The world faces a clear need for innovative biological products to treat and prevent diseases that cause significant health burdens. What might be less obvious is a need for innovation in biomanufacturing processes. If these products are to be made more efficiently and cost-effectively through less wasteful and safer means, then improvements are definitely needed.
“We need innovations in downstream bioprocessing, whether the products are vaccines, recombinant proteins, or other bioproducts,” said Uwe Gottschalk, vice president of purification technologies at Sartorius Stedim Biotech (SSB), at the recent Downstream Processing Day cohosted by SAFC and Sartorius Stedim Biotech in Liverpool, UK, 26 January 2011. “It is also important to follow critical raw materials all the way through biomanufacturing because this is now being watched very closely now by the regulators.”
According to bioprocess consultant Vaughan Thomas of Tillingbourne Consulting, there is a real need for innovation in bioprocessing. “Some ...
France Biotech (the French association of life-science companies) presented the results of its “Life Science Panorama 2010” survey at the BioVision world life-sciences forum in Lyons, France, on 29 March 2011. The survey describes major trends for 2009–2010 in the life-science industry, both in France and internationally. More than 263 companies responded to the survey this year, and 211 were included in the final analysis.
Main Trends in France
Results of the latest survey attest to the arrival of “second-generation” biotech companies to France. Even though a high proportion of companies (48%) work in human or animal health, new companies are emerging in the French medical technology, environmental, and renewable energy sectors. The French government is encouraging creation of such business through its “biotech and bioresources” call for projects under a national bond scheme called
Grand Emprunt
.
Most French life-science companies are located in one of three regions: the Paris Ile de France region (33%...
Biopharmaceuticals, including products approved as biosimilars, must be clearly defined, identified, and named to ensure accuracy in writing and filling prescriptions (
1
,
2
,
3
,
4
). The US biosimilars law enacted last year enables the Food and Drug Administration (FDA) to approve abbreviated biosimilar biologics license applications (bBLAs) or 351(k) filings based largely on their sponsors proving structural, composition, and clinical similarities with an approved biologic (reference product), much like generic drug approvals (
5
). The agency has yet to disclose how it will implement biosimilar approvals. Factors to take into consideration include types of clinical trials, required data, and names to be officially designated and allowed for product labeling, inserts, and marketing.
The established (also referred to as
compendial, nonproprietary,
or
official
) names to be designated by the FDA and used for biosimilars are likely to be highly controversial. The agency will have to make difficult cho...
As most novelists will tell you, if you make substantial changes to the beginning of a story, you may well need to revise your preestablished conclusion. Similarly, as approaches to process design and development change, new tools, technologies, and various shifting “paradigms” also affect the way companies approach final formulation, filling, and finish steps. As yet another ref lection of increased process understanding and quality-by-design’s (QbD’s) holistic approach to biopharmaceutical development, those final steps — traditionally outsourced by most companies — now have to take into account the evolution to smaller-footprint operations in some product classes. Smaller operations require increased attention to reducing waste and ensuring desired profits. Smaller-scale cell-and tissue-culture operations are introducing special packaging and shipping criteria, and at least one such company we editors have visited operates its own filling, packaging, and shipping in proprietary containers (
1
). Biotec...
+1ACMC Strategy Forum held in Washington, DC, on Sunday 28 January 2007, focused on two topics related to protein structure and function. First, analytical techniques used in the glycan analysis characterization included recent advances and correlations among the various tools. And second, current understanding glycosylation’s functional relevance to therapeutic proteins was discussed in the context of its effects on biological activity, pharmacokinetics, and Fc effector functions (for monoclonal antibodies, MAbs). Progress has been made in the field of glycobiology since this forum took place, and those updates can be found in articles referenced herein.
PRODUCT FOCUS: GLYCOPROTEINS
PROCESS FOCUS: MANUFACTURING
WHO SHOULD READ: PROCESS DEVELOPMENT, MANUFACTURING, ANALYTICAL AND QA/QC PERSONNEL
KEYWORDS: CARBOHYDRATES, MABS, ANALYTICAL METHODS, LOT RELEASE, STABILITY, CHARACTERIZATION
LEVEL: INTERMEDIATE
Human Interleukin 2 (IL-2) glycoprotein, a hormone that acts as a signaling molecule for the immune syst...
+4 Normal-flow filtration is used throughout downstream processes for biologics including depth, sterile, and viral filtration applications. Because of its ubiquity in large-scale biomanufacturing, using the most efficient normal-flow filter media area and type can lead to significant cost savings. To determine the most effective media type and area, developers use a scaled-down process model is used in bioprocess laboratories to minimize material requirements. Constant–flow-rate filter evaluations involve direct scale-down parameters that match manufacturing-scale process conditions. This type of evaluation can be time consuming, labor intensive, and complicated because of a lack of specialized laboratory-scale equipment. Clearly an integrated and semiautomated system would facilitate the efficient evaluation of filter media for manufacturing-scale bioprocesses.
PRODUCT FOCUS: BIOLOGICS
PROCESS FOCUS: DOWNSTREAM PROCESSING
WHO SHOULD READ: ANALYTICAL AND PROCESS DEVELOPMENT PERSONNEL
KEYWORDS: SCALE-DOWN, F...
+2 Time and flexibility are essential in purification process development for biopharmaceuticals. Easy translation of experimental ideas into process steps and insight into the effects of changes in chromatography parameters both help speed development and contribute toward achieving quality by design (QbD) objectives. An ability to scientifically design product and process characteristics that meet specific objectives is crucial. Opportunities to eliminate manually intensive steps all support an enhanced development process.
A typical monoclonal antibody (MAb) purification process includes three chromatographic purification steps. However, we propose a more time-efficient two-step approach (Figure 1) using the ÄKTA avant 25 system for fully automated process development. With design of experiments (DoE) software incorporated, the ÄKTA avant 25 system can easily and quickly establish optimal chromatography conditions, further reducing process development time (Figure 2).
PRODUCT FOCUS: MONOCLONAL ANTIBODIES
Syringe Technology
Product:
Dual-chamber Lyo-Ject syringe and V-LK cartridge
Applications:
Delivery of lyophilized, liquid-powder, and liquid-liquid mixtures
Features:
Vetter offers two efficient and user-friendly systems for freeze-dried parenteral drugs: the dual-chamber Vetter Lyo-Ject syringe and dual-chamber V-LK cartridge. Lyophilized drug is contained in one chamber; diluent in the other. Reconstitution occurs immediately before administration in a few simple steps. This technology simplifies administration, increases API yields (by reducing overfill), and improves dosing precision. Syringes come in 1-mL, 2.5-mL, and 5-mL sizes; cartridges cover fill volumes of 0.1–1.4 mL in their first chamber and 0.1–1.3 mL in their second.
Contact Vetter Pharma International
www.vetter-pharma.com
Sterile Connections
Product:
Opta SFT sterile fluid transfer connectors
Applications:
Fluid-management systems including filters, tubing, and disposable storage containments; bulk material management and transfer...
Two years after drafting a comprehensive revision of the 1987 process validation guidance, the FDA finalized the document this year. The revision elaborates on modern quality by design (QbD) techniques for developing a process, analyzing risks, and monitoring for control. The initial draft update remains largely intact, with some important adjustments focused on clarifying the FDA’s intent for how the industry is expected to validate its processes.
1 — Minor Changes:
The guidance includes more references to the
Code of Federal Regulations (CFR),
an added glossary, and references to subject matter and the risk-based ASTM E250007 verification standard. Expectations for tracking operator errors have been deleted. To clarify different Stage 2 (process qualification) activities, the guidance now refers to technical evaluation as
process performance qualification
(PPQ).
Stage 1: Process Design
2 — Criticality:
The guidance specifically eschews categorizing parameters and attributes according to their crit...
