The aim of any company making protein-based therapeutics is to get to the clinic quickly with a product formulation that has the best chance of success. Any number of specific formulation development and manufacturing issues can keep such drugs from advancing expeditiously to the clinic. To be successful organizations must balance the strengths and weaknesses of each individual molecule against timelines, budgets, and priorities. Ultimately, it’s not just about deploying the best methodologies and processes, but of applying them appropriately and at the right time.
This first of a three-part series describes a new contract research organization (CRO) business model that integrates functions in early clinical formulation development and manufacturing. An integrated contract development and manufacturing organization (CDMO) executes science, technology, and manufacturing compliance to address the typical issues that prevent protein products from moving swiftly from laboratory to clinic. Ultimately, this int...
Biopharmaceutical manufacturers are striving to maintain productivity and profits while controlling increasing costs. Historically, validation has been seen as an expensive, non–value-added necessity to gaining regulatory approval to manufacture. Less often is it seen as a key element of an overall quality management system (QMS) that supports the safety, quality, and efficacy of end products for patients while also providing invaluable knowledge and experience for enhanced process control and management. When fully integrated with a QMS, a modular validation platform can offer biopharmaceutical companies considerable benefits:
Traditional Approaches
Regulatory compliance can be a veritable mine-field for biopharmaceutical manufacturers. Facilities and processes that are “validated” to an inappropriate standard inevitably incur the wrath of the regulatory reviewers. Withdrawal of a license can result in loss of credibility and incalculable costs due to necessary remedial work, lost sales, and lost custome...
Biopharmaceutical manufacturers use a range of bioprocess containers (BPCs) during the production and storage of biopharmaceuticals. Plastic bags, bottles, flasks, and carboys are all types commonly used in bioprocessing (
1
). A suitable BPC must be able to maintain aseptic integrity and be constructed of materials that will not harm product efficacy and/or purity.
The trend of “single-use” or “disposable” BPC technologies in the biopharmaceutical industry enables greater flexibility and better use of production facilities that are increasingly designed for multiple products (
2
). In some areas of biopharmaceutical manufacturing (e.g., cell culture), the shift has already become institutionalized, and single-use BPCs such as flasks, roller bottles, and spinners are in wide use (
3
). The paradigm is not yet as pervasive to the rest of biomanufacturing processes, but a growing trend is evident from the large number of conferences devoted to single-use technologies.
PRODUCT FOCUS:
BIOLOGICS
PROCESS FOCUS...
Production of biologics is expensive. To optimize capacity use, bulk protein solution produced in manufacturing campaigns is often converted into drug product based on market demand, so it may be stored for relatively long periods. To decouple production of bulk solution from that of a final drug product, the bulk is often stored frozen.
Transport of frozen bulk between sites offers several practical advantages over bulk transport in the liquid state (2–8 °C). Maintaining 2–8 °C requires accurate systems control to ensure that bulk product does not get too cold and (partially) freeze. A liquid shipment also subjects proteins to shear and agitation stress at air–liquid interfaces. A successful bulk storage program therefore enhances bioprocess capacity use and reduces overall production costs. But success requires careful consideration of biophysical and engineering principles in the development of a frozen storage operation and its effects on products.
PRODUCT FOCUS:
BIOLOGICS
PROCESS FOCUS:
DOWNSTREAM ...
+2Cell-culture–related in vitro recombinant protein production is currently a $70-billion/year business. In 2007, biotech drug sales grew by 12.5%, twice as fast as standard pharmaceuticals (
1
). Current ongoing efforts to maximize productivity in both time and volume directly affect the scale and capital investment required for a bioreactor suite. As cells reach higher concentrations more quickly while each cell pumps out more product than ever before, the number and scale of bioreactors can be reduced. To that end, not only cell engineering, but also culture media and related chemical and physical environments are used to assist cells in reaching peak performance quickly and maintaining such a high level as long as possible.
Most culture schemes currently involve some form of nutrient supplementation after inoculation. Numerous approaches have been tried. Only by considering a number of variables can an informed decision be made to yield maximum cell productivity of a specific protein in specific cells u...
The global vaccine market is growing annually by 16% and is expected to reach $21 billion by 2010 (
1
). Much of the predicted growth of this market is expected to come from the introduction of new vaccines, either against diseases for which no vaccine currently exists or as second-generation products to replace existing ones.
Much research is still centered on developing vaccines to prevent infectious diseases caused by microbial and viral pathogens. This segment is being fueled by a number of factors including
PRODUCT FOCUS:
VACCINES
PROCESS FOCUS:
R&D, TESTING
WHO SHOULD READ:
PROCESS AND PRODUCT DEVELOPMENT, QA/QC, AND ANALYTICAL PERSONNEL
KEYWORDS:
OPK ASSAY, VIRAL PLAQUE ASSAY, AUTOMATION, CLINICAL TRIALS
LEVEL:
BASIC
Because many vaccines have a limited lifespan (a short period of clinical usefulness because of the changeability of antigens), pharmaceutical and biotech companies are increasingly under pressure to get their products to market quickly. This translates to a need for speed in manu...
According to a recent industry survey published in
Pharmaceutical Manufacturing
, the top three goals of most biopharmaceutical manufacturing companies are to improve in these areas: manufacturing agility, capacity use, and internal quality management. Close on the heels of those top three are improved alignment of internal goals with those of business partners, improved on-time delivery, and reduced inventory. The BMD Summit is the best forum to gain the data and consultation you need to enable you and your interdisciplinary team members to achieve these important goals.
At this event, you can choose to attend any presentations you wish from two tracks: Flexible Facilities and Operational Excellence. You will receive all presentation materials provided by the presenters from both tracks. Hear the latest from FDA on CMC microbiology review and inspections for therapeutic biological proteins. And you have the chance to learn even more by seeing firsthand how leaders in the field put it all together if you...
Disposable Component ID
Product:
Single-use tubing and molding components
Applications:
Biopharmaceutical manufacturing
Features:
The industry wants reliable identification of components in single-use products. AdvantaPure addresses that with identification solutions that include the AdvantaLabel molded silicone labeling system, PET process-equipment tracking, and GammaTag gamma-irradiation–sterilizable RFID tags. The new DocuLink identification product (patent pending) will soon be launched to provide users a way to reference batch, lot, and validation documentation after installation of a molded-silicone manifold.
Contact AdvantaPure
www.advantapure.com
Hydrophobic Interaction
Product:
HIC membrane adsorber
Applications:
Removal of hydrophobic contaminants
Features:
Sartorius Stedim Biotech has launched the first commercially available membrane adsorber for hydrophobic interaction chromatography (HIC). Sartobind Phenyl membrane adsorbers allow increased flow rates to ensure faster processes and ...
In preparing for our October supplement on bioprocess design, BPI’s contributing editor Lorna D. McLeod spoke with Bayer Healthcare’s Harald Dinter (vice president of global biological development) and Jens Vogel (CMC development team leader and head of isolation and purification in global biological development) about the downstream bottleneck. Is it or isn’t it a real problem? Does the answer depend on your point of view?
BPI:
“Does a company’s downstream capacity place practical constraints on increasing production titers? Is that something you’re giving thought to early in development? Will we be able to handle the titers that we’re seeing in these early phases?”
Harald Dinter:
“This is a big discussion with commercial products and facilities that were designed so the fermentors are matched to a purification train. They said, ‘OK, we’ll have antibody titers up to 1–3 g/L. So we’ll have so many grams of antibodies in a batch, and we need these kinds of columns downstream.’ But suddenly the titers are...
