Only recently did I finally get to watch the film
Contagion
, which was released this past fall. Sometimes the most provocative tests of our imagination come from our extreme fictional interpretations, and I was hopeful. (But remember
Outbreak,
the disappointing (if earnest) movie from the 1980s?) And I do believe this is a film worth recommending — both within and outside the industry.
Mostly taking place in biosafety-level laboratories,
Contagion
does show how hard it is to isolate and grow a virus before even developing a vaccine. This is an intelligent attempt to convey realistically the potential course of a worldwide epidemic, mainly from the perspective of investigators and government-employed researchers and clinicians. It is a different sort of disease disaster film, very subdued and largely focused on epidemiological investigations. Human interest is provided by Matt Damon’s quiet, desperate intensity as a man who happens to be immune trying to keep his daughter safe. Meanwhile a blogger pr...
Our “manufacturing” theme could be considered a sort of catch-all, encompassing much of what
BioProcess International
covers. You could argue that “the whole development process” is all about manufacturing biotherapeutics. But we instead consider this “pillar” of bioprocessing to include everything that isn’t strictly “upstream” (production) or “downstream” (processing) of biomolecules. Facility and supply-chain isssues come into play here, as do formulation and fill–finish (and of course, outsourcing). We discuss quality systems and their associated analytics in this context, as well, and product testing too. And increasingly over the past decade, the topic of cost control has entered and then begun to dominate our vernacular.
Facilities:
In BPI’s 10 years, the image of a typical bioprocess facility has been transformed. What once was dominated by gleaming stainless steel and hard piping is now a vision of smooth plastics and self-contained processes. We’ve gone from “the disposables option” (our firs...
The weakest link in the chain is also the strongest. It can break the chain.
— Stanislaw Jerzy Lec, Polish writer, poet and satirist (1906–1966)
Biologicals ushered in a new era for treating debilitating and life-threatening illnesses. According to a Pharmaceutical Research and Manufacturers of America (PhRMA) 2011 report, more than 900 biotech medicines and vaccines are in development that are targeting more than 100 diseases (
1
). Market researchers expect annual sales of biologics (now at about US$100 billion) to grow two to three times faster than conventional small molecule drugs during the next five years (
2
). Advances in cell line development, bioreactor design, and purification techniques have led to a sevenfold increase in global protein output from mammalian cell cultures alone from 2000 to 2005 (500 kg versus 3,600 kg) (
3
).
From a virological safety standpoint, biopharmaceuticals have had an excellent safety record during the past quarter of a century (
4
). This excellent safety profile h...
Almost every aspect of the biopharmaceutical and medical device industries raises regulatory compliance concerns. Heightened scrutiny is required across product lifecycles — from clinical trials to manufacturing, pricing, formulary placement, and promotional practices. Those areas (as well as patient privacy and adverse event reporting) require close attention to and compliance with healthcare laws, regulations, and guidelines. Part 1 of this two-part article describes statutes, regulations, and guidances applicable to the biopharmaceutical and medical device industries.
Anti-Kickback and False Claim Laws
Under the US federal anti-kickback law (
1
), it is illegal for any individual to offer to pay to induce a person to
Illegal payments include — directly or indirectly — kickbacks, bribes, rebates, cash, or “in kind remuneration. A person need not have actual knowledge of the anti-kickback statute or a specific intent to violate that statute.
Violations of the anti-kickback statute are deemed “federal hea...
Not long ago, I was playing the popular board game
Snakes and Ladders
(also known as
Chutes and Ladders
) with my son. Based on an ancient Indian board game, it has over the years become a worldwide classic. The game is rather simple to play: Two or more players place their tokens on a game board that has numbered, gridded squares. They take turns rolling a single die to move their tokens by the number indicated by the die, following a fixed route marked on the game board. A number of ladders and snakes (or chutes) are pictured on the board, each connecting two specific board squares.
The object of the game is to navigate your game piece from start to finish, helped or hindered by ladders and snakes, respectively. If, on completion of a move, you land on the lower-numbered square with a ladder, you can move their token up to the higher-numbered square. If you land on the higher-numbered square with a snake (or chute), you must move your token down to the lower-numbered square. The winner is the player ...
The US FDA’s quality by design (QbD) initiative and associated ICH Q8, Q9, and Q10 guidance documents are increasingly embraced by the biopharmaceutical manufacturing industry for ensuring consistent product quality and lower costs of development and manufacturing. One critical problem the industry faces involves understanding how to implement QbD and determine the benefit of such projects — which require the work of many groups across quality, manufacturing sciences, and engineering departments. Here we present the results from a survey of biopharmaceutical manufacturing professionals undertaken to determine current QbD understanding in the industry. We outline key gaps and show how QbD has been implemented in practice. We focus on simple, practical implementation of QbD principles and show the perceived value of such investment by industry.
QbD and ICH: A Primer
Extensive definitions of QbD and the associated ICH Q8–Q10 framework can be found in the references (
1
,
2
).
PRODUCT FOCUS:
ALLBIOLOGICS
PRO...
+1Due to the molecular complexity of monoclonal antibodies (MAbs) and potential impurities in cell culture media before purification (host-cell proteins, DNA, media components) (
1
), subsequent downstream operations must consistently and reproducibly purify products to ensure safety and efficacy.
The latest member of GE Healthcare’s MabSelect family is called MabSelect SuRe LX (
2
). As Table 1 shows, it has been developed using the same highly cross-linked agarose base matrix and protein A ligand as for other MAb affinity resins (Table 1). Here, we provide an overview of a novel system for MAb capture from a user’s perspective.
Table 1: Comparing the specifications for MabSelect SuRe and MabSelect SuRe LX protein A adsorbents; a higher dynamic binding capacity is observed (using a longer residence time) with MabSelect SuRe LX (MabSelect media, technical information, GE Healthcare).
Characteristics
Interaction involves fragment B of protein A, which establishes a highly selective interaction with IgG and i...
+2 Most biopharmaceutical production platforms are based on fed-batch cell culture protocols, which can support high volumetric productivity while maintaining low operational complexity (
1
). The industry is interested in developing or refining high-titer cell culture processes to meet increasing market demands and reduce manufacturing costs (
2
). Although advancements in cell engineering have enabled development of high-performing recombinant cell lines (
3
,
4
,
5
,
6
), improvements in cell culture media and process parameter settings are required to realize the maximum production potentials of those cells (
7
,–
8
).
In a fed-batch process, a basal medium supports initial growth and production, and a feed medium prevents depletion of nutrients and sustains the production phase (
9
). Those media can contain different assortments of nutrients to accommodate the distinct metabolic requirements during different production phases. Process parameter settings — including feeding strategy and control paramete...
+5 Knowledge of
k
L
a
(the volumetric mass-transfer coefficient that describes the efficiency with which oxygen can be delivered to a bioreactor for a given set of operating conditions) is not new. Here I provide information for those who are unfamiliar with the measurement method and/or issues that must be considered when making these measurements. Advances in this area now make it advisable to run
k
L
a
measurements routinely in many bioprocesses.
The Importance of Measuring
k
L
a
Before examining the process theory and tactical specifics of
k
L
a
determinations, it is essential to understand why
k
L
a
measurements are relevant and how they add value to bioprocesses. Dissolved oxygen (DO) is often the limiting substrate in fermentation and cell-culture systems. For bacteria and yeast cultures, the critical oxygen concentration is usually 10–50% of air saturation. Above that critical level, the oxygen concentration no longer limits growth. For optimum growth, it is therefore important to maintain D...
Biobanking Resource
Product:
CryoFeed microsite
Applications:
Cell and tissue banking
Features:
Wheaton offers a curated collection of information about preserving cryogenic biospecimens online. The company responded to an influx of questions about sample containment by creating the CryoFeed website. It provides biobanking-related news and technical tips as well as a place where users can discuss related issues. As samples are collected and cryogenically stored at hospitals, universities, research institutions, and pharmaceutical companies, Wheaton says interest in biobanking and long-term storage is increasing. The information is free, as is registration for using its interactive features.
Contact
Wheaton
www.cryofeed.com
Disposable Containment
Product:
TepoFlex biocontainers
Applications:
Fluid management
Features:
Meissner offers TepoFlex biocontainers in 50-L, 100-L, and 200-L sizes for use with cylindrical drums. These single-use containers can be configured with end-user–specified tubing len...
Plan now to attend this highly technical conference for just the right mixture of practical tools, regulatory trend overviews, emerging technologies, and product case studies. Bioassay scientists are intensifying their use of new technologies. Quality by design validations are becoming common, with statistical tools implemented during development, and cells are being developed for single-use applications. This is the must-attend event for bioassay professionals who want to keep up with these changes — where scientists gather to discuss how to overcome real technical obstacles.
If you are involved in developing critical assays, attend this meeting to find out new approaches and hear practical discussions centering on real-world problems and solutions. Learn how to get assays approved and functioning with today’s technologies. This conference focuses on tools you need to develop biological assays quickly and efficiently for successful product development.
Knowing what is state-of-the-art and expected by reg...
