The average cost of developing a drug was $1.3 billion as of January 2011.  The average first-cycle approval rate for standard new molecular entities (NME) has increased from an average of 30% in 1992 to 38% this year.  Priority NMEs have fared better with the FDA, with approvals rising from 46% to 68% during this same period.

The Food and Drug Administration Amendments Act (FDAAA) of 2007, which allowed FDA to require post-marketing studies and clinical trials to address outstanding drug safety questions, lowered the percentage of new drugs, biologics, and efficacy supplements approved by the FDA to below 80% in 2Q 2009.  By 1Q 2011, that percentage returned to the mid 90% range, about the same as in 1Q 2005.

The current forth authorization of the Prescription Drug User Fee Act (PDUFA IV) expires at the end of September 2012.  According to the Draft Commitment Letter signed by the Federal Drug Administration (FDA), Biotechnology Industry Organization (BIO), and Pharmaceutical Research and Manufacturers of America (PhRMA),  to increase the chances of successful first-cycle approvals, PDUFA V will delay the start of FDA’s clock for its first review cycle to after its 60-day administrative filing review period.  Once the clock starts, however, FDA is committed to reviewing and acting on 90% of standard NME, New Drug Application (NDA), and original Biologics License Application (BLA) submissions within 10 months —12 months from the date of filing.  FDA has also committed to reviewing 90% of priority NME, NDA, and original BLA submissions within 6 months, or 8 months from the filing date.  Furthermore, once the PDUFA V review clock starts running, drug developers and FDA officials must meet 3 times:

•    A pre-submission meeting at which “the applicant is strongly encouraged to discuss the planned content of the application.”

•    A new mid-cycle meeting, to which the FDA will call an applicant, will generally be held within 2 weeks after the Agency holds its own internal mid-cycle review meeting on an application.

•    A late-cycle meeting at which FDA’s review team will meet with an applicant to discuss the status of Agency review of the application late in the review cycle.

The new mid-cycle review meeting is meant to provide an opportunity for the Sponsor and Agency to discuss what issues have been identified and how to resolve those issues.  It also provides an earlier opportunity for the Agency to alert the Sponsor if additional information is needed related to labeling, Risk Evaluation and Mitigation Strategies (REMS), and post-marketing commitments.

PDUFA V raises to $3 billion the amount of user fees to be collected by the Agency from a Sponsor.  User fees of $2.9 billion are required by PDUFA IV.  This user-fee increase will enable the Agency to hire additional staff to review drug and biologic applications.  PDUFA V also commits the FDA to develop staff capacity to review submissions that involve pharmacogenomics and biomarkers and to fund the FDA regulatory science initiatives.  To this end, target dates for completion of new initiatives have been set.

• Oct. 24, 2011: FDA will hold a public meeting to discuss PDUFA reauthorization.

• Sept. 30, 2013: FDA will develop a dedicated drug development communication and training staff within the Office of New Drugs (OND) in the Center for Drug Evaluation and Research (CDER), and increase the existing manufacturers’ assistance staff at FDA’s Center for Biologics Evaluation and Research (CBER).   The CDER Rare Disease Program within OND will increase the number of staff focused on rare disease drug reviews, which is particularly important due to the increasing emphasis placed by Big Pharma on orphan drugs.

• Sept. 30, 2014: OND drug development and communication staff will provide training to all CDER staff involved in review of Investigational New Drug (IND) applications.

• March 31, 2015: FDA will publish draft guidance for review staff and industry describing best practices for communication between FDA and IND sponsors during drug development.

And finally in regards to drug safety and as an effort to lessen the effect of politically-induced risk aversion by the Agency, PDUFA V also calls for greater integration of patient perspectives into the review criteria.  The Agency has explicit plans over the course of the PDUFA V period to change the way it assesses benefits and risks, as well as the endpoints used to assess safety and efficacy, based on the advice it receives from patients.

Sources: Genetic Engineering and Biotechnology News, BioPortfolio, BioCentury, Legal News Directory, FDA

In order to keep our competitive edge, the Federal Drug Administration (FDA) is placing increased emphasis on strengthening both the field and application of regulatory science relative to pharmaceutical research, development, review, and post-market surveillance.  The FDA also has a mandate to recognize areas of unmet public health need and try to galvanize action to move appropriate new products through the pipeline and into the market.  The FDA has the responsibility, therefore, not just to review and approve products if the data support that decision, but also to follow these products once marketed to answer critical questions about efficacy and safety.  Examination of products across their life cycle enables not only the identification and analysis of emerging safety signals, but also facilitates the continual balancing of risks and benefits.

Research studies, both preclinical and clinical, that form the basis for approval of medical products are increasingly being performed in other countries and often in networks of other countries.   For this reason, international recognition of both the scientific appropriateness and ethical conduct of those studies becomes increasingly important to global regulatory bodies.  A key understanding is that if a safety concern develops for an approved drug, it does not necessarily reflect that a mistake was made.  It may instead reflect new emerging knowledge about that drug in practical use.  Regulatory safety has to be a dynamic process.  The desire is to proactively ensure that the right studies are done so that the best possible decisions result.  However, there isn’t always an absolute, clear decision to be made; resolution, therefore, requires a dynamic balancing of risks and benefits.  Questions need to be asked about whether certain subpopulations of patients may benefit from targeted use of a drug, or whether the safety concerns are sufficient to mean a more active withdrawal of a product from the market.   Advances in science and technology need to be better incorporated into the regulatory process, with a key area being safety science.   To continue to strengthen the science of regulatory safety, the need is to broaden not only the kinds of preclinical and clinical studies that can be done to deepen our understanding of safety, but also to broaden our understanding of how to apply and weight that data to further the science of risk management.

Source: Interview between Dr. Eli Adashi, Professor of Medical Science at Brown University and host of Medscape One-on-One, and Dr. Margaret Hamburg, Commissioner of the US Food and Drug Administration.  MedScape Today.

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

The Australian TGA has adopted the EU Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals (ICH M3(R2)bb).  The effective date was November 5, 2010.   The purpose of this document is to recommend international standards for, and promote harmonization of, the nonclinical/preclinical safety studies recommended to support human clinical trials of a given scope and duration as well as marketing authorization for pharmaceuticals.  This guidance should facilitate the timely conduct of clinical trials, reduce the use of animals in accordance with the 3R (reduce/refine/replace) principles, and reduce the use of other drug development resources.

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

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 .

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

The Federal Register and the ICH S9 Guidance for the nonclinical evaluation for anticancer pharmaceuticals issued today.  The guidance provides recommendations for preclinical studies for the development of pharmaceuticals, including both drugs and biotechnology derived products, intended to treat patients with advanced cancer.  The recommendations describe the type and timing of preclinical studies to support an investigational new drug application (IND) and the submission of a new drug application (NDA) or biologics license application (BLA).