Host Cell Protein Testing: Perspective of Current and Future Techniques
Biologics are produced using living cells or organisms. The living cells can be derived from prokaryotic, eukaryotic, and mammalian cells that are genetically engineered to encode the protein of therapeutic use. During the protein expression process, thousands of endogenous proteins, or host-cell proteins (HCPs), are produced and needed to maintain cellular function and regulation, as well as the protein of interest. In cells, the HCPs have a wide range of functions such as growth, proliferation, survival, gene transcription, and protein synthesis, but they are unwanted impurities in the biologics product. Due to their highly diverse physicochemical characteristics, these HCPs can co-purify with the drug substance, and—despite purification steps meant to remove them from the therapeutic protein of interest—low levels can remain in the final drug product, contaminating it. Good Manufacturing Practices (GMP) require that manufacturers demonstrate that they have cleared drug substances
of residual HCPs to the lowest level possible prior to releasing their drug products. The methodologies for meeting this
challenge are changing rapidly as new instrumentation and techniques are becoming available to laboratories. The following paper outlines the latest developments, focusing on emerging best practices.
Stability Study for EMLA Cream Using In Vitro Percutaneous Absorption “IVPT”
EMLA Cream (lidocaine 2.5% and prilocaine 2.5%) is an emulsion in which the oil phase is a eutectic mixture of lidocaine and prilocaine. It is a numbing cream that can be placed on skin to provide pain relief. It is often used to numb an area before placing an IV, drawing blood, or giving injections.
Typical stability study is conducted by the assay of active pharmaceutical ingredient (API) in the drug product. However, the assay results may not indicate drug product’s penetration rate similarity between different products over a certain period of time frame because of the differences in its topical product qualities (such as rheology, particle size, excipients, penetration enhancers, etc.). Therefore, it is important to evaluate the penetration of compounds into human skin during drug product stability study.
In vitro human cadaver skin model using Franz diffusion cells (invented in 1975) is widely regarded as the most valid in vitro model for evaluating the penetration of compounds into human skin. It can be used to determine the product equivalence.
Determination of Pregabalin in Human Plasma by Liquid Chromatography Tandem…
Pregabalin, (S)-3-(aminomethyl)-5-methylhexanoic acid, is an analogue of the neurotransmitter gamma amino butyric acid (GABA). It is used for the treatment of peripheral and central neuropathic pain in adults and as an adjunctive therapy for refractory partial seizures. Pregabalin binds potently to the α2δ (alpha2delta) subunit of the voltage-dependent calcium channel in the central nervous system and its binding at this site reduces calcium influx at the nerve terminal, leading to the release of several neurotransmitters, such as glutamate and noradrenalin. The aim of this study is to develop a sensitive, specific, robust and rapid LC-MS/MS method: Use simple extraction procedure; With no interference from matrix; With short run time.
IVRT Insights From CMC Experts Of Frontage Laboratories, Inc
Growing experience confirms the value of in vitro release test (IVRT) in the measurement of drug release properties in topical semisolid dosage forms. IVRT is increasingly used to profile drug performance characteristics in the development of both innovator and generic
Nondetectable Or Minimal Detectable Residue Levels Of N-(N-Butyl)…
N-(n-butyl) thiophosphoric triamide (NBPT) (Figure 1) is an active ingredient in nitrogen stabilizer (urease inhibitor), which temporarily inhibits the action of the urease enzyme to improve the efficiency of urea-containing fertilizers. Given the potential for NBPT residues to be present in milk and tissues of dairy cattle, due diligence is needed to demonstrate the safety of NBPT in urea-based fertilizers used on forages and crops intended for consumption by Holstein dairy cows.