Caroline Eichberger, Laurie Mastellone
Bristol-Myers Squibb (BMS) presents a one-of-a-kind isolator system as a spectacular addition to an award winning facility. The BMS Clinical Supplies Manufacturing and Drug Product Technology Center was the ISPE 2008 Facility of the Year Award winner in equipment innovation. BMS has continued that world class innovation with the implementation of a potent compound capable isolated syringe filler.
Pernilla Korsgren, Ph.D., Annika Langborg Weinmann
Purification of crude compounds in drug discovery is often performed using RP HPLC with mixed (UV/MS) triggered fraction collection. This technique allows high-throughput achiral separations to be performed using traditional reversed-phase stationary phases, but the platform is not successful for all compounds.
Radhakrishna Tirumalai, Ph.D.
While many contributing factors can play a role in affecting the quality of a medicine or its ingredients, microbial contamination control and issues related to sterilization must always be major considerations for any manufacturer. For both sterile and non-sterile pharmaceutical products, manufacturing processes must minimize potential risk to the patient and the product.
Wenning Qin, Ph.D., Jeffrey L. Stock, Rosalba Sacca, Ph.D.
Genetically modified models have been proven to be a powerful tool in drug discovery. The ability to genetically modify the mouse genome by removing or replacing a specific gene has enhanced our ability to identify and validate target genes of interest. Humanized mouse models include genetic modifications at the gene level ranging from single base changes to complete replacement of the murine gene with an orthologous human gene.
Igor K. Lednev, Ph.D., Vitali Sikirzhytski, Ph.D.
Since the discovery of inelastic (Raman) scattering nearly 90 years ago, Raman spectroscopy has become well-established as a powerful analytical method for various applications, including biochemical research. A Raman spectrum is a molecular vibrational signature of a (bio)chemical system, which offers information about structure and chemical composition.
George L. Reid, Ph.D., Howard W. Ward II, Andrew S. Palm, Koji Muteki, Ph.D.
The first steps in an Analytical Quality-by-Design (AQbD) method development include understanding the analysis needs (e.g., purpose, specificity, sensitivity, cycle time, on-line/off-line, qualitative/quantitative, accuracy, precision) and selection of the technique (which is at the receiving lab) that will meet these criteria.
Yiyun Huang Ph.D., Richard E. Carson Ph.D.
Drug development is a lengthy and costly endeavor. It is estimated that it costs close to one billion dollars to advance a single drug from discovery to the clinics [1]. This is a significant burden on the pharmaceutical industry, and in turn, on society as a whole, and may have contributed to the fact that despite the rapid advance in molecular biology in the last two decades and the identification of an increasing number of druggable targets, the number of approved drugs has been stagnant [2]. One way to contain the rising cost of drug development is to incorporate biomarkers and surrogate endpoints in drug discovery and development, as advocated in an FDA report entitled, “Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products [2].”
Justin Pritchard, Martin Warman
In pharmaceutical development, particle properties contribute to the process variability of a drug product and often the efficacy of the product. Studying particle properties during development builds process knowledge to ensure less variability and proper efficacy. The particle measurement capabilities typically employed in the pharmaceutical industry are expanding to enable Qualityby- Design (QbD) through enhanced particle characterization tools and process analytical technology (PAT) applications. Presented here are various methodologies that examine the physical and chemical attributes of drug product intermediates. NIR analysis coupled with Partial Least Squares (PLS) modeling enables a direct correlation between granules properties and product performance. Granulation states, specifically under-granulation, are investigated by morphology targeted Raman spectroscopy to provide the physical and chemical identities of particles in mixed populations. A method for testing granule hard
What challenges has MPI Research faced in offering bioanalysis of small molecules and how has the company overcome these challenges? The complexity of new chemical entities that our Sponsors are bringing forward continues to challenge our scientists’ expertise in developing and validating bioanalytical methods
1.In your particular realm of biologics manufacturing services, what are your biggest challenges in general and how are you working to overcome these challenges?
The industry trends we are seeing ask for flexible and cost-effective manufacturing facilities and processes.
1. What recent changes in the pharmaceutical industry led to an increase in handheld usage?
Increased government regulations for QbD/PAT led by the US and Europe that mandate 100% testing of incoming raw
Weiguo Dai, Ph.D., Sen Xu, Ph.D.
The number of poorly water-soluble compounds has increased dramatically thanks to the advancement of high-throughput compound screening methods and combinatorial chemistry. Such compounds are difficult to formulate, and tend to precipitate in vivo due to their low solubility, leading to low bioavailability. Formulation screenings are needed to overcome the issue of drug precipitation. In vitro high-throughput precipitation methods have been developed to evaluate drug precipitation of a large pool of formulations and identify precipitation inhibitors using a limited amount of materials within a short turn-around time. This article provides a brief review of such precipitation screening methods for oral formulations.
Luigi G. Martini, Ph.D., Patrick J. Crowley, Sarah Ibrahim, Ph.D.
Drug efficacy and safety have traditionally been considered as predicated by dose, its frequency and the duration of drug or active metabolite at the site of activity. Such variables are usually explored in investigative clinical trials prior to pivotal studies. It is increasingly apparent however that many additional influences can determine drug effects. Traditional clinical assessment programs can accordingly, and with hindsight be considered rudimentary. “Trial and error” was essentially the modus operandi. Simplistically “the wrong patient could be taking the wrong amount(s) of drug at the wrong time” (delivered to the wrong place). Such practices could also explain, to some degree the limited effectiveness of some current medications [1 and Table 1].
Peter Kraemer
Single-use components have been a well-established practice in laboratories and even for small-scale manufacturing for many years. Its migration into mid-scale biotechnology production of biopharmaceutical products, particularly for cell culture technology, is now also being promoted heavily. Key drivers are the arguments that it permits very cost-efficient and shorter implementation as compared with conventional stainless-steel components as well as tremendous flexibility with respect to product changeovers.