In the heady days of the biotech boom of the early 1990s, the ground shook as salvo after salvo of innovative regulatory guidance documents emerged from the US Food and Drug Administration (FDA). Even their titles were innovative: “Points to Consider in the Production…” rather than the stodgy “Code of Federal Regulations, Volume X, Part XX.” The FDA was supporting the development of the emerging biopharmaceutical industry through rapid uptake of technological and clinical developments and speedy conversion into guidance documents. The Europeans appeared to be following the FDA’s lead and developing their own versions of guidance documents reflecting similar themes and emphasis. However, as biopharmaceutical production has matured into the industrial manufacturing phase, the European Union is becoming the driving regulatory force on biopharmaceutical manufacturing.
Harmonious Disharmony
Despite a prodigious production of paper by the International Conference on Harmonisation (ICH), when it comes down to ma...
Both FDA and EMEA guidelines require integrity testing of filters used in processing sterile solutions such as large- and small-volume parenterals (LVPs and SVPs). The same regulatory agencies also require that corresponding test documentation be included with batch product records.
PRODUCT FOCUS:
PARENTERALS
PROCESS FOCUS:
DOWNSTREAM PROCESSING, SCALE-UP
WHO SHOULD READ:
QA/QC, PROCESS ENGINEERS, AND ANALYTICAL PERSONNEL
KEYWORDS:
FILTRATION, INTEGRITY TESTING, VALIDATION, AUTOMATION
LEVEL:
BASIC
The function of integrity testing is to determine whether a particular filter is within or outside the validated specifications of its manufacturer’s range for an integral filter to provide a sterile effluent. Successful integrity tests provide users with maximum performance assurance. Nondestructive testing may be performed on filters before and after use. Integrity testing of sterilizing filters before use (after the filter has been sterilized) verifies their integrity before batch processing and prevents...
+3Filtration Pumping
Product:
620RE filtration pump
Applications:
Dead-end filtration and tangential flow filtration (TFF)
Features:
Gentler on the product in terms of shear stress when producing higher yields; provides unrivaled performance with a control ratio of 2650:1; requires minimal maintenance with no valves or seals to clog, resulting in reduced downtime; offers exclusive innovative PIN-secure protection feature that provides two levels of PIN protection; speed range can be capped to prevent accidental damage to delicate filters; keypad functionality can be disabled to avoid inadvertent changes to pump settings in sensitive fermenation processes; pumps contain fluid in the tubing at all times, never allowing the fluid to come into contact with the pump mechanism and ensuring gentle, low shear handling
Contact
Watson-Marlow Bredel
www.watson-marlow.com
Pressure Sensors
Product:
Single-use pressure sensors (patent pending)
Application:
Single-use processing systems
Features:
Caustic-resistant...
In 2007, TIDES attracted a record number of attendees and exhibitors. More than 700 conference delegates participated — and even more are expected to attend in 2008. TIDES is the only forum that covers manufacturing, formulation, delivery, process and analytical development, and overall market trends for peptide- and oligonucleotide-based therapeutics and diagnostics.
A Billion-Dollar Industry
Over the past two years nearly $3 billion worth of deals were made in the siRNA space. In addition, eight of the top 12 pharmaceutical companies have siRNA programs. The peptide category is growing twice as fast as overall pharmaceuticals, with its market size in 2007 estimated at over $3 billion and a projected growth rate of over 10% per year. There are 67 therapeutic peptides on the market, 150 in clinical trials, 400 in advanced preclinical research, and over 100 pharmaceutical and biotech companies active in peptides.
What’s more, research into microRNA is exploding, resulting in novel potential therapeutic tar...
A mammalian cell exists, interacts, reproduces, and dies as a result of intricate biochemical and biophysical mechanisms — many of which remain unknown or not fully understood even today. Technological advances have allowed us to investigate the details of organelles and cell membranes, of the types of molecules synthesized within cells, and their distribution and trafficking and the effects they have in their environment. Among the main macromolecules that make up a living cell, DNA and protein structures were studied in detail long before technologies enabled analysis of the inherently more complex and less predictable carbohydrate structures. Today, detailed analysis of complex carbohydrates remains challenging because of the close similarity between them and the very large number of possible molecular species involved.
PRODUCT FOCUS:
GLYCOPROTEINS
PROCESS FOCUS:
ANALYTICAL
WHO SHOULD READ:
QA/QC, PRODUCT DEVELOPMENT, PROCESS DEVELOPMENT, AND ANALYTICAL PERSONNEL
KEYWORDS:
GLYCANS, CARBOHYDRATES, O...
Assurance that monoclonal antibody (MAb) therapeutics produced using large-scale animal cell culture are free of adventitious agents is based on three complementary approaches. First, a master cell bank is extensively characterized to demonstrate its freedom from adventitious agents. In addition, end-of-production cell culture material is tested and demonstrated to be free of adventitious contaminants. Finally, the viral clearance capacity of a purification process is assessed using model viruses.
PRODUCT FOCUS:
MONOCLONAL ANTIBODIES
PROCESS FOCUS:
PURIFICATION
WHO SHOULD READ:
MANUFACTURING, PROCESS DEVELOPMENT, REGULATORY AFFAIRS, AND PROJECT MANAGERS
KEYWORDS:
MMV, XMULV, CELL CULTURE, CHO CELLS, CENTRIFUGATION, VIRAL CLEARANCE, CGMP
LEVEL:
INTERMEDIATE
Model viruses are used to determine the viral clearance capacity of purification process unit operations. Xenotropic murine leukemia virus (x-MuLV) and mouse minute virus (MMV) are commonly used during validation of the viral clearance potential fo...
+3 Challenges and approaches in demonstrating comparability of a well-characterized biotechnology product after manufacturing changes can be as varied and complex as the products themselves. Participants at the January 2005 CMC Strategy Forum sought to discuss and agree on common implementation strategies for different manufacturing change scenarios. Development of flexible, comprehensive approaches in strategy development addressed evaluation of critical product characteristics, appropriate process steps to test, numbers of lots and levels of testing required, and assessment of product comparability (e.g., trending analysis, additional characterization studies, accelerated stability data). The change scenarios we discussed can occur throughout the life-cycle of a product from early development through postapproval manufacturing.
PRODUCT FOCUS:
WELL-CHARACTERIZED BIOLOGICS
PROCESS FOCUS:
UPSTREAM AND DOWNSTREAM PROCESS DEVELOPMENT
WHO SHOULD READ:
MANUFACTURING, PROCESS DEVELOPMENT, ANALYTICAL, AND PRODUC...
In summer 2007 the MaRS (Medical and Related Sciences) center in downtown Toronto broke ground for a massive expansion. The fact that this innovative science and technology commercialization facility is more than doubling in size — to 1.6 million ft
2
— less than two years after its official opening, indicates the healthy state of life sciences in Ontario.
MaRS is a state-of-the-art convergence center where leading venture capitalists, pharmaceutical companies, research funding agencies, and cutting-edge businesses come together under one roof. The center is within a ten-minute walk of the University of Toronto and the internationally renowned Samuel Lunenfeld Research Institute. MaRS tenants include GlaxoSmithKline, Heenan Blaikie, the University Health Network, MDS Sciex, Ontario Cancer Research Institute, and RBC Financial Group. The center also provides extensive business advisory services and incubator facilities for innovative technology start-ups.
Leading the Pack
Recent headline stories in scient...
All bioproducts heading to commercialization go through a rigorous process that includes research and development, proof of concept, and validation studies. Furthermore, the fabrication process of a biological product is very different from that of a classical (synthetic small-molecule) pharmaceutical. That’s not only because of specific characteristics and requirements of the molecular entities involved, but also environmental considerations and specific issues related to human health and safety. Such differences are reflected in the cost drivers of approved manufacturing plants.
Herein we identify those cost drivers by examining real-life examples of biological products manufactured in Canada. Specifically, we contrast cost drivers of biopharmaceuticals and industrial bioproducts, especially with regard to current good manufacturing practice (CGMP) regulations. We examine a CGMP plant and two CGMP-compliant plants. The data are compared with those and an industrial bioproduct (bioethanol) for which ther...
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