Newly approved XGEVA and its First Step (TM) Coupon Program

In case you would want to listen to the shorter version



Enjoy!

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On November 18 2010, the FDA approved Amgen's Xgeva or denosumab to be used in the prevetion of cancer-related bone injury. (Note: The FDA indicates multiple myeloma as solid tumor but in fact multiple myeloma is a cancer of plasma cell residing in the bone marrow.  So it's not really a solid tumor)

Denosumab is a monoclonal antibody that works to inhibit RANKL or nuclear factor kB ligand.  In general, RANKL binds to RANK receptor to increase differentiation and maturation of osteoclastic precursor cells into mature osteoclast.  Osteoclast works to increase bone resorption (in other word, increase the destruction of bone cells in order to release mineral contents within the bone cells).  Under normal physiological situations, osteoclastic activity is important in bone development.  When the activity is out of control, bone resorption can occur and make the bone more prone to fracture.

Denosumab inhibits RANKL and as a result denosumab will prevent RANKL from binding to its receptor.  This results in less differentiation and maturation of osteoclast.  Hence, less bone resorption will occur.

Currently denosumab is marketed under the brand name Prolia by Amgen.  Prolia is approved for the treatment of postmenopausal women with osteoporosis at high risk for fracture.  Prolia was approved in June 2010.

Other Medications that have been approved for the same indication as XGEVA:

• Zometa (zoledronic acid) of Novartis.  Zometa works differently from denosumab even though the exact mechanism is unclear
• Aredia or pamidronate sodium of Novartis.  Same as Zometa, the exact mechanism of Aredia is still unclear.

Regulatory and Marketing Information

• Other marketing applications for XGEVA have been submitted for review in the EU, Australia, Canada and Switzerland.
• Daiichi-Sankyo Company is its licensing partner in Japan.  A marketing application was submitted in August 2010.
• Upon approval, Amgen plans to launch XGEVA by the end of November.

 Safety Information

• Most common serious side effects:
• low level of calcium in the blood (hypocalcemia)
• osteonecrosis of the jaw that could cause pain, swelling, numbness or infections
• dyspnea
• Other side effects:fatigue/asthenia, low level of phosphate in the blood (hypophosphatemia) and nausea

Supply:

• XGEVA is available in a single-use vial which contains 120 mg of denosumab in 1.7 ml of solution.
• XGEVA needs to be stored in refrigerator at 2oC to 8oC in the original box.  Do not freeze.

Financial Help

•  Amgen has XGEVA First Step (TM) Coupon Program that could help patients having access to XGEVA.
• If eligible, first XGEVA injection will be of no charge and subsequent injections will be charged to a maximum of $25.
• Patients can access it @ Amgen Assist

Clinical Information

• The FDA approved XGEVA based on the results of three international, randomized, double-blind, active-controlled, noninferiority trials which compared XGEVA against zoledronic acid.
• In all three trials: patients were randomly assigned into either the XGEVA group or zoledronic acid group.
• Patients in the XGEVA group were instructed to perform subcutaneous injection of 120 mg XGEVA every 4 weeks
• Patients in the zoledronic acid group were given intravenous solution of 4 mg zoledronic acid every 4 weeks.
• Trial 1 evaluated XGEVA and zolendronic acid in patients with advanced breast cancer and bone metastasis
•  The result showed XGEVA was significantly increased median time to Skeletal-related events (SRE) compared to zolendronic acid.
• It was noninferior to zoledronic acid
• Trial 2 evaluated XGEVA and zolendronic acid in patients with solid tumors other than breast and castrate-resistant prostate cancer with bone metastasis and multiple myeloma.
•  It was noninferior to zoledronic acid.  
• Median time to SRE was similar to both groups.
• Trial 3 evaluated XGEVA and zolendronic acid in patients with castrate-resistant and bone metastasis.
• The result showed XGEVA was significantly increased median time to Skeletal-related events (SRE) compared to zolendronic acid (20.7 mons vs 17.1 mons)  
• It was noninferior to zoledronic acid

Sources:

• FDA
• Amgen
• Nasdaq 
• Package Insert

Axitinib of Pfizer demonstrated significantly longer progression-free survival compared to sorafenib

A phase III trial using axitinib of Pfizer in patients who were treated for metastatic renal cell carcinoma demonstrated a significantly longer progression-free survival (PFS) compared to patients who were treated with sorafenib.  (NCT00678392)

Axatinib is an oral, vascular endothelial growth factor (VEGF) receptors 1, 2 and 3 inhibitor.  VEGF receptors play important roles in tumor growth, vascular angiogenesis and metastatic progression of cancer.

• Comments: Being a VEGF receptor inhibitor, axatinib is expected to produce hypertension in treated patients.  Diarrhea is also a common side effect in tyrosine kinase inhibitor which axatinib is.  However, until the final results are released, information cannot be extrapolated.
• Sorafenib is a tyrosine kinase inhibitor that also inhibits VEGF receptors as well as others (such as PDGFR).  It's currently marketed by Bayer Healthcare Pharmaceuticals.  Due to its effects on both VEGF and PDGFR, its side effect will include hallmark symptoms of hand-foot syndrome.  HFS is characterized by pain, swelling, numbness, tingling, or redness of affected areas (usually hands or feet).  It's often called palmar-plantar erythrodysesthesia. Package insert

For those you are not familiar with terminology: progression-free survival is measured from the time patient starts the treatment until disease progresses. It may be used to evaluate how well the new treatment works in clinical trial or study. 

Besides being studied for other indications, Pfizer is recruiting patients for another phase III trial to demonstrate the superiority of axitinib over sorafenib in delaying tumor progression in metastatic renal cell cancer patients.  The study is to be completed on April 2012 (NCT00920816)

The following is the detail information about the reported trial (NCT00678392)

• The study enrolled 716 patients starting July 2008.
• According to the listed trial information, its primary completion date was August 2010.
• Expected study completion is June 2011.
• Patients were randomized into two groups: axitinib or sorafenib
• 5 mg of axitinib were given twice a day initially.  Patients would receive continuous dosing
• 400 mg of sorafenib were given twice a day initially.  Patients would receive continuous dosing
• However, once randomized, patients were allowed to know the medications that they would be treated with.  (This study design is called open-label)
• The primary outcome was:
• progression free survival 
• The secondary outcomes were:
• Overall survival (time from starting treatment to death)
• Response rate 
• Safety and tolerability of axitinib
• Duration of response in each arm
• Kidney specific symptoms and health status
• Patients were included in the trials based on the followings
• Inclusion criteria
• Age: at least 18 years or older
• Have confirmed renal cell cancer with a component of clear cell subtype with metastasis using histology or cytology
• Evidence of measurable disease
• must have failed one prior systemic first-line treatment for metastatic renal cell cancer
• Exclusion Criteria
• Have more than one systemic first line therapy prior to treatment for metastatic renal cell cancer
• Have major surgery in less than 4 weeks or radiation in less than 2 weeks of starting the study drug.

Source 

Propoxyphene is to be withdrawn from the market

 

• The FDA issued a market withdrawal of propoxyphene-containing products on November 19, 2010 citing potential risk of serious or even fatal heart rhythm abnormalities.  This information combines with others have shown that the risk of taking propoxyphene outweighs its benefits.
• Xanodyne, a marker of Darvon which is the brand name of propoxyphene and Darvocet which contains both propoxyphene and acetaminophen, has agreed to withdraw the products from the market.  
• Darvocet and Darvon are two of a few products that Xanodyne currently markets
• Several of its products are:

§  Zipsor: diclofenac potassium liquid filled capsules

§  Oramorph SR: morphine sulfate sustained release

§  Hycet: hydrocodone and acetaminophen

§  Roxicodone: Oxycodone hydrochloride

§  Amicar: aminocaproic acid

• According to the company website: it currently has 2 products in development

§  XP20B: combination of propoxyphene/acetaminophen: Phase III. With this new development, I suspect this project will be discontinued.

§  XP21B: diclofenac potassium for the treatment of acute pain

• In addition, the FDA has informed other generic markers of propoxyphene-containing products about its decision.  The FDA has also requested other generic propoxyphene-containing products to be withdrawn from the market.
• Several companies that currently market propoxyphene-containing products are: Cornerstone Therapeutics, PD-Rx Pharmaceuticals, Stat Rx USA, West-Ward Pharmaceutical Corp, Altura, Keltman Pharmaceuticals, Qualitest, Par Pharmaceuticals, Mylan, Heritage Pharmaceuticals, Teva Pharmaceuticals, Andrx Pharmaceuticals, Aritos Pharmaceuticals and others.
•  Propoxyphene is a centrally acting opiate analgesic.  It works by inhibiting sodium channels to produce local anesthetic effects.  It was originally approved in 1957.

FDA

Recent updates from: Merck, Intercell and Aastrom

It's been a while since I did the podcast. Life has been busy. Here is a quick & short one!

Enjoy!

• The top-line results of the phase II trial using V710 of Intercell in patients with end-stage renal disease showed V710 was able to elicit a sustained immune response in the study population.  V710 was discovered by Intercell and is being developed as a Staphylococcus aureus vaccine by Merck. In 2004, Intercell and Merck entered an exclusive world wide basis under which Merck is responsible for clinical development, manufacturing and marketing.  Milestone payments and other royalties will made to Intercell.   Merck is currently recruiting patients for the phase II/III proof of concept clinical trial. The first critical interim analysis is expected for 2011.
• Source - Intercell Press Release
• The Second Interim Analysis of the phase II trial using Aastrom's Vascular Repair Cells (VRCs) for the treatment of peripheral vascular disease-related critical limb Ischemia showed the study met its primary safety endpoint and primary efficacy endpoint of time to first occurrence of treatment failure.  Compared to the controlled group which received injection of electrolyte solution instead of VRCs, the time to first occurrence of treatment failure in the VRCs group was significantly different from the controlled group.
• The study currently enrolled 86 patients. According to the company website, it plans to enroll 150 patients.
• In addition, Aastrom announced its plan to initiate the phase III trial under special protocol assessments (SPA) with a Fast Track Designation by the FDA. Aastrom - Press Release
• On Nov 17, 2010, Merck said in its press release that the FDA Advisory Committee has recommended the use of Gardasil (Human Papillomavirus Quadrivalent - Types 6,11, 16, and 18) Vaccine for the prevention of anal cancer and anal intraepithelial neoplasia in both males and females whose ages range from 9 through 26. Source - Merck Press Release
• Gardasil is currently marketed and approved in the US for the treatment of cervical, vulvar and vaginal cancers caused by HPV types 16 and 18, genital warts caused by HPV types 6 and 11, and precancerous or dysplastic lesions caused by HPV types 6, 11, 16, and 18 in females whose ages range from 9 through 26.
• It's currently approved in 121 countries.
• Three doses of Gardasil can be administered intramuscularly in a period of 6 months at three separate sites: deltoid region of the upper arm or in the higher anterolateral area of the thigh.
• The phase III trial using anacetrapib of Merck in combination with statin therapy and optional other lipid-modifying agents in patients with or at high risk for congestive heart disease who were already taking statin therapy and were at goal LDL-C level based on guideline showed that anacetrapib in combination with statin was effectively and significantly lowering LDL-C level and increasing HDL-C level when compared to patients who were not on the combination therapy. More than 1,600 patients were enrolled in the study.  Anacetrapib was accounted for 11 deaths and placebo group was accounted for 8 deaths.  The statistical analysis showed that this difference was not statistically significant. Anacetrapib is CETP inhibitor. Merck - Press Release

New Drugs Approved by the FDA has been updated!

November Approval has been updated!

Enjoy! ^_^

Roche announces its plan to cut 4800 position worldwide

Roche announces its plan to cut 4800 position worldwide as parts of its Operational Excellence Program which will be initiated in 2011 and 2012. 

• Cut will be focused on the Pharmaceuticals Division with the following departments: sales and marketing and manufacturing.
• Most eliminated positions will be in the US.
• Part of the restructuring process is plan to discontinue the activities in certain areas of research and early development which includes RNAi research.  In 2009, Tekmira and Roche entered into a product development agreement under which Tekmira would help Roche to advance its RNAi product candidates into human clinical study using its LNP's technology.  A press release from Tekmira has been released after the announcement.
• LNP technology is developed by Tekmira. LNP is formerly known as SNALP: stable nucleic acid-lipid particles).  It wraps (encapsulates) siRNA with high efficiency in uniform lipid nanoparticles in order to deliver the RNA to the sites of actions.   Source

•  It will plan to place the majority of Diabetes Care activity in Mannheim, Germany (including the research and development of insulin pumps)
• Diagnostics Chemical manufacturing and analytical services will be moved to Penzberg, Germany (from Mannheim, Germany)

The plan is expected to result in annual cost savings of 2.4 billion Swiss francs from 2012 onwards (and 1.8 billion Swiss francs in 2011)

For more information, please visit the press release

The FDA approved eribulin mesylate (Halaven) of Eisai

On Nov 15, 2010, the FDA approved the used of eribulin mesylate (marketed as Halaven) of Eisai to be used as treatment in metastatic breast cancer patients who have undergone at least two chemotherapeutic regimens which have included an anthracycline and a taxane either in the adjuvant or metastatic setting.

• Other agents that have been approved to be used in the treatment of late-stage, refractory breast cancer: 
• Xeloda (capecitabine)for patients with breast cancer resistant to paclitaxel and anthracycline-containing chemotherapy
• Ixempra (ixabepilone) for patients with late-stage disease after failure of an anthracycline, taxane, and Xeloda
• Ixempra plus Xeloda: for patients with late-stage disease after failure of anthracycline- and taxane-based chemotherapy

The following will be addressed:

• What is Halaven?
• How does Halaven work?
• Marketing/Manufacturing Information
• Regulatory and Safety Information
• Safety
• Clinical Evidence

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

•  What is Halaven
• Eribulin mesylate is a non-taxane, microtubule dynamic inhibitor.  It is a synthetic analogue of halichondrin B (isodlated from the toxic marine sponge Halicondria okadai) If you are familiar or not familiar with the cell cycle, it's worth to take a note.  The cell cycle as the name implied often depicts different stages in which the cell has to go through.  The body has billions of cells that are in various stages of the cell cycle which consist of a few main stage: G1, S, G2 and M
• S phase or often called the synthesis phase.  The DNA is synthesized in this case and the chromosome is replicated.
• G2 phase is the phase in which the cells now have duplicated chromosome.
• M phase or often called Mitotic phase.  In this phase, the duplicated chromosome starts to separate.
• G1 is the resting phase during which it grows.
• My note: Erbulin appears to work by interrupting the M phase 
• How does Halaven work?
• As mentioned above, it works to block the G2/M cell-cycle, disruption of mitotic spindles, and ultimately this will lead to cell deaths.
• My note: Cell deaths occur when we assume that P53 (a important cell regulator) is working properly.  If p53 is mutated into which it could not recognize problems in the cell cycles, cell death might not occur.
• Marketing and Manufacture information
• Eribulin or Halaven was discovered and developed by Eisai. 
• It is manufactured by NerPharMa based in Italy
• According to Eisai, the product will be available within 10 days (meaning around the 26th of November)
• Regulatory and Safety Information
•  Other Regulatory applications have been submitted in Japan, the EU, Switzerland and Singapore
• The followings are some of the common adverse events that patients could experience when taking Halaven
• neutropenia (reduction of neutrophil, a component of the immune system)
• anemia (low red blood cell)
• leukopenia (reduction of white blood cell)
• alopecia (hair loss)
• fatigue
• nausea
• weakness
• nerve damage (peripheral neuropathy)
• arthralgia/myalgia 
• constipation
• Urinary Infection
• pain (Back, bone)
• Clinical Evidence
• Halaven is approved based on the data collected from the phase III study funded by Eisai called EMBRACE
• EMBRACE was an open-label, randomized, global, multi-center study comparing the effectiveness of Halaven to Treatment of Physician's Choice (TPC) in the overall survival in patients with metastatic breast cancer who previously had been treated with an average of four prior chemotherapies.
• Note from me: being a global study, treatments can different from centers to centers.  Patients can be different from centers to centers. In addition, guidelines can also be different.  This could lead to the difficulty in comparing the group receiving Halaven and the group receiving TPC due to differences in outcomes of TPC.

• The study enrolled 762
• According to the press release: TPC is defined as: a single-agent chemotherapy, hormonal treatment or biologic therapy approved for the treatment of cancer, or palliative treatment or radiotherapy administered according to local practice.
• Note from me: this again emphasized the fact that these practices were different and some of them had different efficacy from others.  Making it harder to compare the two treatment objectively.  In addition, I found it odd that they use single therapy treatment in patients with metastatic breast cancer. 
• Results
• The result showed that Halaven-treated patients survived a median of 2.5 months longer than patients who received a "single-agent therapy" chosen by the physician.
• The overall survival which is their primary endpoint: 
• Halaven-treated group: 13.12 months
• TPC group: 10.65 months
• p value = 0.041
• this makes the difference in the overall survival between Halaven group and TPC group significantly. 
• Meaning: patients in the Halaven group had higher overall survival than patients in TPC
• Overall survival means: time from treatment started to death. 

Source - Press Release
Source - Package Insert
Source - FDA 

RXi Pharmaceuticals reported its third quarter result with a net loss

RXi Pharmaceuticals reported a net loss of approximately 4.1 in its third quarter 2010, an increase of 1.1 M compared to the same quarter of last year.

• In its third quarter, RXi Pharmaceuticals spent 1.9 M in research and development, a decrease of 0.2 M compared to the same quarter of last year.  RXi attributed this loss ward a decrease in license maintenance fees and patent costs.
• At the end of its third quarter which ended on September 30, 2010, the company had 8.8 M in cash, cash equivalents and short-term investments, an increase of 3.1 M from December 31, 2009.
• RXi Pharmaceuticals has recently been awarded over 1.5 M in grants to advance RNAi therapeutics from the United States Internal Revenue Service as part of the Patient Protection and Affordability Care Act of 2010.
• RXi Pharmaceuticals focuses its research and developing in the use of RNA interference as a therapeutic tools.  
• Here is how RNA interference works
• Double stranded RNA is manufactured and injected into the cells.  It is then being cleaved. 
• In the cell, there is a complex called RISC (RNA-induced silencing complexes) which is a multiprotein complex. The dsRNA is unwounded and becomes single stranded.  Single stranded RNA will be incorporated into the RISC.  RISC is able to recognize the mRNA using the single strand RNA as a template.  Once it finds the respective mRNA portion, it will cleave it out of the mRNA.  The mRNA this time will be either dysfunctional or functional depending on which mRNA portion is taken out.  
• Here is a graphic picture that I found Source 

Source

Pfizer reported positive results from its phase IIIb trial using eplerenone in heart failure patients

Pfizer reported the result of the multinational phase 3b trial using INSPRA or eplerenone in addition to standard Heart Failure therapy in heart failure patients with mild symptoms at the American Heart Association Scientific Sessions in Chicago.

• Study population: patients who had New York Heart Association (NYHA) class II chronic systolic heart failure with mild symptoms were enrolled in the study. 
• Patients who had severe systolic heart failure symptomatic at rest despite optimal medical therapy or have estimated glomerular filtration rate < 30/ml/min/1.73m2 were not included in the study.
• For further information, please refer to the original article (the list is too long for me to list here, PMID: 20388647)
• Study medication
• Pfizer didn't clarify what the specific standard therapy of heart failure was. The study designed indicated that ACE-I (or/an an ARB) and beta blocker were used. (Note from me: ACE-I and ARB work differently and they do have different properties.  Using them in combination will offer different results than using them individually.  The complete paper has not been published, so I'm curious as to how they analyze their data).
• Eplerenone: 25 mg daily in the first 4 weeks
• After 4 weeks: eplerenone was increased to 50 mg daily based on serum potassium level.
• Results:
• The study showed significant reduction in the risk of cardiovascular mortality and morbidity in patients who took eplerenone compared to the placebo group.

Update from Transcept Pharmaceuticals

•  A few days ago, Transcept pharmaceuticals based in Point Richmond, CA announced a net loss of 2.8 M in its third quarter 2010, a decrease of 1 M from the same quarter of last year.  
• The company had 3.1 M in revenue in its third quarter, an increase of 1 M from last year.  
• Research and development expense has also increased by 0.8 M from the same quarter of last year (2.9 M vs 2.1 M).
• In this quarter, Transcept received a portion of the 25 M non-refundable license fee from Purdue Pharmaceuticals following the collaboration agreement of commercialization of Intermezzo in the US.  The license fee is to be paid over a period of 24 months starting August 2009.
• Transcept Pharmaceutical is a specialty company that focuses on developing therapeutic needs for the treatment of neurological diseases. 
• It has developed zolpidem tartrate sublingual tablet called Intermezzo for the treatment of insomnia in patient who often wakes up at night and has difficult falling back to sleep. The NDA was submitted in 2008. A complete response letter from the FDA was received on

Specificity vs Sensitivity

Sensitivity vs Specificity

• Often time, in statistics (at least in medical statistics), we are heard and confused about what sensitivity and specificity mean. Many times, I have to look back (take a step back) and think about this a bit more carefully (otherwise I might get these two switches).
• In any case, I realize maybe I should dedicate a post for it... you can see a shorter definition in the glossary. 

When you are given a test, you would like to know how accurate the test is.  In common term, we want to know the accuracy of the test.  For physicians and other healthcare professionals, we tend to refer to accuracy as either sensitivity or specificity.

Before we begin, statisticians have given us a great table that could help us a bit (or confused us a bit more)

	Disease Present	Disease Absent
Test Positive	TP	FP
Test Negative	FN	TN

So when you are given a test, 4 possible scenarios

• True Positive (TP): you have the disease and the test gives a positive result
• True Negative (TN): you don't have the disease and the test gives negative result
• False Positive (FP): you don't have the disease but the test give positive result 
• False Negative (FN): you have the disease but the test give negative result => probably not a good thing

In many cases, we want the test to give us the exact diagnosis (such as, if I have the disease, please just give me a positive test.   or if I don't have the disease, please just give a negative test).  This is the ideal situation.  In real life, we don't have a test that give us 100% accuracy.  This is where sensitivity and specificity come in.

• Sensitivity: is calculated by = TP / (TP + FN) => so when you look at the equation, the higher the sensitivity, the higher the number of true positive (given TP + FN stay constant).  So the test with high sensitivity will tell us: when the test result is positive, the chance that it is a true positive is very high. high specificity will minimize false positive
• Specificity: is calculated by = TN / (FP + TN) => so again, when you look at the numerator, the higher the true negative, the higher the specificity ( given FP + TN stay constant).  in this case, test with high specificity will us: when the test result is Negative, chances that it is a true negative is high!
• So when do we want the test to have high sensitivity or high specificity?
• usually, tests don't have both high sensitivity and high specificity
• A test with high sensitivity tends to have low specificity and vice versa
• so we have to choose appropriate test for appropriate condition
• If the disease is curable and the procedure to do the test is not terribly invasive: we want to have the test to have high sensitivity.  Why? We want to catch everyone who has a disease.  We want to know whether the person has a disease.  If they do, we have a treatment.  So we really really want to treat the patients who have the disease.  So having a positive test -> high chance of having a disease -> we are able to catch the disease at the right time -> better chance when pt undergoes treatment.  Also, when the test is high in sensitivity, false negative is low. So the test really goes out and catches all the positive patients.
• If the test procedure is very invasive to the patient, we want the test to have as high specificity as possible.  The reason is: when you look at the equation, there is a part False positive. Having a false positive will make patients to go through more testing which can  be even more invasive.  So, minimizing false positive so that if the test comes out as negative -> high probability that it's a true negative and no further test might be needed.  this also means that: if the test is positive, chance of it going to be a false positive is also low -> workup is needed. 

• Let's talk about Positive Predictive Value and Negative Predictive Value
• I don't know how often these are used.
• Positive Predictive Value = TP / (TP + FP)  => tell us % of patients whose tests show positive are actually positive.
• Negative Predictive Value = TN / (TN + FN) => tel us % of patients whose tests negative are actually negative.
• I hope I haven't confused all of you....

Medical Device Recall!

I rarely post anything related to medical devices in parts because I don't know much about its regulation.

Maybe I should spend time learning more about this area (when I have time).

A few terminology in regard to different "Classes" of recall (taken from the FDA website)

• Class I recall: 
• a recall is classified as class I when the use of a defected product presents a reasonable probability of causing serious adverse health consequences or death
• Class II recall: 
• a recall is classified as class II when the use of a defected product may cause temporary or medically reversible health consequences or when its use does not pose a high probability of causing serious adverse health consequence.
• Class III recall: 
• a recall is classified as class III when the use of a defected product is not likely to cause adverse health consequences.
• Market Withdrawal
• a device is withdrawn when a minor violation is found in the product but this violation is not subject to FDA legal action.  The company marketing this product would remove this product voluntarily from the market to correct the violation.  
• Medical Device Safety Alert:
• An alert is issued when a medical device has potential of posing an unreasonable risk of substantial harm.  Recalls could be issued in some cases.

Here comes the recall!

• On September 15, 2010, Sigma International General Medical Apparatus, LLC (part of Sigma) issued a Class I recall in regard to SIGMA Spectrum Infusion Pump Model 35700.
• Affected Sigma Spectrum Infusion Pump Model 35700 were manufactured between Oct 2006 to March 2008.
• These pumps according to Sigma might cause inaccurate flow conditions during use without setting of an alarm.  The defect could alter the flow directions: back flow to over-infusion including free flow.  Serious death and injury might occur.
• For additional information please contact the company at: 1-886-482-2893.  The office opens on M-F from 8 AM to 5 PM Eastern Time.
• Sigma Spectrum Infusion Pump is designed to delivery fluids, solutions, drugs, agents, nutritionals, electrolytes, blood and blood products via parenteral (not by gastrointestinal tract, meaning not going through mouth, stomach and intestines), enteral, intravenous, intra-arterial, subcutaneous, epidural, or irrigation route of administration.
• Source: