USP 232/233 – Contending with the looming January 1st deadline

USP 232/233

Many of our Pharma clients are facing a common issue – how to complete risk assessments and validate methods for their raw materials and finished products – prior to the January 1, 2018 deadline.

Over the past few years, CSL has been conducting matrix and element-specific validations and verifications for the pharmaceutical industry.  If you’ve been following our blogs, you’ve no doubt seen several references to this, along with helpful links to tools such as the ICH Q3D training modules.

Recently we’ve heard from clients who, recognizing the fact that they can’t possibly complete validations for 100% of their raw materials or drug products in advance of the deadline, have adopted an approach we thought we’d share with you.  Please note that, although we share this approach, we can’t speak for regulators when it comes to sufficiency of any approach for FDA compliance.  Nonetheless, the approach makes sense, and may help you achieve your goals of good faith efforts for compliance within a reasonable timeframe.

In short, the approach is:  Complete your risk assessments now (in advance of the deadline), then develop a plan and timeline for completing validations of raw materials and/or finished drug products.  The testing component of the risk assessment can be completed relatively quickly, and typically involves screening of your materials for a logical subset (e.g. Class 1 and 2A elements) or all of the 24 Elemental Impurities (EIs) specified in USP <232>.  How many EIs you screen for is up to you, and Module 5 of the ICH Q3D Training Modules provides guidance to this regard based upon route of administration and other important considerations.  Click here to see the modules. The screening that we perform typically involves performing pre-digestion matrix spiking at levels of 30% or less of the target specification level.  Including matrix spikes of this nature with your testing provides confidence that the specific methods utilized for the testing are analytically appropriate for the elements and associated specification levels necessary for meeting risk thresholds for your material.

Once screening and risk assessments are completed, you can develop appropriate validation plans.  The screening helps narrow-down the number of EIs of interest, saving time, money and effort as you embark upon the validation process.  With the number of elements defined for each matrix, CSL can provide you detailed pricing and timelines for completion of the method validation process.  This results in the drafting of formal protocols and quotes which are signed by both parties (CSL and the Client), and which lay out a definitive plan for completion of validations in a timely manner.

If you find yourself in a situation where a validation timeline will extend beyond the January 1st deadline, this approach affords a logical plan to meet the critical risk assessment mandate of USP <232> with support of solid analytical data to make keen decisions on future control strategies.

We hope you find this helpful and, as always, welcome your comments and questions.  Either email us at or give us a call at (717) 697-7536.

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