Another Memorable Holiday Party at Flat Top Johnny’s

by Christopher Ciampa with photos by Doyle Johnson and the author

Once again erasing any doubt that the ISPE Boston Area Chapter isn’t solely focused on professional/educational events, the annual Holiday Social was held at Flat Top Johnny’s Billiards in Kendall Square on January 15th, 2009. This date has become a tradition (the Holiday Social used to be held in December but that changed thanks in part to the ill-timed blizzard of 2007) and, thankfully, the weather did cooperate! This annual gathering of the brightest minds in the life sciences again drew over a hundred guests from a cross-section of the Chapter’s membership, with operating companies, academic and research institutions, vendors and contractors all well represented.

Guests were treated to an array of hearty hors d'oeuvres: finger sandwiches, beef teriyaki, egg rolls, meatballs, potato skins and buffalo tenders. Not to mention warm chocolate chip cookies for dessert. The food was plentiful and enough to satisfy both your typical process engineer and water analysis consultant. Even better than the food was the constant buzz of conversation regarding the latest what’s what and who’s who in the industry. And some folks even shared ideas for other types of Chapter social events, including a bowling night and a fishing trip. One thing is certain: members of the Boston Area Chapter don’t lack for ideas when it comes to future social events!

In addition to food, drink and conversation, there were raffles and prize giveaways throughout the evening sponsored by A/Z Corp, Columbia Construction, CRB Consulting Engineers, F.W. Webb, GxP Automation, RDK Engineers, Sentrol and Spectra Automation. Prizes included gift cards to Capital Grille and Legal Sea Foods, and Bruins or Celtics tickets! Not only did the Chapter reward its valued members, it also used the Social as a benefit for the Care Package Project sponsored by Marineparents.com, an organization devoted to supporting marines overseas. Attendees donated requested items such as single-use cameras, toiletries, batteries and food items for shipment to marines in Iraq and Afghanistan.

Along with the raffles and prizes, attendees were treated to a speech by Chapter President Doyle Johnson, who daringly “took the stage” (and set a new Chapter precedent) by standing on a high chair, hoping not to fall off! A great speech - Doyle thanked people for attending and being a part of the Boston Area Chapter. Following Doyle, Dan Ramsey introduced the Young Professionals Initiative (YPI), a venture that is being piloted by the Boston Area Chapter.

Dan explained that the initiative is just getting underway and is looking to expand its membership. Its goals are to provide younger Chapter members a chance to network with one another and to develop programs geared towards people who are fresh in their careers. It may even go as far as to reach out to the ISPE Student Chapters whose members may end up joining ISPE upon graduation and will look for new ways to “bridge the gap” between students and young professionals and the Chapter’s seasoned members. (Currently, the majority of ISPE programs are geared towards seasoned professionals already well-established in their careers.)

Who says scientists, engineers and validation specialists don’t know how to party? Once again, the Chapter proved that its hard-working members are interested in having fun, not to mention networking with their peers in the industry. Networking is even more important in these difficult times, with the economy weak and the job outlook uncertain, and the Chapter does a wonderful job of getting everyone together to share information with contacts both old and new.

Many thanks to the sponsors of this event and to the many hard-working Chapter volunteers who made this tremendous night possible. Kudos to you! We’re already looking forward to next year!

LEED – The Path to Environmental Enlightenment

by Lee J. Ward with photos by Doyle Johnson

January 20th saw the ISPE Boston Area Chapter host a program designed to whet your appetite. The often discussed but not widely understood subject of LEED was tackled from two different perspectives and delivered to a mixed audience of facility owners, supporters and generally interested attendees.

Realizing the Value of LEED

The first presenter of the evening, Mr. Fred Doherty, LEED AP and Certified Energy Manager, approached the subject based on the definition of LEED and what is generally understood by this far reaching concept. He then went on to describe what LEED will not do for a facility. “It’s all about the need to attain a desired level and the process you take to get there,” explained Doherty, as it became clear that there are implications and hidden secrets to LEED than are not apparent at first.

Fred proceeded to educate the audience on the areas of interest LEED initiatives can delve into, then quickly turned to the subject of cost as attendees asked questions regarding the perceived “On Cost” of pursuing a LEED project. This prompted Fred to adopt a more light-hearted tone and neatly segue onto the subject of energy and how we all curse the energy companies for their high prices and equally high profits, likening them to being the “devil.” Fred was then swift to point out that these companies themselves are targeted to reduce their output.

The presentation then took a turn in a related direction: how the energy companies actively compensate end users for employing energy efficient systems in their facilities. Fred explained that this gives energy companies a direct impact on the cost of implementing LEED design in a new or existing structure. He then quickly disavowed his original disparaging comment and proclaimed, “In fact, energy companies are not the devil. They can help fund these initiatives, leading to long term cost reduction and sustainability.”

Next, Fred focused on a subject with a serious impact on all of us, the subject of “carbon footprint” and how each and every consumer will begin to feel the effect of its reach in all that we buy or use. He went on to explain how this concept will begin to creep into legislation, as it has done in other major economies throughout the world, and the financial impact this will have. This, in turn, bought us cleanly back to the subject matter we began with and the simple message that could help us all. Namely, that what we do now by employing green initiatives will help defer the impact of carbon taxation in the future.

This ended the first presentation and opened up the room to questions, all of which were met with the enthusiasm I have come to admire in Fred. He tackled each question head on and offered to discuss various specifics directly with individuals at the end of the night.

LEED Certification Overview

The second presenter of the evening, Ms. Susan Dieker, an MBA and LEED Accredited Professional focused on Commercial Interiors, approached the subject from an entirely different perspective. Susan focused her presentation on the process involved in gaining accreditation and the associated requirements and pitfalls. In complete contrast to the first presentation, Susan added her own brand of entertainment to the proceedings. In an Educational Program Committee first, she introduced an interactive element that tested the ability of the attendees to absorb the information presented and measured their answers to specific questions.

At one point, Susan asked the audience a multiple choice question regarding the program. Amazingly only 5 percent indicated that they were attending for the “social” aspects of the event, a great endorsement for the choice of subject matter. Statistics are not my thing, let me tell you, however it is interesting to note how my concentration and interest level increased when I knew I would be faced with a question requiring a “public” answer. This concept certainly added another dimension to the program, an idea we would certainly like to explore in a future program.

Susan proceeded to enlighten us all by providing detailed insight into the differing requirements and who or what resource to engage when faced with the daunting prospect of attaining LEED certification. Useful Web sites and online templates, as well as some of the associated costs, were all made clear to the audience.

In summary, a lot of valuable information was delivered over the course of the evening to a very discerning audience. Excellent as the presentations were, they only just “broke the ice” with respect to this new and exciting topic. The Educational Program Committee plans to further explore the practical aspects of LEED with two other events to be scheduled over the course of 2009. Be sure to look for them as the year progresses.

• ISPE and GAMP synergized in a first ever, day long session
• ISPE International attended the show
• Patriot Hall of Famer John Hannah was a keynote speaker
• CNN (that’s right, THE CNN we all watch on TV) visited the show and shot footage

ISPE Annual Meeting 2008: A Student’s Perspective

by Jason Lajoie and Jeremy Sauer with photos by Doyle Johnson

Wow! I think this exclamation pretty much sums up my week as a student poster contest competitor at this year’s ISPE Annual Meeting in Boca Raton Florida. But I won’t leave it at that. As I flew into Ft. Lauderdale I wasn’t sure what to expect, since this was my first trip to the ISPE Annual Meeting. When I arrived in Boca Raton on Saturday night the gorgeous and expansive Boca Raton Resort and Club was alight with activity. The resort, located on the beautiful Intercoastal Waterway, featured restaurants, bars, tropical plant life, and the one-of-a-kind architectural style of Addison Mizner. To say I was impressed with the location and facilities is an understatement.

The student activities kicked off on Sunday with the Student Luncheon. This luncheon offered the opportunity to meet other students from across the US and around the world. I met students who came from as far away as Singapore and Turkey. We also had the great pleasure of eating lunch with a number of industry leaders dedicated to mentoring the up and coming generation of ISPE. This is one of the greatest assets of ISPE membership from a student standpoint.

Meeting and interacting with pharmaceutical and biotech industry professionals allows us to learn the tricks of the trade and establish valuable relationships with people eager to help us succeed. These are things you can’t learn from a textbook or in the lab but I consider them just as valuable as my education. It is simply amazing to be involved in an organization that shows such dedication to developing its student members.

I’m sure you are all wondering what it was like competing in the International Student Poster Competition. Up to this point in my ISPE career, I have never been disappointed with an event or activity and the poster competition was no exception. The caliber of students and their research was exceptional. I enjoyed speaking with many of my fellow competitors about their work and I certainly learned a lot about the research that is ongoing around the world. I’ll admit I was a little nervous as I walked into the judging room. But once the butterflies settled I really enjoyed presenting my research and interacting with the judges.

I’m normally a pretty humble guy and I don’t like to brag. But I am proud to say that I won first prize in the undergraduate category of the poster competition along with Maureen Cheung of the University of Akron. It was truly an honor to walk up to the stage and receive the award in front of hundreds of ISPE members. I was especially proud to be representing the University of Massachusetts Amherst and the Boston Area Chapter of ISPE.

On Monday night after the judging for the poster competition drew to a close, UMass ISPE president Jeremy Sauer and I had the great pleasure of going out to dinner with Rick Pierro, Mike Denault, and Andre Walker. We had a wonderful time and this was yet another example of how the senior members of ISPE are interested in mentoring and forming relationships with the student members.

This experience was truly once in a lifetime. The Boca Raton resort was magnificent and the program put on by ISPE was first rate. All of the people that Jeremy and I met there were as enthusiastic and excited to talk to us students as we were to meet them. The Annual Meeting also gave us a great opportunity to meet with fellow students and talk about classes, the job search, and strategies for building a better Chapter. During the meeting, we even consulted with a student from Boston University on how to start up his own student chapter. For all of these experiences, we cannot thank ISPE enough. We only hope that as we embark on our careers that we can stay involved in this wonderful organization and continue to learn and grow within the industry.

ISPE Young Professionals Initiative First Meeting a Big Success

by Jim Grunwald with photos by Chris Ciampa

On Thursday, November 6th, the first official meeting of the ISPE Young Professionals Initiative was held at Flat Top Johnny’s in Kendall Square. Attendees included Christopher Ciampa of Thermo Fisher, Anthony Giragosian, formerly of Epic Therapeutics, Carmen Ho of Shire HGT, Zeke Johnston of Genzyme, Joe Rajewski of Shire HGT, Chris Lewis of Beth Israel Hospital and Dan Ramsey of Commissioning Agents.

In addition to these young professionals, ISPE National Young Professionals Initiative Committee Chair, David Novak, ISPE Boston Area Chapter Vice President, Sylvia Beaulieu and Young Professionals Initiative Local Liaison and Boston Area Chapter Board Member, Jim Grunwald provided an introduction to the program and hosted this event. The premise underlying the Young Professionals Initiative is a desire to promote the development of our young professional membership and provide a dynamic environment where education, networking, career development and volunteer opportunities can be offered to these future Chapter and Society leaders.

Within a short period of time, it became obvious that our core group of attendees really had a lot of common concerns and aspirations and it didn’t take long before an agenda was developed and a second meeting scheduled, this time at the Asgaard in Cambridge.

This is a great opportunity to get involved with like-minded professionals and help shape the future of ISPE and the industry. If you are interested in learning more about this dynamic group, please consider attending an upcoming meeting; or should you have questions regarding the program, please do not hesitate to contact jgrunwald@a-zcorp.com .

Six Sigma Part II - Efficient Innovation and Cost-Effective Manufacturing

by Jim Verhulst with photos by Doyle Johnso n

On September 16, the Boston Area Chapter presented another educational seminar at the innovative, LEED-certified Genzyme Center corporate headquarters in Cambridge. The topic was Six Sigma Part II - Key to Efficient Innovation and Cost-Effective Manufacturing Processes. The speakers for the evening were Dr. Philip Ramsey, of North Haven Group, and Philip Werth, of Wyeth BioPharma.

Dr. Ramsey is an industrial statistician with more than 20 years of experience in applying statistical methods to products, processes and R&D programs across diverse industries. During that time, he has been designing and delivering industrial training courses in statistical process control, design of experiments and response surface methods for process optimization. In his presentation, Design for Six Sigma , Ramsey explained that today’s highly competitive global markets and the rapid commoditization of new products require companies to innovate efficiently. Being early to market with the right product is now considered essential to long-term financial success.

Traditionally, management has focused on continuous improvement and cost reduction using Lean6Sigma, which integrates Lean and 6 Sigma tools and methods. Lean6Sigma programs have been very successful in helping companies improve quality and reduce costs for existing products and services. In contrast, Design for Six Sigma (DFSS) has evolved as an approach to shorten time to market, and to design and produce high quality products that are aligned with customer expectations.

Attendees were exposed to a full menu of jargon and acronyms. The talk covered the key elements and tools of DFSS, and linkages between DFSS and the traditional Lean6Sigma DMAIC (Define, Measure, Analyze, Improve, Control) process for continuous improvement. As Ramsey explained, the basic algorithm for all variants of DFSS is known as IDOV which is an acronym for Identify, Design, Optimize, and Validate. The first step in IDOV, identifying the Voice of the Customer (VOC) and translating and prioritizing the customer needs into functional responses (CTC's), is crucial.

So why are we interested in Design for Six Sigma? It turns out that nearly 80 percent of the overall costs of a product are established during the design phase. DFSS invests time and resources early in the product development cycle to lower overall product cost, speed time to market, utilize resources more efficiently, produce more robust designs and, in the end, better satisfy customer needs. DFSS helps move from “tested-in” to “designed-in” quality.

The presentation then turned to tools available to implement DFSS. Conjoint Analysis is a quantitative approach that can be used during the Voice of the Customer (VOC) phase. Conjoint Analysis is a cousin of design of experiments (DOE). It allows designers to uncover characteristics that are important to the customer as well as important interactions among those characteristics. A second tool, Quality Function Deployment (QFD), is used to facilitate requirements flow-down. The tool uses the concept of “houses” (named after the house-like appearance of the data graphs) to define relationships between functional responses (CTCs), design characteristics (DCs), process variables (PVs) and process controls. Other QFD tools available include Transfer Functions, Scorecards, FMEA, Design Validation Test Plans, Communications Plans, Design of Experiments, Robust Design, Tolerance Design, and Control Plans. The presentation gave an overview of how these QFD tools can be used together.

A brief case study centered around how to build a better bicycle was presented to demonstrate some of the DFSS methodology. This was more complicated than it first appeared. The example showed how to use the basic tools, but it quickly became apparent that this was an involved effort that required trained resources.

The second speaker for the evening was Philip Werth of Wyeth BioPharma, a chemical engineer with diverse industry experience. His presentation was entitled Use of Statistical Quality Control to Improve the Productivity and Quality of a Biopharmaceutical Process . Drawing on examples from his work at Wyeth, Werth explained how he has used statistical techniques to help define and implement numerous improvements to the manufacturing processes and demonstrated that monitoring a manufacturing process to detect costly and recurring problems can pay big dividends.

Furthermore, he explained that by carefully monitoring a process one occasionally finds opportunities for significant improvements. The presentation covered how this can be done from both univariate and multivariate points of view. It also examined how equipment and processes can be designed to facilitate the monitoring and gathering of relevant process data.

Univariate statistical process control (SPC) is the simplest type of analysis. The investigator looks at only one variable at a time to detect and learn from process changes over time. Because the changes may be small, one of the most important considerations in these kinds of investigations is the accuracy of the measurements. Multivariate SPC, as the name suggests, treats variables as a group. This has certain advantages in that one can see the covariance between the variables, and one can also see the effect when small changes in individual variables add up to a significant indication when viewed together.

A number of multivariate SPC techniques were presented using real life examples with two to seven variables. Batch histories may contain a lot of useful data. By plotting many batches, the many process variables measured can be summarized into a few new variables (scores) that create a fingerprint of a good batch. Scores provide overviews that are easier to use. Ultimately these can be used to facilitate a root cause analysis. Multivariate analyses are often restrained by having only partial data. Werth's advice: “build your skids and equipment to measure and record many variables.” From an analyst's point of view, one cannot “over-instrument.”

However useful that approach, it does leave the statistician with a huge volume of data. Werth described the utility of a Design of Experiments (DOE) approach. He pointed out that “one good DOE with 10 data points is better than thousands of points SPC.”

The presentation offered suggestions on how best to do SQC and some common pitfalls to be avoided. Werth showed examples of problems with production data that may result in false correlations. In the end, the key to successful SQC is to develop a deep understanding of the manufacturing processes.

Many thanks to the Educational Program Committee for a stimulating program that left many of the attendees thinking about where and how to apply what they had learned to situations in their own workplaces.

Members Tour Siemens Diagnostic Healthcare State-of-the-Art Facility

by Lee J. Ward with photos by Peter Teague

September 24th found the ISPE Boston Area Chapter being hosted at another landmark facility within the life sciences realm, that of Siemens Diagnostic Healthcare located in East Walpole, MA. Following a sumptuous buffet dinner in the plant’s cafeteria, 60 Chapter Members and guests were treated to a tour and presentation that illustrated the business needs and wants, project engineering and fiscal management that resulted in the world class, state-of-the-art facility we see today.

Michael Canary, Director of Engineering for Siemens Diagnostic Healthcare, presented the challenges of the project from the perspective of what Siemens (formerly Bayer) was looking to achieve. Fred Scribner, Project Executive for Columbia Construction, the project’s general contractor, described how those challenges were met and overcome during the implementation phase. With a budget of $110 million and a schedule that could not change, they had a monumental mountain to climb and consequently conquer. Jacobs Engineering was enlisted as the process design company and, together as a cohesive team, worked with local government agencies, environmental groups and the Commonwealth of Massachusetts EPA such that all concerned reached their goals and objectives.

Gently nestled in a well-appointed, 81-acre site bordered on the east by I93 and on the west by residential properties, the Siemens facility fits in like a piece of a jigsaw puzzle. Great care was taken to ensure that the design of the building was environmentally responsible as well as aesthetically pleasing and the results were phenomenal. The landscaping artfully blends the 500,000 sq/ft structure into its surroundings, creating a vista that draws the visitor in. At the same time, the plant harbors engineering “secrets” that many owners would wish they had incorporated in their own facilities.

An example of the latter would be the genius that went into placing the HVAC equipment in the basement (instead of on the roof), a nontraditional approach and a testament to “smart design” that produced two major benefits. First, the equipment is protected from the elements and, second, with the nearby residential area in mind, both noise and aesthetics are successfully managed.

Another example was the approach to ground water management. A system was engineered that takes all the run-off from the site and directs it into the ground where it cannot impact the surrounding environment. “Who would have guessed we had the only creek where “cold stream” trout exist today in Massachusetts,” said Mike when explaining how the design team worked with environmentalists during the planning phase to resolve the difficult challenges the scenic site presented.

The tour that followed stressed that this is, first and foremost, a manufacturing facility and is pragmatically engineered as such. Care was taken to design in benefits to optimize operation of the plant. In addition, extensive use of predictive modeling was used in the design stage to ensure smooth progress during construction. As a seasoned professional who has spent a great deal of my working life in close proximity to construction engineering, I have to say this was achieved to great effect. Absolutely nothing was left to chance. For example, Fred described how the building had to be built to a point of near completion, then partially disassembled so that process equipment could be installed, all according to a carefully orchestrated plan that worked perfectly. In addition, forethought and planning ensured ease of future expansion, with extra space included in the manufacturing suites for additional reactor vessels.

And let me not forget the “piece de la resistance:” the viewing gallery overlooking each manufacturing suite where visitors are offered an awe inspiring view of the operation - in all of its gleaming, stainless steel complexity. A high tech console standing atop a pedestal in front of each operation displays a schematic providing visitors with an understanding of the inner workings of the equipment before them.

It never ceases to amaze me that the tablet swallowed or the diagnostic test kit used - so often taken for granted - comes from the minds of researchers and the engineering marvels of facilities such as this one. The way in which the myriad elements of this project have culminated in healthcare products used every day by millions of people throughout the world will generally never be appreciated by the public. That is, except for those of us lucky enough to attend the evening’s presentation and tour, where members and guests of the Boston Area Chapter were privileged in being able to see the results first hand.

Finally, our visit above all else demonstrated that with constraints of cost and time, the right planning and a well-managed delivery organization, it truly is possible to complete a project of this magnitude, complexity and aesthetic appeal ahead of schedule and under budget.

“From Biotechnology to BioFuels” Draws a Crowd to Worcester’s Gateway Park

by John Sheridan

On November 5, over 80 attendees spent an evening learning about cutting-edge technology for the production of cellulosic-based biofuels in a beautiful state-of-the-art academic research facility in Worcester, MA. On a site that once teemed with the machinery of the Industrial Revolution, the WPI Life Sciences and Bioengineering Center merges a new life sciences laboratory structure with a former industrial building constructed in the 19th century by Stephen Salisbury II, a Worcester merchant and a WPI founder.

The Center, built by Consigli Construction, is the first new structure built at Gateway Park, an 11-acre mixed-use life sciences-based campus that WPI is developing with the Worcester Business Development Corporation (WBDC). The project was completed in April 2007, on time and on budget, and consists of 124,600 square feet, four stories and a $50 million investment by WPI. Gateway Park will eventually host three additional laboratory buildings and will encompass about a half million square feet of space designed to help fuel the development of Central Massachusetts as a center for the emerging life sciences industry. But this is getting into the first speaker’s presentation.

After announcements and introductions, Stephen Flavin, Associate Provost and Dean of WPI Corporate and Professional Education, spoke about all the exciting things happening not only on campus but all around Worcester. In his current role, Mr. Flavin works in close collaboration with faculty and staff to lead all aspects of corporate education programs. Talking about WPI, he noted that it was founded in 1865 by industrialists who recognized the need for a more highly skilled work force and currently offers over 50 graduate science, engineering and management programs plus over 60 professional development offerings.

To name only a few of its functions, the Center is home to four WPI Departments (Biology and Biotechnology, Biomedical Engineering, Chemistry and Biochemistry, and Chemical Engineering), WPI Interdisciplinary Research Groups (“Centers”), the Bioengineering Institute (an interdisciplinary organization dedicated to turning life-sciences technology into workable products) and houses the headquarters of WPI’s Corporate and Professional Education Programs. Among its many amenities are an Internet café and a state-of-the-art amphitheater-style auditorium, where the ISPE event was held.

The presentation then shifted to the tremendous opportunities in Central Massachusetts and the biotech migration westward. Stephen spoke about the major investments the Commonwealth of Massachusetts is making in Central Massachusetts as a life sciences, bioengineering center. These include the BMC-Biomanufacturing Initiative in 2006 and the Massachusetts Growth District Initiative in 2008. In the past five years 20 biotech companies, including 14 from Cambridge, have moved into space along Route 128 and 49 of the 100 largest biotech firms in Massachusetts are located between 128 and Worcester. Although Genzyme’s headquarters is in Cambridge, their largest research facility in the world is in Framingham.

Stephen described the vision for WPI as everything from acting as a launching pad to enhance its own leading-edge research programs in life sciences, biotechnology and bio/chemical engineering, as well as those of other academic and medical institutions; to adding new life to downtown Worcester by creating a mixed-use destination which includes companies, residential and retail establishments.

He also described partnering with industry to develop effective educational solutions and used Polaroid’s efforts to transition its laid-off workers into biotech manufacturing as an example. When Polaroid was going under, a partnership was formed between WPI, industry and government to develop a custom re-training program utilizing WPI resources and bioprocessing knowledge, industry experts and government funding. The result was a five-week, hands-on training program conducted in a simulated cGMP environment. The program proved to be a great success, with a high percentage of the employees landing new jobs during or shortly after the training was completed.

Mr. Flavin’s presentation was followed by a very detailed presentation on the research and development that sets WPI apart from other campuses. Although scheduled speaker Alexander Di Iorio, PhD, Director of the Bioprocessing Center at WPI and Affiliate Assistant Professor in the Department of Biology and Biotechnology, was unable to present, he was very ably represented by Christopher McPhee, MS, whose presentation covered “Biofuels: Ethanol for The Future.” Although some left WPI shaking their heads in wonderment at the complexity of the topic, it was apparent to all attending that Christopher had both complete mastery and real passion for the subject he spoke on.

He began by presenting the issues and roadblocks to biofuels but quickly got everyone’s attention when he asked (and quickly answered) the question, “Why use ethanol?” He explained that ethanol is a relatively simple product to make, the technology for large scale production is already available, blending ethanol with gasoline increases oxygenation and boosts octane rating, ethanol can be used directly in fuel cells and enables independence from fossil fuel. After explaining the chemistry, he stressed that ethanol yield is critical to the overall cost of production and the economic viability of the process. Next question: where to get the biomass?

The initial development used food-starch crops however there is not enough cropland available to use corn-starch ethanol as the solution to our energy problems, in and of itself. This has forced research to examine other options like cellulosic ethanol with its low impact on food crops and agricultural land, higher yields and greater efficiency than corn, independence from foreign supplies of energy, and utilization of biomass that otherwise goes unused. Some candidate cellulosic crops are poplar, sugar cane, switchgrass, miscanthus and practically any crop residue. Christopher identified a number of development issues such as the typical two-stage system is time consuming and costly and it is apparent there is no silver bullet. At that point he was the professor discussing the idealized one-step process (where enzymatic digestion and ethanol fermentation occur simultaneously in the same bioreactor), biomining/strain improvement, process development, etc.

This is where a fascination for how nature works becomes a potential solution. He described biomining, nature’s slow degradation process and how many organisms use wood for energy, including the homeowner’s worst enemy: termites. Termites are cellulose-degrading machines that have proven to be one source of cellulolytic micro-organisms and after squashing many termites, BP Center is currently working with several termite microbes with proven potential for development. He went on discussing screening for enhanced cellulose and β-glucosidase, and other enhanced producers of enzymes and induction agents. He then pulled it all together with his summary and conclusions:

• Biofuels have made significant progress in the last decade.
• Corn-starch ethanol, the first large-scale biofuel, is insufficient to handle our energy needs.
• Cellulosic biomass appears to have advantages for the fuel ethanol market.
• The choice of crop will probably be specific to a given region.
• Technology advances in crop yields, enzymatic digestion and overall production are necessary for an economically feasible process.
• No alternate energy strategy will succeed without a healthy dose of conservation!

After acknowledgements, it became apparent that many in the audience not only understood what he was talking about but were hungry for more. There was over ten minutes of questions and a recognition that what is going on at WPI can and will make a difference in this world of bioengineering. The location outside of Boston and the reduced registration fee was intended to entice additional members to attend. Anyone who had the opportunity to see the facility, partake in the excellent cuisine and beverages (everything from cheese and crackers, fruit, vegetables and dip; to mini hamburgers, grilled sausages and open bar) and the excellent presentations on these interesting subjects will be back at the next ISPE Boston Area Chapter event. In the meantime, to view the actual PowerPoint presentations, please visit the ISPE Boston Area Chapter Website at www.ispe.org/boston .

The Sun Shines on the 6th Annual Golf Outing

by Sylvia Beaulieu

On August 18th, the Boston Area Chapter once again hosted our annual golf tournament. During a summer plagued by nonstop rainy days, we lucked out with beautiful, sunny weather. And we tried a new course - Ferncroft in Middleton - that proved to be a great venue. I heard many good things about the course and the service and all the golfers seemed to have a wonderful time - even if the pin placements were hard or, as someone stated, “I think they’re illegal.”

The day started early at 6:30am for registration/breakfast and a 7:30am shotgun start. As folks came around to the 10th hole, they were greeted at the putting green by Sherri Pelletier of Structure Tone who sponsored the $10,000 Putting Contest. They also got to sample Dewar’s Scotch at the Dewar’s table. (No one was quite sure whether that helped or hindered their putting skills.) In any case, no one won the big bucks but Eric Hoaglund came the closest by sinking a 30-foot putt. Congratulations, Eric!

As the golfers started to come in from the course, they gathered on the deck for appetizers and cocktails and told stories about their golfing adventure. We then moved into the tent for dinner and raffle prizes. Doyle Johnson, the Chapter’s new President was master of ceremonies and once again brought his quirky sense of humor to the task. I will miss that. I have had the pleasure of running the tournament for 4 years but as the Chapter’s new Vice President, I think it is time for someone else to plan, worry, stress out, shop for raffle prices and get up at 5am to get everything ready for registration. Bob Lewis of Erland Construction has graciously agreed to take over from me next year - Bob, get ready to receive my box full of golf stuff...

Congratulations to all of the day’s winners. The winning teams:

 And the individual winners:

Many thanks to all of our Golf Outing corporate sponsors who help to make this event a big success for the Chapter year after year. This year the thanks go to Steris, DECCO, Structure Tone, GxP Automation, Superior Controls, Invensys, Integra, CRB Consulting Engineers, A/Z, Bovis Lend Lease, Columbia Construction, Commodore Builders, Erland Construction, GMP Lab Products & Services, North Shore Mechanical, Parsons, RDK Engineers, The Richmond Group and The Chisholm Corp. I also want the thank A/Z, Plastic Concepts and Integrated Process Technologies for their donations to the raffle.

Water, Water Everywhere at May Educational Program

by David MacDonald

The topic of water - a topic that always draws a crowd - returned to the educational program of the ISPE Boston Area Chapter on May 20, 2008. The room at the Royal Sonesta in Cambridge was filled with members who had turned out to hear two of the area’s long time experts (each with 20+ years experience) discuss this ubiquitous but complex topic. The first speaker gave a wide-ranging overview of purified water: types, specifications, contaminants and contaminant removal techniques, while the second explored the use of ozone as a technique to produce purified water and maintain good biological control.

Brian Hagopian, Vice President of Research and Development for MarCor Purification, spoke first. His was a daunting challenge, covering “Water Purification 101: From Tap to Pure, Understanding the What, Why and How” in less than an hour. Hagopian quickly demonstrated his enthusiasm for his topic and his high skill as an educator, keeping the entire room with him during the whirlwind tour of the subject. The talk covered three areas. First, “What contaminants are found in water?” - second, “Which of these contaminants must be removed and why?”- and finally, “What are the basic technologies for removing these contaminants?” Interlaced with the technical discussion were many humorous asides, keeping the room light and the audience alert.

The basic groups of contaminants discussed were suspended solids, dissolved salts, low molecular weight organic materials, high molecular weight organic materials (also known as colloidal materials), bacteria (and other biological contaminants) and dissolved gases. Each class of contaminants has its own properties and requires differing approaches for removal.

Hagopian then raised the issue of why we should care about water contaminants and which contaminants need to be removed. The simple answer is that water is the most abundant single ingredient coming into contact with our products. It is the carrier fluid in the vast majority of the pharma / biotech processes. Reducing the variability of pure water quality increases the repeatability and robustness of these processes. The second simple answer is that there is a long list of organizations (led by FDA and USP) that say that we will control the quality of water used in pharmaceutical operations.

Then there was a quick review of specifications for various grades of water. The FDA is mainly concerned with two types of Pharmaceutical Grade Water: USP Purified and USP WFI. Hagopian compared these two grades versus semiconductor grade water. The comparison was eye opening, with semiconductor grade having many more specifications and much tighter limits. And semiconductor grade water is routinely produced in high volumes.

The next topic was a survey of the technologies used for contaminant removal. For particles, the technologies include (in order of increasing fineness) particle filters, membrane filters, ultra filtration and reverse osmosis. Salts are removed by ion exchange, small organics by carbon filters and bacteria by UV sanitizers or TOC-reducing sanitizers. Distillation is the gold standard as it removes the water from its contaminants and the heat effectively kills all the bacteria.

Hagopian concluded by reviewing the largest local problem contaminants. These are the seasonal turnover in the local surface water supplies and the low molecular weight organic contaminants present in many public water sources. In closing, we were reminded that this was just the very basics of purified water, barely scratching the surface of a vast and complex subject.

Bob Livingston, President of Arion Water, was the next speaker, on “Best Practice for the Use of Ozone in Life Science Applications.” This talk started with an introduction to using ozone as a key part of the water purification system and then presented some real life case studies. Livingston’s thesis is that ozonation is an attractive choice to replace heat shock and chemical sanitization in high purity water production. Ozone is especially useful in improving the microbiological aspects of purified water production.

Livingston noted that purified water is too often conducive to microbiological growth. The relatively high limits on TOC and conductivity specified by USP Purified Water can support the growth of biofilms in the water production and distribution systems. Biofilm is a thin layer of bacteria and organic matter that occurs under the viscous boundary layer, at the interface between the bulk water phase and the solid system components, such as piping, filters and resins. Typically biofilms are kept under control in pharmaceutical water systems by the use of periodic heat or chemical sanitization cycles. Heat sanitization will control the growth of biofilms but will not completely remove existing biofilms. In comparison, semiconductor purified water systems operate at ambient conditions without heat sanitization cycles. Instead, they use nutrient deprivation as their control strategy. In extremely nutrient deficient environments, bacteria will not attach to surfaces. If the bacteria don’t attach, they won’t form biofilms in the distribution loop or elsewhere.

Ozone can be added to the water production system and /or the water storage and distribution system. Ozone serves two purposes. First, it is very effective at killing a wide range of microbial actors including spore forming species. It is orders of magnitude more effective as a sanitant than chlorine. Second, it can be used to remove the TOC contaminants of purified water through oxidation. Livingston stated that you can’t get control of the microbiological aspect of purified water until you get high purity (and low TOC) in the distribution system.

In one case study, a 500-gallon DI water system had been idle for 6 years. When the system was restarted, the bacteria count was too high to measure. Ozone was injected into the water and in less than a day the TOC was reduced to < 5 ppb and the bacteria count was <1 CFU/100 ml. In a second case study, an operating system of good design produced water with acceptable TOC and bacteria counts for 14 months. The system still exhibited build up of biofilms and started showing periodic bacteria excursions. The system was modified to use ozone to reduce and control the TOC level. By reducing the TOC level to < 2 ppb, the bacteria count was reduced to < 10 CFU/100ml with no excursions, without the use of chemical sanitization. When Livingston stated that ozonated water cleans out existing biofilms, light bulbs went on over the heads of many in the audience.

Livingston then briefly reviewed the choices for ozone manufacturing methods, means for dissolving ozone in the water and destroying the residual ozone. When introducing ozone into a water system, use of the appropriate materials of construction is one key. Another key consideration is the need for online measurement of effective ozone level control. There has been recent progress in this measurement.

Ozone has been used for intermittent sanitization of distributions loops, passive microbial control via TOC reduction and routine process sanitization. One key point is that there is a need to rinse the use points with ozonated water to keep them sanitized. One real advantage of ozone sanitization is that is creates no additional wastewater and doesn’t leave a residue which must be cleaned from the system before use.

The speaker’s conclusion is that TOC control - at levels well below that required for USP Purified Water - is essential to the good operation of a DI water system. And ozonation is an effective treatment for reducing TOC and bacteria counts and removing biofilms.

Both speakers’ presentations are available for members at the ISPE Boston Area Chapter web site at www.ispe.org/boston/events .

A Successful ISPE Summer Social Proves All Is Well in the Boston Area Chapter

by Christopher Ciampa

Beer, laughter, commotion, talk about the biotech and pharmaceutical sectors: What do these things have in common? They are just some of the sights and sounds that took place during the Boston Area Chapter’s Summer Social at Boston Beer Works on June 11th. The gathering started at around 6pm on the second floor of the Canal Street facility. Owner companies, large and small, as well as a vendors, suppliers and consultants to the industry were all well represented. What better way to network with an impressive group of people who work in the life science industry? And better yet, as a thank you for their participation in the Chapter, the event was free for Members!

Speaking of impressive, the room on the second floor we had set up for us was phenomenal. It had an area with cozy chairs, dinner tables for 10 or more people, plus a few pool tables for those who are pool players. Throughout the evening there were plenty of hors d’oeuvres and entrées available. The food included salad, chicken tenders, buffalo chicken strips, pork dumplings, steak tips, mashed potatoes, green beans, rice and more. Of course, for drinks attendees enjoyed an assortment of the brewery’s homemade lagers and ales. (I personally tried a Belgian white ale [it looks like Budweiser beer and has that beige/tan color], which was very smooth and pleasing to the palate.)

At about 6:20, our fearless Beer Works tour guide, Dennis, began our tour of the brewery. He knew we would be a tough crowd: pharmaceutical folks, who, to his thinking, were well-versed in chemistry and biology. Because of this, he asked people to bear with him (or “beer” with him, however you want to look at it) while he attempted to explain the process of making beer to people who were biotech-savvy.

The beer-making process begins by storing the malts in a grain silo. Specialty malts (to give beer characteristics such as color, flavor, and body) are added to the grain silo, and the malts are weighed out and run through a roller mill (to gently crush the grain into grist). The entire amount of malt for a single brew is then stored in the grist case. Next, the malt is transferred to a mash tun, where the malt mixes with hot water to become mash. It rests in the mash tun for an hour while enzymes convert the malt starch to fermentable sugars. Later, there is a sparging process, in which the grains are rinsed with water and the resulting liquid (now referred to as “wort”) drained into the “brew kettle.”

In the kettle, the wort is boiled for an hour and 15 minutes and varying amounts of hops are added to give bitterness, flavor, and aroma characteristics. After the boiling process, the wort needs to be prepared for fermentation, so a counter-flow heat exchanger (using glycol and city water) is used to cool it down to 65°F. Oxygen is also infused into the wort at this point to help with yeast respiration.

Next, the fermentation process that we have all been waiting to read about takes place. Here, yeast mixes with the cool and aerated wort; the process usually takes about six hours to initiate. Once it does take place, the yeast utilizes fermentable sugars to create alcohol and carbon dioxide. To make ale, this process takes 3 to 6 days at 70°F and for lagers, about 7 to 10 days at 52°F. After the initial fermentation takes place, a secondary fermentation follows in a closed “conditioning” tank. For beer, this process takes two weeks at 45°F and for lagers, four weeks at 38°F. As Dennis reminded us at the end of the tour, “Brewers don’t make beer; they simply provide the right conditions so the yeast can make beer.” Beer is “beer” once the yeast has fermented the wort.

Once the conditioning process is completed, the beer is cooled to 35°F, filtered and then transferred to dispensing tanks. The beer can be served from the dispensing tank or it can be put into kegs. And of course, the final (and most important) step is to drink and enjoy!

Later in the evening, Boston Chapter President Rick Pierro gave a toast to the Chapter’s members. He said that the Boston Chapter has grown 13 percent in the past year! He also presented one of two “Committee of the Year” awards to the Communications Committee and congratulated Chairperson Janet Tice and the Committee for their good work over the past year (The second award was presented to Dave MacDonald and the Educational Program Committee at an earlier event.). Next came a raffle sponsored by A-Z Corporation, M.A. Olson Co., Particle Measuring Systems, Plastic Concepts and the Chapter. Gifts ranged from Red Sox tickets to gift certificates to fancy Boston restaurants!

All in all, the Summer Social was a huge success. Many thanks to Amy Poole, Rick Pierro, Doyle Johnson, and Sylvia Beaulieu and the entire Chapter Board of Directors for making this event possible and for making it a memorable one! “Beer’s” to you!

You Want it When?!?

If you’ve ever wondered how in the world you’re going to get your MVR done in time to get the FDA to approve your HPH2Os, CDAs, and CEs as scheduled, you might want to hear what these experts had to say about phasing your C&Q and building your BOD to finish PDQ and report more ROI to your CEO!

by Joseph A. Naughton

Over 100 of ISPE’s finest gathered at the Royal Sonesta Hotel in Cambridge on June 17, 2008 to catch up with fellow industry professionals and to engage in some light conversation focusing on challenges and solutions in merging quality and facility requirements with accelerated schedules, the never ending desire to change the plan once it’s set, and the pressure to get on line faster. Leading the discussion were two of the region’s seasoned facilities implementation and validation gurus: Michael Marino and Charles E. Pappalardo. They spoke at both the micro and macro scales about common challenges and solutions to relieve the pressure and reduce the temperature the process often involves.

Mike began the discussion with a presentation titled “Controlled Environment Commissioning and Qualification: Using a Phased Approach to Meet Schedule Demands.” The setup is as follows: For virtually every project there is a firm construction schedule and a firm manufacturing startup schedule, and stuck in the middle is the Commissioning and Quality (C&Q) system process, which would be fine except for what Mike refers to as the C&Q “squeeze” factor. The C&Q squeeze typically results from construction delays pushing the construction finish out and/or operational pressures that pull the manufacturing start date in. The net effect is that C&Q typically gets squeezed into an increasingly narrow crevice of time between the finish of construction and the start of manufacturing activities. To deal with this recurring challenge, Mike recommends a phased approach to C&Q.

The phased approach is designed to document and execute a logical and defendable Qualification Plan (QP) to commission, certify and qualify Controlled Environments (CEs) and systems that saves time by synchronizing simultaneous construction and C&Q activities. This synchronized and simultaneous approach allows C&Q activities to start as individual systems are finished and turned over, as opposed to waiting until the entire construction process is complete before starting the C&Q plan. The way this works is as follows: The team must allow the qualification process to be split up into phases for each of the areas being constructed and generate, execute, and approve each document set as the individual systems comprising the project are turned over by the construction process. Of course all this synchronization and simultaneity sounds great but it can only happen by building the right plan which Mike recommends you lay out with a QP flow chart showing the major steps in the process including:

1. Defining the roles and responsibilities for each team member;
2. Identifying the specific team players including a third party commissioning team;
3. Developing the project quality scope including a task list with durations and assignments;
4. Formalizing multiple Master Validation Plans (MVPs) that document in detail the scope of each qualification with acceptance criteria; and
5. Establishing systems boundaries for the MVPs and C&Q plans.

Once the structure is set, you can advance your C&Q plan with the commissioning component. The commissioning process starts with the development and approval of a Design Intent Document (DID) that goes to a third party commissioning company as early on in the design and construction process as possible. The DID should be structured to accommodate a parceled approach to approving building systems such as the HVAC system, building automation system, and pure water system, to name a few. The plan should be integrated into the design phase with agreed-upon formats for reporting well in advance of construction (synchronized) in order to reap the time-saving benefits of simultaneity mentioned above.

The Qualification process starts with the development of an “all-encompassing” quality plan that documents the phased approach and establishes multiple MVPs for each of the individual systems approvals. The MVP is usually the first document read by the Qualification auditor, which is why it needs to describe in detail what you’re going to do and include the “why rationale.” The MVP should also describe at what point in the qualifications process manufacturing can begin.

Qualification requirements are organized into Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) categories. The IQs should cover the as-built conditions for your Controlled Environments (CEs) and related systems including High Purity Water (HPH2O) and Clean Dry Air (CDA) to name a few. The IQ is a formal verification that the rooms were installed as designed and working properly with respect to temperature, humidity, particulates, etc.

Upon approval of the IQ, the room or system is ready for the OQ review. The OQ is a verification that the CEs and related systems and critical utilities are operating over time as required by the MVP. The OQ includes static tests reflecting “at rest” conditions as well as dynamic tests on a 24-hour/5-day operation capturing the “in operation” conditions and any variation. Upon successful retest and approval of any corrective measures or deviation remediation, the OQ is approved and the CE and related systems can be released for process validation runs (though not in-human use manufacturing) and the PQ stage.

The final qualification, the PQ, is intended to test the “routine” operation of the CE and related systems and usually involves a minimum of 2-3 manufacturing weeks and/or 2-3 lots worth of product. Once again, following any corrective action needed, retest and approval, the PQ is approved for the given system. The qualification results for the IQ, OQ, and PQ are summarized in a Master Validation Report (MVR) that identifies any failures and resolutions, system acceptance documentation, and which is approved by the auditor, and the CEs and systems are released for in-human manufacturing. Another benefit of the phased approach is that it can be planned at the front end to accommodate “staggered” manufacturing process validations at the back end.

It should be noted that while the phased approach is a good shock absorber to C&Q squeeze, it also often results in more paperwork to “stitch” the parcels together in the documentation for the MVR. Mike indicated a threefold increase in paperwork should be contemplated when using this time-saving but more documentation-intensive approach. Clearly the C&Q process leading to a successful validation is onerous, but using the phased approach can help take some of the pressure and heat out of the “squeeze.”

Following Mike’s in-depth view of the validation process, Chuck took a step back and focused his discussion on the larger issue of moving a project quickly from concept to completion in a presentation titled “Accelerating Advanced Infrastructure Delivery.” He began by outlining some of the most commonly voiced challenges facing the prototypical development project. These include the need to:

have it yesterday,
cut the budget,
comply with the regulations but keep it “flexible,”
make major changes to the program when you’re pouring concrete,
understand that every end user is “Customer #1,”
keep multiple team members “in the loop,”
minimize maintenance,
maximize product production,
get to market now, and
keep quality job number 1.

While there is no perfect solution to such a complicated process with as many variables as you will find in your every day biopharm development project, there are some key measures that, when carefully applied, will make the process move much more smoothly and ensure a higher degree of success: Based on his own experience, Chuck outlined the following success factors:

• Stressing the importance of team coordination,
• Achieving an early integration of key stakeholders,
• Developing comprehensive programming up front,
• Setting realistic budget expectations,
• Setting credible schedule expectations, and
• Driving execution.

Team coordination starts with appropriate prequalification and selection of critical consultants to assure that the team chemistry is balanced and the necessary areas of expertise are well covered. In a market where every consultant is trying to win every commission, prequalification is critical to prevent an inadvertent “perpendicular” selection to a specific project need.

The team process also needs to be well defined and consistently visible in meeting notes, action items, gate keeper logs, accountability, critical dates, and milestones. The gate keeping process is the structure that allows the team to rigorously track changes to the project plan after a program or Basis of Design (BOD) has been approved by the project’s key stakeholders. The log provides a formal presentation and reflection record of team decisions that may have both short-term and long-term impacts. The log will show, for example, that a conscious team decision was made to change the chiller plant from two 1,500 ton chillers to three 1,000 ton chillers to achieve operational redundancy, even though it cost more money and could take more time to complete. The log keeps the entire team involved and the project memory current. This brings us to the next critical component which is the early integration of key stakeholders.

The early integration of key stakeholders and functional experts during the BOD process will increase internal project support, maximize scope capture from the outset, and provide for an “all in” BOD. Key stakeholders should include representatives from Quality, Validation, Engineering, OPS, Facilities, IT, Security, R&D, Procurement, and Real Estate departments in addition to end users. And by having an “all in” BOD, the chances for establishing a truly realistic budget and schedule are maximized.

The BOD process, also referred to as programming, generally represents about 2 percent of the total project cost for a facility. The BOD derives from the strategic plan and typically results in a physical space program describing the types and sizes of spaces contemplated for a particular capital asset, with concept design and specification defining the basic scope of the project. Key stakeholders, designers, planners and cost estimators should be integrated into this process to confirm that needs are adequately identified and project costs including design, construction, furniture, equipment, land and financing are covered by the BOD.

This information is then packaged and used to develop return measurements, such as Return on Investment (ROI), Net Present Value (NPV), Internal Rate of Return (IRR) and Payback, for presentation to management and the request for a “go- no go” decision. As stated above, the BOD typically represents about 2 percent of the project cost, so if the response is a no-go, your risk is limited. If the response is a go, the next step is to refine the BOD and request the next level of funding for the Design phase which represents another 10-12 percent of project cost. This incremental approach to project funding requests is part of Chuck’s approach to setting realistic budget expectations.

Setting realistic budget expectations can be promoted by first organizing the development process into three manageable slices of work effort and owner resource commitment:

1. The Basis of Design (BOD) or programming and concept development effort representing approximately 2 percent of project cost;
2. Design and preconstruction leading up to a Guaranteed Maximum Price (GMP) or “Bid,” representing approximately 12 percent of project cost, and
3. Construction, commissioning and validation, representing approximately 86 percent of project cost.

By requesting approval for each of these phases incrementally, you avoid the potential to over commit owner resources and keep expectations within well defined limits. Upon approval of the BOD phase described above, the design and preconstruction phase can begin. This phase involves issuance of Request for Proposals (RFPs) and selection of a design team to prepare construction documents and produce the project performance specifications. Once again it is critical to integrate your key stakeholders into this process, as was done in the BOD phase, to assure a continuity of the “all-in” support system and scope capture that will undergird your cost and schedule estimates.

Toward the end of the design and preconstruction phase, Chuck recommends utilizing the 80-100 percent complete design documents for inclusion in a Request for Proposal (RFP) to Construction Managers (CMs). The CM RFP is intended to solicit qualitative and quantitative proposals, including estimates for construction cost and schedule reflecting the BOD and current design. Upon receipt of the CM proposals, and often a third party check estimate, you will have the scope, cost, and schedule information, as well as stakeholder buy in, to make another financial presentation to management for your next “go- no go” decision. A positive response from management at this stage allows you to move into the construction commissioning validation phase that will bring the new facility on line.

Setting credible schedule expectations is akin to the discussion on programming and budget above, in that you will want to assure full integration of all support team schedules (Commissioning, Quality, Validation, Engineering, OPS, Facilities, Equipment, IT, Security, R&D, Procurement, and Real Estate, and Construction) in a master schedule prepared by the CM. This process, for example, can help to avoid the C&Q squeeze that Mike spoke of earlier, with construction commissioning, quality, and validation all integrated in the planning and implementation phases of the development. It is also important to revise the schedule regularly to accommodate any refinements or necessary adjustments that may require a recovery plan to maintain set milestones. A two-week look ahead is also recommended, and constant communication among the stakeholders is critical and can be encouraged by the use of a project FTP site to host project data.

Finally, driving execution of the plan relies on strong leadership, enforcement of accountability and measurement of key performance indicators (KPI) to gauge progress and make course corrections as necessary. Chuck recommends carefully interviewing critical team members such as the CM superintendents and project managers to ensure appropriate experience and team chemistry. Strong leadership will also benefit from periodic team building to maintain focus, direction, enthusiasm, and productivity. Enforcing accountability by each project team member is critical and can be done by penalizing low performance and rewarding achievement. Accountability also entails identifying team weaknesses and making changes and other corrective action early to maintain project momentum and efficiency. Finally, defining and measuring KPI in terms of schedule adherence, budget adherence and team coordination is critical to good project management.

Clearly the facilities development process, on both micro and macro scales, is faced with challenges that require careful advance planning to achieve positive outcomes. We can see how a phased C&Q plan is a great way to deal with the C&Q squeeze that so often occurs as construction dates are pushed out and manufacturing dates are pulled in. It is also helpful to know that these large endeavors can be effectively disaggregated into a smaller subset of tasks and incremental approvals to limit risk and better protect owner resources. When coupled with earlier involvement of key stakeholders, these tools allow us to build better solutions to strategic planning needs and report more ROI to the CEO!

ISPE Washington, DC Conference – Education, Networking and Lots of Fun!

by Rick Pierro

It’s entirely appropriate that the ISPE Annual Regulatory Compliance Engineering Conference be held right outside the nation’s Washington DC capital. After all, that’s where the FDA big wigs hang out and they don’t have to go very far to give fabulous talks on regulatory trends and issues for the 500 or so ISPE delegates that gathered from across North and South America this past June 2-6.

Educational talks were well attended, with delegates coming from Canada to Brazil to hear the latest updates on topics like the following:

• Science and Risk-based Approach (for C&Q): Application of the New Guide, Installation and Verification (In Support of ASTM E2500);
• Regulatory Perspectives on Hot Topics, Regulatory Trends, and Observations;
• Application of the New Risk-MaPP ISPE Baseline® Guide GAMP® 5: Enabling Innovation and Technological Advance.

But interesting educational talks were not the only things brewing at the Conference. Approximately 80 of the nation’s top vendors participated in the table top show; 17 national committee meetings (COP, Education, Member Services, Student Development, Regulatory Affairs, etc) were held; and representatives from 15 ISPE Chapters met together for a full 8-hour day (16 hours if you include our networking event) to exchange ideas, best practices and discuss plans for the future.

The Boston Area Chapter was well represented at these meetings with Doyle Johnson (Vice President), Mike Denault (Past President) and Rick Pierro (President) attending the North American/South American Affiliate Council (NASAAC) meeting, In addition, Dave Novak headed up the Membership Services Committee and presented the results to the entire NASAAC.

But the best part, as always, were the networking events. This is often where the deals are made, ideas are hatched, and friendships are formed and the Washington Conference was no exception. For example, the Boston Area Chapter representatives took the Puerto Rico Chapter leaders out for dinner one night and learned all about ISPE in the Caribbean, discussed regulatory requirements with the Argentina Affiliate and chatted about European business growth with the United Kingdom Affiliate. By the time the week was over, many of the delegates, myself included, were already looking forward to the next Conference to be held in Boca Raton, Florida in October!

Preparing for an FDA Audit: Everything You Need to Know but Were Afraid to Ask

by Joyce Chiu with photos by Mike Denault and Rick Pierro

The March 18th educational program sponsored by the ISPE Boston Area Chapter was held at Biogen Idec in Cambridge. Chapter President Rick Pierro opened with a thank you to our generous hosts, commenting that the event was sold out, with about 95 members and nonmembers in attendance. He then turned the floor over to Program Manager Dave Truex who introduced the evening’s speakers: Ron Branning, President of Ron Branning & Associates and former Vice President of Quality Operations at Genentech; and Mike Cross, Senior Manager of Quality Engineering at Biogen Idec.

FDA Inspections: A Management Perspective by Ron Branning

With 38 years as a Quality professional in biologics, biotech, devices, pharmaceuticals and plasma, Ron was a highly energetic and entertaining speaker.  Drawing upon his worldwide experience working with small to large companies on everything from consent decrees to new product approvals, Ron’s presentation was accentuated with war stories and interesting anecdotes.

What are senior management concerns when it comes to FDA inspections?  Senior management wants to avoid business interruptions and personal liability.  Therefore, preparedness is the key, including a professional compliance team, internal and external assessments, and mock inspections. The main areas for focus include the quality system, facilities/utilities/processes, adverse events, laboratory out-of-specifications, CAPA and validation, as well as product release and rejections.

From a management perspective, Ron advised a focus on the top 10 issues - those that FDA inspectors will inevitably look for, based on a company’s own documented evidence.  During the inspection, backroom documentation staging and expert presenters, trained and rehearsed, need to be in place.  In addition, the status of any remediation efforts needs to be updated and preemptive discussion with FDA considered.

During Prior Approval inspections, a company needs prepared responses to FDA’s questions, with appropriate backup documentation and internal experts available. Tours of the production area and QC lab, batch records and stability data all need to be ready as well.

Senior management’s role is to open the meeting, set the tone, obtain daily updates, preside over the closeout and lead continuous improvement efforts afterwards; but should stay out of the way and let subject matter experts do their job. In closing, Ron emphasized the importance of management’s commitment to compliance, creating credibility and transparency, and sticking to “the truth, the whole truth, and nothing but the truth” as the golden rule when it comes to FDA inspections.

Regulatory Inspections: A Deckplate Perspective by Mike Cross

Biogen Idec is a licensed commercial drug supply facility, with its products distributed worldwide, from five trains of 2,000L scale in two distinct areas.  There are more than five products and about 30 lots annually, with a staff of 300 in manufacturing, engineering and support and 35 in QA. With 10 years at the company, Mike has had experience with CMO inspections as well as several major agency inspections. Based on Mike’s presentation, Biogen Idec has a well planned and executed inspection process in place, with attention paid to every detail.

In the past six years, Biogen Idec has had inspections by nine agencies; these include FDA, EMEA and Mexican, Japanese and Brazilian agencies.  In order to remain ready, weekly inspection preparation meetings are held with senior staff. For actual inspections, there is a well laid out flow with a “war room,” document room, inspection room and other closely related areas. Each room has a designated lead, scribes (for note taking), topic leads and inspection consultants; internet access, projection and video conferencing capabilities, etc. are provided where needed.

Mike described the sequence of events comprising the inspection process beginning with the opening day, including organizing presentations and daily wrap-ups.  Inspections usually focus on the timeframe between the last inspection and the present, including any citations, utilities, product controls and changeover, supply chain, quality system, stability program and exceptions handling. If caught with a “gotcha,” it is OK to ask for a timeout to strategize and respond, according to Mike. The final wrap-up is done with senior management involvement, to solidify response timing and expectations. In summary, a successful FDA inspection takes a year-round commitment, with an eye towards planning, preparation, a strong quality system, and clearly defined roles.

Despite a rather dry topic, Ron and Mike delivered well-thought out presentations, with interesting details and stories that everyone could relate to.  They both did a wonderful job!

ISPE Boston Area Chapter Student Poster Contest Gets Tougher!

by Rick Pierro with photos by Yatao Liu, Mike Principato and Eric Marchese

Seventeen ISPE graduate students and two ISPE undergraduate students carefully and anxiously placed their research posters on the wall and nervously waited for the five judges to approach. The annual ISPE Boston Area Chapter Student Poster Competition had begun.

On April 2, student members of ISPE Chapters from Northeastern University, Worcester Polytechnic Institute (under formation), Boston University and the UMass Amherst assembled at Northeastern’s Dodge Hall to compete for first prize and an all-expense paid trip to Boca Raton, Florida in October to compete in the ISPE International Student Poster Competition and attend the ISPE Annual Meeting. The competition this year was unusually tough. The students were given only five minutes to explain their research and posters and five additional minutes to answer questions fired at them by the five judges.

The judging this year was done by Henry Brush of Alkermes, David Novak of AMEC, Marcia Steger of Massachusetts Biologics, Michael Denault of Denault Associates and Rick Pierro of Superior Controls. Special thanks were given to Professor Rebecca Carrier and the four ISPE Student Chapter Officers of Northeastern University, Lisa Grady, Michael Principato, Kate Forrister and Eric Marchese, who prepared for and hosted the contest. The Student Chapter also provided the pizza and soda which energized the judges throughout the evening.

The presentations went on for several hours and the judges meticulously totaled the points for each one. And finally the winners were announced. Padmaja Magadala, a graduate student attending Northeastern University, won with her poster titled “Epidermal Growth Factor Receptor-Targeted Engineered Gelatin Nanovectors for Gene Delivery and Transfection in Pancreatic Cancer Cells.” Sindhura Ganga, also of Northeastern University, was the runner up with her poster titled “Multifunctional Nanoemulsion System for Combination Paclitaxel and Curcumin Delivery to Human Glioblastoma Cells.”

Incredibly, the top two undergraduate students tied for first place in the undergraduate category. The judges decided that in this unusual situation it was only proper to send both the winners to Boca Raton. They are Jason Lajoie of UMass Amherst with his poster “Directed Evolution of RhII Protein” and Akshay Navaladi of Boston University with his poster titled “Role of Micro-Environment Stiffness in Directing Mouse Embryonic Stem Cell Differentiation.”

Special thanks go to the five judges for their tireless diligence in reviewing each poster and to all the students who participated. I believe I can speak for all the judges in saying we were truly amazed at the advanced and fascinating research being done in our universities and the dedication and expertise brought to each project by the students. Now on to Boca Raton in October for the ISPE Annual Meeting and International Student Poster Competition...stay tuned for the results.

Talking Shop at Science Center

by Arkady Mayblyum with photos by Mike Denault and Doyle Johnson

On Tuesday, April 22nd Genzyme Corporation hosted the ISPE Boston Area Chapter Talking Shop: “The Love Hate Relationship Between Engineering and Quality” at its new Science Center in Framingham, MA. The program format encouraged open dialogue between talk shop panelists and the members of the audience on the issues which have been near and dear to everybody involved with the industry.

All three panelists, Gael DeAmicis (Principal Validation Engineer at Bristol-Myers Squibb), Linda Graf (QAV Manager at Wyeth Biotech) and Greg Ruklic (Principal Engineer at Wyeth Biotech), have worked in both quality and engineering roles throughout their impressive biotech/pharmaceutical careers and had no trouble engaging the audience in a free-wheeling discussion of the topic.

After a short introductory presentation by Greg Ruklic, Linda Graf and Gael DeAmicis each talked about their approach to executing projects with heavy engineering and quality involvement. A few members of the audience, which was slightly tipped towards engineering, went on to share their own “war” stories. Very early in the program it became evident that the quality, validation and engineering groups are acting more and more as partners rather then nemeses as in the past.

Faced with the tremendous pressure, pharmaceutical and biotech companies are looking at the cost of compliance as one of the most significant areas of improvement. The introduction of the ASTM E2500-07 Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment started a new trend shifting a lot of quality responsibilities to engineering. This is forcing engineers to be more involved in quality issues and quality professionals to become Subject Matter Experts (SME) in certain engineering disciplines.

The new ASTM Standard was brought up on numerous occasions throughout the evening, triggering discussions on execution of commissioning and validation activities for projects of different scale; and also led to discussion of the potential effect of other standards like the ANSI/ISA S88 Batch Standard and ANSI/ISA S95 International Standard for the Integration of Enterprise and Control Systems on the industry’s future.

Overall, it was very encouraging to see that there is a lot more Love than Hate in the relationship between engineering and quality.

Special thanks to Genzyme Corporation for hosting the program, to Stan Rotkievicz from Genzyme and Monique Sprueill of Bristol-Myers Squibb for coordinating the event for ISPE; and to the panelists, Gael DeAmicis, Linda Graf and Greg Ruklic and the Boston Area Chapter Educational Program Committee for an extremely interesting and thought-provoking evening.

February’s Joint Program with MIT’s Professional Institute: Continuous Improvement in Biologicals Manufacturing and Process Analytical Technology (PAT)

text and photos by Wes Hyman

In February, the ISPE Boston Area Chapter was very fortunate to have MIT Professor Charles Cooney address our Members as part of a joint educational program with MIT’s Professional Institute. Professor Cooney is a professor of Chemical and Biochemical Engineering in the Department of Chemical Engineering at MIT. In addition to his academic credentials, his extensive background in biotech includes consulting for a number of biotech and pharmaceutical companies, serving on Genzyme’s Board of Directors and chairing the FDA Advisory Committee for Pharmaceutical Science from 2004-06.

Though it is impossible for me to capture the level of sophistication and technical detail Professor Cooney brought to his topic, I will attempt an overview of the broad themes he conveyed during his presentation. His introduction to the topic provides a good place to start:

A major challenge in biological manufacturing is continuing to improve the process while operating to maintain regulatory compliance. There is a normal variation in biological performance; however, in the drive to assure regulatory compliance and replicate the standard batch, we create a tension between learning from the variance and seeking to eliminate it. Analytical technologies provide us with multiple lenses on the process to probe the relationship between operating variables and process performance. The FDA’s PAT initiative creates an atmosphere in which multiple analytical tools can be leveraged for continuous improvement.

He then went on to highlight current trends in biologics manufacturing. From the clinical perspective, these include ever-increasing molecular complexity, larger pipelines, increasing late-stage rejections of candidate drugs and evidence of a more personalized medicine defining the smaller markets. On the regulatory side, there is an increased focus on risk, heightened interest in understanding process science and a heavier regulatory burden from new products and amended applications. Lastly, on the marketing side of the spectrum, he described an increasing number of dosage forms, greater diversity of package inserts in global markets and pressure to reduce prices while increasing access to the latest products.

While discussing the major challenges of process design and operation, Professor Cooney pointed out that metrics and goals are very important. “We need to know where we want to go and have the analytics to measure where we are (relative to our product specifications) and understand how the process affects the important properties of the product.” There is also uncertainty. He said we need to assess and reduce this uncertainty to an acceptable level to manage risk across the value chain.

Professor Cooney described PAT as a system for designing, analyzing, and controlling manufacturing through timely measurements (i.e. during processing) of critical quality and performance attributes of raw and in-process materials and processes with the goal of ensuring final product quality.

Attendee and Chapter Vice President Doyle Johnson was struck by the evolution of PAT “from simple measurements of pH and cell density to more complex analyses of genetic information” as described during the presentation. With this more advanced type of PAT, it should be possible to better ensure bioequivalency and lead to a greater pace of innovation in biopharmaceuticals, according to Johnson.

When I spoke with Professor Cooney prior to his presentation, I asked him about the industry’s acceptance for the use of PAT. He indicated that while there has been slow acceptance of PAT, it is something the people can embrace and should feel comfortable with while translating it into actual practice. He said PAT is being more rapidly accepted by the larger companies, but could help the small firms even more. Biologic process development demands good understanding and requires that you are able to measure what is going on in order to use PAT successfully, he continued, and said he sees it as being an integral part of the future of biologics manufacturing.

In summary, the program was extremely timely and informative, and benefited greatly from Professor Cooney’s academic credentials and real world experience. Audience members paid rapt attention during the formal presentation and followed up with a series of detailed questions that demonstrated the depth of their expertise and intense interest in the topic.

Equally important, the event allowed attendees to trade information about PAT, its use within their own companies and its evolution as a universally accepted continuous improvement methodology. And, as always, the networking reception was well received (especially the lobster thermidor, chicken pot pie, and mac and cheese appetizers) and provided a great way for people to interact with their peers and gain valuable industry insight.

Let’s Get Together and Spread Out: Millipore R&D Center

by Joseph A. Naughton, AIA, LEED ® AP with photos by Warren Patterson

The new Millipore BioProcess R&D Center in Bedford shows us how smart space design and equipment management results in better work space and more of it. According to the company’s Web  site, the 110,000 square foot building contains 47,000 square feet of lab space, consolidates multiple functions and fosters “an even more collaborative approach for the up to 500 professionals who will work there.” About 50 ISPE Members from the Boston Area Chapter gathered at the newly expanded campus on March 11, 2008 to learn more about the design process that created the new facility and to view the results for ourselves during a comprehensive plant tour.

Our hosts included some very proud and gracious scientists from Millipore and an equally proud contingent from ARC/Architectural Resources Cambridge, the designers for the new facility. We began the evening with some light hors d’oeuvres and good conversation in the new dining/presentation room, which, even at dusk, was filled with an abundance of natural light and views out to a carefully manicured natural landscape.

Following a brief introduction by Educational Program Committee member Dave Truex, ARC’s Thomas Loring opened the evening with an overview of the primary drivers behind the project, the internal team Millipore mobilized to guide the decision-making process, and the external team Millipore engaged to implement the plan. He then described the process Millipore and ARC utilized to bring vision to reality in the relatively short time frame of 22 months. The basic components of the planning process included: Master Planning in which goals and opportunities were identified, Program Development in which needs and consolidation possibilities were investigated, and Schematic Design in which a number of options were reviewed and converted into the optimal solution for Millipore.

The physical design concept at Millipore is essentially open labs versus closed, open offices versus closed. According to Robin de la Parra, Millipore Director of Core Research Support and our host for the evening, the culture prior to the expansion project was based on a closed lab and closed office solution so some skepticism surrounding the effectiveness of the open concept was apparent. At the time the concept was first unveiled, she estimated that only about 20 percent of the population was convinced of its benefits; today that figure is in the 80 percent range and climbing.

Even our Millipore tour guide admitted that she could count herself as part of the original 20 percent club and was initially tentative about the functionality of the open configuration. While there are certain advantages associated with the closed office configuration, after approximately 8 months of working in the new facility, she believes that the benefits of communication and collaboration that are now evident every day have moved her firmly into the 80 percent club.

The “parti,” or the basic relationship of the various spaces to one another, arranges the office spaces in banks with a proportionate number of one-on-one meeting rooms opposite the lab zone with breakout areas in centralized areas accessible to each individual lab. These shared break-out areas are marked by a double height interconnecting lounge type area with open stair connecting the floors and surrounded by small, medium, and large conference and presentation rooms. The color palette throughout the building was rich with light warm tones and subtle accents and an interesting assemblage of bamboo, tile and carpet for aesthetic interest and sound control.

The labs were grouped into bench lab pods adjacent to process lab pods, each linked by shared instrumentation and equipment zones in central locations. In addition to the shared instrumentation and equipment rooms, the building includes a secured central store with inventory that is bar code stocked and tracked. Scientists access the store with a security card and obtain materials needed from the store by simply keying in the bar code on the items needed; the system maintains a fully automated and up-to-date inventory with automated purchasing support and a charge account to each lab for materials consumed.

The beauty of both the shared instrumentation/equipment zones and the automated central store is, that by centralizing these functions and automating the scheduling and inventory of each respectively, Millipore scientists have been able to move equipment and materials that used to take up space inside the labs, out of the labs to free up valuable bench and floor space that can be better utilized by people and their work. The Millipore team proved that smart design, lean equipment management and automated inventory and charge accounting has resulted in a better working environment, allowing the many talented individuals who work there to be even more efficient and productive than before.

In terms of real dollar impacts, because Millipore is working at higher equipment utilization than before, their equipment purchasing needs have declined from previous levels, improving their equipment budgets. And the higher usable space that resulted in the labs meant that the 10-foot lab module is effectively more generous than in the previous model. Translation: this building is bigger on the inside and smaller on the outside which means the building cost less money for what is effectively more usable space.

We left the Millipore facility with many good impressions and we would like to thank our friends at Millipore for their hospitality. The people who run the facility have shown how a careful planning and design process will yield impressive results and an optimal facility solution. They were really able to get together and spread out.

Mt. Sunapee Welcomes Boston Area Chapter Annual Ski Trip

by Doyle Johnson with photos by Rick Pierro and the author

This year the (sold-out) ISPE Boston Area Chapter Ski Trip went to a new venue, Mt. Sunapee in New Hampshire. Another difference was a new bus driver, Jack. Jack went to Cornell University (alma mater of your humble author for this article) and had no sense of direction, a characteristic we found curious for a bus driver. Still, he was a pleasant enough chap and as long as we told him (repeatedly) how to get there, it was no problem.

Well, almost. As we entered the Sunapee State Park, Jack told us that the bus transmission had a problem and was refusing to shift. He planned to stop the bus, shut it off, count to 10, and then pray that the transmission reset itself. As luck would have it, Jack’s prayers were answered and we did not end up having to walk up the hill with all of our ski gear.

We arrived at the mountain in time to make the first tracks of the day and the conditions were super thanks to the excellent job of grooming the runs the folks at Sunapee had done, plus the fact that it being Friday there were no lift lines at all. The sun warmed the back side of the mountain first and softened things up just enough to create excellent skiing conditions. We all stopped for lunch on the deck outside to enjoy the sun and the spicy chili.

In the afternoon the front of the mountain was softer and we all made multiple runs up and down the Express Quad and it's assortment of blue and black diamond runs. It was during this time that your author made a valiant attempt to keep up with Mssrs. Crowley and Grunwald but to no avail! By 4pm we were all skied out and enjoying some refreshments in the Horsefeathers bar, and by 6pm we piled back into the bus for our ride home (still telling Jack which way to go: "No, Jack, 93 South!").

When you consider we had a great day of skiing, the company of some 56 fine people, lunch and after-ski drinks plus a bus ride made only slightly longer by a few wrong turns, the $50 cost seemed an incredible bargain. We hope that next year even more people take advantage of this ISPE Boston Area Chapter March tradition!

Project Management: “The Tail Wags the Dog?”

by David MacDonald with photos by Peter Teague

Project Management came to the Boston Area Chapter of ISPE on Tuesday, November 13, 2007. The room was full at the Royal Sonesta in Cambridge, as two excellent speakers explored several facets of the complex area of project management. One speaker focused on small projects and the creation, care and feeding of project teams and the second speaker focused on how to control massive capital projects and how to develop a global project management standard for a multinational.

Niall Johnson, Associate Director of Capital Projects/Facilities, Engineering & Planning for Millennium Pharmaceuticals, spoke first. He described several drivers for utilizing project management and project management tools. First, the FDA has estimated that there is $60 billion of opportunity cost in the pharmaceutical industry. In the FDA’s quest to lower drug prices, the industry will be forced to start minimizing that opportunity cost. Project management is just a set of tools to allow us to do business better. In addition, there is a need to leverage individual project success to business success, which is, after all, our overall goal. Project management includes tools to make sure that individual project goals are aligned with the overall company business goals.

Johnson defined a project as a set of activities having both a start and a finish, leaving a wide range of topics as possible projects. Only about 50 percent of a typical project is in the execution of the project. The rest is in the initiation, planning, verification and closure. The project can succeed or fail just as easily in these phases as in the more visible execution phase. The challenges faced in a project are different for each level of stakeholders - the industry, the individual business, the specific project team and the individual project team member.

One of the keys to project success involves addressing Project Risk. Putting your head in the sand about the risks in a project is not a good option. Likewise, saying that we want “no risk” is unacceptable. Instead, we need to not rely on intuition, but identify what the real risks are and manage, monitor, and mitigate those items. But the list of risks that you are managing needs to be short (less than 10) and well-prioritized (those risks that are real and important).

Johnson discussed two key project documents, the Project Initiation Document and the Project Planning Document. The Project Initiation Document is the project charter. It should be short, 3-4 pages, and should clearly state the business case, project boundaries, risks, constraints, expectations and success criteria. The Project Planning Document has more detail, delving into user requirements, process block flows, project work breakdown structure and preliminary schedules (less than 15 tasks). This document should also clearly define the success and acceptance criteria.

Wrapping up his section, Johnson reminded the attendees that all projects are change and so are challenging. The real definition of project success is “Would you be willing to do the project again with the same people?” The soft side of project management and project leadership are as important to the success of the project as the technical skills.

Jeremy Gross, a Principal from PMA Consultants, then continued the evening with a session on Project Controls, Schedule Integration and Project Reporting. Gross reminded the audience that in the structural construction side of the business, GMP means guaranteed maximum price, having nothing to do with the FDA (so we have to keep a close eye on our three letter acronyms).

He went on to discuss Project Controls. This is not project accounting, but a tool kit for project management, used to ensure that past mistakes are not repeated. It includes a disciplined approach to estimating, scheduling, cost controls, monitoring, trending, forecasting and reporting the project. And it includes a feedback loop to capture data and lessons learned. Gross reported that the benefits of using this tool kit include early warning signs and reliable forecasting as well as lower cost growth, lower total cost and less slippage in the project schedule.

PMA was involved with developing a global standard for project schedule integration for large scale projects for Johnson & Johnson. One single large project could consist of 30,000 items, so no single person looks at all the items. Each smaller portion of the project has to be managed with a schedule and plan which an individual could understand. These individual plans then have to be wrapped up into the overall master schedule. Only with a very disciplined approach could all of the sub-project schedules be managed, integrated, updated and reported successfully. The updating of the project progress and its schedule becomes an intricate task in itself, with progress data reporting cut-off dates and schedule-update dates.

Even the reporting of the status of a project becomes a disciplined art. Gross pointed out that there needs to be multiple levels of reports generated, depending on the needs of the report users. At the highest level, there are Executive Level Reports which quickly capture the essential high-level information on project costs and schedule. They must be quickly and easily read and understood, and should be in a standardized format. Dashboards have proved useful at this level to quickly convey the necessary information. Just taking a report from Primavera will not work at the executive level. Meanwhile the Project Manager needs to be looking at detailed tabular reports and resource availability and demand curves. These need to be both customized for the needs of the project manager and as standardized as possible for consistency and ease of understanding.

PMA was so successful in helping J&J on one of their massive capital projects that J&J senior management asked for their help in standardizing the company’s global approach to capital project management. This demonstrated the versatility of the project management tools that both speakers had described, covering the range between a conference room renovation to a global multi-billion dollar a year capital program.

For more detail, readers are invited to view the presentation overheads on the Boston Area Chapter Website at http://www.ispeboston.org/events/ .

Its All in the DOCS: Planning CTD/eCTD CMC Submissions

text and photos by Deepen “DJ” Joshi

At the January 15th Educational Program (EP), the ISPE Boston Area Chapter continued its mission of combining timely information on a topic of current interest to the industry with an opportunity for informal discussion and networking among peers. The topic of discussion that evening - Common Technical Document (CTD), the current worldwide standard for content and format of submissions of Investigational New Drug Applications (INDs) and New Drug Applications (NDAs) - was a welcome one and the first time the Chapter has devoted an EP to the topic of regulatory documentation.

Rick Pierro, President of the Boston Area Chapter, jump-started the program by sharing some of the Chapter's upcoming events and giving a warm welcome to the panel of speakers, all of them distinguished experts from the regulatory domain. Speakers included Michelle Herrera Foster, PhD (CTD Quality Consulting), Fiona Sibley (CTD Quality Consulting) and Yolanda Hall (Datafarm), all of whom gave formal presentations; and panelists James Blackwell (BioProcess Technology Consultants) and Tish Webber (Wyeth BioPharm).

She then went on to describe the data which, under the current EU regulations, has to be contained in Module 3 so that it can be determined whether the drug/biologic in question is of appropriate pharmaceutical quality. She also discussed the importance the electronic version of the Common Technical Document (eCTD) may have now and in the future. The eCTD is expected to fully replace the “paper” CTD, thereby reducing the quantity of paper received by regulatory authorities on a daily basis to a reasonable level. In addition she stated that the CTD is required in EU, Japan and Canada for marketing applications, “highly recommended” by FDA for NDA/BLA and required by Center for Drug Evaluation and Research (CDER) for eCTD submissions.

During the course of her presentation, Dr. Herrara Foster suggested treating CTD as a live document throughout the submission process and explained the advantages and challenges of that approach. She also skimmed through the following sub-topics: key CTD needs and tools that would bring more efficiency to the process, difference between various sections of Drug Substance (DS) and Drug Product (DP) for Module 3, and correlating the CTD Module 3 to the NDA, BLA and MAA. She identified the new sections required by the CTD and listed high level points that would enable the development of CTD from IND (Phase 1). She enlightened the crowd with examples of Module 3 reports and types of reports, namely full report, summary report, high level summaries (for Module 2) and reports on file for inspection. The panelists contributed additional information as needed to fill in gaps and/or provide a different viewpoint or example to clarify the issue at hand. This exchange allowed the audience to appreciate the regulatory documentation challenges and what is considered an appropriate and balanced approach.

The second part of the EP was dedicated to the presentation of CMC CTD case studies by Fiona Sibley. The case studies on purification, process development, viral clearance and sterilization validation helped the audience to understand the applicability of CTD to their respective domains. Although they may not have received a comprehensive understanding of the mundane challenges in the preparation of CTD, the case studies served as a “lens” through which the attendees could view and better appreciate the intricacies involved in CTD/eCTD development. In her conclusion, Ms. Sibley recommended that submission-ready validation reports and other reports be written in advance so that summaries and data tables can be copied for the CTD at filing time, thereby saving effort and reducing stress. The participants acknowledged that following these recommendations would prove valuable in increasing the efficiency of the process.

Following the CTD overview and case studies presentations, Yolanda Hall covered Electronic Common Technical Document (eCTD) Considerations. She said that the eCTD is a part of the ICH initiative to provide a common format for the industry-to-agency transfer of regulatory information that is acceptable across the ICH regions of the United States , Japan , and the European Union. She also explained how the eCTD introduces the use of an “XML backbone” as a new way of approaching electronic submissions. This benefits both sponsors' organizations and agencies by providing a mechanism to record all interactions and highlighting changes between submissions.

Ms. Hall provided highlights on eCTD specifications Module 3, reiterating that granularity is the key to successful eCTD. She explained the relationship between XML and Templates as it applies in Modules 2 and 3, and the importance of defining the directory structure, file organization, file names and their boundary values. Participants requested further clarification on the technological investment (small scale investment vs. large scale investment), Life Cycle Management (LCM) of submissions as well as of documents, including correlation between the two. She remarked that benefits include the efficiencies gained by content reuse between submissions, the ability to submit simultaneously to the three largest pharmaceutical markets around the globe, and the simplification of the maintenance process throughout the submission lifecycle enabled by the XML backbone structure.

During the final wrap-up discussion, the panelists sought to summarize some of the key themes of the three presentations. They handled the follow-up questions round-robin style, providing a variety of perspectives, solutions and applicability, where possible, to add further clarification. Audience members working in the same domain also joined in, sharing strategies that are being used in their own companies.

In sum, attendees gained a better understanding of CTD and eCTD and their applicability to manufacturing, process automation and related domains, and were able to make new friends and meet with existing ones while spending an evening on the cutting edge of all that is new and exciting in the industry. This certainly is priceless!

A Sure Bet: Chapter Officers Enjoy ISPE Annual Meeting in Las Vegas

by Doyle Johnson

The 2007 ISPE Annual Meeting was held this year at Caesar's Palace in Las Vegas . Caesar's Palace is the 12 th largest hotel in the world with 3,348 rooms. Over 2,500 ISPE members from around the world journeyed to Las Vegas . Your Chapter was represented by Rick Pierro, President; Mike Denault, Past President; Doyle Johnson, Vice President; and Amy Poole, Chapter Manager.

The first event was a Student Luncheon on Sunday, with 56 Students from all over the country. Rick spoke of the path he took to found his own very successful integration business and also be on the board of directors of several other companies. Doyle spoke of his career path and how even as a young graduate just starting out in the workplace he had an influence on others. Sean Sommer of Parsons spoke about his career through engineering, project management, and into business development. It was fun to talk to the students, answer their numerous questions and be so well-received by them.

Sunday through Wednesday were educational sessions mixed in with committee meetings on ISPE business and future planning. We discovered some best practices of other Chapters that might be useful for us and types of events that could also go over well in the Boston Area Chapter.

Monday night was a social gathering at Margaritaville. There was live music and livelier discussions. For instance, I found out from Nuala Calnan of Project Management Group in Dublin , Ireland that the E2500 standard is already having an impact over there.

Tuesday's luncheon was the main event, with Bob Best (ISPE President) and Bruce Davis (Director of AstraZeneca and incoming ISPE Chairman) telling about the past year and future plans. The Keynote session on Monday morning was also a highlight. Gary Convis, Chairman of Toyota Motor Manufacturing Kentucky, spoke of how he built a company focused on quality and employee empowerment. If you think you spend a lot of time interviewing candidates for jobs at your company, consider this fact: Toyota interviews on average 25 people for each person they hire.

At the same session, Charles Portwood, President of Technical Operations and Product Supply at Wyeth told us about how Wyeth has seen benefits from totally integrating all of their information systems, and Uri Boneh, Director of Global Engineering for Teva explained how to make a cost-effective (he did not like the word “cheap”) generic pill (OSD) plant outside Jerusalem.

Tuesday evening was the Roman Festival at the hotel's Temple Pool , which was a beautiful setting for more camaraderie. Wednesday was the last of the educational and committee meetings before we all returned home. It was great to meet so many people from other parts of the world and realize how similar are the problems we all deal with (both professionally and within the ISPE Chapters). If you have not attended Annual Meeting before, you should plan on joining us next year - 26-29 October, 2008 - in Boca Raton , Florida . See you there! ?¡

• 58% of employees who work in Genzyme Center said they were more productive in the new building than they had been in the company’s former headquarters.
• Genzyme Center employees recorded sick time at a rate that was 5% lower than the combined rate for employees working at all other Genzyme facilities in Massachusetts.
• The building’s energy costs were estimated to be 42% less than those of a comparable conventional building.