Drug Labelling

FDA Aims to Help Drugmakers Update Labeling Format

The FDA is seeking stakeholder feedback on a proposed initiative that would encourage drugmakers to use an updated drug labeling format even if they are not legally required to do so. The Prescription Drug Labeling Improvement and Enhancement Initiative and an associated pilot project would ask applicants with NDAs, BLAs or efficacy supplements (ESs) approved before June 30, 2001, and ANDAs for which the reference drug has been withdrawn for reasons other than safety or effectiveness to voluntarily convert their labeling to the “Physician Labeling Rule” (PLR) format and submit it for approval. The FDA intends to identify and prioritize certain drugs and drug classes for label conversion based on public health impact.

Washington Drug Letter

Reference:

http://www.fdanews.com/newsletter/article?issueId=16575&articleId=153378

Implant for Genetic eye disease

Retinitis Pigmentosa (RP) is a rare genetic eye condition that damages the light-sensitive cells that line the retina. In a healthy eye, these cells change light rays into electrical impulses and send them through the optic nerve to the area of the brain that assembles the impulses into an image. In people with RP, the light-sensitive cells slowly degenerate resulting in gradual loss of side vision and night vision, and later of central vision. The condition can lead to blindness.

FDA approved the Argus II Retinal Prosthesis System, the first implanted device to treat adult patients with advanced retinitis pigmentosa (RP). The device, which includes a small video camera, transmitter mounted on a pair of eyeglasses, video processing unit (VPU) and an implanted retinal prosthesis (artificial retina), replaces the function of degenerated cells in the retina (a membrane inside the eye) and may improve a patient’s ability to perceive images and movement. The VPU transforms images from the video camera into electronic data that is wirelessly transmitted to the retinal prosthesis.    

 This new surgically implanted assistive device provides an option for patients who have lost their sight to RP – for whom there have been no FDA-approved treatments. The device may help adults with RP who have lost the ability to perceive shapes and movement to be more mobile and to perform day-to-day activities.

The Argus II system is intended for use in adults, age 25 years or older, with severe to profound RP who have bare light perception (can perceive light, but not the direction from which it is coming) or no light perception in both eyes, evidence of intact inner layer retina function, and a previous history of the ability to see forms. Patients must also be willing and able to receive the recommended post-implant clinical follow-up, device fitting, and visual rehabilitation. 

In addition to a small video camera and transmitter mounted on the glasses, the Argus II Retinal Prosthesis System has a portable video processing unit (VPU) and an array of electrodes that are implanted onto the patient’s retina. The VPU transforms images from the video camera into electronic data that is wirelessly transmitted to the electrodes. The electrodes transform the data into electrical impulses that stimulate the retina to produce images. While the Argus II Retinal Prosthesis System will not restore vision to patients, it may allow them to detect light and dark in the environment, aiding them in identifying the location or movement of objects or people.

The FDA approved the Argus II Retinal Prosthesis System as a humanitarian use device, an approval pathway limited to those devices that treat or diagnose fewer than 4,000 people in the United States each year. To obtain approval for humanitarian use, a company must demonstrate a reasonable assurance that the device is safe and that its probable benefit outweighs the risk of illness or injury. The company also must show that there is no comparable device available to treat or diagnose the disease or condition. 

The FDA reviewed data that included a clinical study of 30 study participants with RP who received the Argus II Retinal Prosthesis System. Investigators monitored participants for adverse events related to the device or to the implant surgery and regularly assessed their vision for at least two years after receiving the implant.

Results from the clinical study show that most participants were able to perform basic activities better with the Argus II Retinal Prosthesis System than without it. Some of the activities tested included locating and touching a square on a white field; detecting the direction of a motion; recognizing large letters, words, or sentences; detecting street curbs; walking on a sidewalk without stepping off; and matching black, grey and white socks.

Following the implant surgery, 19 of the 30 study patients experienced no adverse events related to the device or the surgery. Eleven study subjects experienced a total of 23 serious adverse events, which included erosion of the conjunctiva (the clear covering of the eyeball), dehiscence (splitting open of a wound along the surgical suture), retinal detachment, inflammation, and hypotony (low intraocular pressure). 

Three government organizations provided support for the development of the Argus II. The Department of Energy, National Eye Institute at the National Institutes of Health and the National Science Foundation collaborated to provide grant funding totaling more than $100 million, support for material design and other basic research for the project.

Stivarga - GI Tumour

FDA approves Stivarga for advanced gastrointestinal stromal tumors.

GIST is a tumor in which cancerous cells form in the tissues of the gastrointestinal tract, part of the body’s digestive system. According to the National Cancer Institute, an estimated 3,300 to 6,000 new cases of GIST occur yearly in the United States, most often in older adults.

The U.S. Food and Drug Administration today expanded the approved use of Stivarga (regorafenib) to treat patients with advanced gastrointestinal stromal tumors (GIST) that cannot be surgically removed and no longer respond to other FDA-approved treatments for this disease.

Stivarga, a multi-kinase inhibitor, blocks several enzymes that promote cancer growth. With this new approval, Stivarga is intended to be used in patients whose GIST cancer cannot be removed by surgery or has spread to other parts of the body (metastatic) and is no longer responding to Gleevec (imatinib) and Sutent (sunitinib), two other FDA-approved drugs to treat GIST.

Stivarga is the third drug approved by the FDA to treat gastrointestinal stromal tumors. It provides an important new treatment option for patients with GIST in which other approved drugs are no longer effective.

Stivarga was reviewed under the FDA’s priority review program, which provides an expedited six-month review for drugs that may provide safe and effective therapy when no satisfactory alternative therapy exists, or offer significant improvement compared to marketed products. The drug was also granted orphan product designation because it is intended to treat a rare disease.

The safety and effectiveness of Stivarga for this use were evaluated in a clinical study of 199 patients with GIST that could not be surgically removed and progressed after treatment with Gleevec or Sutent. Patients were randomly assigned to receive either Stivarga or a placebo. All patients also received optimal supportive care, which includes treatments to help manage side effects and symptoms of cancer.

Patients in the study took Stivarga or placebo until either the cancer progressed or the side effects became unacceptable. Results showed patients who took Stivarga had a delay in tumor growth (progression-free survival) that was, on average, 3.9 months later than patients who were given placebo. Patients who received the placebo were given the opportunity to switch to Stivarga when their cancer progressed.

The most common side effects reported in patients treated with Stivarga were weakness and fatigue, hand-foot syndrome (also called palmar-plantar erythrodysesthesia), diarrhea, loss of appetite, high blood pressure, mouth sores, infection, changes in voice volume or quality, pain, weight loss, stomach pain, rash, fever and nausea.

Serious side effects, which occurred in less than one percent of patients, were liver damage, severe bleeding, blistering and peeling of skin, very high blood pressures requiring emergency treatment, heart attacks and perforations (holes) in the intestines.

Stivarga was approved in September 2012 to treat colorectal cancer and it is marketed by Bayer HealthCare Pharmaceuticals. 

Reference:

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm340958.htm

Working for a CRO's

What is it feels like to work in a CRO and how to start a career in this booming industry. The article in the web link shares us the most exciting views on this industry. With an average growth rate of 7% in R&D positions in CRO, seems to be a major player in bringing the drugs / life saving pharmaceutical products for the betterment of the society. Experts and well experience Professionals in this field share their views and experiences on the clinical research industry. 


CRO one acronym with two meanings ?

Contract research organizations and clinical research organizations share an acronym; sometimes the names are even used interchangeably. Whether this is one kind of company or two depends on whom we talk to.

While contract research organizations can span the entire pharma pipeline from drug discovery to clinical trials and beyond, a clinical research company mostly manages clinical trials. People in the R&D business often consider clinical research management companies a subset of the broader CRO category. 

But those in the medical and public health sector tend to consider clinical research organizations their own species, unrelated to CROs that focus on bench work. That’s something to bear in mind when applying for a CRO job: Make sure we research prospective companies well so we know what kind of company we're talking to.

Reference:

http://sciencecareers.sciencemag.org/career_magazine/previous_issues/articles/2012_05_25/caredit.a1200059

Clinical Trial Process

Drug Development Process:

Following figure shows the outline of the Drug development process during the various phases of Clinical Trials.

Cancer - Generic Drug -Approved by FDA

FDA approval of generic version of cancer drug Doxil is expected to help resolve shortage. FDA has approved its first generic version of the cancer drug Doxil (doxorubicin hydrochloride liposome injection). Doxil is currently on the FDA’s drug shortage list. For products on the shortage list, the FDA’s Office of Generic Drugs is using a priority review system to expedite the review of generic applications to help alleviate shortages.

The agency is committed to doing everything we can to address drug shortages so that patients can get the medicines they need when they need them. During the past year, FDA has been working to ensure that supplies of doxorubicin HCl liposome injection were not interrupted. Generic drugs approved by the FDA have the same high quality and strength as brand-name drugs. The generic manufacturing and packaging sites pass the same quality standards as those of brand-name drugs.

Manufacturer of Doxil : Sun Pharma Global FZE (Sun)

Mode of Administration of the drug: Doxil injection is administered intravenously by a health care professional.

Concentration: 20 milligram and 50 milligram vials.

In order to compensate the shortage of Doxil injection, FDA announced that it would exercise enforcement discretion for temporary controlled importation of Lipodox, an alternative of Doxil produced both by Sun and Caraco Pharmaceutical Laboratories Ltd, which is not approved in USA. Enforcement discretion was also used to release one lot of Janssen’s Doxil made under an unapproved manufacturing process.

For the present time, FDA intends to continue exercising enforcement discretion for importation of Lipodox, and limited supplies of Doxil are available. Once supplies of Sun’s generic doxorubicin hydrochloride liposome injection are sufficient to meet projected demand, FDA expects to stop exercising enforcement discretion for any unapproved doxorubicin HCl liposomal product.


Reference:

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm337872.htm

IEC - Redefining benefits to Subjects - India

Ethics Committee - Redefining compensation benefits to the Individuals in case of SAE (Serious Adverse Events)

In India, Pharmaceutical companies conducting clinical trial of drugs in India will no longer be able to get away with meagre and arbitrary payment of compensation in case of injury or death of subjects participating in such trials. 

For the first time in the medical history in the country, the Government has notified rules for grant of compensation in case of Serious Adverse Events (SAEs) like death and injuries on account of participation in clinical trial of drugs including biologicals and medical devices. 

There were no compensation provisions so far under the Drugs and Cosmetics Rules which govern approval of clinical trials by the Government. 

Compensation would now be awarded within three months of the reporting of injury or death. In the past five years, 2,242 people have died during drug trials in India, with an average compensation being awarded per death being a meagre Rs 2.2 lakh as per Health Ministry data. 

"With the notification of procedures of compensation, the Government has ensured the safety and rights of subjects participating in clinical trials. Henceforth all trials will be monitored at all the stages," a senior Ministry officer said. 

Drug Controller General of India, the apex drug regulator, will be the final authority for deciding the causes of injuries or death in clinical trials and also approving the final compensation amount in each case. Categories for grant of compensation have also been fixed depending on death, severe injury and minor injury and minimum compensation amount would soon be notified. 

So far, Ethics Committees set up by the sponsors of clinical trials, have been deciding the amount of compensation to be awarded in case of drug trial related injury or death. 

The amount would often be very low, a fact also pointed out by the parliamentary standing committee on health in its report on drug trials. 

According to the new notification, Ethics Committee of the medical institute conducting the trial, the sponsor of trial and its principal investigator will have to report the injury or death within 24 hours and submit their separate reports to the independent expert committee set up by the DCGI to review the case. 

The DCGI would recommend the final payment based on the independent probe panel's report, thus ruling out bias and unfairness.

Reference:
Economictimes.inditatimes.com

Clinical Trials Registry - EU

EU Clinical Trials Register

The EU Clinical Trials Register website allows us to search for information on clinical trials in European Union (EU) member states and the European Economic Area (EEA) and clinical trials which are conducted outside the EU/EEA if they form part of a paediatric investigation plan (PIP). The information on the website is collected and entered by national medicine regulatory authorities or by the addressee of a PIP decision for trials conducted outside the European Union. They are required by European Union law to enter details of clinical trials into a database called EudraCT. The information stored in this database is now being made publicly available through a new website, the EU Clinical Trials Register. The website is hosted by the European Medicines Agency (EMA). National medicines regulatory authorities and the addressees of PIP decisions collect and enter the information in the EudraCT database, this information is then displayed through the EU Clinical Trials Register website. Public personnel can find information on the design of each clinical trial, the sponsor, the investigational medicinal products and therapeutic areas involved and the status of the clinical trial. 

Treatment for Acute Lymphoblastic Leukemia in Children

FDA has now approved Gleevec (an TK inhibitor) for children with acute lymphoblastic leukemia

The U.S. Food and Drug Administration have now approved a new use of Gleevec (imatinib) to treat children newly diagnosed with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL).

This product is now marketed by Novartis.

ALL is the most common type of pediatric cancer, affecting approximately 2,900 children annually, and progresses quickly if untreated. Children with Ph+ ALL have a genetic abnormality that causes proteins called tyrosine kinases to stimulate the bone marrow to make too many immature white blood cells. This leaves less room for healthy white blood cells needed to fight infection.

Gleevec, a tyrosine kinase inhibitor, blocks the proteins that promote the development of cancerous cells. It should be used in combination with chemotherapy to treat children with Ph+ ALL.

“We are pleased that the number of cancer medications for children are on the rise,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval is the result of continuous interactions among the FDA, the Children’s Oncology Group and the National Cancer Institute to provide new and better treatments to American children with cancer.”

Gleevec’s safety and effectiveness for this new indication were established in a clinical trial conducted by the Children’s Oncology Group, sponsored by the National Cancer Institute. The trial enrolled children and young adults 1 year and older with very high risk ALL, defined as patients with a greater than 45 percent chance of experiencing complications from their disease within five years of treatment. Ninety-two patients with Ph+ ALL were enrolled in the trial and divided into five treatment groups, with each successive group receiving a greater duration of Gleevec treatment in combination with chemotherapy.

Fifty of the Ph+ ALL patients received Gleevec for the longest duration, and 70 percent of these patients did not experience relapse or death within four years (event-free survival). Results also showed patient deaths decreased with increasing duration of Gleevec treatment in combination with chemotherapy.

The most common side effects observed in children with Ph+ ALL treated with Gleevec in combination with chemotherapy included decreased levels of infection-fighting blood cells called neutrophils; decreased levels of blood platelets, which assist in blood clotting; liver toxicity; and infection.

Gleevec was granted accelerated approval in 2001 to treat patients with blast crisis, accelerated phase or chronic phase Ph+ chronic myeloid leukemia (CML) who have failed interferon-alpha therapy. It has since been approved to treat several conditions, most recently regular approval to treat children newly diagnosed with Ph+ CML (2011) and regular approval to treat adults whose Kit (CD117)-positive gastrointestinal stromal tumors (GIST) have been surgically removed (2012).

Reference:

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm336868.htm