Figure 1:
ZAP-CHO enhances performance of mammalian cell culture by optimizing cell growth and reducing apoptosis, leading to higher antibody production yield. It achieves these performance advantages in commercial media, especially chemically defined media and serum– or animal-component–free media. Because ZAP-CHO is defined and free of animal components, it is an ideal additive for cell culture media formulations.
ZAP-CHO is an important breakthrough in mammalian cell culture operations. Previously, the performance seen with ZAP-CHO required the use of hydrolysates, FBS (fetal bovine serum), BSA (bovine serum albumin) or plasma-derived HSA (human serum albumin). However, those components can cause unwanted variability or concerns about adventitious contamination of infectious pathogens. ZAP-CHO eliminates these concerns because it optimizes cell culture performance and is a defined component that is completely free of animal components.
ZAP-CHO is used for faster cell line development and seed train exp...
Interruptions in bioproduction pose serious setbacks for biopharmaceutical companies. Shipping delays, performance variability, quality unknowns, and regulatory issues can delay time to market and ultimately depress a producer’s financial results. Unforeseen variability in process parameters has led the US Food and Drug Administration to insist that biopharmaceutical manufacturers find ways to ensure batch quality of a drug product during manufacture without relying solely on finished product characterization. This challenge is daunting, considering the large number of raw materials required for production and the complexities of cell culture systems.
To meet the industry’s requirement for enhanced raw material characterization, SAFC Biosciences® has developed innovative analytical and assay methods that provide customers with biopharmaceutical raw material standards that ensure process development control, production quality, and supply chain security.
Defining Undefined Components: Hydrolysates
Hydrolys...
While CMOs have traditionally been used to play a critical role in the manufacture of drug product, Althea has evolved beyond being a role player to a strategic development and manufacturing partner that can drive value to a client’s product or product candidate. As drug development costs are always increasing, a properly integrated development and manufacturing scheme can significantly decrease development time and expense, while increasing the probability of clinical success and product differentiation. To allow clients to leverage such an integrated development plan, Althea has greatly expanded its expertise and capabilities across the spectrum of product development activities and manufacturing scale.
Product Development: Process Development, Formulation Development, Lyo Cycle Development
Understanding that every product is unique, our process development team uses DOE and QbD methodology to develop CGMP-ready processes that are optimized to yield the highest quality product in the most efficient way ...
Angel has provided contract development and GMP manufacturing services for recombinant proteins, antibodies, and vaccines since 2001. Responding to market demand, Angel has also built an impressive track record delivering advanced (live) biologics comprising cell therapies including stem cells, cellular vaccines, and bacteriophages. Angel is one of very few European companies providing specialist GMP manufacturing support of these products for international clients.
Comprehensive Solutions
Angel offers vertically integrated manufacturing solutions reducing risk, cost, and timelines for clients. We believe that flexible partnering with our clients to meet their needs is essential for successful delivery and realizing their longer term product strategy. We underpin our partnering approach with high-quality project management and effective communication. We understand that these are essential to ensuring that our clients’ projects are delivered on time and within budget. Angel also offers management of subco...
Adedicated contract manufacturing organization supporting the biotechnology and pharmaceutical industries from preclinical process invention to postlaunch, commercial scale manufacture
.
Avecia’s industry-leading expertise enables customers to improve the cost-effectiveness and profitability of new therapies, while maintaining fast-track progress into, and through, its clinical development program.
Process Development and Scale Up
Avecia’s experience ensures process development is applied appropriately dependent upon the development needs of customer products at different clinical stages.
CGMP Manufacturing
Four CGMP streams for the manufacture of microbially-derived biologics provide capacity from 100 L to 5,000 L
Quality and Regulatory Support
Independent Quality Unit with representation on program teams
Program Management
Avecia brings a distinctive management approach to programs:
Mammalian Cell Culture
In addition we are also able to help customers working with mammalian cell culture derived biologic...
Baxter Bioscience’s Hayward CGMP manufacturing facility offers dedicated capacity backed by 15 years of experience in developing and manufacturing monoclonal antibodies and recombinant proteins. We offer the firepower you need at any stage of development. Our goal is simple: to advance your biologic at any step — from preclinical to commercial — in the most timely and cost-effective manner possible.
This state-of-the-art, licensed facility is located in the premier Biotech Bay for fast and flexible service. Just under 30 miles from San Francisco (in Hayward’s mixed industrialized area), this facility offers global regulatory expertise, intensive yield-improvement programs, mature quality systems, continuous improvement initiatives, and a proven track record for operational excellence.
The one-story facility has two main buildings with a combined area of 70,000 ft
2
. Bioreactors on the two CGMP manufacturing lines have capacity sizes of 70–400–1,500 L and 110–530–2,130 L. Furthermore, the facility has inc...
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 138 affiliates in 47 countries and 41,300 employees. Since its foundation in 1885, the family-owned company has been committed to researching, developing, manufacturing, and marketing innovative products of high therapeutic value for human and veterinary medicine. Our therapeutic areas are respiratory, cardiovascular, central nervous system, urology, virology, rheumatology, metabolism, immunology, and oncology.
Boehringer Ingelheim is one of the leading companies for industrial customer manufacturing of biopharmaceuticals by offering the entire production technology chain in development and production at its facilities in Biberach (Germany) and in Vienna (Austria).
The large-scale manufacturing sites deliver products such as therapeutic proteins, fusion proteins, protein scaffolds, monoclonal antibodies, antibody mimetics, and plasmid DNA. The Biberach si...
Catalent Pharma Solutions offers a total solution for the development and manufacture of biopharmaceutical and sterile products. Our proprietary technology — and expertise in working with proteins, peptides, and other biotechnology-derived active materials and small molecules — helps maximize the potential of your API and accelerate your product’s speed to market. From cell line engineering to manufacture of API and drug product for clinical trials, our team of highly experienced protein chemists, biochemists, pharmacists, and pharmaceutical scientists provides the exceptional service, focus, and expertise that your project needs.
GPEx® Technology
Setting a New Standard in Mammalian Cell Line Engineering and cGMP Manufacturing:
Catalent’s proprietary GPEx® (Gene Product Expression) technology enables genetic engineering of highly stable, high-yielding mammalian cell lines with unmatched speed and efficiency. More than 150 different antibodies and antibody fusions and more than 40 different recombinant pr...
Figure 1:
An appropriate fermentation scale-down model is critical to allow comparison of lab scale studies to the manufacturing case. Modeling of fermentors increases confidence that a fermentation process is scalable within the confines of available equipment and that the data acquired are an accurate representation of production fermentations. Modeling fermentation oxygen transfer between development scales of 1–100 L and production scales of 1,000–10,000 L+ has been extensively studied, and there are numerous approaches including P/V, K
L
a, and OUR models. In the current analysis, key parameters were varied in small-scale fermentors until the key output parameters matched the manufacturing case. These modifications led to the development of a functional small-scale fermentation model that is highly sensitive to oxygen transfer and can mimic variations seen at scale. Application of this model to other programs has great benefit and increases Diosynth’s confidence in scale-up and scale-down between the...
Eden Biodesign is a globally integrated biopharmaceutical and vaccine contract biomanufacturing company. We are an expert provider of consultancy, biopharmaceutical process development, and CGMP manufacturing services. Our rarely found blend of experience and expertise, gained from providing services to a worldwide client base, ensures that the clinical medicines we develop are regulatory compliant and optimally positioned for further clinical and commercial development. Our state-of-the-art facility in Liverpool, UK, is licensed to produce clinical products, which is best in class for its scale of manufacture, whether for microbial or mammalian recombinant proteins, cell products, and viral vaccines.
We do not develop any proprietary products; we develop and manufacture only for our clients. Although we provide access to the world’s leading production technologies, we do not seek royalty payments. Providing a development and manufacturing service to our clients receives 100% of our attention and investme...
KBI Biopharma is a leading contract development and manufacturing organization for the biopharmaceutical industry. We accelerate and optimize drug development and manufacturing programs for our client partners, including global pharmaceutical and biotechnology companies and organizations in biodefense. Our clients benefit from faster time to market and lower cost of manufactured goods.
Ongoing Innovation
We are continually employing new technologies for the analysis of proteins and developing new partnerships, technologies, and services to enhance biomanufacturing. Our expertise in biophysical and biochemical protein characterization makes us highly successful in delivering optimal product stability and bioactivity for our clients. We achieve this through our ability to integrate the characterization data into the manufacturing process and formulation development.
Proven Approach
Biophysical characterization early in the process can accelerate the development trajectory of the molecule. Through this chara...
Profiling of impurities in biopharmaceuticals and their associated intermediates and excipients is a regulatory expectation. Since residuals are typically present at low levels in difficult sample matrices, development and validation of assays can be quite challenging (Figure 1). Matrix types can vary greatly due to the fact that sampling at a variety of process steps is required to accurately monitor throughout the production process.
Figure 1: ()
Some residual impurities are introduced in the upstream steps as required components of the fermentation or cell-culture media. Various impurities result from the culture growth and harvest.
Some residual impurities are introduced throughout the process
Other residual impurities are introduced to aid in the purification of the product downstream.
Figure 1:
Analytical Techniques
Mass spectrometry
(MS) yields both qualitative and quantitative information and is one of the primary tools for monitoring and identifying residual impurities. The technique consists of...
Fusion proteins are generating a lot of excitement these days because of their targeted use in therapeutic treatments of cancer, autoimmune diseases, and metabolic diseases. The webcast “Recent Trends In The Development and Manufacturing of Fusion Proteins As Therapeutics” examines the practical applications of fusion proteins and the challenges that manufacturers face.
Created by joining two or more genes originally coded for separate proteins or protein domains, a fusion protein results in a single polypeptide that includes functional properties from both genes. These functional properties can include:
Two types of fusion proteins are used today.
Fc fusion proteins,
which offer increased biological half-life and greater therapeutic exposure, are the most popular.
Non-Fc fusion proteins,
which are designed to deliver specific combined functions, are quickly becoming accepted as scientists increase their understanding of how diseases progress.
The use of fusion proteins is enabling the pharmaceutical ...
ProBioGen AG is a specialist for mammalian and nonmammalian high-producer cell engineering and GMP manufacturing of biopharmaceuticals. Combining a deep molecular understanding of cells, scientific expertise, state-of-the art industry process engineering, and production know-how, ProBioGen is the partner of choice for biopharmaceutical companies seeking outstanding cell line development and manufacturing capabilities. Moreover, the company’s proprietary AGE1.cell lines® are licensed to several key players in the industry and enable cost-efficient and safe production of vaccines and proteins.
ProBioGen has established a GMP unit based on disposable bioreactor technology, supporting all currently available manufacturing processes (stirred tank and wave in fed-batch and batch mode). The company possesses the manufacturing authorization from the competent authority and meets the quality standards of the EMEA and the FDA guidelines. ProBioGen is located in Berlin, Germany.
Products and Services
ProBioGen offer...
Who We Are
Based in Grenoble, France, PX’Therapeutics (formerly known as Protein’eXpert) is a contract research and manufacturing organization devoted to the development of biotherapeutics. Our 50-person staff offers custom-designed services ranging from recombinant protein and monoclonal antibody discovery and optimization up to clinical cGMP manufacturing for preclinical and clinical studies.
Acknowledged Scientific Expertise
We have demonstrated our high level of expertise in protein science and our capability to tackle complex and recalcitrant projects. We have indeed worked on more than 500 projects for 140 clients worldwide and released clinical batches for trials performed in Europe and in the United States.
Integrated Organization for Seamless Transfer
We differentiate from other CMOs by our integrated way of working from discovery stage to phases 1–2 clinical production. This original and science-driven approach ensures seamless transfers during the project’s life and therefore leads to significa...
Recipharm Biologics is part of Recipharm AB of Sweden, one of Europe’s leading contract development and manufacturing organizations. Privately owned and financially robust, Recipharm specializes in providing customers with a full-service, one-stop-shop approach — from formulation and analytical development through to commercial manufacturing. We employ some 1,400 people and have been operating since 1995. With manufacturing facilities located in Sweden, France, the United Kingdom, and Switzerland, we can handle a wide range of dosage forms including solid dose, sterile (liquids and freeze dried), semisolids, beta lactams, hormones, dry powder inhalers, granulates, and powders. This is complemented by a dedicated development center where our scientists can formulate, develop analytical methods, and manufacture clinical trial materials into most dose forms from just an active pharmaceutical ingredient (API).
Development and Supply of Recombinant Proteins and Monoclonal Antibodies
Recipharm Biologics is loca...
Rentschler Biotechnologie GmbH is a full-service contract manufacturer with over 30 years of experience in the development, production, and approval of biopharmaceuticals in compliance with international GMP standards with a highly skilled staff of 450. As part of the Rentschler Group and headquartered in Laupheim, Germany, Rentschler is one of three leading European CMOs operating globally. Dedicated to delivering high-quality biopharmaceuticals produced in mammalian cell culture, Rentschler has nine stand-alone GMP suites with volumes of 30 L, 250 L, 500 L, and 2,500 L, which allows producing material for clinical trials and supplying the market. Rentschler Biotechnologie is a pioneer in the development and production of biopharmaceuticals — it was the first company in the world to gain market authorization for an interferon-containing drug.
Rentschler Excels with Expertise and Full Service from “Gene to Drug Product”
Rentschler provides customized, integrated biopharmaceutical services: from the cell l...
Sandoz is one of the leading specialists in microbial fermentation of classic and recombinant microorganisms. The company’s comprehensive know-how is based on more than six decades of experience in the field of classical microbial products and more than two decades in recombinant microbial production at commercial scale. Building on this know-how, Sandoz offers a broad variety of integrated services including innovative expression systems, process development, scale up and production of recombinant products derived from microbial systems, and mammalian cell culture in state-of-the-art facilities.
Our expertise is based on numerous projects successfully performed in collaboration with our customers. Currently, Sandoz is manufacturing more than 25 different recombinant products for well-known pharmaceutical and biotechnology companies located in the United States, Europe, and Japan. Our FDA-approved facilities fulfill worldwide quality requirements.
Services Offered
Production of Recombinant Peptides and Pr...
Symyx CDMO (contract development and manufacturing organization) provides a faster, more reliable route to clinical trials by delivering drug product manufactured with a highly optimized and robust formulation. We have over a decade of experience working with the smallest biotechnology start-ups and the largest pharmaceutical companies. Symyx combines formulation expertise, high-productivity research technology, and CGMP manufacturing capability in a single facility.
Biopharmaceutical Development and CGMP Manufacturing
Symyx has the subject-matter expertise and technologies to integrate the development and manufacturing of preclinical and clinical trial–ready formulations. We are uniquely positioned to tackle complex formulation problems in the context of specific client constraints. We ensure that when our clients take a formulation to clinical trials, they’ll be testing the efficacy of the drug candidate rather than the limitations of a formulation.
Symyx integrates formulation development and CGMP fill...
SynCo Bio Partners believe that contract manufacturing should not be “one size fits all” and that the biopharmaceutical contract manufacturing industry needs to explore different collaborative business models in the development of production processes with prospective clients.
Most CMOs, including SynCo, offer complete, full process, and analytical method development from the upstream fermentation/cell culture stages to the final purification steps. For small virtual companies to larger organizations with limited available internal resources this can be a good option. However, for the client, loss of control over its development project can be a genuine concern.
There are a number of options for working with a CMO on a process development program including the following.
Outsource Full Process and Analytical Development
Outsourcing full process and analytical development to the CMO thereby empowers the CMO to deliver and simplifies reporting lines, which makes this type of project relatively easy to manag...
Pressure is bearing down on all sides. Pharmaceutical and biotechnology companies face stress from increasing costs, intensifying global competition, growing regulatory stringency, and more. For years, they have relieved a little of this pressure by outsourcing functions to a limited extent, such as packaging or distribution. Allowing a contract manufacturer to perform some operations frees up companies to focus on their core competencies. Today, however, some of the industry’s most eye-opening success stories are the result of even more extensive outsourcing strategies. Effective outsourcing in these industries requires more than simply finding a contract manufacturer who can perform restricted tasks. For a truly successful outsourcing strategy, companies must find a true partner.
Contract Manufacturing Basics
Of course, this all starts with effective and reliable manufacturing techniques. By choosing the right contract manufacturer, companies can actually improve their products and gain faster regulator...
Asahi Kasei Medical Co., Ltd. is pleased to announce the commercial launch of Planova™ BioEX, its new generation of hollow-fiber membrane virus filters. Planova™ BioEX filters are specifically designed to meet the urgent need in downstream biopharmaceutical processing for robust virus filters that not only enhance safety, but also have higher filtration capacities and shorter processing times, even under demanding filtration conditions such as high protein concentration and high filtration pressure.
Developed using Asahi Kasei Medical’s unique technology base in cellulose hollow-fiber virus filters and polymer science, Planova™ BioEX filters incorporate a durable hydrophilic PVDF (polyvinylidene fluoride) hollow-fiber membrane, enabling them to cope with the harsh processing conditions typical of state-of-the-art biopharmaceutical manufacturing. Using Planova™ BioEX filters, it is now possible to safely and efficiently filter large volumes of high-protein concentration solutions, which are typically probl...
Figure 1:
Process Analytical Technology (PAT)–based in-line buffer dilution (IBD™) systems produce either binary or ternary blends with tight adaptive control. Up to 100× concentrates are diluted to meet the final dilution end product (1×) specifications. The conductivity of the diluted end product can be controlled to within ±0.1% of the upper limit of the user-defined conductivity range of the detector, and to ±0.1 pH units. Two experiments that were designed and performed to illustrate this blending accuracy are discussed below.
Experiment 1
In the first experiment (Figure 1), a standard preparation of 10 mM sodium phosphate buffer, pH 6.7, was created using a 5 L/min IBD™ skid. The product was prepared by blending a 10× concentrate (100 mM) of sodium phosphate, pH 6.7, with deionized water using patented adaptive PAT feedback control. For this run, the span of the conductivity detector was set from 0 to 100 mS/cm, which allowed for a specification limit of ±0.1 mS/cm. The conductivity set point for th...
Figure 1:
Due to potentially very dangerous flu outbreaks in recent years, the need for production of influenza vaccines in sufficient quantities has been expressed. Also, the time needed from vaccine design to the market and overall process efficiency needs to be improved. This, along with drawbacks of the traditional viral vaccine production in embryonated chicken eggs, has led to the use of reverse genetic techniques and cell-culture–based virus propagation. Because existing downstream processes of virus purification were developed primarily for egg-derived and inactivated influenza vaccines, the need for alternative, efficient, robust, and scalable purification methods has emerged.
Chromatography is quickly becoming a method of choice for virus purification and the relevance of CIM® monolithic supports was recently demonstrated for various viruses (measles, mumps, hepatitis A, adenovirus, rotavirus, herpes, various bacteriophages, and plant viruses). CIM® chromatographic supports are single-piece cont...
The Zeta Plus Encapsulated System is a disposable depth filtration system designed for the bioprocessing industry where upstream cell culture clarification or downstream impurity removal is required. The Zeta Plus Encapsulated System consists of two product lines: a small system that is ideal for lab-scale production or scale-up studies, and a large system designed for production-scale biomanufacturing. Each is composed of a filter holder, a set of top and bottom manifolds, and a flexible number of capsule filters.
The Zeta Plus Encapsulated System features an ergonomically designed large holder (model #16EZB) that can be pivoted between horizontal and vertical position to allow convenient loading and unloading, minimal footprint during filtration, minimal fluid spills during unloading, and full use of the filter media. A patent-pending capsule design offers a translucent plastic shell for easy liquid level detection, a CAM locking mechanism for fast and robust capsule-to-capsule connection, and the indus...
Figure 1:
Production of biopharmaceuticals has over recent years evolved from simple scale-up of lab-based techniques into a much more engineering-driven task. The entire industry has matured. Safety and efficiency are key drivers in this new era. Large and increasing production volumes of biopharmaceuticals create a need for further development of chromatographic stationary phases. The main focus of resin development has been to increase productivity, which can be achieved by a combination of improved pressure-flow resistance along with increasing the pore diffusion coefficients (dynamic capacity). In combination with sufficient accessible binding sites, higher pore diffusion coefficients result in higher dynamic binding capacities for proteins. Tentacle-based resins such as Fractogel® EMD are known to combine the best of both.
Superior Productivity for MAb Capture
Eshmuno™ S strong cation-exchange resin exhibits a superior binding capacity for antibodies than other modern ion exchangers. Figure 1 shows ...
Buffer preparation and distribution are among the most common unit operations in biotherapeutic production. Despite the sheer volume of buffer consumed in bioprocessing and the importance of buffers in nearly every process step (e.g., cell growth, chromatographic separation, final formulation), buffers generally receive less attention from process development and process improvement teams than more challenging areas such as media preparation or active pharmaceutical ingredient (API) production. As one researcher stated, “buffer preparation is not valued as a strategic core competence and is often relegated to junior staff” (
1
).
Nevertheless, buffer quality can have an impact on process efficiencies and final product quality. Proper buffer preparation, filtration, and distribution are key to the protection of chromatography columns and ultrafiltration operations from microbiological and particulate contamination.
Buffer Preparation
Buffer storage was one of the first unit operations to transition to sing...
Figure 1:
The recent successful production and application of new therapeutic antibodies has increased the demand to develop the next generation of antibodies. The race to develop new antibodies requires excellence in process development and full-scale production. Following the discovery phase, potential drug targets are taken from early clinical phases to market approval. During this process, efficient screening tools are important for the exploration of the experimental design space — in line with US FDA quality by design (QbD) initiatives — and subsequent optimization of the downstream protocol to develop robust and high-yield processes in a short time.
In this case study, the primary goal was to develop a robust and highly productive downstream purification protocol for a challenging antibody feedstream containing high levels of aggregates. The secondary but equally important goal was to scale up the optimized process conditions for the two chromatographic steps in a short time, thereby meeting the pr...
For over 50-years, W. L. Gore & Associates has earned its reputation for providing innovative, high-value products such as GORE-TEX® outerwear, Elixir® guitar strings, and GORE-TEX® vascular grafts. As the company invented expanded polytetrafluoroethylene (ePTFE), Gore offers an unparalleled level of technical knowledge and experience with this versatile material.
This know-how starts with a deep scientific understanding of fluoropolymers, particularly PTFE processing and fluoropolymer development. Gore’s unique technical agility enables the development of a wide range of processes, products, and creative, reliable technologies.
Performance Characteristics
Gore’s configuration engineering of ePTFE and other materials can result in products that offer a wide range of performance characteristics, including biocompatibility, chemical and thermal resilience, low dielectric constant, antibacterial functionality, odor absorbency, radiation resistance, selective permeability, transparency/opacity, dimensional st...
EndoTrap HD® manufactured by Hyglos GmbH (former Profos AG) is a new revolutionary tool especially designed to meet the needs of pharma and biotech industry for the efficient removal of endotoxins in biomanufacturing processes. EndoTrap® HD fulfils all requirements for industrial applications, and it can easily be integrated in/at early or late-stage purification processes of biological substances such as proteins, drugs, antibodies, or vaccines.
Background
Endotoxins (lipopolysaccharides, LPS) are major contaminants found in commercially available proteins or biologically active substances. LPS are highly potent immune stimulators able to cause side effects in host organisms such as endotoxin shock, tissue injury, and even death. Due to these reactions, it is essential to remove LPS from injectable drugs and other biological as well as pharmaceutical products (
1
,
2
).
Purification very often represents the most time consuming and cost intensive step of the whole production process. Therefore optimizat...
