Julianne Wolfe, Karen Smith
Foreign particulate matter (FPM) can affect product efficacy, but more critically, it can affect product safety leading to recalled product or regulatory action (eg, FDA warning letter). FPM investigations can be costly and sometimes inconclusive which complicates decisions about product release. There are ways to streamline these investigations through an approach in line with Quality by Design (QbD). Particulate programs couple the right characterization technique, a proven method for historical data organization, more enhanced manufacturing process understanding, and risk-based decision making. These attributes of a particulate program come together to enhance the quality of FPM investigations in a manner that is cost effective, efficient, and, most importantly, conclusive.
Igor Gorsky
The primary aim of this article is to stress the importance of equipment cleaning as an official process.
The main advantage to working with EMD Millipore is that in addition to a full range of products for both traditional and rapid sterility testing, we also have 40 years of industry, method and regulatory expertise in sterility testing.
John E. Essex III
Horseshoe crabs, those unassuming, overturned bowls of the sea, have
an amazing hidden superpower. What makes them so special? There
are a few factoids you might see in a biology textbook—they have blue
blood, 10 eyes, are more closely related to spiders and scorpions than
crabs, and, during their approximate 450-million-year existence, have
survived more than one mass extinction and global catastrophes1—
but those facts aren’t what really makes them special.
Microbiological monitoring plays an important part in
assessing product quality, although foremost consideration
should be given to environmental and process controls. Through the
use of smart risk assessment, monitoring can be orientated to those
parts of the process that are theoretically at greater risk. An example
would be open processing.
Jane Li, PhD, Hong Lin, MS, Christine Gu, PhD, Priscilla Mantik, Stefanie Gee, Peter Yehl, PhD
Drug formulation starts with the selection of various suitable excipients for the desired or required dosage forms. Drug-excipient interactions can greatly impact pharmaceutical development on multiple aspects, including drug properties (eg, polymorphic forms), manufacturability and processes, drug product stability, and bioavailability, which in turn affects product efficacy and safety.
Pharmaceutical excipients are broadly defi ned as, ‘"Any
component other than the active principle added
intentionally to the medicinal formulation." Thus, although by defi nition
excipients are required to be pharmacologically inert, their use in drug
products is ubiquitous. Excipients are used in virtually all pharmaceutical
formulations and serve valuable function in one or more domains of
drug product development.
NIR spectroscopy provides fast, reliable and non-destructive
measurements, and it can evaluate many different parameters.
Laboratory NIR instrumentation is robust and flexible, and various
sampling accessories could be used—depending on the sample
nature—to improve the sample presentation. Modular sampling
accessories allow for analyses of powders, granules, solids, slurries,
gels, pastes, and turbid or clear liquids. Since NIR analyses are
performed on unmodified samples, presenting the samples to the
instrument is the most important aspect of NIR analysis. The modular
design of laboratory NIR instruments ensures that analyses are
optimized for specific sample types.
Bei Ma, Le T. T. Huong, Yong Liu, Ph.D., Magdy M. Kamel, Edward Zhao, PhD, MBA
Counterfeit drugs are a global problem with significant and well documented consequences for global health and patient safety, including drug resistance and deaths. This multibillion-dollar industry exists beyond geopolitical borders, and threatens public health in both developed and developing countries and regions.
Millrock focuses on sophisticated laboratory freeze dryers as well as custom pilot/production systems up to 200 square feet. Our laboratory equipment can be supplied as a basic freeze dryer or with the most sophisticated control systems for developing protocols. The demand for sophisticated/custom lyophilizers continues to increase.
C.J. Venkatramani, Mohammad A. Al-Sayah, PhD.
Synthesis of Active Pharmaceutical Ingredients (APIs) is a multi-step
process involving the use of reactive chemicals, reagents, solvents,
catalysts, and salts. Residual levels of process-related impurities,
byproducts, and degradants could have adverse health effects.
To ensure patient safety, global regulatory agencies require API
manufacturers to reduce the levels of such compounds to safe levels.
International Conference on Harmonization (ICH) documents Q3A(R2)
and ICH Q3B(R2) provide guidance on limiting the majority of these
less toxic impurities in new drug substances and drug products
respectively.
Thorsten Lorenz, PhD, Jocelyne Fiaux, PhD, Daniel Heitmann, PhD, Kapil Gupta, PhD, Hans P. Kocher, PhD, Hans-Peter Knopf, PhD, Steffen Hartmann, PhD
Turning a biologics candidate into a viable drug requires consideration of two major aspects. On the one hand, excellent biological properties are needed to ensure safety, efficacy, and desired pharmacokinetics; on the other hand, an optimal developability profile is needed to ensure that a treatment option can be translated into a true therapeutic through technical development.
Harshada Sant, MS, Hemant N. Joshi, Ph.D., MBA
A number of patents are issued every month to pharmaceutical companies. The purpose of this column is to highlight and summarize key patents issued in the last quarter by the US Patent O ffice.
Cheryl Platco
Low endotoxin recovery (LER) was first described publicly at the PDA Annual Meeting in Orlando
Florida, in April, 20131 but the phenomenon has been observed by pharmaceutical scientists for
years, mostly as classical “inhibition” during sample qualification testing.
Tim Sandle, PhD
The Limulus amebocyte lysate (LAL) assay is the compendial test for the examination of bacterial
endotoxin in pharmaceutical products (as described in USP chapter <85>), in-process material,
and pharmaceutical grade water.
Jeffrey Weber, Gerard Ryan Jr., Susan Berlam
Bacterial endotoxin (or lipopolysaccharides), are structural parts of many Gram negative bacteria cell
walls released during cell lysis that can create a pyrogenic (fever inducing) response in humans. All
major compendia prescribe bacterial endotoxin testing (BET) and/or pyrogen testing to ensure that
pharmaceutical products will be safe for use. The most common testing method is measuring the
enzymatic reaction between bacterial endotoxin and the white blood cells of the horseshoe crab,
Kevin L. Williams
Bacterial Endotoxin Test (BET) users seek ways to overcome low
endotoxin recovery (LER) from direct spikes into undiluted biologics.
These studies have come about from Chen’s initial observation1 that
Control Standard Endotoxin (CSE) spikes, when placed into undiluted
biologics, buff ers, and other constituents often cannot be recovered.
By changing the endotoxin spike requirement from diluted product to
undiluted product, users will unsurprisingly encounter test interference;
what is unexpected from Chen’s LER fi nding is that recovery sometimes
cannot be improved by dilution. This is indicative of a still undefi ned
binding phenomenon.
Karen Zink McCullough
Various Bacterial Endotoxin Test (BET) assays, starting with the gel clot test and working through
endpoint and kinetic assays, have been used in our industry for almost 40 years, and have performed
remarkably well as tools for predicting pyrogenicity in parenteral products–all of which is thanks
to the horseshoe crab. To think that this simple, ancient creature can make such a difference in
the quality of the world’s medical supply is astounding. Dr. Frederick Bang, one of the fathers of
Limulus amoebocyte lysate (LAL) technology termed this, “serendipity.” Isn’t that the way most great
discoveries are made?