The Big Red Biotech Blog

Ooooh! This isn't Good for US Manufacturing Economy

Here's a sobering report from Xconomy on a new study out of MIT.  In it, MIT researchers claim that US manufacturers (150 in study from diverse industries) hit problems when they go to scale operations at full commercial level.  This leads them to seek foreign investors and set up foreign facilities. Wave bye-bye to some good jobs.

That's not good and is why there is beginning to be more clamoring for manufacturing supports in the US (i.e. tax credits and the like).  It would be nice to have the manufacturing base remain strong (US is still No. 1) bu there is a trend toward moving to Asia and other sites abroad. We need to nip it.

Posted by Bruce Lehr Feb 28th 2013.

 

 

GAO Report Places Primary Blame on Manufacturing Failures for Drug Shortages

New supplies of two unavailable cancer drugs will be allowed by the FDA.

Dow Jones Newswires(DJN) reports that the FDA will allow the temporary importation of Lipodox as a substitute for Johnson & Johnson’s Doxil. The drugs have the same active ingredient.  Doxil has been in short supply since about mid-2011. New supplies of Lipodox are “expected to end the shortage and fully meet patient needs in the coming weeks,” the FDA says.

The FDA has also approved a new manufacturer, APP Pharmaceuticals, of preservative-free methotrexate, a drug that is used to treat a type of children’s leukemia and has also been in short supply. The drug should be available in March.  The agency “is actively working with other manufacturers … including Mylan and Sandoz Pharmaceuticals” to meet patient needs.

DJN notes that both shortages can be traced back to the closing of a Ben Venue Laboratories plant in Ohio. Ben Venue, a unit of Boehringer Ingelheim, shut down the plant to deal with manufacturing issues. See here.

The GAO just issued a report that stated the majority of drug shortages now being seen were due to manufacturing problems. See WSJ article. 

While the Pharmalot blog reports that more than two dozen patients who suffered due to drug shortages filed a lawsuit today in DC federal court against the US Dept of Health and Human Services (DHHS), the FDA, and NIH.  The suit argues that FDA licenses to drugmakers that cuase shortages should be invalidated and their patents declared unenforceable (how did they miss the patent office in suit too?).

The poster boy for this suit is Genzyme with its celebrated manufacturing issues at the Allston plant which caused repeated delays in the supply of both Cerezyme and Fabrazyme (which is still not back to normal).

Posted by Bruce Lehr Feb 21st 2012.

 

 

Genzyme Stumbles Again. This Time It's Cerezyme

Genzyme is at it again. After last month's letter to Fabry patients alerting them that they would not be able to get ample supplies of Fabrazyme, Genzyme is now forced to tell Gaucher's patients that they will need to ration Cerezyme for the treatment of that disease.

Genzyme Stumbles Again: New Cerezyme Problems // Pharmalot.

This just continues the multi-year saga of being unable to supply ample amounts of either drug consistently due to persistent manufacturing and quality problems -- primarily at its Allston manufacturing facility.  Genezyme now appears to be pinning its hopes on the opening of its new Framingham facility in Qtr 1 2012 -- though up to now the Company has not been too reliable with time estimates.

Analysts report that this may be another opportunity for a competitor to come in and steal share (Shire already encroaches on Fabrazyme with its Replagel).  Protalix BioTherapeutics is going to the FDA with its taliglucerase to compete with Cerezyme -- and all the quality issues may make the former's case for approval that more compelling.

With all the product supply problems - Genzyme is bringing new meaning to the term Orphan and Neglected Diseases.

 

Posted by Bruce Lehr Sep 16th 2011.

Genzyme Too Little Too Late with Fabrazyme

Genzyme again has had to admit that it won't be able to supply Fabrazyme in August and September to Fabry's patients in desperate need.  This time the Company has issued an apology but still can't say when it will be able to return to full scale production and supply.  Thus continues a two-year saga of disappointment.

Genzyme Apologizes For Fabrazyme Screw Up // Pharmalot.

Genzyme may be sincerely sorry -- but I feel really sorry for the patients waiting on their life saving drugs -- some of whom are in dire need. I don't know how the competitive Shire product, Replagal, can NOT be made available under such circumstances. 

 

Posted by Bruce Lehr Sep 8th 2011.

Contract Manufacturing Will Explode for Pharma

In a new report, Visiongain says contract manufacturing in the pharma industry will hit $64 billion by 2016 and more than double in the next 10 years. The manufacturing of final dosage forms is expected to grow fastest (CAGR 8.7%) - though making APIs still constitutes more than 71% of the total market.

US companies currently enjoy a 42% masrket share of contract manufacturing business, but this is expected to change as India and China are increasingly, successfully competing in this segment. The Asia and Pacific region is expected to grow by 9.6% annually over the next 5 years compared to an overall market rate of 6.7%. 

While these emerging regions are expected to grow more rapidly in the next 5-10 years, analysts also expect that costs of labor and raw materials will rise over time dampening the rate of future growth.  Markets can be expected to level out to a greater degree as the industry establishes its global footprint. See Pharmalot.

Posted by Bruce Lehr Aug 23rd 2011.

 

Will biosimilars really have an impact on capacity?

Here's an interesting point of view from The Bioprocess Blog where they weigh in on the question of whether or not biosimilars will have any impact on the worldwide need for biological manufacturing capacity.  Short version: they conclude they will not have a significant impact.

Will biosimilars really have an impact on capacity?.

I don't really agree with their reasoning. I think when yo ufocus on the current pipeline and use it as a surrogate for what will happen you aren't properly viewing success rates.  In the current pipeline you end up with lots of failures from the novel drug candidates.  But with biosimilars, you should see much higher success rates in development as the targets are proven. 

Secondly, the authors focus on the impact of biosimilars that have hit Europe to date -- mainly molecules like EPO and hgh.  I think this neglects all the mAbs that we should be seeing soon and I think those will have a higher impact on manufacturing needs. 

Thirdly, the discussion seems to be centered on what is happening (or not) in Europe and the US.  The post was ostensibly about "worldwide biological manufacturing" capacity.  If so, there should be much more attention paid to what will happen as biosimilars start coming on line in China, India, Korea, etc.  I don't think the EU model will be a very good surrogate for what will happen in those local markets when local producers start bringing their drugs to market. 

So I respectfully disagree with the authors conclusions. I think the new players in the new economies will have a much bigger impact and represent a much larger opportunity.

Posted by Bruce Lehr July 26th 2011.

 

SAFC Launches CHOZN ZFN-Modified CHO Cell Lines for Bioproduction

SAFC today launched the first of its new offering of zinc finger nuclease (ZFN) modified CHO cell lines for use in production of biological drugs. The CHOZN cell lines have been designed to allow customers to reach the market faster and more cost effectively by reducing timelines in early-stage drug development. The features embodied in the lines should appeal to organizations trying to build a robust and comprehensive monoclonal antibody or therapeutic protein platform.

The first cell line to be introduced is the CHOZN DHFR-/- CHO line.  The line was developed with the use of the CompoZn ZFM mediated knock out of the DHFR gene locus in a well-documented CHO-K1 host.  The new line allows process development scientists to use any common DHFR expression system for the selection and amplification of their gene of interest in the CHO-K1 background.

SAFC is planning to introduce a CHOZN GS -/- CHO line next followed by a complete platform system based on the CHOZN GS -/- cell line matched to chemically-defined media and feeds and protocols allowing one to go from DNA to bioreactor harvest for the biological protein of interest.  Pharma companies like - Pfizer and Lilly - have reported savings of 8-9 weeks during clone development and selection using similarly ZFN-engineered CHO-K1 cells altered at the GS locus.

See www.safcglobal.com/chozn for more technical and application information.

 

Posted by Bruce Lehr July 7th 2011.

Survey Says "Improve Downstream Processing"

BioPlan Associates just reported results of its 8th annual Survey of Biopharmaceutical Manufacturing Capacity and Production -- a summary of which appeared in July's GEN Vol. 31 No. 13, page 1. The number one issue cited by the 352 respondents as needing more attention was bottlenecks in downstream processing.

Due to the rapid increases in titer being achieved in upstream processes -- through improved expression systems, better cell lines, more optimized media/feeds, and more efficient bioreactors -- many are producing more product than the downstream processes were designed to handle. A total of 68.5% of respondents said that their facility was experiencing at least some bottleneck due to downstream issues -- with a historic survey high of 11.8% characterizing these as serious (up from 4.6% in 2008).  Respondents further indicated they were goign to spend more money to try to solve the issues with budgets for downstream work projected to increase by 6.4% in 2011. 

Technologies that were identified as important to downstream improvements included high-capacity resins, in-line buffer dilution systems, single use filters, and disposable UF systems.  Additionally, several platform level technological improvements were identified by companies as areas they were investigating, including:

• simulated moving bed chromatography
• improved resins that were cheaper, faster-flowing, more selective, and have higher bindng capacities
• novel separation methods like chromatography monoliths
• alternatives to protein A
• disposable protein A columns for mAb purification
• improved depth filters, ultrafiltration and membrane filters to replace columns
• more product-customized affinity purification media
• improved modeling of separation at the molecular and process level

The burden of improvement has clearly shifted downstream for the next phase of biopharmaceutical production optimization.  Downstream is now challenged to meet the improvements achieved upstream over the past 5-10 years to bring the system more into balance.

 

 

 

Posted by Bruce Lehr July 5th 2011.

  

Genzyme Has More Fabrazyme Production Problems

Genzyme says it will be short of supply with Fabrazyme again due to a lot failure in fill and finish.  This continues the problems the manufacturer has had with this product for more than 2 years.  Genzyme is still under an FDA consent decree due to its past failures in manufacturing Fabrazyme (and other products) at its troubled Allston facility.

Genzyme Has More Fabrazyme Production Problems // Pharmalot.

The latest setback will cause the company to change its distribution plan and many patients will need to take less than their normal dose (if they even remember what their normal dose is anymore) or skip a dose. Genzyme says it will still be able to remedy the situation in the second half of 2011 -- is that July 1st or December 31st?

Genzyme's celebrated manufacturing problems in the past lead to shareholder and patient unrest which arguably allowed Sanofi to enter the picture and buy the troubled company.  As part of that deal, Sanofi issued contingent value rights (CVRs) based on Genzyme being able to hit certain manufacturing milestones with products like Fabrazyme and Cerezyme, as well as achieving clinical milestones with its late stage product for MS. 

A failure to meet the Fabrazyme unit production level of 79,000 units will result in the forfeit of $1 per share CVR.  Genzyme says it will still have no problem achievng this milestone.  It is expecting its new Framingham plant to come on line later this year but says it can even hit the milestone if Framingham doesn't materialize.  In the meantime, Genzyme will shift more of its fill and finish work to its contractor, Hospira, in Europe.

It has to be noted though -- that continued problems like this open the door for Shire to gain more of a foothold for its competitive Fabry's disease product known as Replagel.  At present, Replagel is NOT FDA approved and can only be taken [legally] in the US under a special protocol from FDA.  Shire however now plans to file with the FDA.

 

 

Posted by Bruce Lehr March 26th 2011.

CEO: Sanofi may provide Genzyme with fill/finish long term

Sanofi's CEO, Chris Veihbacher, said that the parent corporation may look to provide fill/finsh capability to Genzyme following the completed acquisition.  He stressed, however, that any such move woudl be further in the future as Sanofi will concentrate on executing Genzyme's existing manufacturing recovery plan following the deal close.

CEO: Sanofi may provide Genzyme with fill/finish long term.

So for the near term, Hospira can rest soundly on the knowledge that it will continue to provide fill/finish services for Cerezyme and Fabrazyme until supplies can be built and stabilized.  Over the past two years, both these drugs have been plagued by supply issues due to problems at Genzyme's Allston manufacturing site - which is still operating under FDA oversight as part of the consent decree.

Posted by Bruce Lehr Feb 17th 2011.

A Closer Look at the Capacity Glut

This interesting post from the BioProcess Blog examines the worldwide capacity for mammalian cell culture based manufacturing.  It notes recent studies have concluded there is a worldwide excess.  But, in looking deeper one really needs to examine the 10 companies that control 80% of the world's capacity. 

A Closer Look at the Capacity Glut.

Due to mega-merger activity, some capacity is being retired (or mothballed) as the merged firms rationalize their internal production.  Examples would include Pfizer's shutting down capacity in Pearl River due to the Wyeth acquisition, and Roche's closing manufacturing in Nutley and mothballing Vacaville-2 near SF.  Lilly is also closing one Erbitux plant (BB-36) due to its age. These reduce "world" supply but clearly are not needed by the companies shuttering them to produce their planned production.

A few new CMO facilities are slated to be coming on line - namely DSM's Australian facility in 2013 and CMC's expanded Seattle site.  BI also announced last month that it will be taking over the Fremont manufacturing site from Amgen. There is some suggestion in this activity that CMO capacity needs to ramp up and that is further bolstered by Lonza's earnings report showing its capacity utilization is up.

The blog notes that 10 new products have progressed to phase II in the past few months and 50% will go to CMOs.  This includes GSK utilizing Lonza to make 5 of its new antibody drugs. So with the growth on the CMO side, will that specific capacity be enough to serve the market's needs or will CMO space be scarce resulting in price competition between clients to secure needed space?  We'll need to watch in the next few years.

Posted by Bruce Lehr Feb 15th 2011.

Informex 2011: Tracking the Fortunes of Chemically Synthesized APIs

This article from the PharmaTech Talk blog comes to us from this year's Informex meeting in Charlotte, NC. It summarizes the pressures faced by US small molecule API manufacturers in a rapidly competitive and shifting environment.

PharmTech Talk » Informex 2011: Tracking the Fortunes of Chemically Synthesized APIs.

The gist?  Big Pharma is increasingly consolidating its vendor base.  It is looking to outsource more of its operations to gain flexibility. It is looking to both cut costs and to access emerging markets -- and can do so in one fell swoop by establishing more relationships with manufacturers in places like India and China.

Couple this with the issues Big Pharma is having with its dwindling pipeline, patent cliffs and recognition that large molecules, rather than small , are the more vigorous growth engines of the future -- you have a strong movement toward non-US API manufacturers.

Again, this is another reason, the US goverment needs to get behind our biotech industry to maintain its growth and prosperity so we can further develop a sustainable leadership position.  There are not that many industries where we still have clear leadership and it would be a monstrous mistake to let this one go too.

Posted by Bruce Lehr Feb 8th 2011.

Generics Companies Eyeball World Biologics Market

The WSJ  gives a good recap of the major generic producers and analysts views of the relative attractiveness of the emerging biosimilars market. World-wide sales of all biological drugs reached $130 billion in 2009, according IMS Health, and are expected to grow much faster than conventional drugs. The market is considered attractive due to the large number of big biologics coming off patent but is challenging from a regulatory/quality perspective to mimic the reference biologic - and pricing is uncertain at the moment.

In the U.S. and European market , biologics drugs with more than $60 billion in annual sales will lose patent protection by 2015, according to Datamonitor. Should the market develop as predicted,  biosimilar copies of these complex drugs alone could make up 50% of the expected $10 billion biosimilars market by 2016, according to Capgemini Consulting. The rest will come from simpler biosimilars of insulin and human growth hormone.

Patents due to expire soon are Roche's Rituxan (aka MabThera),  Remicade, co-marketed by Merck and J&J, and Amgen's and Pfizer's Enbrel. Each drug had more than $5 billion in annual peak sales.  Roche's Rituxan will expire in Europe in 2014.  Three generic players have started copies - Sandoz started midstage trials, following similar steps by U.S.-based Spectrum Pharmaceuticals, in early January and Israel-based Teva Pharmaceuticals last year.

Sandoz, with a roughly 50% market share, ahead of Teva and U.S.-based Hospira, expects the entire biosimilars business could reach more than $20 billion by 2020, up from a current $250 million.  Lonza, teaming up with Teva in its biosimilars venture, expects solid growth because patients, insurance companies and governments want drugs to be cheaper.

The generics companies base their argument on the high price of many complex biological medicines.  But some experts question the generics companies' pricing rationale, saying the current constraints could even force larger generic producers such as Sandoz or Teva to rethink their operating models. Much will depend on how the price of these drugs will develop. 

Prices for biosimilars could be just 30% lower than the prices of the originals, because only a couple of generics firms will compete against an original drug.  The main risk, analysts say, is that if prices don't come down much, original drug producers will be able to retain a large market share. On the other hand, if prices fall too fast, generics firms' margins could suffer.

Industry insiders are also concerned the market may need longer than expected to establish itself, as R&D for these complex drugs is difficult and costly. One of the difficulties with biosimilar of complex biological drugs is that, unlike simple-to-produce chemical generics, which are identical to the originator product, biosimilars aren't exact copies. The are produced in genetically engineered cells.  At best, a biosimilar can only be similar to the original protein - thus the name.  And, because biosimilars aren't identical copies, biotech and big pharma are looking to check the movement by raising bioequivalence and quality-control issues. 

The EMA has so far approved 13 simpler biosimilar drugs. In the U.S., the FDA is currently working to establish how intensive testing for biosimilars needs to be and how the traditional three-phase drug-approval process can be abbreviated. A key concern is to make sure that biosimilar drugs are safe and effective.

It may cost too much time and money for a number of small to midsized generics manufacturers to survive in biosimilars production.  Specific processes, data, research and experience are needed to ensure that a biosimilar has the same profile, efficacy and safety as the originator product.  Some doctors and patients may be reluctant to use biosimilars as a new class of products with no track record in terms of safety and benefits.

Time will tell.  In the meantime, the Big 3 Generics producers and many other Big Pharma companies are not only eye-balling this market but have announced their intentions to enter.  Not too mention all the Asia Pacific competitors who are gearing up to serve local and global markets.

 

 

 

Posted by Bruce Lehr Jan 31st 2011.

Challenges And Changes in Vaccine Manufacture

Here's a post in the PharmaTech Talk blog that covers a presentation given by my colleague Hikmat Bushnaq-Jostings,Technical Manager at SAFC.  The talk addresses changes in the manufacturing of vaccines - particularly pandemic vaccines - and some of the associated challenges. 

PharmTech Talk » Challenges And Changes in Vaccine Manufacture.

In general, we are beginning to see manufacturers begin to switch from non-cell culture based methods, e.g. eggs, to cell culture based manufacturing utiilizing chemically-defined media and feeds, along with use of new adjuvants in final dose forms. Change may be slower than we'd like sometimes due to economic or regulatory hurdles but it seems to be steady in its progress.

 

 

Posted by Bruce Lehr Jan 28th 2011.

 

 

Genzyme Builds new Myozyme/Lumizyme Plant in Belgium

Genzynme will spend Eu 250 M on a new manufacturing plant for its Pompe's disease drugs Myozyme and Lumizyme.  The plant will be located in Geel, Belgium and the company expects commercial regulatory approval of the site to be secured by 2014.

Genzyme to build New €250M Myozyme/Lumizyme Production Plant in Belgium.

The new Geel plant will have a maximum batch production capacity of 8000L and the existing Geel plant will add a thrid 12,000 L bioreactor. The expansion is meant to provide more capacity and better risk management for Genzyme. In recent years, the company has experienced well documented manufacturing failures (and is currently under a FDA consent  decree as a result) that have led to global drug shortages of its orphan products. 

Lumizyme and Myozyme are the only approved therapies for Pompe's disease at present.  Genzyme services more than 1400 of the estimated 10,000 patients with these afflctions. The commercial potential of these Pompe's disease drugs are expected to rival its best-selling Cerezyme for the treatment of Gaucher's disease. Genzyme is projects sales growth in excess of 30% with these products - especially if supplies are available for the full year in 2011. Sales wereup 39% ($128 M total) in the 4th quarter of 2010.

 

Posted by Bruce Lehr January 20th 2011.

Novartis strikes deal to build Russian drug manufacturing plant

Novartis announced it has signed a Memorandum of Understanding with St. Petersburg, Russia to build a new $500 M pharmaceutical manufacturing plant.  It is part of the company's plan to invest more heavily in the important Russian emerging market. The MOU addresses a 5-yr partnership fo local manufacturing, R&D partnerships and public health development.

Novartis strikes Russian allegiance; builds manufacturing plant.

Construction is expected to be completed in 2011. The plant will make both branded drugs and generics to serve initially the Russian domestic market but ultimately other markets outside of Russia. Novartis further plans to partner on R&D projects with Russian companies and Universities - as well as in-license and out-license products.

Said a Novartis spokesman, "With its increasing commitment to and demand for better healthcare, the Russian government is well suited to partner with Novartis to address their healthcare priorities and improve healthcare outcomes."

 

 

 

Posted by Bruce Lehr December 21st 2010.

SAFC and SartoriusStedim Biotech New Mixing Application Guides

 

As part of the collaboration between SAFC and SartoriusStedim Biotech (SSB), the companies have worked to produce application guides showing rapid and scalable preparation of powdered media and buffers with single-use magnetic mixing systems and the LevMixer^R technology.

For media, batch sizes ranged from 50 L to 1000 L and utilized SAFC's Ex-Cell^TM CHO Fusion and Ex-Cell^TM EBx^R GRO-I formulations. For buffers, sodium citrate, PBS and Tris were used in tests in batch sizes from 50 L to 1000L at various transient concentrations of powders (16 g/L, 73 g/L, 224 g/L) before final dilution. The purpose of the study is to assess the performance of the Flexel^R for Magnetic Mixer technology or the LevMixer^R to dissolve the test powders.

In this study mixing time to achieve complete product dissolution was determined both by visual inspection and by conductivity measurements.  In the case of the media, conductivity measures to determine when the product was completely dissolved is a novel application. Complete study details and results are contained in the reports below.

The study concluded that large volumes of media and buffer solutions were easy to prepare using the combination of SAFC product and the high efficiency mixing provided by the Flexel with Magnetic Mixer technology or LevMixer technology.

Download SAFC SSB Media prep with Magnetic Mixer

Download SAFC SSB buffer preparation single use magnetic mixer

Download SAFC SSB buffer preparation with LevMixer

  

 

 

Posted by Bruce Lehr December 19th 2010.

 

Putin More Emphasis on Russian Made Drugs

Outsourcing.Pharma.com reports that Vladimir Putin has charged Russian drug manuafacturers to raise their game.  He warned that foreign nationals control too much of the Russian drug market at more than 80%.  He's challenging Russia's 160+ manufacturing firms to increase their share of the market to 50% of all drugs and 90% of all vital medicines by 2020.

The Russian government is prepared to invest $3.9 B to support novel engineering technologies for Russian plants - while calling on producers to make further investments that are need to modernize. Thos that do not invest will be restricted in the Russian market - particularly those neglecting to increase production or technology transfer activities.   Russia will also adopt GMP manufacturing standards in 2014 to get it in better position to compete in international regulated markets.

“In essence we will need to ensure that manufacturing technology and infrastructure in Russia measure up to the standards used in the most advanced production facilities in Europe and the US”, said Russian industry minister Viktor Khristenko.

Frost & Sullivan predicted that the Russian drug market will grow from %15.3 B in 2009 to more than $37.1 B in 2016 - thus helping to explain why Big Pharma investors Nycomed, Novo Nordisk and AstraZeneca have announced plans to invest in the country too.

Posted by Bruce Lehr December 14th 2010.  

 

Roche Cuts to Hit Genentech But No R&D

In a follow up story to Roche's announced operational excellence cuts this morning, Xconomy reports that Genentech manufacturing staff will see cuts in South San Francisco (350-450), Vacaville (100) and Oceanside (90), but nobody from R&D or early drug development is expected to go. 

Roche Cuts to Hit Hundreds of Genentech Workers; Scientific Staff is Spared.

The handwriting has essentially been on the wall for a lot of the manufacturing operations in South San Francisco. As far back as 2006, Genentech said it was planning to shift the manufacturing group on campus away from commercial output, and gear it more toward producing batches for use in clinical trials, said Genentech spokeswoman Robin Snyder.  The cuts will commence now and be completed by 2012.

 

Posted by Bruce Lehr November 17th 2010.

Dendreon Seeks OK to Grow NJ Factory

According to this article from Xconomy, Dendreon has applied to the FDA to quadruple the capacity of its New Jersey manufacturing site for Provenge.  The FDA is expected to make a determination over the next 4-6 months.

Dendreon Seeks OK to Grow NJ Factory.

 

In the meantime, Dendreon is also building similar manufacturing facilities in the Los Angeles and Atlanta regions - all in an effort to provide enough capacity to meet the demand for its newly approved prostate cancer vaccine. 

Posted by Bruce Lehr November 11th 2010.

Dendreon Struggles with Supply - Slightly Below Expected Revenue Goal

 

 

As reported in Xconomy, Dendreon fell slightly short of the expected revenue goals projected by analysts for Q3 - hitting $20.2 M versus an expected $24 M figure. This is despite the company selling $9.5 M in October with its plant at full capacity.  Dendreon is still hamstrung with inadequate capacity to meet full demand until its new plants come on line in 2011.

Dendreon expects to spend $460 M in cash this year to expand its plant in New Jersey by 75% and add plants in Atlanta, GA and Los Angeles, CA.  Construction is substantially completed and the plants are going through validation in preparation for FDA pre-market inspection.  When approved, Dendreon expects to be able to sell $350-$400 M of Provenge in 2011.  The plants will have the capacity to produce up to $1.25 B to $2.5 B worth of the drug annually. The New Jersey plant should come on line in March. Dendreon expects to service approximately 2000 prostate cancer patients in the first calendar year that Provenge is on the market from May 2010 to May 2011.

Posted by Bruce Lehr November 3rd 2010.

Onyx Pharma Encounters Small Black Cloud

Onyx Pharmaceuticals will have to delay its planned end of year filing with the FDA for its multiple myeloma drug, carfilzomib.  The FDA today asked that the company to show it can match smaller amounts of the drug used in clinical trials with new runs made a greater scale. Perhaps this shows greater attention to scale up by the agency given some issues other companies have had with their manufacturing of biologic drugs this year - Genzyme, Dendreon, etc.

Onyx did encounter some problems with scaled up material that was believed to be related to temperature control problems with manufacturing equipment used in the runs.  Onyx will now generate data to show the larger scale process is reproducible. There is no suggestion that the clinical profile of carfilzomib has changed in any way.

“This is a timing issue,” Onyx CEO Tony Coles said today on a conference call with analysts. “We believe the fundamental value proposition for carfilzomib is unchanged and the commercial opportunity is significant.”

The new drug is vitally important to Onyx’s growth prospects, as it seeks to diversify beyond its lone marketed product at the moment, sorafenib (Nexavar) for kidney and liver cancer. If the drug is approved, it would be a new treatment option for a disease that hits about 20,000 people each year in the U.S., and kills about half that many every year.  Onyx expects to file with the FDA as early as mid-year 2011 after resolving the delay.

See Fierce Biotech and Xconomy.

 

Posted by Bruce Lehr October 8th 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.

Can't Anybody Here Play this Game?

With sincere apologies to Casey Stengel, recent manufacturing failures in pharma industry make this question every bit as pertinent as when it was formulated about the 1962 Mets.

Genzyme. J&J's McNeil. Abbott. Amgen. Not exactly neophytes to the manufacturing and quality control of critical products serving the healthcare market.  Yet all have experienced problems in their manufacturing resulting in recalls, and in some cases shortages, and illness.

What's more? Many of these instances have been marked by a seemingly leisurely attitude in senior management toward getting to the bottom of the issues.  Or worse, lack of transparency in dealing with the problem with the patient base - lack of availability information, dealyed or phantom recalls, and stonewalling regulators.

Results? Loss of consumer confidence or anger among patients who are without their needed medications.  Plant closings and job losses for those employees. Senior management resignations (albeit too little too late).  Proxy fights. Consent Decrees.  And even an acquisition attempt (which could go hostile) in play.

Like most things. It would appear that this would come down to fundamentals.  Companies need to go back to spring training and work on basics of attention to detail, institution and adherence to strong quality systems - but even more importantly a return to responsibility, forthrightness and a commitment to ethics at the top.  These are ethical businesses correct?

Posted by Bruce Lehr September 27th 2010.

GEN Webinar: Impact High Titer Processes on Protein Quality

Over the past decade it has been all about titer, titer, titer in the biopharm industry as process development groups strove to reach "holy grail-type" production levels of 10 g/L or more (at least for MaBs). 

Now, many groups in the industry have reached that level or even exceeded 10 g/L and have concluded that may be too much. There seems to be a consensus building in the industry that 5 g/L is fine from a COGs perspective and that gains above 5 g/L don't save that much in additional COGs and create more problems with protein quality.

 

GEN will present an educational webinar on September 27th and 28th entitled, "Impact of High Titer Process on Product Quality".  Registration for the webinar is FREE.

Topics covered will include the following:

• Comparing cell-line productivity using a traditional fed-batch system versus high-density cell culture to express Fc-fusion proteins or antibodies
• Impact on aggregation, glycosylation, and in vitro activity resulting from high-density cell culture processes
• Increasing titer output without changing the genetic construct or process media
• Downsizing bioreactors while maintaining high yields of a biopharmaceutical product
• Reducing cost of goods and time to market 

The event will be moderated by GEN Editor in Chief, John Sterling.  Industry Panelists include: David Bienvenue, Assoc. Dir., VLST Corp., Wei-Kuang Chi, VP and Director, cGMP Biopharmaceutical Plant, Development Center for Biotechnology, Rolf Douwenga, VP, Global R&D, DSM Biologics

Posted by Bruce Lehr September 21st 2010.