Reference Standards to Support Quality of Synthetic Peptide Therapeutics.

Purpose: Peptides are an important class of therapeutics. Their quality is evaluated using a series of analytical tests, many of which depend on well-characterized reference standards to determine identity, purity, and strength.

Objective: Discuss approaches to producing peptide reference standards, including vialing, lyophilization, analytical testing and stability studies.

Understanding Quality Paradigm Shifts in the Evolving Pharmaceutical Landscape: Perspectives from the USP Quality Advisory Group.

Recent changes in the pharmaceutical industry have led to significant paradigm shifts in the pharmaceutical quality environment. Globalization of the pharmaceutical industry, increasingly rapid development of novel therapies, and adoption of new manufacturing techniques have presented numerous challenges for the established regulatory framework and quality environment and are impacting the approaches utilized to ensure the quality of pharmaceutical products. Regulators, industry, and standards-setting organizations have begun to recognize the need to rely more on integrated risk-based approaches and to create more nimble and flexible standards to complement these efforts.

Quantitative Analysis of Impurities in Unfractionated Heparin of Bovine Origin.

The USP heparin sodium monograph lists impurities with specifications developed for porcine derived products. Most of these impurities are of biological origin and are present in porcine intestinal mucosa, the tissue source used in the production of porcine heparin. One of the specified impurities, oversulfated chondroitin sulfate (OSCS), has been introduced in the monograph to detect intended adulteration of heparin products with this impurity.

The US regulatory and pharmacopeia response to the global heparin contamination crisis.

The contamination of the widely used lifesaving anticoagulant drug heparin in 2007 has drawn renewed attention to the challenges that are associated with the characterization, quality control and standardization of complex biological medicines from natural sources. Heparin is a linear, highly sulfated polysaccharide consisting of alternating glucosamine and uronic acid monosaccharide residues. Heparin has been used successfully as an injectable antithrombotic medicine since the 1930s, and its isolation from animal sources (primarily porcine intestine) as well as its manufacturing processes have not changed substantially since its introduction.

A quantitative PCR method to quantify ruminant DNA in porcine crude heparin.

Heparin is a well-known glycosaminoglycan extracted from porcine intestines. Increased vigilance for transmissible spongiform encephalopathy in animal-derived pharmaceuticals requires methods to prevent the introduction of heparin from ruminants into the supply chain. The sensitivity, specificity, and precision of the quantitative polymerase chain reaction (PCR) make it a superior analytical platform for screening heparin raw material for bovine-, ovine-, and caprine-derived material.