New Warnings for Aliskiren & FDA / Novartis to Pull Valturna

The FDA issued new warnings about antihypertensive medications which contain aliskiren (Tekturna, Amturnide, Takamio, and Valturna) when used in combination with ACE inhibitors or angiotensin receptor blockers (ARBs). The FDA indicates that the drug combinations are contraindicated in patients with diabetes, and it is adding a new warning to avoid the use of this combination in patients with moderate to severe renal impairment (GFR <60 mL/min).

Novartis has announced it will pull Valturna from the U.S. market.  Valturna contains aliskiren (Tekturna^®) as one of its ingredients.

New EU Pharmacovigilance Legislation and Signal Detection

The new European Union Pharmacovigilance legislation was published in December 2010 and regulations go into effect in early July 2012.  A number of significant changes will take place.  The Regulations and Directives are legally binding.

One of the major changes is found in signal detection.  Industry will now need to have specific measures in place that document the process of signal detection.  Issues that need to be considered are the frequency of monitoring data, prioritization of signals...and a documented process.

This change has potential advantages and disadvantages.  Capturing and identifying signals in a timely fashion is essential.  The benefit to early detection of an Adverse Drug Reaction (ADR) is the possibility of improving patient safety.  ADR determination is based on a number of pharmacological and medical considerations.  Sometimes an ADR determination is made after a number of events are detected.  For serious and rare ADRs it is reasonable to make a determination with fewer events; one event may be enough to make an ADR association between the drug and the adverse reaction.

Considering the Benefit : Risk ratio or profile is quite important.  As in many of life's situations there are associated benefits and risks to any medical intervention.  Before starting a treatment or having a procedure these need to be taken into consideration.  The same holds true during the development of a product; the pros and cons must be weighed during this period as well as into the later stages of the product's lifecycle.  Patients who are on a treatment or who have received a medical device need to understand the potential impact of the detection of a signal that is related to their treatment or medical device in order to make an informed decision regarding choices that they may make in their healthcare.

For some people the benefit will be of greater importance than a possible risk.  Others will not want to take on the risk associated with a particular treatment.

Update on Breast Implants

Poly Implant Prothèse (PIP), a French medical devices manufacturer  produced breast implants   from 1991 to 2011.  The company utilized silicone in its implants.  In 2000 the US FDA launched a moratorium on silicone implants.  Some reports indicate that PIP introduced the use of industrial-grade silicone in 2001 in some of their products rather than approved medical-grade silicone.  Other sources say that the change in grade of implant may have occurred as early as 1997.

French surgeons began reporting a significant increase in the rupture rate of the implants in 2009.  This led to legal action against PIP and ultimately the company went bankrupt.

In December 2011, following the death of a female patient in France from Anaplastic Large-Cell Lymphoma (ALCL), which has an increased incidence in women with silicone breast implants, the French government recommended that the PIP implants with the industrial-grade silicone be removed from 30,000 women in France.

The company also made male chest, testicle and buttock implants.  The majority of these implants were exported to Latin America.

In the United Kingdom, it is estimated that 47,000 British women have received PIP breast implants.  The Medicines and Healthcare products Regulatory Agency (MHRA), which is England's agency responsible for enhancing and safeguarding the health of the public by ensuring that medicines and medical devices work and are acceptably safe, advises that there is no evidence to recommend routine removal of the implants.  Nevertheless, there is concern amongst women who have the PIP breast implants, plastic surgeons and other physicians.  The National Health Service (NHS) has stated that the private firms that placed the implants would remove them without charge.  The NHS  also said that any woman who is not given help by a private facility could visit their General Practitioner and have access to NHS services.

Outsourcing Pharmacovigilance

Not long ago many within Pharma thought that Drug Safety was an evil, unnecessary cost center. Over time the perception has changed and it's now recognized that Pharmacovigilance is an important function which is essential to protect the patient, public and product. Nevertheless, budget restraints and the rising costs of maintaining a professional workforce have led many across the industry to consider outsourcing. There's yet another reason for outsourcing: The shear volume of data coming in which needs to be collected at call centers, entered into databases, queried, cleaned, analyzed and reported makes this a task that must be shared round the clock and globe.

Reporting a Reaction to a Drug in the EU

In the European Union (EU), patients do not report directly to the Regulatory Authorities. The EU agency that is responsible for Drug Safety (Pharmacovigilance) is the European Medicines Agency (EMA), similar to the US Food and Drug Administration (FDA). Patients in the EU should report side effects to a medicine by informing their doctor or pharmacist. According to the EMA, these health care professionals can help put the information into the right medical context for further evaluation by the authorities, particularly if they suspect a serious or severe reaction. The EMA's goal is evaluate each case and when indicated take action, which

will involve warnings to the public and the medical community aimed at ensuring the safe use of a medicine and the prevention of future side effects. In extreme situations and, when justified, medicines have been removed from the market in order to protect public health. This is when the balance of risks outweighs benefits of the particular medicine. The EMA maintains a very informative website www.eudravigilance.ema.europa.eu

The Campaign for Modern Medicines

Eli Lilly and Company, a large US based pharmaceutical company, has created a website at modernmedicines, which is geared to providing information related to a petition that they have created to inform Congress that The Prescription Drug User Fee Act (PDUFA) needs to be "cleaned." The objective of the website and petition is “that patients deserve timely access to lifesaving medicines and that the U.S. must remain the global leader in discovering and delivering these breakthrough cures and treatments." They are asking public citizens to stand with the Campaign for Modern Medicines and urge Congress to pass PDUFA by July 4th free of extraneous additions that bring new costs and burdens to the FDA.”

The Benefits of Drug Safety in Early Stage Drug Development

I am presenting a talk on "The Benefits of Drug Safety in Early Stage Drug Development" at the upcoming Early Stage Clinical Development conference in Boston, MA on May 29, 2012. Information about this event can be found at the following LINK.

Learn About Pharmacovigilance

Drug Safety or Pharmacovigilance is an important endeavor that helps to protect patients and the public health. There are agencies throughout the world that have been set for this purpose. Additionally, pharmaceutical companies conduct activities on an ongoing basis to assure that patients and the public are protected and that medicines are being used safely and effectively. A variety of courses are given throughout many locations that help to educate individuals who are responsible for Pharmacovigilance. In April 2012 there was a meeting in Boston, MA "World Drug Safety Congress Americas" that provided a venue for learning and discussing a wide range of relevant topics concerning patient safety and new regulations that will have a major impact on how Pharmacovigilance are conducted. I was one of the speakers at this event and reviewed "The Key Clinical Safety Challenges: Signal Detection and Analyzing Safety Data Efficiently and Effectively." Information about the meeting can be found on the World Drug Safety Congress link here.

Reporting A Safety Issue in the US

The U.S. Food and Drug Administration (FDA) is the agency that is accountable for protecting and promoting public heath in the United States. It does this by setting regulations, conducting inspections and analyzing adverse events (AEs). The FDA maintains a computerized database where information related to AEs is stored and then analyzed. This database is called the Adverse Event Reporting System (AERS). The FDA monitors the AEs in the database to determine if there are signals that could represent a health risk to the patients and public. The reporting of AEs is done on a voluntary basis by healthcare providers, patients and the public. Manufacturers of medications are required to report information related to AEs that they become aware of either through the conduct of clinical trials or that occur spontaneously in patients taking medicines that are marketed by the company. Reporting of Adverse Events can be done as follows: Consumers and Healthcare Providers can report Adverse Events online or using a form available through the FDA by clicking here or pasting the following URL into their web browser: https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm

Drug Safety

Drug Safety is also known as Pharmacovigilance (PV). The World Health Organization (WHO) has defined PV as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. WHO established its Programme for International Drug Monitoring in response to the thalidomide disaster detected in 1961. Together with the WHO Collaborating Centre for International Drug Monitoring, Uppsala, WHO promotes PV at the country level. At the end of 2010, 134 countries were part of the WHO PV Programme. The aims of PV are to enhance patient care and patient safety in relation to the use of medicines; and to support public health programmes by providing reliable, balanced information for the effective assessment of the risk-benefit profile of medicines.