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?

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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?

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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?

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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!

  

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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.

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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.

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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