by Cheryl Scott, Senior Technical Editor, BioProcess International
At least one innovator company has embraced the concept of biosimilars wholeheartedly, calling it “our next chapter in healthcare” in a 2016 report. That publication cites product characterization, preclinical studies, nomenclature, reimbursement, and regulatory pathways as the primary challenges facing companies in biosimilar development. (Note: See Amgen’s 2017 biosimilars report here.) For our own featured report on biosimilars this month, we asked the contributors about those topics. The answers below come from Bruno Speder (head of clinical regulatory affairs at SGS) and Mario DiPaola (senior scientific director at Charles River Laboratories).
Product Characterization: What is the most challenging aspect of biosimilar characterization? How are companies obtaining originator samples to compare against?
SPEDER: One major challenge in developing biosimilars is to obtain sufficient originator product for characterization testing in both the preclinical and clinical development phases. The supply of originator product is very closely monitored by the manufacturers of those products because they seek to slow down the development of biosimilars. So this can be a difficult task. Originator product samples usually are obtained through specialized distributors.
Preclinical Studies: Can nonclinical/animal studies aid in supporting extrapolation of indications? Continue reading “Biosimilars: Technical and Regulatory Challenges Featured Report”
The implementation, maturation, and benefits of single-use technologies in biopharmaceutical development and manufacturing are well documented and understood. As analytical methods and testing services also rapidly improve, it is clear that management of risk associated with extractables and leachables also must evolve. Standardization is universally accepted as a goal; how to define, implement, and educate the industry is where debate resides.
The container–closure segment has had more experience dealing with leachables and extractables than those implementing single-use process components do — they’ve just been doing it longer. BPI takes a closer look at relevant guidance and regulations and examines how groups such as BPSA, ELSIE, ISO, and USP are helping users make sense of it all.
This eBook reviews the industry’s approach to leachables and extractables to address an underlying question: How close are we to making standardization a reality?
Read an excerpt from the eBook below:
Continue reading “Extractables and Leachables: Standardizing Approaches to Manage the Risk [eBook]”
As single-use technologies have grown in importance and acceptance, offering more solutions every year, their biggest challenges have come in downstream separation, purification, and processing that follows product expression in cell culture. Many technologies in downstream processing present technical and economic problems. BioProcess International magazine has produced a featured report that delves into many of these issues and innovations. They discuss automation, depth filtration, continuous processing, alternatives to resin chromatography, and fill and finish technology.
In the drive for reduced costs and more economical manufacturing of biopharmaceuticals, alternatives to resin chromatography are being examined. One article in the featured report focuses on the use of membrane adsorbers. Here, we provide an excerpt of Membrane Adsorbers, Columns: Single-Use Alternatives to Resin Chromatography:
Continue reading “Downstream Processing Single-Use Technology”
Because they occur after two highly engineering, and science-driven phases of biomanufacturing – expression and purification – biopharmaceutical fill and finish processes have not received the respect traditionally that they deserve. Yet of all competencies associated with bringing biopharmaceuticals to market, fill and finish arguably are the most specialized.
This eBook reports on the technical and operating challenges impacting the latest formulations and devices including: outsourcing, contamination, standardization (pre-filled syringes), lyophilization, and serialization.
Here is an excerpt:
Continue reading “Biopharmaceutical Fill and Finish [eBook]”
It is well recognized that the cost of Protein A resins is substantial, especially if the cost of Protein A can’t be amortized over a large number of purification cycles. When monoclonal antibodies in development don’t pass the clinical trial stage, the money and resin are spent, raising the overall cost of bringing a successful therapeutic to market. So what can be done?
One solution is to use a less expensive Protein A resin designed specifically for early phase clinical trials, then switch to a resin designed for manufacturing.
This ebook, published in the November issue of BioProcess International, details a comparability study conducted in high-throughput format to support the strategy of switching resin between phase 2 and 3. The three resins evaluated are based on the same base matrix and immobilization chemistry and differ only in the type and amount of immobilized Protein A.
The study consisted of 20 purification cycles under identical conditions for each of the three resins studied. Comparability data for yield, product purity, host cell proteins, DNA, and leaked Protein A were assayed. The feedstock was a clarified CHO cell culture supernatant containing an IgG of subclass 1. All the resins passed the 20 cycles without changes in product or contaminant profiles. No significant difference was observed in performance or product quality among the three resins under the conditions used. Thus, from a scientific point of view, the three resins could be exchanged for each other without negative impact on the quality of the purified product.
The following three agarose-based resins were packed in 600-μL RoboColumn® units (Atoll, Germany) and used for the cycling study:
Praesto AC resin: recombinant Protein A, 35–50 g/L (native sequence, good binding to antibody fragments (Fabs) belonging to the VH3 family)
Praesto AP resin: alkaline stabilized Protein A, high capacity, 50–65 g/L
Praesto APc resin: alkaline stabilized Protein A, 35–55 g/L.
The feed stock (clarified CHO cell culture supernatant) was provided by Alvotech.
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BioProcess International (BPI), has announced the finalists for the 2016 BioProcess International Awards. The awards recognize the outstanding individual and team achievements, emerging companies and their technologies, groundbreaking business collaborations and strategies, corporate responsibility, and technology applications that will allow the industry to deliver better, more effective treatments to a global patient base. The finalists were chosen from 125+ nominations from around the world. The finalists and winners will be recognized on Wednesday, 5 October 2016, at the Awards Dinner and Ceremony at the Boston Convention and Exhibition Center in Boston, MA.
“The BioProcess International Award program has come to represent the very best this industry has to offer. In 2016, a record number of submitted nominations ensures that this group of BPI Award finalists reflects and represents the dedication, innovation and imagination embodied by this industry as a whole,” said Brian Caine, Co-Founder and Publisher of BioProcess International. “Congratulations to all the nominees and finalists.We look forward to introducing the 2016 BioProcess International Award winners and their incredible achievements.”
Continue reading “Finalists announced for the 2016 BioProcess International Awards”
A scale-down model must be statistically similar to its corresponding large-scale process. In this article from BioProcess International magazine, authors from Genzyme report on using 12-L bench-top bioreactors to model a 2,000-L microcarrier-based perfusion cell culture process. They scaled down agitation rate based on a power/working-volume ratio and matched scale-independent parameters to the commercial-scale process. A two one-sided test (TOST) helped them establish statistical equivalency to qualify the scale-down model. Comparing critical product-quality attributes showed that cell culture performance of the model was within specified ranges.
Continue reading “Modeling Large-Scale Microcarrier Perfusion Cell Culture”