Mathias Romacker
The last few years have not been easy for the pharmaceutical industry. There has been a slowdown in sales in developed countries, pressure on drug prices; mega mergers and lay-offs. Quite a few marketed or promising pipeline drugs were either scrutinized by regulatory bodies or may not even make it to market. This decade many mega blockbusters will lose their patent protection; many blogs suggest that existing pipelines will not be able to replace anticipated revenue losses.
Vicky Kett
Development of freeze-dried products can be a laborious and costly process. If knowledge of the critical processing parameters can be obtained, then formulations can be optimized to give the best possible stability, while simultaneously freeze drying protocols can be shortened to reduce costs.
Jennifer C. Gray, Alexandra Stärk, Manfred Berchtold, Manuel Mercier, Gunther Neuhaus, Andreas Wirth
There are many reasons why the traditional sterility test, with its lengthy 14 days incubation time, should be replaced with a Rapid Sterility Test. As a consequence to the 14 days incubation time, possible product-contaminations and the respective corrective actions are delayed resulting potentially in an enlarged amount of affected product batches. Another important advantage of shorter incubation time is for example reduction in the release time for sterile products, therefore reduction of stock keeping costs and earlier market delivery. Furthermore, the use of RMMs (rapid microbiological methods) is highly supported by regulatory guidance documents, which request pharmaceutical microbiologists to use these methods.
David P. Elder, Ph.D
One of the least desired outcomes of utilizing combinatorial and high throughput chemistry has been a marked increase in poorly soluble drug candidates [1]. The number of poorly soluble new drugs entering development has been estimated to be anywhere from 40% to 70% [2]. Most companies are increasingly focusing their attention on the bio-pharmaceutics properties of their drug candidates (particularly solubility and permeability) to understand the impact on clinical exposure. Butler and Dressman [3] advocated a Development Classification System (DCS) that builds upon the pioneering work of the Biopharmaceutical Classification System (BCS) [4).
Rick Stock, Ph.D.
The current state of the world economy, drug pricing control and stricter quality and regulatory standards, are forcing large and emerging biotech companies to change their overall approach to risk compared to a decade ago. This has led to a focused demand for improved process optimization and more efficient overall operations as a way to keep expenses down. This has created an opportunity for bringing disposables from the current growth at the clinical scale to potential implementation of single-use technologies in the commercial landscape.
Christopher John, Christina Bacci
As the pharmaceutical industry has changed, so have the ways scientists use dissolution testing. In today’s drug development process, scientists must carefully balance the need for at least three different types of dissolution workflows. The workflows are listed below in sequential order from early to late stages of drug development.
James M. Roberts, Ph.D., Mark F. Bean, Ph.D., William K. Young, Ph.D., Steve R. Cole, Ph.D., Helen E. Weston
Wide scale adoption of autosamplers attached to analytical instruments enabled a step-change increase in productivity in the laboratory. For the first time, analytical chemists could generate high quality data without being in the lab continuously. Today, we take this capability for granted and it’s difficult to imagine manually introducing every sample to an instrument.
Keith Bader
As Total Organic Carbon (TOC) analyzer technology improves, industry is more able to utilize it for real time release of clean utilities and for cleaning process risk mitigation. As end users determine and communicate their goals in the use of TOC and other process analytical technologies (PAT) for cleaning systems, the requirements and specification for off the shelf analyzers will evolve to meet those goals. Unfortunately, industry has been somewhat reluctant to adopt PAT until a precedent of regulatory acceptance has been set, resulting in a functional evolution of online instrumentation that has been slow to meet current needs. However, through careful analysis of process requirements and corporate quality and risk management goals, currently available instruments can be selected to meet end user goals and still drive the development of improved analytical instrument and sensor technologies.
Jan Möschwitzer, Ph.D.
Over the last decades, production methods for drug nanocrystals have attracted a lot of interest, especially due to the increasing number of poorly soluble compounds in the drug development pipelines. The formulation of these compounds can help to overcome issues generally related with poor aqueous solubility of the active pharmaceutical ingredients (APIs). Typical issues of the compounds are: low oral bioavailability, food effects, incomplete or erratic absorption and a relatively high patient-to-patient variability. By reducing the size of the API to the nanometer range, the effective surface area is significantly increased which leads, consequently, to a faster dissolution rate. This relation is explained by the well-known Noyest-Whitney equation. Furthermore, very small drug nanocrystals show also an increased saturation solubility, which is explained by the Ostwald-Freundlich equation [1]. Distinctly increased dissolution rate can compensate the negative influence of the poorly so
Zhong Li, Ph.D., Joe A. Schariter, Jingtao Zhang, Ph.D.,, Jared C. Davis, Anthony M. Leone, Ph.D.
The discovery of RNA interference (RNAi) as a mechanism to selectively silence messenger RNA (mRNA) expression holds potential for revolutionizing biomedical research and drug development. The use of small interfering RNA (siRNA) as a target validation tool and therapy has become a major focus of industrial and academic laboratories. One of the primary challenges in realizing the full potential of siRNA therapeutics is the efficient systemic delivery of siRNA to the target cells. Liposome-based formulations in lipid nanoparticles (LNPs) have become the most promising and widely used strategy for in vivo delivery of siRNA. The complex nature of liposomal formulations containing duplex siRNA oligonucleotides and multiple functional lipid excipients presents a great challenge to the successful physicochemical evaluation of the siRNA LNPs. Ultra-high performance liquid chromatography (UHPLC) plays a critical role in characterizing the chemical properties of the LNP formulations. The high-t
Jennifer Van Anda, Ph.D.
Pharmaceutical drug discovery depends increasingly on speed and efficiency. Currently there is an ever increasing drive to decrease turnaround times for samples. Over the past six years, SFC has been adopted as the instrumentation of choice for the purification of chiral pharmaceutical compounds based on savings in production time and cost [1]. Many researchers have worked on developing an in-house mass directed SFC for achiral purifications [2]. The commercial availability of a mass directed supercritical fluid instrument has now made the purification of achiral pharmaceutical compounds a real possibility. The use of the MS-directed collection of the peak of interest eliminates some of the other steps previously needed to insure collection of the peak of interest using UV detection [3]. The AstraZeneca drug discovery laboratory has now turned to SFC for the purification of both chiral and achiral compounds.
Jun Huang, Ph.D., Saly Romero-Torres, Ph.D., Mojgan Moshgbar
In recent years, vibrational spectroscopic instruments such as Raman and Near Infrared (NIR) in conjunction with multivariate calibration routines have become increasingly important process analyzers in the pharmaceutical industry [1-24]. These analyzers offer several advantages over conventional wet chemistry techniques, which include non-invasiveness, little or no sample preparation and rapid measurements. Raman and NIR sensors can provide critical quality information during different stages of the active pharmaceutical ingredient (API) and drug product manufacturing, and are commonly employed during raw material dispensing, chemical reactions (mostly Raman), granulations, drying (mostly NIR) and powder blending. They can also be used as non-destructive quality verification techniques, particularly for polymorph detection/quantification, blend potency and uniformity, and tablet/capsule assay/content uniformity, among others. NIR and Raman spectroscopy are complementary techniques in
Maria Gerald Rajan, Ph.D., Himanshu Bhattacharjee, Ph.D., Sonia Bedi, Ph.D., Joseph Reo, Ph.D.
As a result of the Process analytical technology (PAT) initiative by FDA known as “Pharmaceutical cGMPs for the 21st century- A Risk Based Approach”, considerable work has been done on developing various analytical technologies that could be used as an integral part of PAT. Of all the efforts that have been put into practice to date, near infrared (NIR) spectroscopy is one of the most important tools that can be utilized in the product development process. The main advantage to this technology is that NIR spectroscopy can be employed at various stages of the process to achieve a more robust product through a more efficient process.
Cynthia S. Randall, William L. Rocco, Pierre Ricou
There is a wealth of published material on specific pharmaceutical applications of XRD [1-6]. The non-destructive nature and relative ease of sample preparation make XRD ideal here. In particular, the XRD pattern represents a crystalline drug “fingerprint” needed for patent descriptions, and to identify different drug batches. Other XRD pharmaceutical applications are excipient compatibility, optimization of process parameters, detection of form impurities, crystal morphology of active, and monitoring batch or dosage uniformity.
Sheng Qi, Duncan Q.M. Craig
The use of solid dispersions, defined broadly as involving the dispersion of a drug in a polymeric carrier via a liquid intermediate, has been a highly studied approach for drug delivery since the 1960s [1-4]. The greatest single driver for the use of this technique has been the remarkable improvements in dissolution rate that may be observed for poorly water soluble drugs, with increases that went up to orders of magnitude being frequently reported [5,6]. Development of formulation strategies for poorly water-soluble are perhaps even more important now as significant numbers of new chemical entities which show highly promising pharmacological effects for many severe diseases such as HIV and cancer, have low aqueous solubility and fall into Class II or IV of the Biopharmaceutics Classification System [7].