Recent Events

MIT Professional Institute Co-Sponsors “Bridging the Gap between Laboratory Research and Industrial Applications”

by Paul L. Smock, ISPE Boston Area Chapter Past President, with photos by Chris Opolski, Alexion Pharmaceuticals

On Tuesday, April 8, the Boston Area Chapter presented an educational program at the Cambridge Hyatt Regency. The venue was the Charles River room, high atop the hotel with a spectacular view of the Charles River and the Boston skyline. We were also treated to some really excellent hors d'oeuvres while networking prior to an outstanding program that began with Joyce Chiu of the Membership Services Committee outlining the benefits of ISPE membership. She was followed by Chapter Past President Doyle Johnson, who introduced the program and speakers.

Our first speaker was Professor Bernhardt L. Trout, Professor of Chemical Engineering at MIT and Director of the Novartis-MIT Center for Continuous Manufacturing and Co-Chair of the Singapore-MIT Alliance Program on Chemical and Pharmaceutical Engineering. His talk was centered on his group's research on modeling protein degradation processes to develop rational approaches to stabilization. Aggregation, oxidation, deamidization and hydrolysis were all presented as degradation pathways, but the bulk of the presentation was focused on aggregation and the application of molecular level quality by design (QbD) to counter this process for antibody stabilization.

Dr. Trout's group has used modeling techniques followed by application of a tool to assess spatial-aggregation-propensity (SAP) to identify both highly hydrophobic and highly hydrophilic regions of the antibody molecule, recognizing that the interactions of these regions is one of the major causes of aggregation. In addition, the SAP tool can predict both protein binding regions, and can be used to rank prospective molecule variants in terms of their potential for development as stable products. Lastly, he presented some experimental data demonstrating how well the actual results fit the predictions, and argued that this approach should be used from early product/process development forward to develop a mechanistic understanding and allow for the rational design of stable products.

Our next speaker was Dr. Anirban Chatterjee, Scientist at Fraunhofer Center for Manufacturing Innovation (CMI). At CMI, teams of engineers and scientists work closely with clients and partners to design, manufacture, test and optimize prototype devices and instruments in the areas of mechanical, biotech/biomedical, photonics, and alternative energy. His talk was focused on some work done in partnership with Boston University on the design and development of medical devices, biomedical instruments and research tools. He highlighted porous polymer monolith, invented by Dr. Catherine Klapperich at BU, and its application in lab-on-a-chip diagnostics and automated sample preparation. In the case of the lab-on-a-chip application, he showed us how that had been integrated into an instrument system comprised of three major systems - fluidics, thermal, and optical - and went on to demonstrate how that instrument had been put into service as a high throughput nucleic acid sample preparation tool. Dr Chatterjee concluded his talk with three other examples of innovative work around automated tissue homogenization, bacteria concentration and purification, and automated myocite cell isolation.

For those in attendance, these talks did indeed demonstrate the bridges being built between research labs and industrial applications in the life sciences. Many thanks to Dr. Trout and Dr. Chatterjee for taking time out of their busy schedules to enlighten and inspire us; to our co-sponsor, the MIT Professional Institute; and to Educational Program Committee Chair Dave Novak and the EPC for organizing this event.

AstraZeneca Hosts Labs21 Training Session in Waltham

by Chris Leary, KlingStubbins

By their nature, laboratory buildings with once-through ventilation air, high plug and process loads, and 24x7 operating hours leave a large environmental footprint. Even with increased demands to reduce operating costs and environmental impacts, laboratory designers, owners, builders and operators are challenged to find innovative new ideas, case studies of best practices and benchmark building performance data to inform new buildings and renovations.

Laboratories for the 21st Century, or Labs21, a program co-sponsored by the Environmental Protection Agency (EPA) and the Department of Energy (DOE) , is dedicated to the pursuit of sustainable, high performance and low-energy laboratories that will minimize overall environmental impacts, protect occupant safety, optimize whole building efficiency on a life-cycle basis, establish goals, track performance and share results for continuous improvement.

On April 6^th the ISPE Boston Area Chapter, in partnership with the Boston R&D Network of the International Facilities Management Association (IFMA), National Grid and the University of Massachusetts, held a Labs21 "Introduction to High-Performance, Low-energy Design" Training Session. Topics covered included Planning and Programming High-Performance Laboratories, Energy Efficient Lab HVAC, Lighting and Daylighting, and Optimizing Ventilation Rates. Just over 100 attendees, including laboratory owners, facilities and design & engineering professionals, and builders participated in this day-long event.

AstraZeneca graciously hosted the event at their recently expanded and LEED Gold Certified R&D campus in Waltham, a facility that demonstrates many of the design and operational practices recommended by Labs21 including minimal impact on surrounding natural ecosystems, energy and water conservation, sustainable construction materials, and a safe healthy indoor work environment. Additional information about Labs21 can be found at http://www.labs21century.gov/ .

Biotech and Pharmaceutical Manufacturing Sustainability – New Efficiencies and Cost Savings

by Lee J. Ward, Rockwell Automation

On March 18th, an unusually bright and sunny spring evening welcomed attendees to the Royal Sonesta in Cambridge for another excellent Boston Area Chapter Educational Program. Our speaker, David March of Rockwell Automation, opened by launching a spirited and energetic fusillade, suggesting that the "cumulative brainpower surrounding us in Cambridge" may well have had this "old chestnut" and currently overused term "sustainability" on their collective minds from time to time. He went on to cite some profoundly disturbing facts and figures regarding the enormous waste typically associated with the manufacture of pharmaceuticals including a recent audit that reported that pharmaceutical manufacturing is the "least efficient of all chemical process industries." Judging by the nods of many in the audience, the attendees seemed to agree.

The calculation is a simple ratio: Kg Waste/Kg Product. According to David, it is not uncommon for a pharmaceutical product to see a ratio of 200:1 up to 800:1. Biopharma is even worse, with ratios of up to 10,000:1. He went on to say that this is not yet part of mainstream understanding within the industry; however, the quest for higher productivity and cost management is beginning to expose this "dirty secret." In other words, the landscape is changing. A number of European countries have already implemented "carbon taxing," one of a number of "green" initiatives aimed at controlling waste and emissions and generally favoring clean manufacturing practices. "Do we here in the US need to be concerned?" he asked, then answered his own question with a resounding "yes" and went on to explain why.

There is an indirect financial impact that will be realized once a US manufactured pharmaceutical product is exported, as an example, to France. In addition to the usual "landed" cost of goods in the form of duty, a "carbon tax" on imported goods will be applied. Now it becomes clear why we need to be concerned. In order to remain competitive, we need to take steps to reduce the "carbon footprint" associated with the manufacture of pharmaceutical products so that those taxes can be minimized.

How do we do that? One contributor to the carbon footprint is solvents. David loves talking about solvents (as was immediately evident) - in fact, solvent recovery is his specialty. He spends many days during the course of the year talking to companies that use a lot of solvent, including traditional pharmaceutical manufacturers.

Solvents are carbon-based. They are also expensive and tough to deal with once they have been used. Let's look at manufacturing costs again. You have the cost of the product ingredients, the cost of the process materials and the cost of manufacturing time. Solvents come under the cost of process materials. This is a double hit since first you have to buy them and then you have to dispose of them safely and cleanly. And solvents can be highly toxic. As an example, toluene escaping through a leak in a piping system once decimated the population of Bhopal, India. As you can imagine, a substance as dangerous and toxic as that will be very expensive to dispose of properly.

One answer to the disposal question could be, "Let's burn it to make heat and power." After all, solvents generally burn really well. Furthermore, using solvents for this purpose is seen as a green solution since they burn relatively cleanly and have a high calorific value. So that makes it a good solution, right? Not so fast. While the combustion of spent solvent (ie. solvent waste) to make steam that can provide heat and power may be a good use of process waste, it might not be the best answer. While you are disposing of the liquid solvent, the combustion process itself will be contributing to carbon emissions that require monitoring and scrubbing.

Look at it from yet another angle, that of the accountant. Environmentally responsible process people look at the good they are doing by producing energy through the "no-cost" disposal of spent solvent. Yet the accountant will happily tell you the ROI calculation is flawed since it overlooks the original cost of the fuel. You might argue that the fuel is free (since it is reutilized waste) but it is not. You see, solvent is expensive when you first purchase it. If you have a method of recovering a large percentage of that solvent once it is used in the process and then you burn the recovered solvent, you have just used a very expensive fuel, one far more expensive than oil or natural gas. In any case, this use of recovered solvent, now common, may cease in the future when emissions-based carbon taxing will be applied.

A much better answer is not to burn the solvent but to recycle it. Fractional distillation can be employed for this purpose. If, as in most biopharma processes, solvents are employed for the chemical stripping of elements, there is likely to be a voluminous amount used. This solvent tends to be used once, then burned or discarded. Today's modern methods of fractional distillation enable upwards of 92 percent of the virgin solvent to be reclaimed, then reused in the manufacturing process, over and over again. So don't burn it, recycle it, and use natural gas to produce steam - its more cost effective that way.

But wait. There are further efficiencies to be had in the quest for sustainable solutions. Ever heard of "pinch" analysis? While fractional distillation is an answer to recycling solvent, it is an inefficient process. Well, normally. David explained that by using pinch technology we can reduce the cost of running a distillation system by making use of available efficiencies. In basic terms, we harvest the differential between hot and cold processes within the distillation system and recover heat or cold. David illustrated the concept using a series of graphs which had attendees scribbling away at their note pads. For me it signaled that we in the industry have so much more to explore in terms improving manufacturing efficiency and minimizing environmental impact.

Thanks go to our speaker for an exceptionally well-organized and lucid introduction to a complex topic; and to Meeting Manager and Educational Program Committee Chair Dave Novak for an information-packed and enjoyable evening.

A Perfectly (Long) Day - Chapter Ski Outing Tackles Sunday River

by Jim Grunwald, SciTech Builders, LLC with photos by Chris Opolski, Alexion Pharmaceuticals

March 5th found the attendees at the Chapter's Annual Ski Outing making the long trek to Sunday River in Newry, Maine. Between the chartered bus and those that drove to the event, over 50 Chapter Members and guests joined in. And how lucky they were! Everyone was treated to the best ski conditions of the winter - and perhaps the last 10 years - with every trail, marked or unmarked, full of great snow.

Event veterans joined with first-timers to celebrate the 10th anniversary of this Chapter favorite.

It was truly a rare day, with perfect bluebird conditions, temps in the high 20s and nary a breath of wind. Those with an adventurous streak were treated to powder stashes in the trees that one can usually only experience in a Warren Miller movie or perhaps hanging around the bar when the stories begin to fly. Despite the additional travel time associated with the trek to Maine, everyone was very stoked by the experience.

Sunday River provided the best ski conditions of the winter and
picture-perfect weather for the 10th Annual Ski Outing.

Many people commented on the many newcomers at the event, which was celebrating its 10th year. This was in addition to many veterans who have attended every year since the first. We also had in attendance a half-dozen members of the Chapter's very successful Young Professionals group, along with a very diverse group of ISPE Members and their guests.

Special thanks to Chapter Member and Event Manager Gene Dennen and to Chris Opolski, Chapter Board of Directors & Social Programs Director, for another great Ski Outing. This year they got the weather just right! And remember to mark your calendars for the first Friday in March 2011, when the Chapter heads north again!

Boston Area Chapter Scores with Bio-Ball Sponsorship

by Marita King, MARITeK, Inc., with photos by joebrownphotos.com

Bio-Ball team members and volunteers filled the gym to overflowing.

It was a cold and sunny morning on Saturday, March 27th, as volunteers arrived in the early hours at a Cambridge gymnasium to prepare for the arrival of Special Olympics Massachusetts athletes and their biotech industry teammates for the sixth annual Bio-Ball basketball tournament. Much of the set-up had already been done the previous evening by another team of volunteers, which left the morning focused on breakfast preparation, final set-up and organizing the basketball courts for the various skills challenges and play.

Boston Area Chapter members were a part of this effort, which pulled together one of the most successful Bio-Ball tournaments to date. The Chapter Board of Directors approved a first-ever financial contribution in support of Bio-Ball, while Chapter members had the opportunity to participate as players and volunteers and experience this fundraising event first-hand. As the CEO Free Throw sponsor, Chapter recognition was front and center following the Opening Ceremonies. Chapter President Sylvia Beaulieu, who was also on the Bio-Ball organizing committee, congratulated each free throw participant and handed out a small gift on behalf of the Chapter - a whistle with an ISPE lanyard. Whistles were also presented to all Chapter Member volunteers at the event as appreciation for their participation.

Chapter President Sylvia Beaulieu with industry leaders who participated in
the ISPE-sponsored CEO Free Throw event, a tournament favorite.

Following the CEO Free Throw event, and inspirational words from one of the Special Olympics Massachusetts Hall of Fame athletes, the tournament was officially underway. At last the teams were sent off to play and put forth their own version of March Madness. Participating industry teams included AMAG Pharmaceuticals, Archemix, Cubist Pharmaceuticals, Genzyme, Momenta Pharmaceuticals, Novartis Institute for Biomedical Research, PAREXEL International, Pfizer, Sepracor, Shire and Vertex Pharmaceuticals.

The event raised almost $85,000 for the Special Olympics Massachusetts, which is nearly half of their operating budget. Sponsorships came from other service and supplier organizations that work with the biopharma industry as well as donations from participating teams and individuals. The Shire team, headed by Team Captain and Chapter Board member Kevin Lynch was edged out by AMAG for top team fundraising honors. Sean Brown of Lantheus, a Chapter member, was credited as the top individual fundraiser.

The one-day tournament raised over $85,000 for the
Massachusetts Special Olympics!

For those keeping score, Genzyme came out on top in tournament play (and won the CEO Free Throw by a wide margin), but everyone was a winner - particularly the Special Olympics athletes with their hard work and determination - and all who participated and experienced their spirit, joy, and enthusiasm. Boston Area Chapter Scores with Bio-Ball Sponsorship

“Vaporized Hydrogen Peroxide (VHP) Decontamination” Draws a Crowd in Cambridge

by David S. Allen, Allen Consulting, LLC with photos by Brian Hagopian, Mar Cor Purification

On Tuesday, February 23rd the Boston Area Chapter presented an educational program at the Royal Sonesta Hotel in Cambridge. Our presenters were Peter Harris, Director of Operations for B & V Testing and Larry Zanko, Project Manager with Steris Corporation. Each brought a career's worth of expertise to the evening's topic. Peter and the decontamination specialists at B & V Testing have executed hundreds of gaseous space decontaminations at life science facilities ranging from small pilot plants to full aseptic production and fill/finish facilities and have been using Vaporized Hydrogen Peroxide (VHP) technology since 2005. As a Project Manager for Steris, Larry collaborates with customers in the pharmaceutical and research industries to engineer application-specific solutions. His technical expertise includes extensive knowledge of multiple-effect water stills, pure steam generators, steam sterilizers, COP washing systems, and VHP generators.

After a brief introduction by David Allen, the evening's event manager from the Educational Program Committee, Peter took us through the history of VHP sterilization, a typical VHP process, effectiveness and equipment compatibility data, and two application case studies.

Educational Program Committee Member & Meeting Manager David Allen (left)
with speakers Peter Harris (center) and Larry Zanko (right).

He explained that VHP sterilization was introduced in 1991 by the American Sterilizer Company for use in isolators where it is still the most popular method of sterilization. Since that time, the use of VHP has expanded to include room decontamination for both new facilities and remediation. It is also used in aseptic process environments and for product sterilization.

Peter next walked us through a typical VHP decontamination cycle with the phases being dehumidification, conditioning, decontamination and aeration. We learned that one of the appealing attributes of VHP is that when the process is finished, all that is left is water and oxygen. There are no toxic residues. He then went on to explain the extensive testing that has proven the efficacy of VHP against bacteria, viruses, molds and yeasts. There are prescriptive doses for contaminants and various ways to confirm the dosage that has been delivered including electronic sensors and chemical test strips.

Peter concluded by explaining the steps in planning and carrying out a VHP decontamination project and told us the stories of two actual decontamination procedures. The first case was the emergency sterilization of a 240,000 square foot pharmaceutical manufacturing facility to remedy a contamination. The space included bioreactor rooms and the VHP was injected directly into 65 rooms and the air handling systems. The second case was an 84,000 cubic foot pilot production facility with 28 rooms that were sterilized as a routine preventive measure during a facility shut down.

After a short break, Larry took the stage and described the different types of equipment available for VHP applications: modular and portable. He explained that for facilities of less than 10,000 cubic feet that do not require routine sterilization, portable equipment is typically used. Portable equipment requires the use of fans to ventilate the room after decontamination. For spaces up to 80,000 cubic feet, fixed modular equipment can be installed. This is particularly valuable for rooms that require frequent, routine decontamination and for rooms that are isolated and could be compromised by bringing portable equipment into the space. Modular systems are typically integrated with the HVAC system.

Larry then went on to describe several aspects of modular installations. Since VHP passes through HEPA filters and sterilizes them, they need not be removed for decontamination. He also told us about the two cycles, single-pass and recirculating. In single-pass systems, the decontamination phase occurs while the HVAC system is shut down; in a recirculating system, the HVAC system continues to circulate air. In both cases, the HVAC is used to exhaust the air during the aeration phase. In concluding, Larry summarized the benefits of VHP compared to other sterilization techniques that can leave toxic residues.

The presentations were followed by a flurry of questions from the audience, the answers to which helped to further round out the presentations. A final thank you to Larry and Peter for their excellent technical presentations and to Claire Fritz of Steris whose behind-the-scenes efforts helped to organize the joint presentation between Steris and B&V.