The Big Red Biotech Blog

The Lilly Giveth and the Lilly Taketh Away in Singapore R&D Center

Foxbusiness reports this morning that Eli Lilly will close its Singapore Center for Drug Discovery in December as the revenue challenged company looks to shave costs.  The center is a collaboration between Lilly and Singapore Economic Development Board and has been in operation since 2002.

Lilly has decided to close the site, move all projects there that will be retained in their pipeline back to the main R&D center in Indianapolis. About 130 staff will lose their jobs with the site closing and that will save costs for Lilly who faces revenue challenges with both an impending patent cliff and recent failures in its late stage pipeline.  Lilly has been active at outsourcing R&D in and out of the US for several years now - a trend it is apparently reversing in this case at least with regard to doing work outside the US.  Presumably the retained projects will move to its partner Covance in IN as both companies inked a deal for early stage work back in 2008.

"We regret Lilly's decision to close the Lilly Singapore Center for Drug Discovery, and are working closely with the company to place affected staff," says EDB Director of Biomedical Sciences Beh Kian Teik.

More from Fierce Biotech.

 

Posted by Bruce Lehr October 18th 2010.

SAFC Completes High-Potency Fermentation Expansion in Israel

  

SAFC announced the completion of its state-of-the-art expansion of its Jerusalem, Israel facility. The additional capacity expands SAFC's contract manufacturing capabilities in large molecule recombinant proteins and small molecule Active Pharmaceutical Ingredients (APIs) through fermentation, including High Potent APIs (HPAPIs) and secondary metabolites.

The 50,000 sq. ft. cGMP fermentation expansion, which is expected to begin production in October 2010, will focus on niche fermentation of APIs and bulk drugs, producing secondary metabolites (antibiotic-like molecules), cytotoxins and large-molecule proteins. A 30,000 sq. ft. area of the new facility has been designed to be Biosafety Level 2 compliant - enabling manipulation of human pathogens. Capabilities include 1,000 and 4,000-liter tank capacities for bacterial and fungal fermentation, as well as explosion-proof suites.

"Fermentation is a long-standing technology, yet new applications have been recently discovered, including the synthesis of high potency compounds, which is a major growth area currently driving contract manufacturers such as SAFC to look beyond traditional active pharmaceutical ingredient (APIs)," said SAFC President, Gilles Cottier.  See here for full release.

 

 

 

 

Posted by Bruce Lehr October 6th 2010.

Check Out New Content on SAFCLive

SAFCLive is a new web site for live news, views and opinion.  There are a host of links to videos and articles, and to key industry publications and industry body websites.

Content is update regularly. Here's some highlights from this month.

• Article explaining SAFC's new Zinc Finger Nuclease (ZFN) technology for CHO cell engineering for biopharm production and human cell drug discovery models
• My interview with BioPharm International discussing trends in biopharm cell culture
• SAFC's expansion plans with its HPAPI manufacturing footprint and facilities
• The FDAs perspective on supply chain security

And, there is more for you - once you check out the site.

 

Posted by Bruce Lehr October 3rd 2010.

 

 

 

Manufacturing Issues for High Potency Drugs under cGMP

My colleague Trevor Calkins, director of process development and manufacturing, wrote a nice article in the latest (Sept) issue of BioProcess International on the manufacturing and handling of high potency APIs.  Trevor is located at our HP-API facility in Madison, WI.

As Trevor points out, HP-APIs are a key component in the manufacture of antibody drug conjugates (ADCs).  With the increasing success of Seattle Genetics SGN-35 for Hodgkin's disease and Roche's T-DM1 for the treatment of breast cancer, ADCs are expected to play a larger and largers role in the pipelines of companies developing new oncology drugs.  SAFC has invested heavily in two state-of-the art manufacturing facilities for HP-APIs - both in WI - and serves as a key outsourcing option for the manufacturing of HP-APIs and ADCs. 

Trevor's article discusses the challenges and capabilites that a manufacturer must have to handle these difficult products.  He describes engineering controls and personnel training/protection embodied in the Madison and Verona facilities that allow safe manufacture of these key compounds under GMP conditions - in these multipurpose facilities. (Link to isolator photo inside Madison facility).

Pharma magazine also has coverage on SAFC HPAPI expansion plans.

 

Posted by Bruce Lehr October 3rd 2010.

Facility News in Pharmerging Markets

A couple of new facility announcements coming from geographies that are considered to be part of the pharmerging markets. 

First, Ranbaxy announces that it will be building a new $24 M Euro facility in South Africa, the 3rd facility to be built in that country.  The plant will make analgesics, cold and flu medicines, as well as medication for blood pressure and CNS problems. The plant will be able to produce 2 B tablets annually at full capacity. The South African government has made support of pharmaceutical manufacturing a key strategy to boost exports and reduce its trade deficit.  This is increasingly appealing to Indian manufacturers to set up operations there.

Second, Boehringer Ingelheim announced its plan to build a $100 M Euro "Center of Competence" in China's Waigaoqiao Free Trade Zone.  The CoC will optimize API and chemical intermediate sourcing in China.  It will be supported by BI's main offices in Shanghai. This is a move to strengthen the supply chain in East Asia as China is targeted to play a stronger role in the company;s global procurement plan. The CoC will have two divisions focusing on Process Development and Quality Control respectively. BI is also considering an expansion of its production capacity in its Shanghai plant in Zhangjiang High-Tech Park.  

 

 

 

Posted by Bruce Lehr September 2nd 2010.

Erbitux NJ Plant Closes

in-Pharma Technologist reports that Imclone's Branchburg, New Jersey manufacturing facility that makes Erbitux has closed.  That plant employed 140 manufacturing personnel who will now be eligible to bid for up to 90 jobs elsewhere in Imclone or take severance.

Lilly acquired Imclone in 2008 and announced plans to cut its global manufacturing workforce by 5000 by 2011 as it will be one of the companies hit harder by oncoming patent cliff. Coincidentally (perhaps), it had a monumental failure of its lead Alzheimer drug candidate, semagacestat, in Phase III and announced its abandonment yesterday.  Likely, a good strategy when the drug actually worsens the patinet's condition in a phase III trial.

5000 - 140 = 4860 to go.  And maybe more incentive to look closer at entering the Genzyme bidding?

Posted by Bruce Lehr August 19th 2010.

cGMP Cell Culture Manufacturing for Sale

 As shown in Fine, Genmab is offering its Brooklyn Park, MN cell culture manufacturing facility for sale.  The 215,000 sq ft facility was completed in 2004 at a cost of $200 M. It was designed to produce monoclonal anitbodies at commercial scale.

Posted by Bruce Lehr August 19th 2010.

SAFC's Verona CMO for HPAPI and ADC Manufacturing

 As evidenced by the Seattle Genetics and Genentech deal announced today, high potency active pharmaceutical ingredients (HPAPIs) and antibody drug conjugates (ADCs) are seen as important new technologies within the oncology fields.

The idea of targetting a cancer cell with a potent payload of toxin that hits the mark is a powerful new tool in the cancer fighting battle. It is also a means by which companies can take their naked antibody drugs and create a new drug with lengthened market life and improved effectiveness.

Recognizing the trends in this area for some time, SAFC has been a leader in manufacturing capability for high potent products.  We have had the Madison, WI site for a number of years and have just opened a new facility in Verona, WI that extends our capability for manufacturing HPAPIs or ADCs by using state of the art containment designs.

in-Pharma Technologist.com is hosting a video interview with Dave Bormett, the SAFC Director Operations for its new Verona site. Follow the link for an exclusive look inside the facility. 

Posted by Bruce Lehr August 3rd 2010.

 

 

 

 

 

 

Ireland Invests Pot O'Gold in Biotech Research Center

As reported in Fierce Biotech yesterday, Irish interests are considering building a $6 B pharmaceutical "center of excellence" in Tralee that could provide 4800 new jobs in R&D and manufacturing plus a slew of other jobs in management and academic positions.

The current plan calls for 30 campuses and creation of one of the world's largest R&D sites.  Work at the site could begin as early as 2012.  A final announcement as to whether this plan will be activated or not is expected within 3 months.

Posted by Bruce Lehr July 21st 2010.

More on J&J Costs from WSJ - Reputation and Revenue

Yesterday's WSJ health blog had more on the costs J&J is absorbing to its revenue column and to its reputation related to all the OTC recalls. The series of manufacturing issues at its Fort Washington plant,  and now expanding to other plants (Puerto Rico & Lancaster, PA), is expected to cost the company more than $600 M in 2010 revenues. Ouch!

Analysts asked CEO Dominic Caruso if the troubles would have spill over effects on the reputation of other J&J products.  He answered "it was too early to comment on that".  A further probe as to whether J&J would make management changes was met with No Comment.

You can hear the heads rolling about now.

Posted by Bruce Lehr July 21st 2010.

Real Costs of Quality Lapses at J&J

Here's a post from the NY Times Helath blog via the PharmaGossip blog. It details J&J's decision to layoff 75% of the workers in the J&J Fort Washington, PA plant responsible for producing a series of recalled children's and adults OTC medicines - including Tylenol, Benadryl, Motrin, and Zyrtec among others.

PharmaGossip: Tylenol Plant Lays Off 300 - Prescriptions Blog - NYTimes.com.

The recalls have not only resulted in economic loss to the Company in terms of sales of those products, the recalls have cost J&J dearly in terms of its reputation. Congressional investigators are still probing how J&J conducted itself during this so-called "phantom recall",  as J&J tried to pull back product from the distribution channel without informing consumers and regulators that there was a problem.  This type of ethical lapse has gone a long way toward undermining (destroying) the reputation of a company known for high ethical standards in its handling of the famour 1982 Tylenol crisis.

Now more than 300 workers in the Fort Washington plant pay with their jobs.  J&J indicates that it may never reopen this plant and it could close for good in early 2011.  The Pharmalot blog asks this morning if job losses should be confined only to these workers?  Or should the management Team at McNeil lose their jobs? 

Given the hundreds of millions in lost revenues, lost Company reputation, lost morale internally, and the closing of the facility with concommittent employee job loss - I think 'sauce for the goose' is appropriate.  Key management didn't do its job to produce a safe and effective product, and then tried to cover it up.  Why not share the pain at the top?

Posted by Bruce Lehr July 16th 2010.

Genzyme to Expand R&D & Manufacturing Facility

As reported in Fierce Biotech, Genzyme plans to build a 757,000 sq ft expansion in Framingham to its existing space, 400,000 ft of which will be new R&D space. The R&D time frame is slated between 2015 and 2018.  Genzyme will add 600 to manufacturing and another 400 employees to R&D by the time the expansion is completed. 

This is somewhat remarkable given that Henri Termeer was being ousted as President only last month by some observers' accounts.  Termeer seems to have recovered nicely and is on the "offensive" so to speak with not only these manufacturing & R&D plans, but with a large stock buy back, and plans to divest non-core parts of the business.  Genzyme also received good clinical news n several of its products. 

Quite a turn around in perception in just over a couple of months.

Posted by Bruce Lehr July 12th 2010.

Merck Closing Numerous R&D Facilities

Merck announced yesterday that it will be closing 8 R&D facilities.  This is parto fits planned initiative to save up to $3.5 B annually as a result of its purchase and megamerger of Schering-Plough. 

Merck Closing Numerous Labs & Manufacturing Sites // Pharmalot.

Ultimately, the company has stated it will layoff 15,000 workers.  Merck also has plans to close 14 manufacturing facilities since the merger reducing its worldwide total to 77 from the original 91 at the time of the purchase.

"These changes are crucial to drive future growth and realize the promise of being a global health care leader for the long term" said Merck CEO Richard Clark as reported in Fierce Biotech.

Once again, a megamerger really results in immediate loss of jobs as the company has to restructure to help pay for the merger which ironically provides some short term revenue relief but may not provide the boost out the the pipeline that is really needed.  Merck will still be pursuing many other outside collaborations to fill that pipeline - thus the R&D layoffs and manufactuirng closings.

Posted by Bruce Lehr July 9th 2010.

SAFC - New Cell Culture Raw Materials Centers of Excellence

SAFC is investing in the expansion of its manufacturing sites to support biopharmaceutical cell culture production in Lenexa, KS, St. Louis, MO, and Irvine Scotland - creating new Centers of Excellence. This is a $17.3 M program aimed at optimizing its global manufacturing footprint in the US and Europe.

The Lenexa site will be enhanced as the US Center of Excellence for dry powder medium manufacturing. This $6.25 M program, supported by a $250,000 grant from the Kansas Bioscience Authority, will include explanded pin milling and blending capability. The expansion will increase batch capacity by 30% and is slated to be complete by the end of 2010. It will also result in completely separate Animal Component Containing (ACC) and Animal Component Free (ACF) manufacturing spaces. Powder scale up will be seamless from 25 to 4000 Kg in pin milling technology.

Similarly, the St. Louis, MO and the Irvine, Scotland facilities will be augmented as the liquid media, feeds and reagents Centers of Excellence. The improvments will result in an additional ACF manufacturing space in Irvine, and both ACC and ACF dedicated spaces in the St. Louis Broadway facility. Batch capacities will range from 1L to 10,000L at both sites. These are also slated to have construction completed by the end of 2010 with qualification extending into the 1st Qtr of 2011.

"As the biopharm market continues to mature and place an increasing emphasis on efficiency, cost containment and increased regulatory compliance, SAFC will continue its strategy to invest in manufacturing capabilities and facilities that uniquely address these requirments," said SAFC President Gilles Cottier.

Posted by Bruce Lehr July 4th 2010.

Pharma Facilities Springing Up Like Weeds

Let's catch up on some of the new facilities announced in the Pharma industry the past couple weeks.

Fierce Biotech reports that Eisai will build a new R&D center in India.  It will be their first R&D building outside of Japan. The facility is budgeted at $50 M and will employ 100 focused on formulation development.

in-Pharma Technologist.com reports that Tanabe Reesearch Labs will open a new facility in San Diego.  The site will focus on mAbs and other biologicals aimed at autoimmune diseases - diabetes & RA. The new site is part of the parent's, Mitsubishi Tanabe Pharma, global R&D expansion plan which calls for aggressive in- and out-licensing in US and Europe.

That gives us stories in India and the US, now another from Europe.  Again, in-Pharma Technologist.com reports that Baxter will expand its European R&D operations into Belgium. Located in Alliance Park Braine l'Alleud, Belgium, the new facility will house scientists working onnew projects from "conception to registration". These will be plasma based therapeutics, vaccines and packaging and delivery systems.

Posted by Bruce Lehr June 28th 2010.

No BRIC Without Russia

Again, another post pulled from Ed Silverman's Pharmalot blog.  This one reminds us that the pharma market in Russia is every bit as active as those seen in India and China - perhaps more so - Russia is expecting 18% growth in 2010.

To Russia, With Drugs: The Russian Market Expands // Pharmalot.

What's more? A large number of MNCs have stated they are considering plans or are underway in building new manufacturing capacity in Russia. These include AZ, GSK, Novartis, Novo Nordisk, Nycomed, Pfizer and Servier with about $1 B in investment under consideration. The Russian government plans to spend another $4 B on local industry players to boot.

Za Vas!

Posted by Bruce Lehr June 22nd 2010.

DSM Cuts New CMO Deal With Aussie Government

DSM entered into a deal with the Australian government in Queensland to create a 70,000 sq ft CMO for mammalian cell culture.  The goverment will provide the funding and DSM will provide the design and technical expertise.

DSM will also make its XD and DSP optimization methods available to CMO clients.  DSM will also offer Crucell's Per.C6 cell line for use in recombinant protein and MAb production.

The facilty will come on line in 2013.  It is part of the Queensland Translational Research Institute (TRI) which is being scoped to provide discovery, production and clinical testing services at one site.

DSM says the new facility forms an important part of its overall CMO strategy.

Posted by Bruce Lehr May 3rd 2010.

Chas River Plots Fastest Way Through Pipeline - via China as the CRO Flies

 Charles River Laboratories, Wilmington, MA, announced yesterday that it was acquiring Shanghai-based Wuxi Apptec Tech for $1.6 B in cash and stock. This apparently represents the largest foreign takeover of a Chinese company.

Charles River, with $1.2 B in 2009 sales, will add $270 M in sales from Wuxi, 4000 employees, and over 1.8 M sq. ft. in lab space in China.  Wuxi also has 3 significant operations in Atlanta, Philadelphia and St. Paul, MN with R&D and manufacturing capability.

Chas River also picks up state-of-the-art, large animal testing capability, including monkeys, and gains access to testing facilities in Shanghai, Suzhou and Tianjin in China - where laboratory and labor costs are a bargain.

Jinsong Du, an analyst at Credit Suisse, states "This is a vote of confidence that China will be the main location for drug R&D outsourcing in the future." He also notes that Chas River gets to take out a competitor with this acquisition.

Because major new drugs may require 15 yrs of development time at a cost exceeding $1.5 B, a growing number of Big Pharma are trying to find ways to cut costs and speed development through the pipeline. Many are moving their research and development, manufacturing and clinical trial work to places like India and China due the current cost advantages.

"This transaction revolutionizes the contract research landscape by creating the only global contract research organization, or CRO, to fully offer integrated research and drug development services from molecule creation to first-in-human testing," said President & CEO James C. Foster of Charles River. Charles River can now offer services in the US, EU and China. Foster says "...many of our clients consider China to be the new frontier for drug development."

The deal likely couldn't come too soon for Charles River as they reported Qtr 1 earnings fell well short of expectations and were 22.4% below last year. Sales were down to $297.4 M in Qtr 1 2010 versus $301.5 M in Qtr 1 2009.

Financial details of the acquisition can be found here and were obtained from Charles River's website.

Download Charles_River_WuXi_Slide_Presentation

 

Posted by Bruce Lehr April 27th 2010

SAFC Moves Toward Excellence

SAFC provided (as reported in PBR) more details on its planned creation of a dry powder medium milling Center of Excellence in its Lenexa, KS facility.  The $6.25 M expansion will provide for 3 manufacturing lines standardized on its continuous milling (CM) technology - and the plant will have the ability to scale up from development to pilot through commercial scale. 

This is part of SAFC's global facility strategy that will reduce its number of cell culture manufacturing facilities from 5 to 3 and create new Centers of Excellence for liquid and dry powder medium manufacturing and deciated animal-containing (ACC) and animal component free (ACF) manufacturing zones.  Centers of Excellence will be created in Lenexa, KS; St. Louis, MO; and Irvine, Scotland.

Posted by Bruce Lehr April 27th 2010.  

Evonik Moves Into China API Facility

Evonik has partnered with a European pharmaceutical company to open a new 70 m³ manufacturing facility to produce APIs.  The new facility, located in Nanning, China,  can quickly double its capacity if required. Evonik's collaboration partner has contracted for API services over the next several years.  The plant will produce cGMP compliant amino acids and amino-acid derivatives. It is part of the Health & Nutrition business unit.

"The new plant is an expression of our horizontal integration strategy," said Hans-Josef Ritzert, an Evonik Business Head. The term "horizontal integration" stands for a network of western (Europe, NAFTA) and Asian production sites from which Evonik offers customers tailored and exclusive solutions along the entire value chain of active pharmaceutical ingredients. "With this plant we will further consolidate our position as a high performing partner for exclusive synthesis," added Ritzert.

This is another example of a raw material supplier to the pharma industry relocating a manufacturing site to the East - and specifically to China.  This, despite, certain reservations among many Western pharma & biotech company Quality departments concerning the sourcing or raw materials in China due to well documented series of quality lapses - some with deadly consequences. 

However, I believe that while - right now - some Companies are gun-shy of Chinese source raw materials that this will necessarily be a passing situation. It is nearly inconceivable to me that Eastern countries like China, India, etc. could be excluded from the supply chain for any lengthy period into the future.  These are rapidly growing economies that will have too much global impact to be excluded.  That also becomes increasingly undesirable as Western manufacturers continue to install plants in this region - clearly you will want to source from these areas for these local plants if for no other reason. 

The Region is here to stay and we need to work to get raise the bar more rapidly in areas where the quality standards are currently lax.  As opposed to excluding these groups from the supply chain altogether. 

Posted by Bruce Lehr April 21st 2010.

 

Map of India Bulk Drug Manufacturing and Formulation Sites

This is a link to an article on in-Pharma Technologist.com that shows the location and density of India's pharma sites for bulk manufacturing and formulation.

  
The sites are marked clearly on maps you can access through the link.  You can refer to above map if you'd like to correlate sites better to India's states.

Posted by Bruce Lehr April 21st 2010.  

Baxter is latest to Build Cytotoxics Manufacturing Capacity

The oncology market is projected to be one of the fastest growing segments in phamraceuticals.  New treatments for oncology increasing include the use of high-potent APIs and antibody-drug conjugates. 

Baxter BioPharma Solutions has announced (PBR) completion of its third expansion of its Halle, Germany manufacturing site. This course added 50% to its capacity for commercial cytotoxic manufacturing and also large scale lyophilization capability.   Their filling process uses cRABS(closed Restricted Access Barrier System) to enchance safety for operators and increase product sterility protection.

Baxter also added capability to do cytotoxic emulsions, liposomes and suspensions, along with a nanoparticle suite equipped with a high pressure homogenizer. The company feels it is now well positioned to support customer oncology projects from small scale development through commercial scale at one location.

If you have been paying attention, you will have notice a lot of market activity with regard to bringing on new capacity for the manufacture of high-potency cytotoxics and antibody drug conjugates.  SAFC has upgraded it facility in Madison, WI as well as opened new facilities in St. Louis and in Verona, WI.  Several companies in India have also brought on new capacity this year or begun new capacity construction.  Again, this speaks to the expected growth of the oncology space.

Posted by Bruce Lehr April 20th 2010.

Sanofi - Go East Young Man Go East!

 Sanofi-Aventis, as reported in the Shanghai Daily, launched its new R&D center in China yesterday.  The new center is intended to accelerate development of therapies for disease more prevalent in the region.

The R&D center in China is in addition to R&D operations that Sanofi has started in Russia, South Korea and India.  The multi-national drug company states that it expects that up to 33% of its sales income will come from emerging markets in the next few years.

Sanofi has a stated goal of becoming first multi-national to bring "home grown" research activities to market, and thus has plans to form strong partnerships with local players. The race in pharma and biotech continues to head East.

Posted by Bruce Lehr April 9, 2010

Isis Payday Funds New Digs?

As reported in Seeking Alpha, GSK will pay $35 M to Isis Pharmaceuticals plus potential license and milestone payments that could reach as high as $1.5 B. This will give GSK access to Isis' antisense drug discovery platform that GSK will apply to new therapeutics for rare diseases.

Isis could earn on average $20 M per project (6 projects) that reaches mid-stage proof of concept.  In addition to this deal, Isis also recieved  a milestone payment of $6 M from BMS this month for its cholesterol drug BMS-PCSK9Rx.

Isis announced today in Medical News that it has signed an agreement with BioMed Realty for a new 176,000 square foot facility in Carlsbad, CA that will be built to design specs for Isis. Isis will lease the facility for 20 years and plans to consolidate the majority of its operations in the new site. Isis also leases 28,700 square feet nearby from the same management company that is newly upgraded manufacturing space to support the launch of mipomersan.  Total leased space is 204,700 square feet.

Isis CEO, Dr. Stanley T. Crooke stated, "Working closely with BioMed Realty, we have been able to design a functional and efficient facility that will meet our needs for the near-term and for the future and our new facility remains close to our manufacturing suites...These capabilities greatly enhance our efforts as we transition toward further development and commercialization of our product pipeline."

Posted by Bruce Lehr April 5th 2010.

SAFC Opens New Verona High Potency API Facility

Last week SAFC held a ribbon cutting ceremony for its new $30 M, 51,000 sq. ft. facility in Verona, WI for the manufacure of high potency active pharmaceutical ingredients. This link will take you to the press coverage of the event with Jim Doyle, Governor of Wisconsin doing the ribbon-cutting honors.

 

Posted by Bruce Lehr April 5th 2010