Laboratory Testing Blog

One of the most important considerations in the drug manufacturing process is safety, not only of the drug itself, but also impurities and degradation products.  Impurities present in the active pharmaceutical ingredient (API) have to be identified to ensure no mutagenic or toxic substances will be administered to patients.  Drug product degradation profiles need to be established to guide stable formulation development and provide suitable drug shelf-life assessment.  Drug regulatory agencies also have requirements for characterization of the impurity profile of a pharmaceutical.

In the European Union and some other countries, it is general practice while performing in vitro skin penetration studies, to exclude the amount of Test article that was found in the first (upper) two tape strips at study completion both in vitro and in vivo.

Driven by regulatory requirements, skin penetration and absorption studies are becoming essential for safety and efficacy evaluation of test substances or formulations.  In vivo, substances topically applied onto the skin surface can diffuse into and penetrate through the skin using three distinct pathways, namely the intercellular and the transcellular route across the stratum corneum as well as the route along the skin appendages (hair follicles and sweat glands).  Both the percutaneous penetration and the absorption into different skin compartments of topically applied test substances can be evaluated by using a Franz diffusion cell apparatus.

Impure substances present in pharmaceutical products have to be identified to make sure no mutagenic or toxic substances will be administered to patients.  Impurity profiling of pharmaceutical products must be established to guide stable formulation development and provide suitable drug shelf life assessment.  Impurity profiling of pharmaceuticals i.e., the identification, isolation, characterization and purification of these impurities is required.  The traditional approach in impurity identification involves isolation and purification by semi-preparative HPLC, followed by characterization using NMR spectroscopy, accurate MS or LC-MS/MS methods.

The most important concern in the drug development process is safety of a drug and its impurities.  The presence of impurities in trace quantities in a drug substance or drug products is inevitable.  Therefore, the level of impurities in drug substances and drug products should be controlled and monitored.

The recent increase in development of protein and peptide therapeutics demands highly informative methodologies.  More than 600 biological drugs are currently approved by FDA.  The interest in analyzing peptides and proteins arises from the need, during preclinical and clinical studies, to quantify levels of the metabolites in protein and peptide drugs.

Many of the challenges facing researchers in the proteomics and biopharmaceutical fields are related to the need to obtain as much information as possible on very limited samples.  UPLC technology with BEH columns can address these challenges.

In general, the main challenge in protein molecule analysis is that there is no single and universal method or approach for separation and characterization of proteins.  As a first choice, peptide mapping methods are a preferred technique for the comprehensive characterization of biopharmaceutical products.  Its applications include:

The in vitro percutaneous absorption method has been described in detail in several publications and previously in our blog posts and whitepapers.  One interesting question that has arisen recently is how to provide data for skin integrity testing.

Throughout 2011, we have been talking to customers about what their testing needs are, what has worked for them, what hasn't worked in 2011 and strategizing about how this will impact their laboratory testing plans for 2012.  This includes reviewing our blog to make sure we understand which articles had resonated the most with our website visitors.