Ralph Lipp, Ph.D.
The oral route of administration is central for the delivery of a large
number of important drugs in various therapeutic areas, and many
patients prefer standard oral dosage forms as well as advanced oral
drug delivery systems over other dosage forms. This preference stems
from various factors including the non-invasiveness, ease-of-use, and
reliability of oral dosage forms.
Michael Pohlscheidt, Robert Kiss
Since the early 1980s, biotechnology products have shaped the
pharmaceutical industry. A large number of monoclonal antibodies
and therapeutic proteins have been approved, delivering meaningful
contributions to patients’ lives, and are anticipated to be the major
growth driver for the industry in the upcoming years [1-5]. In 2012,
the list of the top 20 best-selling drugs included 8 biologics
Andrew L. Fussell, Antti Isomäki, Ph.D, Clare J. Strachan, Ph.D
Nonlinear optical imaging is an emerging technology with much
potential in pharmaceutical analysis. The technique encompasses a
range of optical phenomena, including coherent anti-Stokes Raman
scattering (CARS), second harmonic generation (SHG), and twophoton
excited fluorescence (TPEF).
Fifteen years is actually a short time span for changes in
microbiology. Yet, we’ve seen an increase in considerations for
alternative methodologies (rapid micro). Suppliers of new technology have
begun to ask customers how to apply their technology and have revised
their instrumentation packages to fit many different environments.
Rachel G. Forcino, Ph.D., Glenn R. Williams, Ph.D., Jeff Brum, Ph.D., Frederick G. Vogt, Ph.D.
Milling is frequently used in pharmaceutical processing to achieve
particle size reduction to enhance the bioavailability of poorly soluble
active pharmaceutical ingredients (APIs). The intent is to achieve
particles with favorable size distributions that enhance dissolution
rates due to their increased surface areas. Milling may also be used
to obtain a consistent particle size distribution of the API for ensuring
content uniformity of the dosage form.
Dev Prasad, Harsh Chauhan, Ph.D
Drug targeting is defined as the ability of a drug molecule to accumulate
in the target organ or tissue selectively such that the concentration
of the drug at the disease site is high, while its concentration in nontarget
organs and tissues is low, preferably, below certain minimal level
so as to prevent any toxic effect. Thus, drug targeting can overcome the
non-specific toxic effect of conventional drug delivery.
Sajal Manubhai Patel, Ph.D., Brian Lobo, Ph.D., Ambarish Shah, Ph.D.
Biopharmaceuticals are routinely freeze-dried to improve product
stability and, thereby, achieve acceptable commercial shelf life.
However, freeze-drying is a unit operation coupled in formulation and
process. While selection of excipients is primarily focused on improving
product stability, for a freeze-dried product an additional consideration
is the compatibility of the formulation with the freeze-drying process.
The rational selection of excipients for freeze-dried product has been
reviewed extensively [1-3].
Paul Wu, Ph.D.
When the antibody titer reaches beyond 5g/L in the upstream process,
the downstream process logistics is challenged due to the number of
cycles it must process. In addition, high protein concentration may cause
precipitation or localized dimerization. Such are the common discussions
the industry has when linking upstream to downstream process.
Manuel Ventura, Ph.D.
Often pharmaceutical intermediates require chiral purification by SFC
after a reaction step to isolate enantiomers of divergent biochemical
activity[1-4]. Following a reaction, achiral impurities are always present
at some level relative to the desired product, often significant even after
normal phase “clean up” separation in advance of chiral purification.
Frequently, conditions with one chiral stationary phase (CSP) among
an SFC screening set are found that separate the enantiomers and
concurrently separate interfering achiral impurities such that an
efficient scale up method is possible with one chiral column.
John Duguid
In June 2013, the European Medicines Agency (EMA) approved a realtime
polymerase chain reaction (Real-Time PCR) Mycoplasma test
for lot release of matrix-applied characterized autologous cultured
chondrocytes (MACI®).
Patrick J. Cullen, Ph.D., Ian Jones, Laura Alvarez-Jubete, Ph.D., Jaya Mishra, Carl Sullivan, Ph.D.
Cleaning can generally be defined as the removal of unwanted
contaminants to ensure safety, efficacy and quality of the product
subsequently manufactured using the same equipment [1]. Cleaning
validation is the documented evidence demonstrating the effectiveness
of a cleaning procedure based on pre-determined acceptance criteria.
Intellicentic™ refers to a broad mix of consulting services and advanced
platform technologies developed in concert with key pharmaceutical
manufacturing suppliers, service providers and Pfizer Incorporated’s
experience and broad manufacturing knowledge. These platforms
are based on technologies developed for Pfizer internal use. The main
focus of the Intellicentic solutions is on de-risking the processes,
reducing variation, improving yield, costs, cycle time and overall
agility and predictability of manufacturing processes.
Tim Sandle, PhD
Dry heat is the established method of depyrogenation within the pharmaceutical industry. This
paper describes a series of studies undertaken to determine whether successful depyrogenation
can be achieved practicably using methods other than dry heat. Depyrogenation refers to the
removal or inactivation of pyrogens. In practice, depyrogenation processes are qualified by
demonstrating that they are capable of reducing bacterial endotoxin to an acceptance level.
Kevin L. Williams
Limulus Amoebocyte Lysate (LAL) users are exploring regimens to study the effects of adding
endotoxin to undiluted biologics in reaction to Chen’s studies (Genentech) on Low Endotoxin
Recovery (LER) [1] and, moreover, in response to the addition of verbiage to the FDA Q&A Guidance
[2] on establishing the “stability of assayable endotoxins content”1 in biologics.
Michael E. Dawson, Ph.D., RAC
Within the last two years, there have been developments in two areas of regulatory significance to
endotoxin testing. The first concerns changes to the Bacterial Endotoxins Test (BET) chapter in the
United States Pharmacopeia (USP). The second is the release by the US Food and Drug Administration
(FDA) of a guidance document on pyrogen and endotoxins testing in June of 2012.
Karen Zink McCullough
The fifteenth anniversary of American Pharmaceutical Review prompted my reflection on the 40+ years of
evolution of the Limulus Amebocyte Lysate (LAL) test in our industry. This article will reflect on where the
Bacterial Endotoxins Test (BET) was 15 years ago and predict what the future holds for the next 15.
Kim Bowers, Lynn Johnson
Endotoxin is a lipopolysaccharide structure located in the cell wall of Gram-negative bacteria. Since
endotoxins belong to a group of fever-causing substances called pyrogens, parenteral drug products
that may contain endotoxin can elicit a pyrogenic reaction in patients. The FDA has established
a pyrogenic threshold of 5-endotoxin units/kilogram (EU/kg) of body weight. Endotoxin exposure
beyond this level may induce fever, shock, and death. It is critical that endotoxin levels are monitored
and controlled in biomanufacturing processes and products for reasons of safety and compliance.
The Limulus Amebocyte Lysate (LAL) assay is often used to measure the level of endotoxins in
biological products.
Associates of Cape Cod, Inc.’s (ACC) fourth generation tube reader,
the Pyros® Kinetix Flex, offers the most sensitive bacterial endotoxin
test (BET) available for both turbidimetric and chromogenic kinetic
methods. In addition to flexibility of test method, ACC offers a choice
of 32, 64 and 96 well readers. All of these readers provide the flexibility
to add tubes at any time. Unlike a microplate reader, additional
samples can be added after a test has been started. Also, we shall soon
have an exciting new offering in the area of endotoxin testing.