Genzyme is likely to enter into a Consent Decree with FDA over ongoing cGMP problems at its Allston facility. The company says that FDA plans enforcement action.  Here, reporting from Wall Street Journal today. Blogger Jim Edwards notes a 14-year history of compliance issues at Genzyme on his blog today.

Genzyme Corp. has had numerous regulatory problems at its Allston,  Mass. Facility of late—viral contamination issues last summer, and recently FDA warnings and production shutdowns related to metal and other contaminants found in products manufactured in Allston. The Agency has posted a redacted version of its inspectional observations chronicling specific violations.

Every so often, one gets a major reminder of the strategic importance of manufacturing and the largely invisible "CGMP set" to the drug industry and, yes, its bottom line. Former FDA chief Mark McClellan gave pharma a good one years ago with his famous "potato chips and soap flakes"  comment, immortalized in a Wall Street Journal piece. Typically, manufacturing continues to be thought of something that will get done....quietly, invisibly, wherever and by whomever.

On Tuesday afternoon, a panel discussed ways in which corporations might be able to stimulate the development of more therapies for serious diseases----the world’s top killers such as malaria. The topic is one that I’m very interested, but, unfortunately, I arrived late and missed much of the discussion.

Genzyme has been doing some pioneering work with orphan drugs and its Gaucher’s disease treatment, Cerezyme, has been profitable.

James Geraghty, SVP of International Development with Genzyme presumably discussed the company’s Humanitarian Assistance for Neglected Diseases Initiative, and efforts such as the one underway with the Oswaldo Cruz Foundation in Brazil.

Una Ryan, President and CEO of Avant Immunotherapeutics, Ltd., also participated in the discussion. Her company has been developing drugs for neglected diseases, including cholera and typhoid, as well as an HIV vaccine, in efforts funded by the Gates Foundation.

Elizabeth Bailey of Commons Capital works with venture capitalists to obtain funding for early stage drug development.  Currently, Commons is working with Gates, Rockefeller and  Lloyd's Foundations.to fund research into therapies for neglected diseases.  At the conference she discussed financing models(some of which were touched on in a 2005 paper, which came out of a workshop on this subject). Financing is most feasible in early stages, she said.

Dr. Ryan  agreed, and emphasized the importance of venture capital in funding these efforts. Big pharma or Big Bio is too locked into production schedules and unlikely to recoup investments, so, despite its worthiness, it’s a hard sell to management. Profitability is critical.

Vaccines are excellent candidates for attracting venture capital for global development, Dr. Ryan said. During the Q&A, someone in the audience spoke of the need to develop an infrastructure that would permit scientists in developing nations to develop innovator products, rather than “copy cat” products. Presumably, they won’t face the 10-year, billion-dollar hurdle that innovators face here.

AMS

Reuters reported this week that a patient who became ill following two experimental gene therapy injections for arthritis has died. U.S. health regulators are investigating the cause, officials said yesterday. The gene therapy trial by Targeted Genetics Corp. was placed on hold before the death, after the patient suffered a serious, unidentified health problem.

The hold means that no one else can receive the treatment, called tgAAC94, and no new patients can be enrolled in the study, the Food and Drug Administration said.

The company and the FDA said they were working to determine the cause of the death. "The investigation into the cause of the patient's illness and subsequent death is intensive and ongoing," an FDA statement said.

Gene therapy is being pursued by a number of biopharma companies including Genzyme. Michele Vaccarello took a look at the company's plans in this recent article.

While it may seem that pharmaceutical manufacturers are bitter enemies on the competitive battleground, as it turns out most of them have the same problems and concerns and are willing to help one another if possible. This was the message sent at the BIO conference session, “Management of Global, Diversified Manufacturing Organizations.� Each manufacturer took one global manufacturing topic and expanded on their company’s experiences.

Moderator Blair Okita of Genzyme touched on the importance of the tech transfer process. Made up of the 4 Ps (process, people, plan and plant), the transfer involves formal agreements, quality agreements and philosophy. According to Okita, the key to the process is people. Somehow, you have to have a transparent tech shift despite language and cultural differences. Okita says, “There is no such thing as a stupid question� when dealing with the transfer process.

Stefan Borgas talked about building new plants and understanding the associated problems with hiring talented employees from different cultures. With Lonza in the process of building five new plants all over the world, Borgas half-jokingly stated, “we have turned into a construction company more than anything else.� Lonza is building two new plants in Singapore and will have to hire an estimated 650 biotech professionals in order to fill these plants. According to Borgas, the key aspect in developing new plants is to attract, develop and retain employees. Their approach in Singapore is based on a five-year plan. They started with key hires who have since been training at Lonza sites in the US and Western Europe. They hope to have almost 200 people trained by the end of the year and an entire workforce in place 4 to 5 years before the plants even open.

Borgas says that in the current environment, “buying talent (by pillaging other manufacturers) has been easier than building from within.� He hopes and sees this changing in the near future. He also states there has been an overemphasis on academics when compared to the need for a vocationally-trained, skilled manufacturing workforce.

Pat Yang at Genentech thinks that the size of the footprint of future bio plants will shrink. Genentech has a “2x in 5� program, meaning that they want to double their titers size every five years, thus saving space. He also stressed that a balance was needed between innovation and efficiency. Sometimes these two concepts are in direct competition with one another.

Mike Kamarck of Wyeth Biotech also sees a change of philosophy regarding plants. “Biology is now trumping stainless steel,� says Kamarck. Switching from a single site to multiple sites and retaining efficiency requires harmonization, according to Kamarck. Wyeth has spent $3.5 billion on network infrastructure to enhance their efforts.

Risk mitigation was the topic Andy Skibo of Amgen spoke about. There is risk in all parts of the plant from finance to networking to manufacturing. For manufacturing, risk needs to be explored for capacity, inventory, external capacity and internal capacity. Each one of these processes must be explored on a risk vs. cost basis, according to Skibo. Quantifying these risks is very hard to do. The focus has to be on “prevention not reaction� for a successful program says Skibo
Remo Colarusso from Johnson & Johnson spoke on when and what global systems and tools can be used across a company. Factors J&J use when deciding to implement a system across the whole global network include: money – ROI; compliance issues; and cultural (e.g., process measurements). Colarusso says J&J has developed a process they call “CompStat� that is a balanced scorecard of business metrics. “We want all plants to measure things in certain ways. Without this, we can’t compare across our own facilities
In the question and answer session, the manufacturers stressed collaboration. The companies regularly talk to one another about capacity to meet each of their needs. “Idle capacity is no good for anyone,� says Yang. “Trying to plan capacity is an almost impossible task
 

Bill Swichtenberg

I was fortunate enough to be invited to a private meet and greet with Genzyme CEO, Henri Termeer and taken on a plant tour of the company's new Allston facility. What I had not expected was that I would be the only one speaking perfect American English (It is perfect because it is the only language that I speak fluently). The other 15 participants in the day's activities came from all over the world; Latin America, Europe, Australia...all with the intent to see what new innovations and technologies they could bring back to their own countries, and to get a better look at R&D efforts in one of the largest pharmaceutical companies in the world.

Attendees shot their own questions at Termeer, who handled each region-specific question with a global answer. He approached the subject of biotechnology on an international scale, a scale that would borrow from each country's trials and errors in order to solve the global public health crisis. Termeer envisions great success for bio and the industry if policy and lawmakers allow for collaboration and flexibility to produce drugs globally and exchange technologies that promise to "save the world".  

More on my afternoon with Genzyme to come...

Michele Vaccarello, Managing Editor, Digital Media

My mother is 100% Irish. Her children, 50%. "Don't forget your heritage even though I was forced to give you an Italian last name," she would say hoping she would not have to insert an IV of soda bread into our veins to ensure that we'd remember Ireland.

Needless to say, when I heard the faint bagpipes of the Ireland booth at this year's BIO show, I was inherently forced (by both my mother and my editor) to stop. I already knew that Ireland had produced the greatest band in history (see Blogging from Bio 3), but I also learned that over the past four years, Ireland has witnessed more than $6 billion in investments from some of the largest pharmaceutical companies in the world.

For example, Wyeth Biopharma has invested $2 million in biopharmaceutical manufacturing in Ireland, Genzyme has built a plant in Waterford, Eli Lilly recently announced plans for new Irish facilities, Bristol Meyers Squibb established a development group, and Pfizer has invested $300 million in a new fill finish facility. And this list goes on with other big names such as Abbott Laboratories, Johnson & Johnson, and Roche invested in Ireland.

Why is Ireland such an attractive venue for these large companies? The Irish government and those who have set up businesses there cite a fiscal good environment characterized by a skilled workforce, low corporate taxes, and a strong emphasis on life science research and development. Everyone at Team Biotech Ireland was in good spirits about the outlook of the industry and their contributions to the overall cause.

As I said, it is a good time to be Irish.

PS - I had to promise my friends at the Ireland booth that I would be back Tuesday afternoon at 2pm for their Irish dancing competition...I'll keep you posted on where I place.

Michele Vaccarello, Managing Editor, Digital Media