FDA commissioner Dr. Margaret Hamburg launched a new initiative to innovate regulatory science so that it can keep pace with the evolution of biomedical research.  New pilot and feasibility studies are proposed to investigate early drug safety and efficacy.  In addition, use of genetic data and biomarkers may further elucidate disease targets and support efforts to optimize clinical trial design.  A key part of the plan is to set up centers of excellence in regulatory science, which would most likely be housed in academic centers, and would bring academia, FDA, and industry together in collaboration.  A new office, dedicated to regulatory science, will lead strategic development and co-ordination within FDA.  Initial efforts will focus on recruiting key personnel and building senior leadership.

Source: InPharm

In the FDA’s effort to make both its decisions and clinical trial data more transparent to the public, Agency decisions have become more available for public debate.  Sophisticated analyses (increasingly by third parties) of publically available data may present to the FDA a more complex picture of drug safety, as not all posted clinical trials fit standard regulatory paradigms, are sufficiently powered, have similar patient selection criteria,  or collect and analyze similar parameters. Changes made in the interest of public health, therefore, may further complicate regulatory assessment of potential changes to drug status.  For these reasons, among others, drug safety decisions are rarely “black and white.”  To its credit, the “new” FDA seems more open to try a middle path (e.g., the diabetes medicine Avandia will remain on the market under a restricted access program [risk evaluation and mitigation strategy, or REMS]).  Even more unusual, however, was public admission by the FDA of disagreement about Avandia within its own scientific ranks.  Furthermore, 3 top FDA officials co-authored a New England Journal of Medicine article explaining their rationale.  Interpretation of clinical trial data, however, is relatively easy compared to analyses of post-market safety data, where patient populations and indications are even more diverse.  It will be interesting to see how public access to evolving data (e.g., the anticipated FDA post-marketing drug safety (public) website) will affect Agency decisions, the timing of those decisions, and how much influence third-party analyses will have on regulatory outcomes.  The upside to the ensuing debate may be heightened public awareness of the importance of risk management, as all drugs have risk.  With the down-spiral of new drugs both coming to and remaining on the market, an outstanding question is whether the public and subsequently the regulatory environment will become more or less risk adverse as our perception of drug safety and risk management evolves.

Source: The New York Times

In February 2010 the FDA published “Guidance for Industry on the Contents of a Complete Submission for the Evaluation of Proprietary Names” (Guidance), which describes in detail the FDA’s evaluation methodology for proposed proprietary drug names.  By carefully examining this methodology and incorporating it into name clearance strategies, drug companies can optimize their chances of clearing drug names through the FDA review process.

Source:  Drug Discovery and Development  22 Oct 2010

Prior to drug approval, a potential new drug is usually subjected to the scrutiny of an expert advisory panel, selected by the FDA, who recommend whether or not the product should be marketed.   These recommendations are non-binding.  Industry analysts looked at product-specific decisions, a total of 120 votes, made by advisory committees to the FDA from 2007 through 2010.  The FDA followed its committees’ advice 74% of the time.  Significantly, only 3 times did the FDA overrule a “no” vote from the committee: Tarceva (lung cancer), Avastin (breast cancer), and Micardis (hypertension).  In other words, a “no” vote from an advisory panel is likely to meet acceptance, but a “yes” vote does not mean that the product will be approved.  All of the recent hype over obesity drugs aside, it is important to understand current events in light of historical precedence.  It also highlights the importance of risk management, particularly when dealing with drugs that have blockbuster potential.

Source: Forbes

As of 15 June 2010, the new Food and Drug Administration (FDA) Postmarketing Drug Safety Evaluation website was launched.   The FDA posted postmarket safety evaluations for 26 drugs approved between September 2007 and January 2008 and is reviewing an additional 20 or 30 others. To date, no label changes have been recommended.

In accordance with the Food and Drug Administration Amendments Act of 2007 (FDAAA), the FDA now summarizes information about ongoing and completed postmarketing safety evaluations of serious adverse events (SAE) submitted to the FDA for New Drug Applications (NDAs) and Biologic License Applications (BLAs) that have been approved since 27 September 2007.   These evaluations are completed to determine if there are any new SAE not previously identified during product development, known side effects reported in unusual number, or potential new safety concerns identified post approval.  These postmarketing evaluations will be performed no later than 18 months following approval (i.e., early in the product’s marketed life cycle) or after its use by 10,000 individuals, whichever is later.

To develop these postmarketing safety evaluations the FDA assesses several data sources including:
• The product’s pre-approval safety profile
• The product’s current FDA-approved label
• Reports made to FDA’s Adverse Event Reporting System (AERS)
• Reports made to the Vaccine Adverse Event Reporting System (VAERS)
• Manufacturer-submitted periodic safety reports
• Medical literature
• Drug utilization databases
• Data from post-approval clinical trials and other studies, when applicable

FDA analyses for the safety evaluations include:
• Data mining analysis of all adverse event reports in the AERS or VAERS databases
• Review serious adverse event reports
• Medication error analysis
• Product utilization analysis
• Risk management review
• Analysis of post-approval safety data from clinical trials and other studies, when applicable

Summaries of FDA safety analyses on recently approved products will now be prepared quarterly and posted on FDA’s website along with a brief discussion of the steps FDA is taking to address any identified safety issues.

Related posts:

New On-line Quarterly Drug Safety Summary and REMS are Complimentary Efforts
Postmarket Drug Safety: Institute of Medicine Recommendations to FDA

Sources:

FDA-1,   FDA-2,   Resource Shelf,   USA Today,   World Pharma News

To share this post easily, cut and paste:  New FDA Postmarketing Drug Safety Evaluation Website   http://bit.ly/b79Fqs

On May 24, 2010, the Food and Drug Administration (FDA) and the National Institutes of Health (NIH) launched a new Web site that, when fully developed, will provide a mechanism for the reporting of pre- and post-market safety data to the federal government.  Currently the Web site can be used to report safety problems related to foods, including animal feed, and veterinary drugs, as well as adverse events occurring on human gene transfer trials.  Consumers can also use the site to report problems with pet foods and pet treats.  For the present, however, this safety portal will be of limited use for human pharmaceuticals.

Source: FDA

The Food and Drug Administration (FDA) is responsible for ensuring the safety of prescription drugs.  Though all drugs are tested in clinical trials before they are available to the public, the risks of some drugs may not appear until well after they are approved.  With the passage of the Food and Drug Administration Amendments Act (FDAAA) of 2007, the FDA can now require clinical trials or other studies to assess the safety of approved drugs.  With this new authority, the FDA must decide when it is ethical for the Agency to require or continue to require clinical trials, and how to ensure the safety of trial participants.

The FDA requested that the Institute of Medicine (IOM) examine when and how to conduct clinical trials ethically to evaluate drug safety. The IOM recommended that the FDA should ensure that any randomized, controlled trial to evaluate the efficacy and safety of an approved drug that is suspected of causing serious adverse events is conducted only when a responsible policy decision cannot be made based either on the existing evidence or on evidence from new observational studies.  The IOM suggested that observational studies – often done by reviewing insurance claims and other databases – can yield strong enough evidence to make a decision on a marketed drug.

The Agency should determine that questions about a drug’s possible risks or risk-benefit balance rise to the level of requiring a policy decision, such as whether to revise the product’s label.  In addition, FDA should make sure that trials are appropriately designed to resolve uncertainties about efficacy and safety and to minimize risks to participants.  A conceptual framework broadly applicable to many situations is provided.

This report is part of a larger study of the scientific and ethical issues involved in conducting studies of the safety of approved drugs. A comprehensive report is expected in 2011.

Sources: IOM and Office of News and Public Information.  Free report available from these sites.

Concurrent Information:

Experts urge limits for some drug safety trials;

When is a drug too risky to stay on the market?

Although the Food and Drug Administration (FDA) routinely reviews the safety and effectiveness of all prescription drugs prior to approval, some side effects become evident only after the drugs are taken by millions of patients – far more than it is possible to test in clinical trials.  A drug’s side-effect profile becomes better characterized, therefore, with greater exposure and use.  Additionally, once marketed, many drugs are prescribed for alternate disease states with new target populations; unanticipated safety issues may arise in new target populations.  For this reason, the new on-line quarterly reports (launched 15 June 2010) will  address safety risks that were not identified during a drug’s development or prior to FDA approval.  These reports are targeted to appear within roughly 2 years of a new drug’s approval (back to 27 September 2007) or, for drugs that have Risk Evaluation and Mitigation Strategies (REMS), since the REMS was required or last assessed.  REMS ensure that the benefits of a drug or biological product outweigh its risks.

Quarterly safety summaries incorporate potential signals of serious risks/new safety information identified by the Adverse Event Reporting System (AERS) as well as by FDA-initiated research.  When a potential signal of a serious risk is identified from AERS data, it is entered as a safety issue into the Center for Drug Evaluation and Research (CDER) Document Archiving, Reporting, and Regulatory Tracking System (DARRTS) or into the Center for Biologics Evaluation and Research (CBER) Therapeutics and Blood Safety Branch Safety Signal Tracking (SST) system.  Although potential signals of serious risks are usually based upon groups of AERS reports, a single AERS report could initiate the evaluation of a potential safety issue.  FDA posts each potential signal of a serious risk in the quarter in which it is first identified.  If additional safety information is developed concerning a potential signal that has already been posted, it is addressed by FDA in new safety communications/updates, but does not appear again as a new quarterly posting.  Listing does not necessarily imply a causal relationship between the drug and the identified risk.  The FDA is requiring REMS formulation as well as posting of  quarterly drug safety reports in accordance with Title IX, Section 921 of the FDA Amendments Act (FDAAA) of 2007 (see insert).

Source: The Herald Sun

Relevant References: Mass Tort Defense,  FDA Law Blog, FDA Transparency Blog

Face it, the Food and Drug Administration’s (FDA) website is not the most user friendly of Regulatory options!  For the incredibly low price of $30 USD you can now have a comprehensive superset of 4 CD‑ROMs which provide an up-to-date collection of documents, manuals, publications, and reference sources on the FDA, including drug safety.  Not bad for those of us short on time!

Source:  Product Recalls

On 19 May 2010, a FDA task force proposed 21 ways that the Agency could release more information to the public in areas like drug evaluation, including information about safety problems with the drugs and devices it rejects.  Although the FDA has long operated under strict confidentiality rules with respect to submitted proprietary information from food, drug, and device companies, this policy has been criticized in recent years.  Critics have charged that the Agency is too slow to disclose drug safety issues (e.g., the links between the popular pain killer Vioxx with heart attack and stroke).  Advocates claim that greater transparency would benefit both consumers and companies, who will be able to learn from the success and failures of competitors.  Approximately half of the new suggestions are designed to give more information about experimental drugs and devices under review at the Agency.  Under current FDA regulations, communication about such products is extremely limited.  The Pharmaceutical Research and Manufacturers Association generally supports increased transparency by the Agency, but industry want to ensure that the competitive development process and intellectual property protections remain intact.  Other items under proposal are discussed.  Comments on the recommendations are being solicited by the FDA task force until July 20, 2010 before the final list of changes for implementation will be submitted to Commissioner Hamburg for consideration.  Note that not all proposals will necessarily be implemented.

Source text:  Drug Discovery & Development – May 21, 2010);  Product Applications (including Investigational Applications) – FDA updated on May 20, 2010.