Biologic Drugs

Washington, DC (Dec. 13)-After considerable debate and negotiation, Congress this week passed four bills poised to affect pharmaceutical and biotechnology research, development, and manufacture. All are currently awaiting signature by the President.

Basel, Switzerland (Dec. 5)-Lonza Group Ltd. and Singapore?s Bio*One Capital have formed a joint venture, Lonza Biologics Tuas, to build a large-scale mammalian cell-culture facility in Singapore for as much as $350 million.

Makers of injectable drugs can increase their market share and stay competitive by devising a product life-cycle management strategy.

Virus safety of biotech- and plasma-derived therapeutics is ensured through complementary manufacturing and quality control measures that include the control and monitoring of raw materials, the validation and implementation of effective virus clearance technology and the monitoring of final filled product for the presence of virus. Virus filtration, which is considered a robust and effective virus clearance technology, is a common unit operation in the manufacture of biologicals. In this article, we review the points that must be considered when selecting a virus-retentive filter. The areas covered include regulatory considerations; selecting, optimizing and validating a virus filtration step; and process scale implementation - areas that are critical to users of virus filters.

Why do the biotech ventures mange to have such promising drug candidates while pharmaceutical R&D is facing a drug deficit?

The needle and syringe have long been the standard delivery technology for vaccines. However, a confluence of market factors is driving new interest in alternative delivery systems that hold the potential to meet one or more of the following goals: improved antigen utilization, higher quality immune response, better stability and improved patient acceptance. Of particular interest are microneedle systems, otherwise referred to as microstuctured transdermal systems (MTS), that provide for targeted delivery of the vaccine formulation directly to antigen-presenting cells within the epidermis. This article provides a brief overview of MTS technology with an emphasis on solid-coated MTS for vaccine delivery.

Washington, DC (Nov. 20)-The US Department of Health and Human Services awarded contracts totaling $199.45 million to Sanofi Pasteur, Novartis, and GlaxoSmithKline PLC to manufacture 5.3 million 90-?g doses of influenza vaccine designed to protect against the H5N1 influenza virus strain.

Research Triangle Park, NC (Nov. 13)-Eisai Inc. broke ground here for a new pharmaceutical production and formulation research and development facility for parenteral oncology drugs.

Clean rooms are critical areas in bio/pharma facilities, and it is essential that users are responsible for their care and upkeep, and familiarize themselves with the relevant regulations.

Quality by design and PAT approaches are increasingly being used for the biotech manufacturing of medicines. Complex manufacturing processes can not only be controlled using PAT principles, but optimized with respect to both product quality and economic value. This column describes how the fermentation process is often the first to benefit from this type of implementation.

The ¤9.5 billion therapeutic antibody market comprises over a dozen antibodies that have been generated using recombinant genetic methods developed over the last 20 years.

Robin Hwang, a senior principal scientist at Amgen (Thousand Oaks, CA), led the team that developed the first commercial disposable auto-injector for a biopharmaceutical: a prefilled three-step "SureClick" for delivering Enbrel (etanercept), a treatment for autoimmune diseases.

The US Food and Drug Administration issued a guidance document to provide manufacturers of biological products (other than blood and blood components) with its current thinking on reporting requirements on deviations from current good manufacturing practices for biological products.

Biologics are forecast to account for roughly 60% of revenue growth through 2010 for Big Pharma as growth in small molecules slows. The author analyzes the factors driving demand and how the technology life cycles of these two sectors will affect market potential.

Protein formulation specialists have long sensed that something big could be just around the corner. Over the past few decades, countless companies have attempted to bring to market new protein therapeutics that offer improvements-be they more patient friendly, more effective, or easier to manufacture-over traditional formulations. Earlier this year, the launch of Pfizer's "Exubera" pulmonary insulin met this anticipation head on. The fast-acting, inhaled-powder form of recombinant human insulin brought hope to the millions of diabetic patients waiting for an alternative to injections.

In view of the nature of its complexity, it might be desirable to apply FDA's process analytical technology to lyophilization.

UK science has an outstanding record and we remain strong internationally in terms of achievement, productivity and efficiency.

Scientists from GlycoFi, Inc., a wholly owned subsidiary of Merck & Co, in collaboration with Dartmouth-Hitchcock Medical Center, have engineered yeast cells capable of producing a broad range of recombinant therapeutic proteins with fully human sugar structures (glycosylation).

The overall market size of the Southeast Asia region totals $7 billion, with a projected compound annual growth rate of about 13% through 2010.

For once, casting originators against generic players might end up strengthening the industry across the board.

Washington, DC (Aug. 14)?A new report issued by the Pharmaceutical Research and Manufacturers of America identifies 418 drugs and vaccines developed through biotechnology. All of the biotechnology medicines and vaccines are now in clinical trials or awaiting approval by the US Food and Drug Administration (Rockville, MD).

Dutch biotechnology company Crucell NV (Leiden, Netherlands) and its technology partner DSM Biologics BV, a business unit of Royal DSM NV (Heerlen, Netherlands) will open a new research and development center that will specialize on further developing the "PER.C6" human cell line for the expression of recombinant pharmaceutical proteins.

Drug development opportunities, specification development, and new vaccine technologies were highlighted at the AAPS National Biotechnolgy Conference in Boston this week. More than 1100 attendees from 19 countries participated in the event.

Using Bezier curves, an experimental process controller has been developed for biosynthesis applications in which the inactivity of a pH-sensitive enzyme must be decreased. By taking into account various control scenarios of pH and growth rate, as well as the physical and chemical characteristics of the environment, a suitable human-machine interface can be developed.

Cell-culture technology and financial incentives give influenza vaccine makers a much-needed shot in the arm, but many downstream processing issues remain unaddressed.

Creation and qualification of scale-down models are essential for performing several critical activities that support process validation and commercial manufacturing. As shown in Figure 1, these activities include process characterization and production support studies that are performed to evaluate column and membrane lifetimes, demonstrate clearance of host-cell impurities and viruses and troubleshoot manufacturing issues. While the underlying fundamentals are relatively the same as those when scaling up, some unique considerations should be taken when scaling unit operations down.4

Once the brightest students are interested in bioprocessing, it is vital that they are prepared and inducted into industry.

Human plasma provides a rich source of therapeutic medicines, including gamma globulins, coagulation factors, albumin, alpha anti-trypsin and others. In 2001, sales of immuno gamma-globulin (IgG) were estimated at $2 billion with a production rate of 50 metric tons for the year.1 A number of therapeutic products have been introduced including Gammimune from Bayer, RhoPhylac from ZLB Behring and Octagam from Octapharma.

When it comes to developing a robust lyophilization process, formulators can "pay now or pay later," says Jeff Schwegman, PhD, founder and chief scientific officer for BioConvergence. Because 30% of new drugs in clinical trials are biotech-based therapeutics (compared with 7% 10 years ago), more than ever, the US Food and Drug Administration is paying close attention to lyophilization data and questioning pharmaceutical companies about their development cycles, especially cycle development transfer, shelf-temperature mapping, dryer-to-dryer comparison studies, formulation time, process validation, and cycle deviation. Consequently, this is pushing formulators to optimize formulation variables, conduct additional testing during early-stage development, and understanding critical process parameters, equipment qualifications, and manufacturing conditions that can influence formulation behavior at a large scale. Not taking the time or effort to achieve these goals during early development could lead to redundancies in formulation work - a reality observed too often in today's practices.

Biomanufacturing managers believe the current lack of adequately trained personnel is one of the most serious problems facing the biomanufacturing industry.