Coalition activities and path forward
As described herein, the industry has major concerns about the direction USP has taken with respect to implementation of new
General Chapters <232> and <233> by not aligning with the pending ICH Q3D guideline in terms of targeted metals, limits, and
applicability and implementation timeframes. Many members in the industry believe that realistic implementation should involve
a phased-in approach due to the current lack of information available about metals in products and the need to collect and
evaluate a tremendous amount of data by all stakeholders. The authors believe that coordination of USP's goals with that of
ICH Q3D is essential to facilitate this process.
To that end, industry has organized the Coalition for the Rational Implementation of the USP Elemental Impurities Requirements.
The coalition's mission is to: "develop risk assessment concepts for evaluating the potential for metal impurities in excipients,
APIs and drug products and will evaluate what is a realistic timeframe for implementation of both the USP and the ICH Q3D
requirements based on the PDEs and concentration limits in the [ICH Q3D] pre-Step 2 document. ICH is carefully reviewing all
metal risk assessments and the pre-step 2 PDE limits are subject to change. At this time the Coalition is not specifically
highlighting any concerns with the current ICH implementation strategy or plans, but rather, the seemingly independent strategy
being implemented by USP. To this point the coalition plans to meet with high-level FDA officials involved in this issue to
discuss this information and determine the type of timeframe that is realistic for implementation. The initial mission of
the Coalition is to align USP's implementation timeline with that of ICH for Q3D once the guideline is completed."
The goal of all parties involved is to ensure the safety of patients and the quality of our products. However, there is no
overriding issue of patient safety involved in the USP changes. USP has pursued its current path in a proactive way to prevent
possible safety issues, but there have been no demonstrated cases of metal impurities in drugs at levels of toxicological
concern. Instead, the USP initiative seems to have been prompted by issues with the analytical techniques. These issues need
to be resolved, but there is no urgency that requires USP to adopt requirements independent of ICH. The primary objective
of the coalition is to encourage USP and other parties to follow the same path, with compatible timelines, so that industry
will be able to meet a harmonized standard.
*The Coalition is comprised of members from the following trade and professional associations: IPEC (International Pharmaceutical
Excipients Council) Americas, IPEC Europe, Pharmaceutical Research and Manufacturers Association of America (PhRMA), European
Federation of Pharmaceutical Industries and Associations (EFPIA), NJ Pharmaceutical Quality Control Association (NJPQCA),
Consumer Health Products Association (CHPA), Generic Pharmaceutical Association (GPhA), and the Society of Chemical Manufacturers
and Affiliates–Bulk Pharmaceutical Task Force (SOCMA–BPTF).
Katherine Ulman is a Global Regulatory Compliance Manager at Dow Corning; Neil Schwarzwalder is Quality Consultant, Compendial Affairs, at Eli Lilly and Company; Andrew Teasdale, PhD, is a Principle Scientist at AstraZeneca; David Schoneker is Director of Global Regulatory Affairs at Colorcon and Chair of the Coalition for the Rational Implementation of the USP
Elemental Impurities Requirements; and Priscilla Zawislak* is a Global Regulatory Affairs Manager at Ashland Inc.
*All corresopondence should go to firstname.lastname@example.org
Note: The authors are a subgroup of an industry coalition called the Coalition for the Rational Implementation of the USP
Elemental Impurities Requirements.