DUNS Number - 67-716-4521  |  NCAGE CODE – 2444Y  |  FDA - FEI – 3014694901


Pharma / Bio Pharma

Crop Care




Impurity / Metabolite Qualification

Impurity / Metabolite Qualification

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Impurity profiling or qualification is the process of evaluating data for the biological safety of an individual impurity.

When we consider the benefits of pharmaceuticals, it always comes with certain risk factors and the products in the market available are amalgamated, balancing both the aspects. Whenever we speak of impurities, the cautionary thoughts about their qualification, start crowding our mind. Various guidelines have been in place which describes the process of evaluation and describing control measures to limit the impurities in drug products and drug substances. However, certain issues are not addressed in these guidelines, for example, control of relevant or genotoxic impurities, acceptable limits of the impurities in drugs during the development process. CQR approach, i.e. Categorization, Qualification, and Risk assessment, which is an important tool to understand the requirements of the regulator. In general, impurities in the pharmaceutical products are categorized into five classes i.e., class 1 to class 5.


At JRF, we have strong and proven capabilities of handling animal studies with state of the art animal facility and ample historical control database. The battery includes an assay for the gene mutation, chromosomal aberration, and micronucleus test, repeated dose toxicity in rodents as well as non-rodents for 14 days, 28 days, 90 days or up to Carcinogenicity depending on the class of impurity. JRF’s strong chemistry expertise is available to support isolation, purification, characterization using Spectrometry and quantitation using various chromatographic techniques. The chemistry support could be extended to undertake toxicokinetic studies as well, if and when needed.


Guideline provision to carry out these studies on API containing the impurity seems to be quite insensitive, even for powerful mutagens.


At JRF, with enormous experience, we assist our customers in deciding whether to perform these studies on impurity alone or on API containing an impurity. For impurities with known toxicological data, we refer EP or USP, and if pharmacopoeial data is not available, we set the limit based on available literature. For toxicology, we recommend our clients to use batches containing impurities which help in setting specifications based on administered doses and NOAEL and LOAEL values observed. In the early developmental stage, we do comparisons in mg/Kg and mg/m2 for assessment at the NDA stage. In case, a batch of drug used in phase 1 containing impurities is not tested in toxicology qualification, we follow a conservative approach and apply qualification threshold (0.2%), but specific qualification or bridging in vivo studies is last resort considering the risk of generating new findings.


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