Unusual Investigation Case: What Happened with Assay Reproducibility?

Akmurat Nepesov, Analytical Development, Global R&D, Teva Pharmaceutical Industries, Ltd., Kfar Saba, Israel (akmurat.nepesov@teva.co.il)

Unexpected inconsistency of Assay results observed in routine duplicate testing of sample lead to deep investigation of the phenomenon.

First observation was as follows: During development and release testing, such “fluctuation” of assay results has not been observed. However, in stability testing, when running long series of injections, this variability occasionally occurred for some of samples duplicates. In most cases, reinjection of such duplicates resulted in acceptable consistency.

As an initial step, we created a protocol for systematic investigation of the problem.

Examination of structure of API molecule revealed that it can potentially create complexes with some transition metals, which, as we suspected, may be part of alloys used in the injection system of HPLC instrument. Among the metals under suspect was Molybdenum, which is a typical component of some alloys used for injection needles. This appeared to be a root cause of variability of results.

In support of this assumption, such problem has never been observed when running the testing on the instruments which use Molybdenum-free alloys for needles and other metal parts, which are defined as “biocompatible alloys”.

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Abstract Reference & Short Personal Biography of Presenting Author

Akmurat Nepesov is Analytical Project Coordinator at Global R&D, Teva Pharmaceuticals, Ltd. He is responsible for methods development for small molecules API and drug products in generic development at Kfar-Saba R&D site. Akmurat joined Teva in 2007 and held numerous positions associated with analytical chemistry.

Akmurat holds a B.Sc. degree in Biology from the Hebrew University of Jerusalem, Israel