For over 100 years the United States Pharmacopeia’s (USP) test that provided the specification for heavy metals was general chapter <231> – Heavy Metals. This non-specific test, based on the color intensity of sulfide precipitates, has been replaced by two general chapters. The first, <232> - Elemental Impurities - Limits, is an element-specific, toxicologically-based and risk-based general chapter. It represents a major departure from the previous Heavy Metals test in that a specific list of elements and limits is provided. Each element of concern is associated with a specific permissible daily exposure limit (PDE) for oral, parenteral and inhalational routes of administration. Also, the chapter provides options for assessing the levels of elemental impurities in drug products. The second, <233> - Elemental Impurities – Procedures, discusses two potential procedures for the quantification of the elements of concern (ICP technology with either optical or mass spectrometric detection) as well as validation requirements for this technology and alternative testing. General chapter <232> is globally harmonized via the ICH Q3D document while the testing chapter is under discussion for harmonization by the USP, European and Japanese Pharmacopeias. Both chapters have been effective since January 1, 2018, for both new and existing products.

In 2005, the United States Pharmacopeia (USP) began the process of replacing the sulfide precipitation based Heavy Metals general chapter <231> with atomic spectroscopy based standards. The resulting general chapters are <232> - Elemental Impurities – Limits and <233> - Elemental Impurities - Procedures. General chapter <232> is essentially harmonized with the ICH guideline Q3D, while general chapter <233> harmonization is being discussed by the Pharmacopeial Discussion Group. These standards represent a dramatic departure from the venerable Heavy Metals test in that a specific list of elements and limits is provided. Each element is associated with a specific permissible daily exposure limit (PDE’s) for oral, parenteral and inhalational routes of administration.

ICH Q3D contains identical limits to 232 while providing rationale for each of the limits and the concept of a control threshold to limit the need for a control strategy. On April 26, 2022 ICH reached Step 4 on ICHQ3D(R2). This revision updates several PDE values in the Q3D (R1) tables and provides PDE for cutaneous and transcutaneous products.

The subject is of importance to the manufacturers of new drug products as they are required to comply with the new elemental impurities standards either through risk assessments or through testing as new regulatory submissions are made, and to manufacturers of existing products as they make decisions regarding the extent of risk assessment and testing required to demonstrate compliance with the new standards. If the manufacturer’s compliance strategy involves testing, there are many things to consider regarding the selection of the correct analytical technique (e.g., atomic absorption, ICP emission spectroscopy, ICP mass spectrometry).

The objective of this live training webinar is to provide an understanding of the new USP standards and ICH guideline (including the new recommended PDE for cutaneous and transcutaneous administration) what testing, documentation or rationale is required in order to comply with the spirit of the documents, how to perform a risk assessment, and how to demonstrate that any analytical measurements made are validated to the extent that is suitable for their intended purpose.

Learning Benefits:

• An understanding of the logic behind the development and construction of the new standards.
• A review of ICH Q3D and an update on current revision initiatives.
• An in-depth discussion of USP <232> and <233>.
• Risk assessments.
• Compliance strategies.
• Updated review of key resources.
• Analytical considerations and selecting the best technique.
• Analytical method validation.

Webinar outline and time breakdown:

Time*

10:15 AM Log-In Period

10:30 AM Introduction

                Live Lecture Part 1

11:30 AM 10 Minute Break

                Live Lecture Part 2

12:30 PMLive Questions & Discussion

*Please note all times are Eastern Time (New York Time)

This live training webinar includes the following for each registered attendee:

• A copy of the presentation slides
• A certificate of training for attendee training records

Who should attend:

The following individuals or disciplines will benefit from attending this Webinar:

• Quality Assurance Personnel
• Quality Control Personnel
• Regulatory Compliance Managers
• Analytical Chemists
• Laboratory Management
• Chemical Manufacturing and Control (CMC) Personnel

How to Attend:
All Pharma Webinars live training programs audio and visuals are delivered via Cisco WebEx with a basic system requirement of a computer with internet access. You do not require a Webex account to join Pharma Webinars’ live training courses, participants receive an email invitation that provides the access you need to join the meeting.