Althea is a contract developer and manufacturer of biopharmaceutical and injectable products, with fully integrated product development and cGMP manufacturing expertise to support client projects from preclinical development through commercial supply. Each project program at althea is tailored to the specific needs of your product, allowing you to leverage our entire integrated manufacturing approach, or just the parts you need. While realizing all of the tangible benefits of consolidating your development and manufacturing steps, you’ll also have the confidence of knowing that your product is being championed by seasoned professionals that boast an impressive track record of more than 150 cGMP lots of bulk drug substance and more than 750 cGMP lots of final product delivered-to-date.
Biologics Manufacturing — Recombinant Protein and Plasmid:
Whether it is protein or plasmid production, Althea’s experienced staff can take your microbial-expressed product from cell banking to final formulation. As you adv...
In order to reduce scale-up costs and facility capital expenses, biotechnology companies are adopting single-use systems. To fully enable the single-use paradigm, automation software, hardware, and single-use sensors must be optimized; moreover, both validation documents and materials certifications must be readily available for cGMP implementations.
Finesse provides turn-key, configure-to-order measurement and automation solutions for many single-use bioreactor types: “stirred-tank,” “paddle,” or “rocker” systems. The Finesse turn-key system is optimized for each bioreactor type to maximize product yields. Finesse systems are scalable from R&D to process development to cGMP manufacturing. Finesse also provides full support for its systems, including installation, training, validation packages (FAT, SAT, IQ/IQ), and service/maintenance programs.
The primary enablers of single-use systems, however, are the sensors. Finesse offers disposable sensors for dissolved oxygen (TruFluor DO), pH (TruFluor pH), temp...
In an effort to mitigate potential risks associated with the introduction of adventitious agents from animal-derived media components, the biopharmaceutical industry has largely shifted to serum-free and/or chemically defined media in cell culture production systems. Successful serum-free media formulations have been developed using plant-derived protein hydrolysates in combination with recombinant supplements such as insulin, transferrin, and human serum albumin, produced in nonanimal systems.
The performance benefit provided by any medium supplement is subject to its interaction with other medium components present in the basal formulation, as well as any additional supplements being employed. in some instances, a combination of supplements may provide better performance than is seen when supplementing with the individual entities. Here we demonstrate such a synergistic reaction between a wheat hydrolysate and recombinant human serum albumin used to supplement a chemically defined growth medium for SP2/...
The FDA requires a minimum of two viral clearance steps operating by different mechanisms to provide assurance of viral clearance. To be considered robust, a viral clearance step must be validated to consistently remove model viruses with at least 2 logs of clearance. When filtration is used, the objective is to obtain effective viral clearance without causing protein (product) loss.
3M Purification Inc. Zeta Plus™ VR Series filters can be used upstream in cell culture processes to provide additional assurance of virus removal from serum-based growth supplements. For downstream viral clearance, Zeta Plus VR filters can be used at the final stages of purification before sterile filling (
1
). Zeta Plus VR Series filter media are a family of cellulosic depth filtration media designed to retain contaminants through ion-exchange adsorption. They are composed of high-area process filter aids embedded in a cellulose-fiber depth filter matrix.
Reports from end users and in the literature demonstrate that VR seri...
Single-use systems have become all the rage in the biotechnology industry, driven largely by the need to reduce cleaning requirements and associated time, validation, and cost factors with stainless vessels. A well-developed single-use system will ensure lower risk of contamination in manufacturing while eliminating the cleaning process and cleaning validation.
Providing Solutions
Advanced Scientifics provides specific solutions to process needs in fluid transfer and handling, offering flexibility in the design and componentry of individual systems.
Advanced Scientifics offers a wide assortment of transfer and filtration sets for most any application, providing sets that are used throughout the cell culture/fermentation process, from media or buffer transfer to seeding or harvest — to separation and purification — to final packaging. advanced Scientifics offers more than 80 different tubing sizes and types, as well as more than 900 off-the-shelf connectors. as a leader in the design and manufacturing of s...
Biopharmaceutical companies are increasingly interested in single-use innovations to improve performance and alleviate up- and downstream bottleneck constrictions. High-priority considerations for improvement include decreasing the number of process steps, reducing the risk of cross-contamination, and achieving a higher sterility assurance level. One bottleneck today is a need to collect QC samples at various steps during biopharmaceutical commercial-scale cGMP manufacturing, which typically is a labour-intensive manual activity that holds a potential risk of contaminating product or personnel.
Alfa Wassermann Separation Technologies (
www.awst.com
) is a leading provider of industrial process equipment for biopharmaceutical manufacturing. it recently launched eMPat™, a fully automatic aseptic QC sampling system especially designed for biopharmaceutical cGMP manufacturing. The compact EMPAT system is designed for flexible and reliable operation and seamlessly fits with existing QC sampling planning.
Table...
Following a strong showing at this springs interphex in New York there is little wonder why ALLpaQ® has become established as an industry leader when it comes to the containment and handling of Biopharmaceutical fluids. The ALLpaQ® Cleanroom range of biotech containers was launched at interphex New York 2011. As predicted, it has since created a strong demand in Europe and is now available in the United States.
Rationale
Realizing that a significant proportion of the landed cost of products is in packaging and logistics, the industry continues to strive to keep costs under control. Furthermore, issues concerning maintenance, hygiene, and storage, as well as health and safety of its workforce have an impact on operational efficiencies. For these reasons, ALLpaQ® has developed its biotech range of containers to alleviate stress in the supply chain and procurement management while maintaining integrity of the technical solutions.
Proposition
The ALLpaQ® Cleanroom range is a competitively priced basic solutio...
Research and early process development generally rely heavily on screening and examination of cultures grown in microtiter and shake-flasks. Unfortunately, the growth environment in these formats is extremely different from the bioreactor conditions used in larger-scale production. This application note describes two tools for improving growth conditions at these scales.
The
µ
-Flask:
Cultures grown in traditional microplates are usually sealed using simple plastic lids or adhesive tape seals. Such systems suffer from well-to-well variability, poor gas transfer, excessive evaporation, and cross-contamination. The
µ
-Flask (Figure 1) is a multilayer, reusable cover that eliminates well-to-well variability and provides high oxygen-transfer rates for any mictoplate (96-24-, or six-well plates, either deep or shallow).
The RAMbio® System:
Cultures grown on orbital-shaking platforms are often oxygen limited, and inadequate oxygenation can lead to inconsistent or suboptimal performance. Orbital-shaking platf...
Technology Innovation
ATMI® is an acknowledged technology leader in the development and manufacture of single-use bioprocess systems and consumables. Its innovative disposable technologies, best-of-breed polymer films, ultraclean ISO Class 5 manufacturing conditions and whole-bag integrity testing set a high bar for the single-use industry. Today, ATMI is raising the bar even higher with the introduction of Helium integrity Testing (HIT™).
Helium Integrity Testing
ATMI’s patent-pending HIT technology allows each ATMI 2-D Bioprocess vessel (BPV) to be tested for defects that can compromise sterility but are too small to be detected by conventional pressure-decay methods. The test protocol involves placing each finished BPV assembly into an enclosed test chamber, evacuating the chamber air to create a vacuum, and then introducing a measured quantity of helium gas into the BPV. The helium-filled BPV is then held for a fixed time while the surrounding vacuum is monitored for leaking helium using a sensitive ...
As a CMO partner, Avid Bioservices provides fully integrated services across the process chain to develop and commercialize a biologic including cell line and process development, analytical methods development, clinical and commercial cGMP manufacturing, and regulatory submissions. We provide first-hand expertise and knowledge to navigate a biologic from concept to commercialization because we are a wholly owned subsidiary of Peregrine Pharmaceuticals, a clinical-stage, publicly traded biotech company with a management team experienced in the development and commercialization of therapeutic proteins. This allows us to provide our clients with unique insights to manage the process, scale-up, and validation challenges of drug development and commercialization while mitigating risk, reducing costs, and accelerating time to market.
Our clients benefit not only from our comprehensive service offerings, but also from the experience that comes from navigating our own products through development. Avid has produ...
BioPharma Solutions, a business unit of Baxter, partners with pharmaceutical companies to support your commercialization objectives by providing scientific expertise, sterile manufacturing solutions, parenteral delivery systems, and customized support services needed to meet the unique challenges that parenteral products face.
Experience Makes the Difference:
With 80 years of parenteral expertise, we can help to navigate the pathway of success for your molecule. As a dedicated CMO with over 20 years of experience devoted to our customers’ clinical and commercial success, we understand what it takes to deliver your products at a global level, and we focus on delivering value to our customers throughout their products’ lifecycles.
We Understand Parenterals:
Parenteral manufacturing is an integration of expertise, reliable supply, and technology. As a parenterals specialist, BioPharma Solutions is a proven leader in parenteral contract manufacturing, which offers unique delivery systems and a wide variety ...
Peptones have a long history of use in cell culture media. However, increasing emphasis has been placed on growing cells in animal-free and chemically defined systems for the production of biopharmaceuticals. This has created a demand for cell culture media supplements that equal the performance of peptones but have greater certainty of composition. This demand prompted BD’s efforts to identify the functional components of yeast extract to develop a chemically defined supplement, BD recharge.
Formulation
The keys to making a successful peptone-based cell culture supplement were identifying functional components in the peptone and using DOE mixture designs to find the optimum formulation to elicit a peptone-like response. The correct mixture of nutritional components and bioactive promoters of protein production combined to achieve this goal. Out of this strategy, BD Recharge, a chemically defined, animal-free, and protein-free supplement was developed that provides growth and productivity performance equ...
+1It is important to ensure that testing services meet applicable regulatory standards necessary to support investigational new drug (IND) applications, the clinical development life cycle, and commercialization. However, monitoring and — when possible — anticipating the ever-changing regulatory landscape is a challenge. Yet, the failure to do so can negatively affect both the cost and time needed to move a product from development through to commercialization.
This article describes BioReliance’s position concerning anticipated regulatory changes over the next three to five years. These opinions are based on BioReliance’s experience providing testing services to 600+ clients and regulatory guidance published by the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and international Conference on Harmonization (iCH). These references include
Table 1: BioReliance’s “future vision” for the regulatory testing landscape
Table 1:
BioReliance’s “future vision” for the regulatory testing lan...
+1 Both industrial and research scale protein purification require the development of superior procedures for increasing recovery yields. This places an emphasis on maintaining proteins in fully reduced states to solubilize inclusion bodies, while increasing the recovery of active proteins through improved protein-folding technologies. These concerns have a common theme: the ability to maintain the disulfide bonds in the protein in a sufficiently reduced state so as to facilitate correct folding while simultaneously avoiding protein aggregate formation. Dithiothreitol (DTT) is still a choice reagent to correctly achieve this delicate balance (
1
).
DTT, or Cleland’s reagent, is a low–molecular-weight thiol that reduces disulfide bonds quantitatively and maintains monothiols in the reduced state. These properties enable many varied applications including in vivo studies of protein processing, in situ solubilization of proteins, protein folding, protein purification, induction of genes involved in signal trans...
Two decades of intensive development of novel expression systems for mammalian cells and microorganisms have led to a significant increase in fermentation titers in the biopharmaceutical production of proteins (more than 20 g/L in microbials and more than 4 g/L in mammalian cell culture). However, dynamic binding capacity of chromatography resins is often limited, and very large chromatography columns are needed to purify such large amounts of target proteins. New paths for cost-efficient purification are therefore needed, including downstream processing steps that can cope with high fermentation titers and that can fulfill the increasing market demand for biopharmaceutical proteins. Preparative crystallization of biopharmaceutical proteins has the potential to dissolve bottlenecks in large-scale downstream processes and may be an alternative to costly unit operations such as liquid chromatography.
Because there is a general lack of knowledge about multikilogram cystallisation processes, substantial effor...
Vaccine engineering, antibody quality screening, and glycosylation profiling processes can generate large quantities of protein samples that must be analyzed in a timely manner. Generation of high-quality data and rapid, quantitative analyses are mandatory to determine next steps. Although still heavily relied upon, sodium dodecyle sulfate polyacrylamide gel electrophoresis (SDS-PAGE) is labor-intensive and only semiquantitative, and its throughput capacity is limited. Quantitative analysis techniques such as capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC) do not provide the throughput necessary to move processes forward efficiently. The Caliper Life Sciences’ LabChip GXII system delivers quantitative, high-throughput protein analysis necessary to truly accelerate these development work flows.
LabChip Protein Analysis
The automated LCGXII system performs rapid, quantitative protein analysis. Samples are aspirated from microplates using a single-sipper microfluidic chip. S...
Successful cryopreservation of hematopoietic progenitor cells (HPC) depends on a number of factors: biopreservation media, freezing rates, and storage using sterile, cryogenically durable storage bags. Cell-Freeze® cryogenic storage containers are 510(k) cleared for storage, preservation, and transfer of hematopoietic progenitor stem cells (HPCs). These bags are made from a unique polyolefin film that offers excellent durability while remaining flexible when stored at ultralow temperatures (−196°C). Their proprietary membrane port design offers thinner walls for increased flexibility, and an industry-standard label pocket design lends ease of use and traceability for product labeling. Available interface tubing and connectors are compatible with sterile connection and smart-seal technologies for closed-system applications.
We investigated bioequivalence of a Cell-Freeze® (Charter Medical, Ltd. Winston-Salem, NC) freezing bag to a Cryocyte™ (Baxter Healthcare, Deerfield, IL) freezing bag. The Cell-Freeze® ...
The standard cell line development pathway at many contract service organizations is based solely on selecting clones by growth and productivity with little or no analytical characterization of the expressed protein. The use of protein analytics to support selection of clones that match desired product quality is important for second-generation processes and will be of utmost importance for biosimilar development. CMC Biologics performs sophisticated protein characterization using state-of-the-art analytical equipment combined with our robust cell line development platform to generate and identify production-quality clones with desired product quality attributes in very rapid timeframes.
Implementing protein analysis into the cell line development process requires a robust platform capable of producing consistent results and timeframes. More importantly, it requires flexibility to enable matching of specific product quality attributes in the midst of the ongoing clone selection process. CMC Biologics’ CHE...
As single-use systems (SUS) continue to be incorporated throughout bioprocess manufacturing, a wider range of solutions and flexibility is being requested of the connections currently used in single-use systems. Colder Products Company, the leader in single-use connection technology, has been listening to the trends in the marketplace and has responded by expanding its product offering to incorporate a wider range of connections options for the single-use market.
AseptiQuik
®
DC
is the first all-in-one sterile connection technology to offer both a sterile connection and a sterile disconnection. These connections are made easy by the use of the intuitive three-step CLICK–PULL–TWIST sterile connection followed by the simple one-step disconnection that maintains media sterility within both halves of the connector. With this single connector, manufacturers can now ensure media sterility before, during, and after connection. Some applications include buffer preparation, downstream transfer lines into sterile...
In the development of a new biological product, it is important to remember that a successful R&D development project needs to be converted from a bench-scale concept to a bioproduction platform. This process development stage requires identifying ways to increase cell numbers to meet annual dosage demands, as well as to minimize direct contact with the cell product by developing a closed system for all culture manipulations. identifying a bench-scale platform that can scale to CGMP production scale eases the scaling process.
The Corning Life Sciences gas-permeable family of products — the HYPER
Flask
® cell culture vessel and the newly developed HYPER
Stack
vessels — simplify the transition from bench to production floor. The HYPER
Stack
vessels have been designed for closed-system use to meet the needs of large-scale adherent cell culture.
The gas-permeable technology and product design differs from traditional cell culture products as the cells attach to an ultrathin, gas-permeable polystyrene film i...
+2 Covance is one of the world’s largest and most comprehensive drug development services companies with more than 10,000 employees in 60 countries. Through its comprehensive portfolio of services, Covance has helped pharmaceutical and biotech companies develop one-third of all prescription medicines in the market today.
Working with clients of all sizes, Covance recognizes that your development program is as unique as the product you bring to our facilities. With >250 different biomolecules successfully supported annually, Covance Biotechnology Services provide you with a global, multidisciplinary team of experts and specialized state-of-the-art infrastructure to help achieve your development and commercialization goals.
The comprehensive Covance biotechnology service capabilities include extensive expertise and experience in:
Covance has a complementary portfolio of discovery, nonclinical safety assessment, clinical development, and market access capabilities for full development of biopharmaceutical produ...
Product recovery is a lengthy and costly procedure consisting of centrifugation and depth filtration steps to remove the cells (clarification), followed by multiple cycles of packed-bed chromatography that bind and separate the target molecule from cell culture medium components (capture).
The Rhobust® Technology is a second generation expanded-bed adsorption (EBA) technology that provides an elegant solution to using multiple process steps by combining clarification and product capture into one single step in the first downstream process unit operation. The Rhobust® Technology uses a new generation of Agarose beads that are prepared from a homogeneous mixture of Agarose and Tungsten Carbide (10 vol%) and consequently have a high density (3 g/mL). This allows processing to occur at higher flow rates in the expanded-bed mode when compared with those used for packed-bed chromatography (300–600 cm/h rather than 60–300 cm/h, Figure 1).
Product recovery and purity are comparable to that of product produced usi...
DSM Biologics has developed a highly intensified cell culture process termed XD®, which provides cells with a constant environment for optimal cell growth (Figure 1). The XD® Technology works in a continuous media feeding mode with a filtration unit to retain both the cells and the recombinant protein in the bioreactor. Compared with a standard fed-batch process, the feeding regime in the XD® process can be performed with basal media, and this allows straightforward implementation without the need for extensive feed development. The XD® process is robust and scalable while still maintaining consistent product quality.
The XD® Technology produces very high cell densities while still retaining high cell viability at the end of the batch, resulting in very high volumetric productivity. At the end of the cell culture (~14 days), the harvest is processed as a single batch. The technology has been used successfully with all the relevant mammalian production cell lines (CHO, hybridoma, myeloma, and PER.C6® cell ...
The goal:
Develop a CGMP formulation–fill process for a subunit vaccine–aluminum adjuvant complex.
The challenge:
To engineer a scaled-up process for vaccine–adjuvant suspension formulation and fill, ensuring a uniform fill per dose as well as a sterile product.
The Outcome:
Florida Biologix scientists successfully developed the manufacturing, formulation–fill process and test methods. The process was conducted successfully in a scaled-down engineering run and at full scale, and 2,500 vials were tested, released, and shipped to the clinic on time.
About Florida Biologix
Aseptic fill is only one small part of our business. Florida Biologix is a phase 1–2, complex biologics development, manufacturing, and testing organization that offers a wide range of services to the biotechnology industry. FB will overcome scientific challenges with scalable solutions for phase 1–2 and beyond; provide exceptional customer service with clear and honest communication; and ensure client manufacturing process ownership o...
FrieslandCampina Domo is a subsidiary of the dairy multinational Royal FrieslandCampina, which has 20,000 employees, active in over one hundred countries. Our revenues are over 9 billion Euros.
Formerly Known as DMV International
FrieslandCampina Domo incorporates parts of the companies formerly known as DMV International Nutritionals and Friesland Foods Domo. These entities have over 75 years of experience in ingredient discovery, development, and marketing.
With a new name and an expanded product portfolio, FrieslandCampina Domo is strengthening the presence in the Americas market.
Quality, Consistency, Reliability
For more than 30 years Domo has been a leading innovator in protein hydrolysates. We pioneered the development of peptones for use in microbial diagnostics in the 1970s. Our track record of innovation, manufacturing excellence, and delivery reliability has kept us a vital player in this unique field.
For biopharmaceutical media applications, Domo delivers high-performance protein hydrolysates...
Industry leading biologics contract manufacturer Fujifilm Diosynth Biotechnologies located in Research Triangle Park, NC (formerly Diosynth Biotechnology) and in Billingham, UK (formerly Avecia Biologics) provides third-party contract development and manufacturing services to the biopharmaceutical industry.
Fujifilm Diosynth Biotechnologies has supplied clinical and commercial recombinant proteins produced in cell culture for more than 14 years. We have extensive experience in microbial development and manufacturing and equal experience in the cell culture space. Our development experience includes over 30 cell culture processes, of which two-thirds were CHO derived, and over 20 monoclonal antibody programs. In addition, Fujifilm Diosynth has executed four baculovirus programs with scale-up to 1,500-L for the first time in the industry for human use. To date, Fujifilm Diosynth has produced over 100 cell culture GMP batches, primarily using CHO cell and baculovirus technologies and manufactures one cell cu...
+3 Growing commercial demand for therapeutic monoclonal antibodies (MAbs) has increased the need for efficient and cost-effective manufacturing processes. The development of cell cultures with very high expression levels is one clear example. over recent years, the antibody titers of mammalian cell culture have risen dramatically, and today we often see titers of 5–10 g/L.
Expression levels as high as 15 g/L or greater have even been reported. Chromatography media (resins) that can capture these high-titer antibodies are therefore essential for translating this potential gain into a smooth downstream purification process free from costly bottlenecks. Similarly, media with effective purification performance over a long working lifetime will help ensure good and predictable manufacturing economy.
We describe quantitative studies made on MabSelect SuRe* LX, a recent GE Healthcare protein A affinity medium that fulfills both of the above criteria by offering high dynamic binding capacities for MAb capture as wel...
Traditional influenza vaccine production uses fertilized hen eggs. This method is labor-intensive and requires large facilities with limited scalability. A switch to cellculture–based vaccine production methods and use of disposable products would provide flexibility to substantially reduce the time to vaccine clinical trials and approval, effectively decreasing the time-to-market.
The aim of this work was to establish a process to propagate influenza virus in Vero cell culture using animal-component–free conditions for cell growth and disposable products. The end result would be a fast and simple process enabling scale-up and adaptation to industrial production. The following parameters were evaluated: medium composition, cell detachment, medium supplements, agitation conditions, and infection conditions. After optimization was complete, the robustness and reproducibility of the entire workflow for virus propagation in Vero cells using microcarriers and the WAVE Bioreactor* system were investigated.
Opti...
Biopharmaceutical companies generate a vast amount of high-value process data that are typically stored in paper records, data silos, and in the minds of key personnel. This represents valuable corporate knowledge that is often lost or ineffectively used. The manual transcription involved in recording process data necessitates high QA overheads and makes obtaining a holistic view of the processes problematic. It is both time-consuming and costly to support decision-making, root cause analysis, and continuous improvement.
More than 40% improvements in operational efficiency and greater than 70% reductions in QA overheads have been demonstrated using IDBS’ Bioprocess Execution System, which dramatically streamlines process execution, automates analysis tasks, and removes error-prone transcription steps.
An Enterprise Platform for Process Professionals
IDBS has optimized and integrated workflows and data at many of the world’s leading biopharmaceutical and contract manufacturing and development organizations...
Irvine Scientific is committed to supporting the biopharmaceutical industry in the successful development and commercialization of biopharmaceutical products. A strong understanding of our media products is not the only basis for our successful supply, but the foundation of the innovation we provide to the market. Knowing innovation can result from the next big idea or an incremental change, we look for the small critical elements in our business that provide substantial process improvements and value to our customers. At irvine Scientific our focus is to help the customer through the entire complex cell culture development process in order to achieve the ongoing optimum success they depend on.
Rational Culture Media Design™
Formulation development is a combination of practical experience and the application of a practical, rational approach to media design.
Applied Knowledge Base:
using what we know to discover what we don’t know
Data Driven:
results from each phase guide the design of the subsequent p...
