Availability of the right information to the right people at right time is critical for understanding and improving existing processes within an organization. For a data-intensive industry such as biopharmaceuticals development and manufacturing, access to data and information enables companies to understand and streamline their operating and business processes. But most organizations fail to leverage such information for better decisions because they mismanage it. Some try to fill the gap between information and end users by introducing various applications and building data repositories but suffer from inherent complexities involved in integrating disparate sources.
This two-part article explores some related tools and technologies biopharmaceutical companies can leverage to build an efficient mechanism for capturing and delivering valuable information. In this issue, Part 1 focuses on infrastructure selection and how hardware, software, and information systems form an ecosystem. Simplicity, sustainabil...
It is often difficult to accurately anticipate quality standards across today’s global regulatory environments. In recent years, quality expectations have increased as a result of public demand and government regulation while regulatory requirements are often written with limited specificity. Regulations pertaining to parental cell lines (cells engineered to become biotherapeutic production cell lines) is one such area where current regulations leave room for interpretation. Here we explore some important considerations for determining quality standards for parental cell lines.
Cell Line Development
The science of cell line development is a complex balance of investments in platforms, technologies, and personnel to meet the increasing production demands within shortened development timelines. From expression enhancers to high-throughput screening techniques, the laboratory challenges of cell line optimization continue to grow. They now include the need for improving gene delivery and transfection efficien...
+1Most products in discovery by pharmaceutical companies today are biopharmaceuticals. Made by living organisms, these are typically large–molecular-weight products that rely on their secondary and tertiary structure for therapeutic effectiveness. Synthetic small molecules and biopharmaceuticals both require analytical verification for release, but only biopharmaceuticals require functional potency assays for investigational new drug (IND), biological license application (BLA), and new drug application (NDA) submissions. Those activities often require elaborate transfers of diverse, biological, product specific assays that carry greater chances of error. Shortcomings are common in bioassay transfer documentation, planning, and setting timelines, which cause costly processing delays.
Barriers to Success:
A common negative attitude is that analytical assays are more important than bioassays and given higher timeline and financial priorities. Another is that a binding assay will do for phase 1 release. Althou...
Commercial manufacturing of therapeutic monoclonal antibodies (MAbs) commonly uses mammalian cells to generate large quantities of a drug. Identifying cell lines that stably produce high protein titers is, therefore, a critical part of biopharmaceutical development. Unfortunately, identifying suitable cell lines is traditionally a time-consuming, labor-intensive process. That’s because their productivity and stability can vary enormously, so large numbers of clones must be screened to find those with both the highest yield and a desired level of product quality (
1
).
Cell-line development is unsurprisingly seen as a major bottleneck in biopharmaceutical development (
2
,
3
). With companies facing pressure to reduce costs and shorten development times, techniques to improve the efficiency of this process are in demand. Several methods have been developed, including fluorescence-activated cell sorting (FACS) such as the BD FACS system from BD Biosciences (
www.bdbiosciences.com
) and the ClonePix FL syste...
+4 A number of biopharmaceuticals are enzymes that act in vivo on high-molecular substrates. It can be a challenge to develop in vitro methods for accurately assessing their biological activity. Interest is also developing in using enzyme kinetic parameters as product quality attributes under the quality-by-design (QbD) initiative.
Among biotechnology therapeutics, the conventional method of expressing potency is in units/mg of biopolymer. For enzymes, a unit of activity was defined in 1958 by the International Union of Biochemistry and Molecular Biology (IUBMB) as 1 µmole of substrate per minute under specified assay conditions (
1
). Since then, the term
katal
(kat) has been adopted by International Union of Pure and Applied Chemistry (IUPAC) as a unit of enzyme activity (
2
). A
katal
is defined as 1 mole substrate per second. The IUBMB unit of enzyme activity as defined above is thus 16.667 × 10
−9
K
cat
(
3
).
PRODUCT FOCUS
: ENZYMES
PROCESS FOCUS
: ASSAY DEVELOPMENT
WHO SHOULD READ
: QA/QC, PRODU...
Some of the numerous feeding strategies are more appropriate than others for certain types of cell culture production systems. Once a nutrient supplement has been identified as described in Part 1 of this three-part review (
1
), a supplementation strategy must be chosen. Supplementing at too great a rate may expose log-phase cells to stresses such as increased osmolality and lactate levels that would inhibit biomass expansion. But inadequate supplementation can lead to early apoptosis through rapid depletion of selected important components. For commercially available supplements, guidelines often suggest specific protocols that will usually yield good results and can be further optimized by subsequent experimentation.
Additional culture-specific methods are available to laboratories with access to monitoring equipment. As mentioned in Part 1, monitoring one component is an excellent way of approaching relative nutrient homeostasis in the bioreactor, especially with stoichiometrically balanced nutrient s...
Bovine spongiform encephalopathy (BSE) and its potential to affect humans emerged as a concern in the 1990s. So suppliers of many essential animal-sourced components used in cell culture and fermentation processes became concerned about the potential for material contamination with prions. Viruses also can be present in raw materials derived from animal origins. Many important drug and vaccine products are made by mammalian cell culture or bacterial fermentation, so their biological safety is paramount. However, it is very difficult to ensure that any material from an animal source carries no infection. Even the rigorous cleaning methods designed to minimize carry-over of biohazards from one batch to the next is no guarantee of safety.
Because it’s difficult to identify and purify components made from animal sources, the safest way to minimize risks from associated pathogens is to, whenever possible, use raw materials of nonanimal origin. However, eliminating animal-sourced products from a manufacturing f...
Ireland is an exciting place when it comes to research, development, innovation, and commercialization in biologics and life sciences. The government of Ireland’s strategy for Science Technology and Innovation (ST&I 2006–2013) includes key deliverables stressing the importance of a dynamic infrastructure to enable further growth in these important fields. A strong foreign direct investment policy has secured >US$5 billion from global players including Genzyme, Centocor, Merck, Wyeth, and Pfizer in recent years. Ireland also has built a strong indigenous biotech sector with companies such as Elan, Trinity Biotech, Merrion Pharmaceuticals, Sigmoid, Eirgen, and Opsona. A high level of government funding (through Enterprise Ireland, IDA Ireland, and Science Foundation Ireland) supports growth and a strong foundation of science and technology in the country’s academic institutions as well as its infrastructure for business and academic collaborations.
In January 2009, Enterprise Ireland launched an industry-le...
