John Bray
The adoption of technology for use in the pharmaceutical industry
has historically been sluggish and often late to arrive when compared
to other industries. This is primarily due to concerns regarding both
the physical safety of patients and the protection of private patient
information. While the consumer market has been quick to take
advantage of social media outreach, cloud technology and mobile
software applications (apps), the pharmaceuticals industry has
been hesitant despite potential value.
Markus Haberger, Lea Bonnington, Katrin Bomans, Maria Maier, Susanne Eltner, Markus Dembowski, Dietmar Reusch, Patrick Bulau
Chemical and post-translational modifications, including crystallizable
fragment (Fc) glycosylation, that occur in the marketed IgG1 antibody
trastuzumab have been extensively reviewed. Glycosylation
of therapeutic proteins is crucial for their biological activity.
Glycosylation profiles vary depending on, for example, production cell
type used, fermentation process, or even production scale. Variance
in glycan patterns based on manufacturing variability was described
also for marketed antibody products. This variability might be even
more pronounced during development of monoclonal antibodies as a
result of multiple changes implemented during process optimization.
Tony Cundell, Ph.D.
Recent high profile product recalls associated with mold contamination
has resulted in more attention from the FDA to fungal isolation in
environmental monitoring and product testing in the pharmaceutical
industry. Companies need to anticipate these FDA concerns especially
with respect to the upcoming regulatory inspections and institute
remediation when mold is found in their products and manufacturing
facilities to protect patient safety.
Karen Ginsbury
No think tank or article on hot micro topics
would be complete without discussing rapid methods. There are
many available. For the most part, pharma companies seem to have
implemented these mostly in the area of microbial identification.
However, there are increasing interesting offerings in the area of real
time counts of viable and total particles where the total particles
include and can distinguish viable organisms.
Donald L. Jarvis, PhD, Ajay Maghodia. phD, Christoph Geisler. phD
Since 1983, the baculovirus-insect cell system (BICS) has been used to
produce thousands of different recombinant proteins for diverse areas
of biomedical research.
Since 2009, the BICS has also been used to
manufacture biologics for human or veterinary medicine.
Four BICS
products are currently approved for human use and several others
are in various stages of human clinical trials.
Thus, the BICS is now
recognized as a bona fide biologics manufacturing platform.
Sasmit Deshmukh, Kamaljit Bhandal, Bruce Carpick, Marina Kirkitadze
Manufacturing of vaccines is a lengthy and labor-intensive process
that involves numerous steps. This entire process can take
from 6 to 22 months and each step needs the appropriate controls to
comply with the standards of Good Manufacturing Practices (GMP).
Upon completion of these steps, the vaccine is released for human use.
Márcio B. Machado, Suzanne M. Kresta
The scale-up/down of an industrial process is still a big challenge.
The mixing conditions should ideally be matched between scales but
this is not always feasible. The difference in vessel sizes can vary
from as small as 200 mL in bench scale shake flasks to industrial scale
bioreactors with more than 10 000 L.
Teri McClerklin-Small, Gilberto E. Espinoza, Lisa Mueller
Each year, brand-name pharmaceutical companies spend millions of
dollars researching and developing new drugs. Despite the huge sums
spent, only a handful of the drugs developed become candidates for
further safety and efficacy investigation. Even fewer are ultimately submitted
to the U.S. Food and Drug Administration (FDA) for approval. By
the time the FDA approves a drug, brand-name pharmaceutical companies
have spent tens of hundreds of millions of dollars (if not more)
to obtain FDA approval to market the drug. To protect this investment,
brand-name pharmaceutical companies obtain patents covering their
drug, which the company is required to list in the electronic Orange
Book.
Cheryl Platco, Jordan Kave, Edward C. Tidswell
The Low Endotoxin (LER) and Lipopolysaccharide Recovery (LLR)
phenomena have been debated as a Limulus Ameobocyte Lysate
(LAL) test validity issue peculiar to therapeutic monoclonal antibodies
for over three years. The FDA division reviewing Biological License
Applications has requested that firms provide data which demonstrate
the stability of assayable endotoxins as required in the FDA issued
A major trend among
pharmaceutical companies today is the movement from traditional
microbiology detection methods to rapid micro detection methods.
Traditional microbiology methods require days to weeks to confi rm
the absence of microbial contamination. With current pressure from
the industry to streamline manufacturing processes, pharmaceutical
manufacturers are looking to rapid micro methods to quickly release
product from micro hold.
Alfred C. F. Rumondor, David Harris, Francis Flanagan, Varsha Biyyala, Mary Ann Johnson, Dina Zhang, Sanjaykumar Patel
A multiparticulate formulation technology can be beneficial in designing
a patient-centric dosage form. One such dosage form is
minitablets, which are compressed tablets with typical diameters of
one to four millimeters. Minitablets can offer versatile applications,
including as a pediatric dosage form, for patients with dysphagia, and
uses where rapid or flexible dose adjustments are needed. Variations
of the tablet formulation and coating systems can achieve specific
functionalities such as orally disintegrating tablets (ODTs), extended
release formulations, or gastrointestinal-targeted delivery.
Stefan R. Schmidt
Over the last decade disposable equipment has become an integral
part of many biologics manufacturing processes. But it should not
be forgotten that this revolution started more than 20 years ago in
research labs with the introduction of small scale prepacked columns
and the the single-use, wave-rocking bioreactor introduced in 1999.
Yan-ping Yang
The vaccine industry is one of the fastest growing sectors in the global
economy. Since the year 2000, the global vaccine market has thrived
– reaching over $17B in mid-2008, and almost $24B by 2013. Sales are
expected to reach $100B by 2025, an approximately 10-fold increase
over 2005 ($10B), mainly driven by an increasing demand for existing
vaccines plus new vaccine products.