A Rocking Good Time

The adoption of single-use bioreactor technology is expanding rapidly today because biopharmaceutical manufacturers now recognize the advantages that these systems provide. Advances in single-use bioreactor technology in response to the changing regulatory environment, the introduction of new cull culture systems and processes, and the desire of the industry to leverage process analytical technology are also contributing to the growing application of single-use bioreactors.

Even established bioreactor technologies are being upgrades to meet current needs. One such system is the ReadyToProcess WAVE 25 single-use bioreactor system from GE Healthcare Life Sciences. The new system incorporates all of the key features of the original WAVE bioreactors – and particularly the use of a rocking motion rather than stirring – plus extensive additional functionality, but it is even easier to use than the original system, according to the company.

What are you looking for in single-use bioreactors today? Do the bioreactors that are available meet your needs? Why types of functionality do you want to see – easier bag handling, automated feedback loops for increased automatic control of reaction conditions, the ability to create your own methods, a more friendly user-interface and expanded data management systems, something else?

If you haven’t already, be sure to sign up for the eNewsletter so that you can read what experts in the field have to say. Then let us know what you think. Also check out the Pharmaceutical Technology/Biopharm International Marketplace at www.pharmabiomarketplace.com.

Cynthia Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report 

Seeking Continuous Success

Continuous manufacturing is attracting growing attention as pharmaceutical manufacturers and industry regulators come to realize the potential benefits with respect to improved quality consistency, increased efficiency, and lower costs. Many small-molecule advanced pharmaceutical ingredients require crystallization to achieve the necessary levels and/or the most appropriate form for drug formulation. Therefore, the development of continuous crystallization processes is necessary if fully continuous manufacture of such products is to be achieved.

Several pharmaceutical companies, including GlaxoSmithKline (GSK), Novartis, and Astrazeneca, have chosen to support the Center for Continuous Manufacturing and Crystallization (CMAC) to accelerate the development of practical, commercial-scale techniques for continuous crystallization.

CMAC was established in 2011 with support from these drug companies, equipment and instrumentation manufacturers, engineering design firms, and fine chemical producers. The physical hub is at the University of Strathclyde (Glasgow), with Glasgow, Heriot-Watt, Edinburgh, Cambridge, Loughborough, and Bath Universities rounding out the multidisciplinary academic team. The center has raised nearly $100 million in 2 years, initiated several research projects, implemented a doctoral training program across the network (45 PhD students), and is starting a Maters program. The researchers are targeting ten key areas, including the investigation of appropriate raw materials and synthetic methods, continuous nucleation, growth and habit control, mixing, flow and transport, powder production and processing, and particle properties and performance.

Initial projects have focused on the use of existing equipment, such as a mixed suspension mixer product removal (MSMPR) crystallizer, continuous stirred tank reactors (CSTRs), and meso-scale and full-scale continuous oscillatory baffled crystallizers (COBCs). Others are developing new technologies for which patents have been filed, including a device for inducing nucleation (Heriot-Watt University), customized nucleation units for seed suspension (University of Strathclyde), and a moving fluid oscillatory baffled crystallizer and new flow crystallization technology for multicomponent products (University of Bath).

Do you think this type of organization is the way of the future with respect to technology advancement? Can companies achieve real advances in technology just with their own staff and knowledge base anymore?  How will the economic advantages play out if much of new technology is developed by cooperative industry-funded groups?

Don’t forget to sign up for the eNewsletter here if you haven’t done so yet. Also check out the Pharmaceutical Technology/Biopharm International Marketplace at www.pharmabiomarketplace.com.

Cynthia Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report

Making the Right Choice for Poorly Soluble Drugs

As the number of drug candidates that are poorly soluble increases, so does the number of methods for improving solubility profiles. The challenge, then, is not only to increase bioavailability, but to do so using the most effective route.

When is using a salt form  vs. a  cocrystal appropriate? Is micronization always preferable if the active pharmaceutical ingredient (API) can tolerate the conditions? Or is the use of a lipidic vehicles a better choice? When is the use of an amorphous form preferred, and which method of dispersion – spray drying or hot melt extrusion, for example – will be more effective?

Because the choice of technique for solubilization enhancement often depends on the physical properties of the API, it is critical to understand the solid-state characteristics of a drug candidate, as well as its stability under various conditions. It is also important to understand the method options and the operating parameters and physical property requirements.

Evaluation of the properties of various salts, cocrystals, and polymorphs of a drug candidate must be carried in order to fully evaluate the potential options for increasing solubility in order to. The physical structures of the different forms and their related properties, as well as their chemical stability under different conditions must be determined. Permeability and exposure data are also needed.

Some methods can be quickly eliminated once the physical data is gathered. In some cases, the choices are more complicated. Excipients, such as co-solvents, solubilizers, and permeation- and bio-enhancers, considered as well their use levels, interactions with the API, and stability under the formulations conditions are all important.

Rapid screening of the physical properties and appropriate methods solubility/bioavailability enhancement is vital for reducing both development time and cost. Do you have a formalized screening system in place? Or do you follow an informal system? If you don’t have a well-defined strategy, do you think your development programs would benefit if one was adopted? If you have one, what are the key aspects of your strategy?

Don’t forget to sign up for the eNewsletter here if you haven’t done so yet. Also check out the PharmaceuticalTechnology/Biopharm International Marketplace.

Cynthia Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report

Pharma Open for Business

Time is of the essence when it comes to getting new products to market. Launching innovative solutions that address unmet customer needs is vital for success. The time companies have for product development is ever-shrinking, however. At the same time, technology is advancing more rapidly than ever and the quantity of relevant and information is expanding exponentially.  The most successful firms will be those that can leverage not only the latest technology advances, but also those anticipated on the horizon, while simultaneously accessing the broadest possible skill set and a comprehensive knowledge. In the global market that exists today, that means looking beyond the organization and utilizing all potential resources, or implementing an open innovation (OI) strategy.

Where does your company stand with respect to the OI concept? Do you collaborate with entities outside of your company – universities, institutes, government agencies, even individuals? Have you made use of the services of the various companies that have formed to facilitate OI? What has been your experience? Have you found that people in your company are resistant to bringing technology in from the outside for fear of losing their jobs? What has management done to allay such concerns? What have been some of the stumbling blocks? What about successes?

And don’t forget. If you haven’t already, you can sign up for the Pharmaceutical Sciences, Manufacturing & Marketplace Report here. Also check out the Pharmaceutical Technology/Biopharm International Marketplace at www.pharmabiomarketplace.com.

Cynthia Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report

Pharmaceutical Asset Management: What is the Optimal Approach?

The pharmaceutical industry is undergoing many changes today, three of which in particular are having a major impact of the asset needs of drug manufacturers: the shift away from the development of blockbuster drugs to a focus on smaller-volume therapies that target diseases affecting sub-segments of the patient population; the increasing focus on biologic drugs at the expensive of small molecule APIs; and the growing adoption of single-use systems throughout the production process. The growing interest in continuous processing could perhaps be considered a fourth factor.

As a result of the evolution of the pharmaceutical industry, the conventional approach of constructing large, multipurpose, stainless-steel based facilities for large-volume manufacturing is not longer applicable for most of the drug products coming to market today. Interest in modular facilities that can be rapidly built in locations close to the targeted population is growing, particularly for biologic drugs. Smaller-scale single-use systems can also be more rapidly installed, often in much smaller spaces and in some cases in existing, non-purpose-built structures. We discussed such approaches for modular manufacturing in the Pharmaceutical Sciences, Manufacturing, and & Marketplace Report.

What, then, is to be done with the existing infrastructure? Is there a way to still leverage the equipment and facilities that exist? Is the only practical answer to shutdown these locations and minimize any losses? Or is there a way to breathe new life into older sites and process equipment in some way that will maximize the return on the investment?

What has your company done with older plants and production equipment that has been replaced with single-use systems or smaller, strategically placed modular facilities? Have you accessed the used equipment market, and if so, how have you leveraged these pre-existing assets? What are other options?

Gain a further perspective on asset management of pharmaceutical equipment in the Pharmaceutical Sciences, Manufacturing, and & Marketplace Report.

And don’t forget. If you haven’t already, you can sign up for the Pharmaceutical Sciences, Manufacturing & Marketplace Report here. Also check out the Pharmaceutical Technology/Biopharm International Marketplace at www.pharmabiomarketplace.com.

Cynthia Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report

Extractables and Leachables Add Complexity to the Supply Chain

Parenteral drug manufacturers continually face the challenge of managing extractables and leachables (E&Ls) in their drug products. It is an ongoing problem because materials changes made all the way through the supply chain. The elastomers for tubing and seals, the plastics for containers, and the glass used in syringes all can affect the E&L profile of a parenteral drug. That means that new contaminants can be introduced at any time, and their identification and reactivity must be determined. That in turn means that extensive analyses must be carried out to ensure patient safety.

Clearly, increased awareness throughout the supply chain is critical to gaining some level of control over E&Ls. A recent article in the Pharmaceutical Sciences, Manufacturing & Marketplace Report examines advances in testing and controlling E&Ls.

But has the pharmaceutical industry done a good enough job at educating suppliers on this important issue? What do you think should be done to improve the understanding of suppliers far down the supply chain? What has your company done when working with your suppliers?

If you haven’t already, be sure to sign up for the eNewsletter so that you can read what experts in the field have to say. Then let us know what you think. Also check out the Pharmaceutical Technology/Biopharm International Marketplace.

Cynthia Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report

Going Green

Did you know that proteins developed as therapeutic agents have been produced in plants since the late 1990s?  There have, in fact, been several biologics produced in transgenic plants, including gastric lipase, interferon, and insulin, that have entered human clinical trials. There are also clinical trials underway for cancer treatments based on proteins produced in plants.

The use of plants has several advantages over fermentation and cell-based technologies. There is no use of animal derived products or growth factors, and aseptic handling systems are also not necessary. No time-consuming identification and isolation of appropriate cell is required, either, so plant-based systems can be functional in a much shorter time. In addition, the biological features of bacterial, viral, and plant biology can be combined to achieve high yields and offer significant flexibility.

Have you utilized this technology? What was your experience? Do you agree that plant-based protein expression has significant potential? Or do you see problems with it, and if so, what concerns do you have?

If you haven’t signed up to receive it yet, take the opportunity right now. Just click here. Also check out the Pharmaceutical Technology/BioPharm International Marketplace at www.pharmabiomarketplace.com.

Cynthia Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report