthalate plasticizers
used in pharmaceuticals and foods in Taiwan.
When the earthquake occurred in Fukushima in the Tohoku district of Japan in March 2011, followed by a large tsunami, the
Fukushima Dai-ichi Nuclear Power Station shut down. There were collapsed houses and a cutoff of transportation networks along
the Pacific coast of the district. IPEC–Japan investigated the situation promptly and found that there were few excipient-manufacturing
facilities in the area, and therefore, little influence of the radioactive contamination from the nuclear power station. Consequently,
the Federation announced that the pharmaceutical excipients in Japan were safe and provided regular updates to the public
and the industry.
Similarly, the IPEC Federation developed a frequently asked questions (FAQs) document to address the Taiwan phthalate contamination
situation in Taiwan in order to help companies evaluate any risks related to the two contaminants (DEHP and DINP) involved
in the Taiwan incident. In the wake of that incident, IPEC has begun to investigate, along with other trade groups, the possibility
that packaging may play a role in contamination of drug products and whether migration of certain phthalates into drug products
poses any significant safety risks.
One of the IPEC Federation's key roles is to provide input from the industry perspective into global regulatory expectations.
To that end, the organization has taken a position on the US Pharmacopeia's (USP) draft General Chapters on elemental impurities
(<232>, <233>, and <2232>), which in IPEC's view, call for unrealistic for implementation timeframes (September 2013). USP's
timeline does not give industry enough time to obtain needed data for impurity levels in the majority excipients, which could
lead to a regulatory compliance issue.
The International Conference on Harmonization's (ICH) expert working group on elemental impurities (Q3D) is developing draft
guidance on this topic that will provide the impurity limits that are likely to supersede those set in current monographs.
The federation is gathering information on elemental-impurity levels in multiple excipients through an industry coalition,
with the goal of submitting data to ICH. The IPEC Federation is also considering holding a workshop in 2012 (after the working
group finalizes the limits) to begin sharing actual test data, which will need to be developed within the excipient industry.
Visible particles in excipients
A primary cause of drug recalls during the past year has been the presence of visible particles in pharmaceutical products,
and the IPEC Federation has responded with the formation of a working group to explore the role that excipients can play in
this area. The group plans to develop a guideline on how to measure and properly assess the significance of visible particles
that can be found in excipients. The guidance will ideally dispel any confusion around the presence of particles in excipients
and clarify that it is not possible to achieve zero visible particles in these materials.