E18-21: Evaluation of Trace/Ultratrace Impurities in Pharmaceuticals

One-Day Course
Monday, Nov. 12; 8:30am – 5:00pm

Dr. Satinder (Sut) Ahuja, Ahuja Consulting, Calabash, NC

To assure the quality of drugs, it is important to monitor trace/ultratrace impurities. Impurities at ultratrace levels (at parts per billion) can be carcinogenic, teratogenic, or genotoxic. It is desirable to profile the impurities to assure that future batches will meet the established requirements. To ensure the quality of drugs and meet rigorous demands of regulatory agencies, it is necessary to have a thorough understanding of interactions of drug substances with excipients, especially when residual solvents are present. It is also essential to understand potential degradation reactions that may occur in the formulated product under various stress conditions encountered during storage and shipment in the final package. The main goal of pharmaceutical analysis is to help build and assure the quality of drug products. The initiatives such as quality by design (QBD) and in-process testing are utilized to meet this objective.

The analytical methods frequently used for the drug products are separation methods such as gas chromatography (GC), high pressure or high performance liquid chromatography (HPLC), and capillary electrophoresis (CE), These are the methods of choice for checking impurities in active ingredients, monitoring changes or scale-up of synthetic procedures, evaluating new formulations, and implementing quality control/assurance of final drug products. Impurities profiling helps ensure the new batches match or exceed the purity requirements. Hyphenated methods such as GC-MS, LC-MS, and CE-MS have been found useful for characterizing impurities at ultratrace levels. The key features of the course are listed below.

  • The latest analytical methodology for evaluating ultratrace impurities
  • Methods for monitoring of toxic impurities because the improved sensitivity of the methods has caused the regulatory agencies to begin requesting them.
  • Impurities profiling
  • Implications for pharmaceutical analysis from the new paradigm, “quality by design.” This has also increased emphasis on process analytical technology (PAT).
  • Impurities analysis of biomolecules, as these molecules are gaining significance.

This one-day course will benefit researchers in analytical R&D and QA and QC chemists who perform analyses, develop methods, set up stability programs, and evaluate stability data of pharmaceuticals. Managers and regulatory personnel would also benefit from this course, as they would learn about the optimum means to achieve their goals.


1. Regulation and Requirements for Controlling Impurities
     * Classification of impurities 
     * Rationale for reporting and controlling impurities
     * Qualification of impurities

2. Preformulation and Early Phase Method Development
     * Introduction
     * Physicochemical properties of the active ingredient(s) (AI)
     * Impurity profiling and assessment
     * Preformulation studies

3. In-Process Control Testing 
     * Introduction
     * Analytical considerations
     * In-process control tests

4. Development and Validation of Analytical Methods
     * Introduction
     * Validation requirements
     * Method transfer

5. Kinetic/Stability Studies
     * Introduction
     * Operational aspects
     * Considerations for AI, excipients, and drug products

6. Interactive Exercises and Discussion
     * Participants will discuss several case studies to get a better idea of how impurities should be evaluated for pharmaceutical products.

Dr. Satinder (Sut) Ahuja
 was involved in analytical research and development of drugs for over 30 years. In a number of successive leadership positions, he effectively managed analytical R&D of a number of new drugs at Novartis Corporation for more than 25 years. Since 1994, as President of Ahuja Consulting, he has advised major ethical and generic pharmaceutical companies in the United States and abroad on new drug development, analytical R&D, QC/QA, and regulatory issues. His expertise in analytical chemistry includes separation and characterization of a variety of compounds at trace/ultratrace levels by chromatographic and spectroscopic techniques. He assists with the discovery of new synthetic, natural, or recombinant products, GMP/GLP issues to assure FDA compliance, and various aspects of new drug development (oral, parenteral, inhalation, and transdermal products).

He has published numerous papers and more than 20 books. His recent books include Handbook of Isolation and Characterization of Impurities in PharmaceuticalsChromatography and Separation ScienceHandbook of Pharmaceutical Analysis, Chiral Separations by Chromatography, HPLC Method Development for Pharmaceuticals, Handbook of Bioseparations, and Trace and Ultratrace Analysis by HPLC.