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Re-Posted by Bruce Lehr July 14th 2010.

SOCMA Quality Agreement Guidance for Foreign CMOs

A couple weeks ago, I posted about a recent HHS report on the increasing number of foreign clinical trials that received no FDA oversight.  The HHS report found that 80% of all drugs approved in the US in 2008 relied on some foreign trial data, 78% of all study enrollees were at foreign sites, and 10 new drugs had no US derived data at all. Some members of Congress and others consider that to be a dangerous situation.

A similar situation unfolds when you look at the manufacture of active pharmaceutical ingredients (APIs) made in foreign facilities.  According to the SOCMA website, many of these are rarely inspected by the FDA, especially in the case of ingredients going into OTC drugs.  The majority of foreign facililties manufacturing APIs used in generics rarely see an FDA inspector after the initial inspection. 

To help address the situation, SOCMA created the Bulk Pharmaceuticals Task Force (BPTF) to provide guidance to companies seeking foreign outsourcing partners.  The BPTF several months ago put together a standardized quality agreement for general manufacturers of APIs.  Now, the BPTF announced that it has put together a very similar quality agreement for CMOs and its customers.

BPTF Chairman Brant Zell of Cherokee Pharmaceuticals LLC says, "With today's supply chain issuesand the potential for misunderstandings in a global environment, a quality agreement is the best way to ensure compliance and meet FDA's expectations and filing requirments."

See Quality Template - Download Final-Quality-Agreement-Custom-Template-7-6-10-clean-protected

It is good to see that people, companies, organizations and even governments are now playing closer attention to the integrity of the supply chain. BPTF's role is very valuable in seeking to clarify the current regulatory requirements and to interact with government agencies on emerging issues that impact its members and the public.

Documents like the template rely on the collective wisdom of BTPF members and serve to standardize and educate users on drafting appropriate quality documents for their situation.  Hopefully this guidance also helps streamline the process for the industry.

Posted by Bruce Lehr July 7th 2010.  

CMC Icos Bounces Back from the Economic Downturn

A story in Xconomy reports that CMC ICOS has bounced back from the economic downturn.  The company experienced 90% growth last year over prior year results and reached breakeven.  Now it is running at 85% capacity and has begun hiring once more - up from 130 to 175 in past year.

CMC Icos Mounts Comeback, Resumes Hiring, After Pausing During the Downturn.

CMC-ICOS says it has stable customer base of 8-10 clients currently. The CMO focuses on mid-size projects and clients not trying to compete head to head with the likes of Boehringer Ingelheim or Lonza.

Right now the company is making product for use in clinical trials exclusively and has no products that have reached commercial stages of approval. The goal is to make that transition in the next 12 months.

The company tries to compete by being nimble and responding very rapidly to customer needs.

"We're gaining market share, things are picking up," said President Gustavo Mahler.

Contract manufacturing sector growing at 12 per cent

The global contract manufacturing market was worth $22.5bn (€18.9bn) at the end of 2009, according to new research from RNCOS which also predicts a 12 per cent growth rate through to 2012.

Contract manufacturing sector growing at 12 per cent, report.

The report reinforces predictions that contract manufacturing services will increasingly shift to China, India or Brazil driven by continued cost reduction efforts from large pharma.

Posted by Bruce Lehr July 5th 2010.

FDA To Get Tough On Outsourced Drugmaking

The Wall Street Journal via the Pharmalot blog reports that the FDA may soon require pharma companies to do more on site audits with their outsourcing partners.  This comes on the heels of several celebrated quality incidents with crtical raw materials manufactured in China in 2009-2010 -- but this regulatory edict is expected to apply to outsourcing partners in any geography.

FDA To Get Tough On Outsourced Drugmaking // Pharmalot.

The Rx-360 Audit sharing program, described in a previous post, would seem to be a perfect concept for supporting this regulation. As a reminder, the Rx-360 program will enable members from both pharmaceutical and supplier side to share audit results from more than 30 suppliers from various geographic regions - North America, Europe, India and China. 

Here's the FDA presentation on this topic. Download Fda ppt drug quality

Posted by Bruce Lehr June 17th 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.

Counting CRO's in China - One Upsmanship!

No sooner did Charles River report of its $1.6 B deal to acquire Wuxi Apptec's CRO business hit the street, PPD announced the opening of its new vaccine research center and claimed title of biggest CRO in China.  See Fierce Biotech.

PPD opened its center in Taizhou China Medical City to enable it to conduct the world's largest vaccine trials but with shortened recruitment times due to easy access to study participants. The new center supports the fast growing vaccine market (> 20% CAGR).

Simon Britton, PPD's VP of clinical development for Asia Pacific, stated "Our strong expertise in vaccine clinical research and large presence in China make us well positoned to help our clients ensure adherence to global standards while addressing unique requirements for monitoring vaccine studies"

That's a lot of investment, and a lot of CRO activity in China for this week - or any week.  But, as explained in FierceBiotech's story on China's CRO appeal, China's local authorities are willing to aggresively work with new businesses to meet their needs and make it happen.  This according to Charles Rivers outgoing Chris Perkins.

China is less expensive to build in, has large, less expensive talent pools, far less expensive animal models, and regulators who want to help business. They also don't have any animal rights activists to harry labs and perhaps drive them underground as has happened in EU & US.

That's a number of good reasons for Big Pharma companies to do business with CRO's located in China - but who's counting.

Posted by Bruce Lehr April 28th 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

New SAFC Corporate Video

Below is the new corporate SAFC video highlighting our capabilities to serve regulated industrial markets - including food, pharma, biopharm, and high technology applications. It is a good, short overview (< 4 min) and can be accessed on Brainshark.

 

Posted by Bruce Lehr March 21st 2010 

Tour SAFC Virus and Vaccine Manufacturing Plant

Our Carlsbad manufacturing facility has just completed a $12 M expansion of the plant.  This CMO is focused on the production of virus and vaccines - particularly in support of gene therapy applications. We work with both modified HEK  293 and Per.C6 cell platforms for example. Facility services range from cell banking through virus production and complete fill/finish. 

This web video gives you the opportunity to tour the facility in abstentia.  It highlights key staff.  I like the fact that the video production values are high, but not overly flashy from a marketing viewpoint.  Also, these are our actual staff members speaking about their areas of responsibility in an unscripted fashion.  In that sense, it lends a good deal of authenticity to the tour.

I'd love to hear your comments after viewing.

  

Posted by Bruce Lehr March 21st 2010.

CRAM Outsourcing to India - Zoom, Zoom, Zoom

The current market size for the pharma CRAM (contract research and manufacturing) business in India has been estimated to be $1.2 B, with an expectation that this will increase to more than $5 B in the next 5 years. Indian CRAM providers like Dr. Reddy, Nicholas Piramal, and Dishman have expressed that they are well positioned for this upsurge as India has good infrastructure and quality --- and lower cost structures which are attractive to pharma MNCs. 

  
  
 Outsourcing Pharma reports that Indian generic drug maker Aurobindo Pharma will also enter this segment with its new CRAM businesss. AuroSource.  The new division will provide API development in 6 facilities across India and sport an R&D facility in Pashamylaram near the Hyderabad pharma/biotech hub.

Posted by Bruce Lehr March 8th 2010

ADC Manufacturing

As discussed a few days ago, antibody drug conjugates are seen as perhaps the next wave of advanced therapies for the treatment of many cancers - especially those resistant to current therapies. An ADC of course is an antibody linked to a cytotoxic small molecule.  To deliver enough killing power to a cancer cell, this molecules have to be very toxic and are termed high-potent APIs (HPAPIs).  Often cytotoxic or neurotoxic, HPAPIs need to be managed with the highest level of containment.

Recognizing that there was a market need for HPAPI manufacturing for ADCs and other applications, and that HPAPI manufacture fit with our history of chemistry capability, SAFC has added or is in process of adding a couple new facilities to serve this application, representing a total investment of more than $75M.  This is in addition to our original standout facility in Madison, WI that has been SafeBridge Certified since 2003 - which was augmented with a cGMP kilo lab and pilot facility in 2008.

In September of 2008, we added a 600 ft² suite in St. Louis and that was SafeBridge certified in June of last year, specifically to support ADC manufacturing.

The newest addition to the family is on its way.  A new 45,000 sq. ft facility that meets Category IV standards is expected to come on line this year in Verona, WI close to the Madison facility. This facility includes development labs, a 150 liter mini-processing plant and two large scale cGMP manufacturing suites featuring reactors up to 4000 L.  The facility has been built to support market demand for large scale HPAPI production capacity while meeting the highest quality standards.  The demand in oncology is driving ADCs and this market is expected to grow at CAGR of 15 percent over next several years as compared with 4.5-5% for the rest of the pharma market.

 

Posted by Bruce Lehr March 4th 2010

Antibody Drug Conjugate (ADC) Production and Cancer

Yesterday, GEN published a nice article on antibody drug conjugates (ADC) and their increasing use in cancer therapy. The article used anti-CD30 antibodies coupled to monomethyl auristatin E as one such example.  This ADC by Seattle Genetic's also known as brentuximab vedotin can be used to treat patients with Hodgkins lymphoma (note: NOT non-Hodgkins B-cell lymphoma), various T-cell lymphoma's and some other hematologic-derived cancers - all of which express the CD30 antigen.  PharmTech also did a nice article (2007) summarizing this area as well as outlining a number of the major pharma players active with ADC programs.

The ADC concept allows the clinician to very specifically target cancer cells that express antigens not  expressed by normal tissues and to couple the cytotoxic reagent to the antibody providing this exquisite targetting.  Thus, a chemotherapeutic payload can be delivered specifically to a cancer cell.  This has been particularly useful to many patients who have not responded to other more traditional radiation or chemotherapy regimes in clinical trials to date.

Another example of the ADC concept is Roche's (Genentech) TDM1 therapy - a Herceptin antibody coupled to a chemotherapy agent. TDM1 has had success in clinical with women who have Her-2 positive breast cancer and who have not responded to other chemotherapy regimes.  In a recent study, these women may have seen as many as 7 chemotherapeutic agents prior to their ADC treatment.

Thus ADC's are seen as a new generation of therapeutic compound that can be used to provide the next round of anti-cancer therapies.

 

Challenges Creating ADCs

One of the challenges in creating ADC's is the need to provide the linker chemistry that gives the ADC complex stability in the bloodstream yet allows release of the chemotherapeutic payload at the target cancer cell.  This must also be done in a way that you do not adversely impact the antibody's binding capability or its ability to be internalized to deliver a drug payload. Once it is internalized, the ADC has to release the chemotherapeutic agent to be effective.  See recent review article.

You need good chemistry to create ADCs.  The SAFC Pharma group has developed the conjugation chemstry necessary to allow us to conjugate biological molecules (including antibodies) to high-potent APIs (HPAPI) to meet pharmaceutical industry demands. We have been providing this type of expertise for more than 15 years and can now support manufacturing of ADCs from pre-clinical to commercial scale. See our website for more on Bioconjugation.

My next post will continue this discussion and highlight new SAFC facilities for manufacture of HPAPIs and ADCs. 

 

Posted by Bruce Lehr March 3, 2010

Facility News - Kemwell Partners with BI in India

As reported in PBR, Kemwell will build a new biopharmaceutical manufacturing facility in India.  They will be in partnership with Boehringer Ingelheim (BI).  Kemwell will be able to tap into BI's cell engineering services and their BI-Hex expression system for its clients. Their clients will also receive preferred status for scale up within the BI facilities in Europe for later stage manufacturing.  The Kemwell facility will mirror BI upstream and downstream processes in its design and build out. The partners indicate that clients will receive "european technology at Indian prices". 

Posted by Bruce Lehr Feb 26, 2010.

WWCED: What Would Cell Engineering Do?

If you had the zinc finger nuclease (ZFN) reagents in your hands right now to allow you to knock out – dhfr, GS, fut8, neu3, bax/bak, lactate dehydrogenase A (LDHA), or RACK 1?  What would you do?  You can directly affect selection, fucosylation, sialylation, apoptosis, waste product production – either alone or in combination (so-called trait stacking). 

 

If you could do it, what genes would you want to manipulate?  And what combinations would be interesting for your system and proteins of interest? 

 

I’d like to get some feedback.  It would be great if this could be discussed on the blog, but would even like private feedback if musts be (as my UK colleagues say). 

 

These are the type of questions that we are pondering.  And, we’re looking for market confirmation as well as potentially collaborators who might want to look at these – or even other genes of interest 

Let’s hear from you out there.

 

Posted by Bruce Lehr February 4, 2010

Cool CMO Site

I came across this cool site called CMO Locator by Kymanox.  It allows you to find CMOs among its registrants who have the capabilities that you are looking for to execute your project.  For example you might designate a need for a CMO that can meet following needs -  mfg drug substance API, platform cell culture, scale 2000-5000 L, fed-batch process, phase I/II compliance, biosafety level 3. 

The tool will spit out a list of CMOs matching those criteria.

Posted by Bruce Lehr January 31, 2010