Preclinical models are developed to test lead compounds for toxicity and efficacy.  This report  1) explores novel preclinical models (in vivo, in vitro, in silico, and systems biology) that show promise to expedite and improve the target validation, lead optimization, and toxicity screening timelines, and 2) discusses the various advantages and disadvantages of Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) screening techniques.  In addition, the report provides an outlook for preclinical testing over the next decade.  It focuses on more than 60 companies that are involved in using or developing ADMET technologies to advance preclinical research and provides an update on how new models and systems have been employed to accelerate the discovery and development process.

Scope of this report

•  Understand the basis of ADMET testing and why it is a necessary and important component of preclinical research
•  Up-to-date information on the preclinical models and systems currently used in drug discovery and development.
•  Evaluation of the key recent developments and activities of companies who are developing and licensing new ADMET technologies.
•  Identification of existing models and how new ones are being developed to improve productivity and knowledge.

Source:  Business Insights

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?

On 15 July 2010 the European Medicines Agency (EMA) launched a new comprehensive website to address the regulation and safety of drugs (human, veterinary, and herbal) in the European Union.  The site has been completely redesigned to optimize usability for the Agency’s key online audiences and built on existing activities to improve openness and transparency.  Note that previously saved URLs may not be redirected to the new site.  If you are looking for a particular document or piece of information, contact info@ema.europa.eu or use the document library search to locate the documents.

Sources:Drug Injury Watch and EMA .

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

The recent approval by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) of the 7 protein biomarker panel for use in detecting drug-induced kidney damage means that the biomarkers are now qualified at the same level by all of the ICH regulatory agencies.  In a Critical Path Initiative statement, this is the first biomarker qualification decision by the PMDA and means that the panel is qualified for voluntary use in nonclinical safety studies.  Furthermore, data generated using the panel can be submitted to the PMDA on a case-by-case basis for use in monitoring drug-induced renal toxicity in humans.  The 7 biomarker panel,  composed of kidney injury molecule-1, albumin, total protein, β2-microglobulin, cystatin C, clusterin, and trefoil factor 3, can be utilized in conjuntion with the current standard renal biomarkers, serum creatine and blood-urea nitrogen.  With the exception of trefoil factor 3, the PMDA stated that the new renal biomarkers outperformed the current standard biomarkers.  The renal biomarker panel received approval in 2008 from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for limited use in nonclinical and clinical drug development.  Additional guidelines regarding biomarker qualification are expected in July 2010.

Source: ProteoMonitor and MedHealthWorld

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.

As brought to my attention by Sanchayita Kar, Founder and President, SciClips has created a unique and comprehensive database on therapeutic drug targets (~4000) that have been reported in US patents or US/International patent applications.  The drug targets are classified according to specific drug (e.g., small molecule, protein, antibody, siRNA, miRNA, etc.) and disease types.  Assays and methods utilized for characterizing each drug target are listed as well.  In addition, all the drug targets are linked to PubMed (articles), Google Scholar (articles), GeneBank (nucleotide sequence), UniProt (protein sequence), USPTO database (full text patents/patent applications), WO(PCT) database (full text international patent applications), and Google Patents (full text US patents).  This multifaceted database may be useful in the determination of potential mechanisms for target-organ toxicity.

SciClips is a web-based platform for open innovation and information sharing on topics such as stem cells, proteomics, biomarkers, metabolomics, and drug discovery.  This innovative platform promotes the sharing of ideas through multidisciplinary and global approaches that can be utilized for research or product development without any licensing agreements or fees.