Laboratory Testing Blog

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.

Polysulfated carbohydrates are an important class of biologically active and pharmaceutically important molecules.  The aluminum salt of sucrose octasulfate in particular, is the drug Sucralfate (Carafate), which is widely used in the treatment of duodenal ulcers.

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.

Typical oligonucleotides used as therapeutics or potential therapeutic compounds are 15 to 30 nucleotides (nt) long.  Oligonucleotides <15 nt can be readily resolved by HPLC technology.  However, the separation of longer sequences are more challenging.  Ion-pair reversed-phase (IP-RP) HPLC has been traditionally used for oligonucleotides analysis.  The traditional IP-RPLC eluent system typically uses TEA or TEAA or HFIP and the ion-pairing agent triethylammonium ion and a C18, column at 60^oC.  Under such conditions, the HPLC column's hydrolytic stability becomes crucial and is important to prevent the potential contribution of the oligonucleotide secondary structure from impacting retention.  To overcome this, Waters has an ACQUITY UPLC BEH column that has demonstrated excellent performance for oligonucleotides of similar structures.

The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to have important physiological effects that may reduce the risk of cardiovascular disease.

Presently, several ligand-binding assay concepts are still not widely understood, such as the boundary between method development and validation.  This is mostly due to ligand-binding assays reagents, the use of nonlinear standard curves, the calculation of total error, tolerance and confidence intervals.  Other current issues of major importance include the use of total, bound or free assays and their impact on PK parameters, the emergence of novel and automated technologies and the use of LC–MS technology for the analysis of biotherapeutics.  Stability, quantity and long-term supply of reagents are also critical in the successful application of ligand-binding assays.

The measurement of drugs in biological matrices, such as serum, plasma, blood, urine, and saliva is an important aspect of pharmaceutical product development.  The data obtained in these clinical studies may be required to support regulatory applications for new drug products and generics as well as variations to previously approved drug products.  The results of animal toxicokinetic studies and human clinical trials, including bioequivalence studies are used to make critical decisions supporting the safety and efficacy of a drug substance or drug product. It is critical that the bioanalytical methods used are well established, fully validated and documented that will demonstrate reliable and reproducible results.

Biosimilars, biogenerics, follow-on biologics or by any other name, are second generation versions of blockbuster biologic products that are coming to North America and they are going to have a profound impact on all aspects of the pharmaceutical industry.  The comprehensive characterization of proteins and peptides as drug candidates is a requirement for safety and regulatory agencies.  Challenges include the high molecular weight of biopolymers and the heterogeneous nature of protein drugs.  These challenges require extensive characterization to achieve regulatory approval.

Stroke is predicted to affect more than 600,000 people in the United States a year.  In a 1999 report, over 167,000 people died from strokes, with a total mortality of 278,000.  In 1998, 3.6 billion was paid to just those Medicare beneficiaries that were discharged from short-stay hospitals, not including the long term care for more than a million people that reportedly have functional limitations or difficulty with activities of daily living resulting from stroke.  No therapeutic has been approved to reduce brain damage resulting from stroke through the direct protection neurons from death.

Biosimilars, biogenerics or follow-on biologics – by any name, second generation versions of blockbuster biologic products are going to have a profound impact on all aspects of the pharmaceutical industry.  The reduction of healthcare expenditures is on the top of many governments’ agendas and so many developing nations are introducing regulations to govern biosimilars.  Because biologics are among the highest priced therapies in the world, controlling their cost is one of the key focus points and it has increased the expectations of a regulatory pathway among the biosimilars industry participants.