The following letter came in response to recent articles on lot-release testing and host-cell proteins:
Members of our peer-review board recommended publishing this longer than average communication.
A Rational Approach to Process-Specific Host-Cell Protein Detection
So-called generic host-cell protein (HCP) antibodies and assay kits have proven to be valuable for guiding purification process development. With comprehensive analytical validation, many of these assays demonstrate relevant specificities and sensitivities for use as lot-release tests. But concerns remain: Could they miss certain HCPs? Rather than require a comprehensive qualification/validation to demonstrate adequate reactivity to individual HCPs, European regulators suggest that applicants develop “process-specific assays” under the arguable assumption that the antibodies would be superior regardless how they are generated, purified, and incorporated into an assay.
Concerns about reactivity to individual HCPs are valid, but specific guidan...
During the past 30 years, advances in medicine and pharmaceutical research generated a new class of drugs called biologics. These drugs are complex proteins, carbohydrates, or other large molecules derived from biological sources (
1
). By contrast with more traditional pharmaceuticals (small-molecule drugs), biologics are not synthesized chemically from less complex components, but rather are derived from or manufactured using living organisms or extracted tissue (
2
)
Biologics make up a small but significant percentage of the overall pharmaceutical market. According to a 2009 Federal Trade Commission report, in 2007 American consumers spent ~$40 billion on biologics out of $287 billion spent for prescription drugs overall (
3
). Demand for biologics is also growing rapidly (
3
,
4
)
Because of their complex nature and the laborious processes required to manufacture biologics, they usually are considerably more expensive than small-molecule drugs. The yearly cost for products such as Humira (used to tr...
+1Bioprocess and pharmaceutical production environments must be well designed to meet strict cleanroom and quality assurance (QA) standards and productivity requirements. Managers may also consider innovative ways to enhance the design of these environments to enable the people critical to their companies’ success to be more productive and effective. In today’s work culture, countless hours can be lost to poor teamwork and ineffective communication. CGMP environments present additional, unique challenges to human interaction because of their built-in process and protocol barriers.
Effective space planning and design alone cannot create a culture of teamwork, but a lack of the right kind of space can inhibit it. Providing the right building blocks creates a place where a culture of teamwork can be developed: design of the right kind of space, staff training on how to use that space effectively, and management support of productive teamwork concepts.
Three key design strategies can help create this type of en...
Although a number of biomanufacturers have adopted disposable technologies for small-scale process design, there has been considerable debate over the role of single-use systems in large-scale biopharmaceutical manufacturing— particularly in retrofitting facilities. Some experts have gone so far as to suggest that large-scale stainless steel fermentors are “dinosaurs,” with their large capacities, long installation lead times, and low flexibility. I advocate a systematic approach to look holistically at possible retrofit technologies in existing (stainless steel) facilities, with particular reference to disposables.
My firm’s research suggests that in a retrofit setting, disposables have little proven value for reducing installation, materials, or labor costs. We instead look at such technologies in terms of their ability to reduce complexity in facility design and allow greatest flexibility in making changes to process design.
PRODUCt FOCUS: ALL BIOLOGICS
PROCESS FOCUS: PRODUCTION AND PROCESSING
WHO SHOU...
Single-use systems (SUS) have become an accepted component of animal-cell–based bioproduction. No longer a merely exciting possibility, they have emerged as a significant and growing resource for companies to use from process development to manufacturing of approved products. Having been examined for years in less regulated environments, off-the-shelf SUS are now in regular use to some extent in nearly every segment of the production train by contract manufacturing organizations (CMOs) and biopharmaceutical companies in mid-scale production applications. For many operations, in fact, the question has evolved from, Is there an SUS available that can support my process? to, Which system best supports my needs?
Drivers of this rapid acceptance and widespread use in such a conservative industry have been well reviewed in recent years as early adopters experimented with emerging technologies and products (
1
). In general, advantages are found in capital investment, cost of goods, safety, production scheduling...
RecipharmCobra Biologics, Keele (previously Cobra Biomanufacturing Plc) has been producing plasmid DNA for clinical trials for more than 10 years and has an approved site under the EU clinical trials directive. During this period, the company has produced more than 40 plasmids (ranging from 500 mg to 5 g) for 25 customers in Europe and the United States. These plasmids have been used for gene therapy and vaccines as well as to produce viral vectors. RecipharmCobra has developed its own manufacturing process and related technologies including an antibiotic-free plasmid maintenance system (ORT: operator repressor titration) and cell lysis technologies (
1
).
We assessed PlasmidSelect Xtra chromatography resin from GE Healthcare as part of an internal development program, the aim of which was to improve process robustness and resolution of key contaminants from the plasmid product. Although this work was part of a long-term development program, there was also an immediate requirement to address purity issues...
+3 Reusable bioreactors have been the benchmark standard for many decades, during which a large knowledge base on process control and scale-up has been developed. However, single-use bioreactors are increasingly being implemented in modern bioindustrial upstream processes. Many of these bioreactors deviate from the traditional stirred-tank design, but a number of companies have expressed a strong need for single-use bioreactors based on the strirred-tank design. A traditional stirred-tank design would enable users to optimize their scale-up processes based on both experience and well-established guidelines regarding scale-up elements as tip speed, mixing time, oxygen transfer, and specific power input. To meet that demand for improved scalability using single-use bioreactors, New Brunswick Scientific (NBS) has developed a new stirred single-use bioreactor called the CelliGen BLU system.
Single-Use Benefits
A stainless-steel bioreactor has predefined, fixed vessel port assemblies on both its headplate and ves...
Unexpected events — whether catastrophic like the oil leak in the Gulf of Mexico or a disruptive supply chain shortage — can change the future of a company. To prevent such difficulties or at least minimize their impact, life sciences companies spend millions of dollars on daily analysis of enterprise-wide risks.
Whereas supply chain and logistics are traditionally a focus of risk analysis teams, manufacturing and quality teams are now charged with improving process predictability. Through process understanding, that not only helps minimize risk in the event of a disaster, but it also provides immediate benefits such as predictable product supply, lower cost of goods sold (COGS) and inventory levels, and enhanced product quality, technology transfer, and regulatory compliance. A predictable process helps a company realize those benefits even when using a contract manufacturing organization (CMO).
Predictable Product Supply
Although supply chain logistics are basic to a predictable product supply, process ...
Packaging
Service:
Flexible options in final assembly and secondary packaging
Applications:
Drugs and biologics
Features:
An international specialist in aseptic fill–finish, Vetter offers a range of options for final assembly and packaging of pharmaceutical and biotech products. The company provides semi- and fully automated secondary packaging; labeling, blistering, cartoning with package inserts, and case packing; assembly of pens, autoinjectors, and other safety devices; and high standards of cosmetic integrity.
Contact Vetter Pharma International
GmbH
www.vetter-pharma.com
Microbioreactors
Product:
ambr workstation
Applications:
Drugs and biologics
Features:
TAP’s new, larger “ambr” microbioreactor system automates operation of 48 disposable microbioreactors and closely replicates characteristics of benchtop bioreactors at microscale (10–15 mL working volume). Those 48 are arranged in four sets of 12, each with a miniature internal impeller and individual closed-loop control of dissolved O
2
,...
IBC Life Sciences has been supporting and supplying the life science industry with specialized information through conferences and courses since 1987. IBC Life Sciences events offer attendees the opportunity to gain new insights and hear latest developments as well as provide a forum to meet, connect, and network.
New Directions for Diabetes Therapeutics
(16–17 February 2011): Hilton Boston Back Bay, Boston, MA
Viral Safety for Biologicals
(24–25 February 2011): Walt Disney World Swan Resort, Lake Buena Vista, FL
AsiaTIDES
(2–4 March 2011): Sheraton Miyako Hotel, Tokyo, Japan
Process and Product Validation
(14–15 March 2011): Hyatt Regency, Bellevue, WA
Technology Transfer for Biopharmaceuticals
(14–15 March 2011): Hyatt Regency, Bellevue, WA
Outsourcing Manufacturing of Biopharmaceuticals
(14–15 March 2011): Hyatt Regency, Bellevue, WA
Antibody Development and Production
(16–18 March 2011): Hyatt Regency, Bellevue, WA
Recombinant Proteins and Complex Biologic Development and Production
(16–18 Mar...
