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

X-Ray: Analysis: Seeing Straight Through

Any analytical method that can be carried out without damaging the samples is attractive for pharmaceutical manufacturers. It is not surprising, therefore, that interest is growing in industrial X-ray analysis. This nondestructive analytical technique offers both depth of penetration and reasonably high resolution, making it possible to capture the internal geometric data of a sample along with its density distribution, information that can be useful for process and design verification, product-quality analysis, foreign-material determination (metal, glass, organics), fill-level confirmation, and missing-components detection. In addition, with three-dimensional computed tomography imaging, it is possible to get a true three-dimensional view of the inside of a tablet, capsule, gelcap, or any type of solid or semisolid dosage form. Packaging materials–from medicine bottles to syringes–can also be evaluated.

What is your experience withX-ray analysis of solid or semi-solid dosage forms? Have you found it useful for identifying the source of inconsistencies in the disintegration of fast-dissolve formulations, or perhaps the improper functioning of your syringes or pill container seals? What other applications might there be for X-ray imaging in pharmaceutical manufacturing? What are its limitations? How might it be improved?

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

Turning Challenges into Opportunities

Legislation in both Europe (EU Directive 2011/62/EU) and the US (California’s e-pedigree program) that is designed to help control the transportation of pharmaceuticals across borders and fight the distribution of counterfeit drugs will soon be coming into effect. The need to ensure patient safety is a key driver behind such legislation.

While the requirements can be onerous for pharmaceutical manufacturers, there also may be potential benefits beyond the critical one of eliminating dangerous counterfeit medicines from the marketplace.

All that serialized data that must be collected, monitored, and controlled – if managed properly, may be useful for not only achieving regulatory compliance, but also increase supply chain visibility and control, improve a company’s decision-making ability, and, ultimately, reduce costs and increasing profitability.

How do you look at the need to implement track and trace solutions? Do you see a challenge or an opportunity? What progress have you made so far? Have you overcome any hurdles and gained insight that others could benefit from? Share your thoughts and experience!

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 PharmaceuticalTechnology/Biopharm International Marketplace.

Cynthia Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report

Guiding Cocrystal Development

Cocrystals offer pharmaceutical manufacturers an alternative method to using salts or hydrates for obtaining a crystalline solid form of an API with desirable stability and dissolution behavior.

Recently, the FDA issues its final regulatory guidance on cocrystals (http://www.fda.gov/downloads/Drugs/Guidances/UCM281764.pdf).

Even though nearly all commenters requested that the FDA not classify cocrystals as 'drug product intermediates' but as salts, the agency elected to keep this definition in the final guidance.

Why were so many opposed to this approach, and what impact might the FDA’s decision to retain this classification have on the eventual acceptance of cocrystals in drug formulations?

There is significantly more information required for drug product intermediates, In addition, the decision could benefit generic companies, which may be able to use cocrystals as a means to get around patents. Thus, in the short and long term, this decision may deter branded pharmaceutical manufacturers from developing formulations based on cocrystals.

What do you think of the FDA’s final guidance on cocrystals? Will it have an impact on their further development? Or do you  think the performance benefits that can be gained in certain cases by using cocrystals will outweigh the additional testing and reporting requirements and the potential longer-term threat of generic competition?

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

Out of the Box Thinking

New simple-to-install, universal connectors for asceptic parenteral manufacturing are making it much easier for pharmaceutical manufacturers to combine single-use technologies with permanent, stainless-steel systems and/or with other single-use systems from different manufacturers with different coupling requirements.

This type of connector makes it possible to shrink the footprint of manufacturing operations in the clean room and reduce the steps necessary for achieving sterile manufacturing. Both advantages add up to improved efficiency and productivity.

However, there are even greater potential benefits if this type of technology can be shown to provide an asceptic connection outside of the clean room.

Do you think connector technology can achieve such a level of sterility assurance? What type of evidence would you need to be convinced? Would you then feel comfortable using them outside of the clean room in order to leverage the numerous efficiency, productivity, and cost gains such an approach would make possible?

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

Analysis the Terahertz Way

Terahertz waves are low energy waves that can penetrate up to a few millimeters into substances and detect interactions on the molecular level (intermolecular hydrogen bonding or intramolecular interactions in large biomolecules like proteins), the microscopic level (film thickness, interfacial interactions) and at the structural level (density and porosity), all non-destructively.

These capabilities seem to be a perfect fit for the pharmaceutical industry. So why isn’t the technology more widely used?

Early instruments were unwieldy with respect to their size, for one thing. Advances in the laser, emitter and detector technologies required for the generation of terahertz waves have made it possible for instruments today to be of a practical size. Cost has come down as well, and now is at a reasonable per measurement level. Instrument manufacturers are also now offering easy-to-use platforms for terahertz analysis.

Of course, there is also the fact that the pharmaceutical industry is conservative and takes its time when considering the adoption of new technology. Just look at Raman analysis and where it was 10-15 years ago, and how it has become a much more commonplace analytical tool today.

What do you think about terahertz spectroscopy? Is your company interested in this technology? Have you used it in your product development of processing operations? Have its capabilities won you over, or do you still have concerns? How easy is to interpret the results? Do you see it as an alternative or substitute for some existing analytical techniques?

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

Going Modular

Modular biopharma facilities seem to be attracting a lot of attention these days because of the rapidity with which they can be constructed. Many also incorporate single-use technologies, so not only is time saved, but there is also the potential for reduced capital investment.

Beyond these obvious advantages, the availability of such modular factories creates opportunities for biopharmaceutical manufacturers to install facilities in locations they might not otherwise have considered. With the lower capital investment and ease of construction, it may be possible to construct multiple, smaller production facilities, thus enabling more localized and customized service. In addition, with the growth of niche medicines with smaller volumes, the ability to cost-effectively construct smaller operations more quickly and at lower cost can help manufacturers reduce their time to market and maximize their profitability.

Has your company opted to build a modular biopharmaceutical manufacturing facility? What has been your experience? Are there really significant cost and time savings? Do they functionally equally as well as a conventional, “brick and mortar”   facility? What issues have you come across? What good experiences would you want others to know about? Do tell!

  

And don’t forget. If you haven’t already, you can sign up for the Pharmaceutical Sciences, Manufacturing & Marketplace Report here.

Cynthia Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report

The Benefits of Biodegradability

Interest in biodegradable polymers is expanding rapidly in a wide range of industry sectors and as growing numbers of polymer-chemistries become available. The pharmaceutical industry is no exception. In fact, there are significant benefits to the use of biodegradable polymers in formulated drug products that go well beyond their sustainability, which is what is, in large part, driving the use of such polymers in other sectors.

Biodegradable polymers are, in fact, ideal for the development of sustained release parenteral products or the taste masking of tablets, capsules, and granules. In the case of parenterals, the ability to provide sustained release increases ease of use and may in turn leader to greater patient compliance.

Biodegradable polymers are also being investigated, in conjunction with nanoparticle conjugates, for targeted drug delivery of highly potent APIs. They can even be used to provide sustained release of antibiotics or anti-inflammatory or other actives at the site of surgery or on an implanted medical device.

What is your experience with biodegradable polymers? What applications for these materials are you investigating or would you like to see explored? Let us know.

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.

Cynthia Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report

Can a Process be Too Productive?

Advances in monoclonal antibody (mAb) production have superseded the abilities of downstream processing systems. Current production systems generate much higher concentrations that cannot be handled by traditional separation processes. Whether it is ion-exchange columns or centrifugation systems, processing solutions with higher biomass has become a real challenge for the industry. At the same time, the growth in the biosimilar market is placing downward cost pressures on these downstream processes.

What do you think can be done to address this issue? Is enough progress being made with salt-tolerant and mixed-mode ion-exchange media? Will introduction of single-use systems be effective in reducing costs in general? What about the use of flocculation and precipitation? Membrane technology?

Beyond specific new technology solutions, what new strategies might be adopted to help overcome the challenges faced by mAb producers?

Share  your thoughts and ideas.

Don’t forget to sign up for the eNewsletter here if you haven’t done so yet.

Cynthia A. Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report

INTERPHEX Lesson: The Little Things Really Do Count

In meetings at INTERPHEX, and even while just observing the wide range of equipment offerings on display at the show, it struck me quite strongly that pharmaceutical product quality often relies to some degree on very small parts and components. My experience has largely been related to the chemistry and processing of APIs, and not so much with the physical equipment involved in their final formulation.

Not only is the vast array of required machined parts and the level of detail to which they have been developed quite impressive, the potentially significant impact that even a little wear or damage to these small parts can have on product quality is quite something. As a result of this recent education, I have a new appreciation for the complexity of pharmaceutical manufacturing equipment and the work required to properly maintain it.

Do you have strong feelings about a type of manufacturing equipment that you feel doesn’t receive the recognition it deserves? Let us know.

And what insights did you take away from this year’s INTERPHEX? Did you spot any significant new trends (the growing use of x-ray and terahertz analysis techniques), regulatory concerns (the push for serialization) or facility design issues (modular systems), or something all together different? Share your thoughts!
                                                   

Don’t forget to sign up for the eNewsletter here if you haven’t done so yet.

Cynthia A. Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report

Request For Authors

Calling all pharmaceutical industry experts with valuable knowledge on important subjects and a passionate opinion to go with it: I want you to contribute to this blog or to write an article for the Pharmaceutical Sciences, Manufacturing & Marketplace Report!

Has your company developed a new characterization technique that could reduce production times and help lighten the burden on pharmaceutical QC labs? Have you used a tried and true excipient in a new way that formulators could benefit from? As a biosimilar manufacturer, are there specific technologies that you find help ensure consistent quality that matches the branded drug?

Take this opportunity to demonstrate your expertise to an interested audience. As a journalist with a chemical background and many years of working in the fine and specialty, coatings, pharmaceutical, and related industries, I am in an excellent position to speak with industry experts and synthesize and organize their thoughts and perceptions. But I would like to add to that service by providing direct insights from the experts themselves.

Please contact me (PSMMREditor@gmail.com) with your proposed topic. 

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And don’t forget. If you haven’t already, you can sign up for the Pharmaceutical Sciences, Manufacturing & Marketplace Report here.

Cynthia A. Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report

Mixing It Up

Mixing technology seems like a basic capability with little room for further advancement. Nothing could be further from the truth. Whether working with just solids, solids and liquids, or just liquids, there are numerous factors that must be considered when combining different materials. For solids, there is particle size and size distribution and the stability of the particles. When mixing a solid and liquid, the dissolution rate of the solid and the viscosity and shear stability of the liquid are important. Suspensions involve yet another set of variables.

As a result, each mixing process is unique and requires unique parameters and process conditions.  Recognition of this fact can lead to improvements in mixing and blending processes for even the simplest ingredients.

Have you had such an experience you can share?

I am also curious about the adoption of newer mixing technologies by the pharmaceutical industry.

For example, is resonant acoustic mixing (RAM) (from Resodyn Acoustic Mixers), which is an impeller-free mixing technology that uses propagation of a low frequency, high intensity acoustic wave through the material to cause both bulk flow and micro-scale mixing, appropriate for mixing of pharmaceutical formulations, or is it only suited for mixing processes related to the manufacture of intermediates and APIs?

Are there any other novel mixing methods that are finding use in the pharmaceutical industry?

Any ideas? Let me know!

And maybe I’ll see you at INTERPHEX. Stop by the Pharmaceutical Technology booth (#4139) to say hello!

Don’t forget, if you haven’t already, you can sign up for the Pharmaceutical Sciences, Manufacturing & Marketplace Report here.

Cynthia A. Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report

Gearing up for INTERPHEX

INTERPHEX 2013 is just around the corner, and the show looks to be as big and busy as ever. Our April 24^th issue of The Pharmaceutical Sciences, Manufacturing & Marketplace Report discuss advances in various types of equipment used in the pharmaceutical industry, from mixing and blending equipment for solid dosage forms to visual inspection equipment for parenterals and the use of microreactors for chemical API manufacturing.

According to a survey of members of the American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable, which was conducted in 2012 (1), that although implementation of continuous processes in pharmaceutical API manufacturing is not a standard practice as of yet, eight of the nine responding companies have taken a continuous process to the pilot plant or production scale. The survey also identified several reasons for implementing continuous processing, including simplification and increased speed of scale-up, increased throughput, and increased safety, reduced waste, greater process control, and overall cost savings.

The problem, of course, is that continuous processing, and particularly the use of microreactors, is a new technology that requires significant investment. With existing capacity and facilities in place for batch manufacturing, it is hard to argue for additional investment even though the benefits are measurable.

Manufactures of microreactors have made progress in addressing many of the concerns associated with their systems. Modular reactors have been introduced that can be fit for different reaction processes and run in parallel to address scale-up needs. Issues, however, remain, such as the need for large numbers of connectors and uncertainty about flow distribution. Integration with downstream processing is also a consideration.

It seems, though, that the use of some sort of flow chemistry for continuous chemical synthesis will eventually be adopted in some form.

Are you surprised by the survey results? Or does your experience fit well with the experience of these pharmaceutical manufacturers? As a microreactor manufacturer, how are you addressing concerns regarding the technology?

You can read more about microreactors for continuous chemical manufacture in the April 24^th issue of The Pharmaceutical Sciences, Manufacturing & Marketplace Report.

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.

Cynthia A. Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report

Reference

1. P. Poechlauer et al., Org. Proc. Res. Dev. 16 (10), 1586−1590 (2012).

Biologics in the Spotlight

The 2013 BIO International Convention takes place this month in Chicago, Illinois. Since cell-culture media are such a critical component for the manufacture of biologics, the fourth issue of The Pharmaceutical Sciences, Manufacturing & Marketplace Report includes a roundtable discussion on this subject, with comments on trends in media development from leading manufacturers.

With respect to media for protein expression, the focus, it seems, has moved from increasing protein expression yields to ensuring product quality by gaining better control over the makeup of the cell- culture media. That means closer scrutiny of raw materials and investigation of the effect of each of the numerous media components on cell performance, which has led to increased investment in and development of characterization techniques.

Of course, there is also growing demand for culture media used for the production of therapeutic cells. The media needed in these applications must be carefully designed to encourage proliferation without specialization until the desired time. Isolation of the cells, which tend to be fragile, requires much gentler downstream processing conditions.

The use of chemically defined media seems to offer a solution in both applications. Manufacturers can characterize individual raw materials and ensure that they meet specifications and perform as needed.  The key will be the ability to achieve accurate characterizations and develop methods that allow researchers to make connections between specific component properties and certain cell performance parameters.

Are there technologies available today that can achieve these goals, or do existing characterization techniques require modifications to be of maximum use? How do you evaluate the performance of your cell culture media? What do you expect from your media supplier along these lines?

We’d like your opinion. And suggestions of topics related to biologic API manufacture that you don’t believe receive the attention they should. Think about writing a guest blog – I welcome your input.

Look for the fourth issue of The Pharmaceutical Sciences, Manufacturing & Marketplace Report this week. If you haven’t signed up to receive it yet, take the opportunity right now. Just click here.

Cynthia A. Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report

A Look at Freeze Drying of Parenterals

With the annual meeting of the Parenteral Drug Association coming up this month, we have elected to feature advances in freeze drying in our the upcoming first April issue of the Pharmaceutical Sciences, Manufacturing & Marketplace Report.

Freeze drying, or lyophilization, has been used for many products, beginning with blood plasma products, antibiotics, and vaccines. As the number of biologic drugs, and thus parenterals formulations, has increased in recent years, lyophilization technology has also become more widely used. While the industry has a better understanding of critical issues today and equipment capabilities have improved to address some of these issues, there is much that remains unknown. In addition, as freeze drying is used for greater numbers of high value products, further technical demands will arise.

Even simple questions – such as when lyophilization is appropriate – need to be addressed as potential new applications present themselves. There will be both formulation and process-related issues to consider: protein/nucleic acid stabilization in the solid state, heat transfer, nucleation, vial fogging, handling of high concentration formulations, reconstitution, scale-up, characterization and analysis.

Will new dryer designs address these issues? Or will changes in formulations be the key? Do excipients have a role? What new characterization techniques might be of value?

Share your thoughts. Also, please suggest other topics related to parenteral manufacturing that you feel are not well-covered but could be useful to our readers – especially on new technologies that others can benefit from. You are the experts. Help me make the Pharmaceutical Sciences, Manufacturing & Marketplace Report as valuable a resource as possible.

And don’t forget to sign up for the eNewsletter here if you haven’t done so yet.

Cynthia A. Challener, PhD

Editor

The Pharmaceutical Sciences, Manufacturing & Marketplace Report