The US Pharmacopeia (USP) retired the existing wet chemistry heavy metals methods outlined in USP General Chapter <231> with an instrument-based approach on January 1, 2018. Though the existing wet chemistry methods have been in effect for nearly 100 years, the methods were non-specific and frequently failed to detect or underestimate the presence of some toxic elements that are potentially present in pharmaceutical ingredients. 

Throughout this guidebook, Alcami scientists will discuss heavy metal regulations, moving to a risk-based approach, the role of risk assessment in the manufacturing process, goals and accountability, and agency-accepted testing and filing strategy for elemental impurities. 

The new elemental impurities regulations stress the importance of controlling all sources of elemental impurities in drug products. The regulations also impact all upcoming and current commercial drug products for human use. To comply with these regulations, it is critical to have an efficient, cost-effective, and agency-accepted approach.

Elemental impurities can contaminate or leach into a drug product from multiple sources (i.e. drug substance, excipients, water, equipment, and container closure systems), therefore, it is no longer acceptable to monitor the inlet raw materials only. A conservative risk-based approach is recommended, which should address all potential sources of elemental impurities. If it can be demonstrated that the elemental impurities present in the drug product are under control (less than the control threshold for three lots), then analysis at release is not needed. 

Join Alcami and the Division of Pharmacy Professional Development at UW-Madison for a webinar: Successful Application of the New Elemental Impurities Regulation.

The recent changes to the elemental impurities regulation guidelines increase the level of control necessary in testing for heavy metals in pharmaceutical and biotherapeutic products. The use of inductively coupled plasma (ICP) instrumentation is considered the ideal method to determine elemental impurities present in drug products and raw materials. This approach has been proven to be accurate, sensitive, linear, and satisfactory to include in filing reports.

Join Alcami for a webinar to learn more about elemental impurities and the updated regulatory requirements.

It’s official! The methods outlined in USP General Chapter <231> are retired. If you missed the January 1, 2018 deadline, we are here to help. Our in-house experts will share our approved testing plan that can be submitted to the FDA to help ensure you are moving to compliance, and will highlight experiences gained while working with the new regulations.

With less than three months until the methods outlined in USP General Chapter <231> are retired, there is still much to discuss.

We’ve presented everything you need to know, including potential contamination sources, but we know there are still questions left unanswered.

This webinar will feature an extended Q&A with our panel of experts to answer any questions you have regarding what lies ahead.

With less than six months until the retirement of the methods outlined in USP General Chapter <231> on January 1, 2018, there’s still plenty to discuss regarding this regulatory change. An often overlooked scenario when testing for elemental impurities is the possible contamination from everyday pharmaceutical machinery. It’s important to understand and implement policies that can assist in a successful right-first-time risk assessment that accurately reflects your process.

Replacement of the wet chemistry “heavy metals” limit tests with more modern analytical methodology and conformance to new and specific limits for individual elements was a dramatic, although anticipated, change in the regulation.

The ICH recognized that prior to the Q3D Guidance, regulation of elemental impurities fell under Guideline Q3A for inorganic impurities. Existing pharmacopoeial procedures included the Heavy Metals test, Residue on Ignition/Sulfated Ash test and other wet chemistry tests. The problem with these procedures was that they were non-specific and were never intended to detect the low-level residual metal catalysts and reagents used in some modern synthetic processes. In addition, the acceptance criteria were based upon historical precedent and, although risk factors for metal contamination had changed significantly throughout the 20^th century, the existing limits had not changed accordingly and had little toxological basis.

The introduction of new guidelines relating to elemental impurities in pharmaceuticals from the International Conference on Harmonization (ICH), U.S. Food and Drug Administration (FDA) and United States Pharmacopeia (USP) has created new and complex challenges for the pharmaceutical industry. These challenges include replacing the wet chemistry “heavy metals” limit test with new analytical technology, specifically, inductively coupled plasma (ICP) –based technologies and mandated conformance to new and specific limits for individual elements.  From a compliance perspective, the new guidance for elemental impurities (USP<232>and ICH Q3D) only applies to the drug product and the materials/processes involved.

Are you ready for this regulatory change?

The U.S. Pharmacopeia (USP) intends to remove the existing wet chemistry heavy metals methods outlined in USP General Chapter <231> by January 2018. Although the existing wet chemistry methods have been in effect for nearly 100 years, the methods are non-specific and frequently fail to detect or underestimate the presence of some toxic elements that are potentially present in pharmaceutical ingredients. The USP requires Plasma Spectrometry (ICP-MS or ICP-OES) as the technique to screen and/or accurately quantitate the presence of any elemental impurities of interest.  From a compliance perspective, the new guidance for elemental impurities (USP<232>and ICH Q3D) only applies to the drug product.  There are currently two strategies to meet the requirements for elemental impurities, with the first being a risk-based approach.

In 2013, the International Conference on Harmonization (ICH) approved ICH Q3D, a Guideline for Elemental Impurities, which replaced wet chemistry "heavy metals" limit test, such as USP <231>, with new analytical technology, specifically inductively coupled plasma (ICP) - based technologies, and mandated conformance to new and specific limits for individual elements. This action by the ICH triggered prompt reactions by the U.S. Food and Drug Administration (FDA), United States Pharmacopeia (USP) and European Pharmacopeia (EP) to harmonize with the ICH requirements.