Читать книгу Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition) - William Gregory - Страница 80

This is the prime (and largest) center in the FDA for handling the safety of biopharmaceutical products in the US. The Center for Drug Evaluation and Research (CDER) handles new drugs from the IND stage (when a product first moves into human study) to the evaluation of the NDA/ANDA or BLA for approval or rejection of the request to market the product in the United States. A separate group within CDER then evaluates the post-marketing safety of the product on a continuous basis. Although simple in theory, the actual practice is complex and has evolved over time. It continues to change, often in response to Congressional mandate, and should be viewed as a work in progress.

The FDA organization chart is posted online and is quite useful. It gives names, addresses, and contact information on the FDA organization and key personnel (www.fda.gov). The chart is updated regularly with changes (see below). When this chapter was written, there were 45 “offices” in CDER covering many areas, including biotechnology, new medical product evaluation, counterterrorism, pediatric drug development, generic drugs (including biosimilars), compliance, biostatistics, prescription drug promotion, translational sciences, and, of course, product safety.

See CDER’ s website (www.fda.gov/cder). In 2017, there were 33 advisory committees made up of external members, who provide consultation and give expert and consumer advice to the FDA. The FDA generally follows an advisory committee’s recommendation, but is not bound to do so. There is an advisory committee on Drug Safety and Risk Management that evaluates new products and safety concerns across the product lifecycle continuum.

The FDA reorganizes periodically. As of mid-2018, the structure was as follows: the Office of the CDER Center Director has under it approximately 32 offices, including the Office of Surveillance and Epidemiology (OSE). OSE is considered a safety “SuperOffice”, available for consultation on safety concerns across all of FDA, not only CDER-regulated products. In 2018, were two Offices and six divisions in OSE:

Office of Pharmacovigilance and Epidemiology Division of Pharmacovigilance I & II (two divisions): The staff includes safety evaluators whose primary role is to detect and assess safety signals for all marketed drug products. They work closely with medical reviewers in the Office of New Drugs so that potential safety signals are placed in the context of existing preclinical, clinical, or pharmacologic knowledge of the drug(s) being evaluated.

Division of Epidemiology I & II (two divisions): The staff conducts active surveillance using the Sentinel System and also conducts epidemiologic studies using observational data sources. An increasingly important activity is the review of epidemiologic study protocols, which are conducted by applicants as post-marketing commitments or post-marketing requirements. The Division evaluates various post-marketing surveillance tools that may be incorporated into non-routine risk minimization strategies, such as patient registries and restricted distribution systems. They estimate the public health impact of safety signals by evaluating digital claims databases, healthcare datasets, and the published literature, etc.

Office of Medication Error Prevention and Risk Management Division of Medication Error Prevention and Analysis: The staff provides pre-marketing reviews of all proprietary names, labels, and labeling for CDER-regulated products to reduce the potential for medication errors of a proposed product. The division also provides post-marketing review and analysis of all medication errors received by the Agency.

Division of Risk Management: The staff handles data resources, risk communication, and outcomes and effectiveness research components of drug safety risk management programs (i.e., Risk Evaluation and Mitigation Strategies (REMS)). This division oversees MedWatch, risk communication research, and activities such as Medication Guides, Patient Packet Inserts, and pharmacy information surveys, and international regulatory liaison activities (such as videoconferencing) for all drug and post-marketing safety issues for therapeutic biologics.

In 2005, the FDA created a new Drug Safety Oversight Board (DSB), which advises the CDER Center Director on handling and communicating important and emerging drug safety issues. The board meets monthly and is composed of representatives from three FDA Centers and six other federal government agencies: the Agency for Healthcare Research and Quality (AHRQ), Centers for Disease Control and Prevention (CDC), Department of Defense (DOD), Indian Health Service (IHS), National Institutes of Health (NIH), and Department of Veterans Affairs (VA). The DSB provides scientific and regulatory recommendations on drug safety and communication issues and policies to the senior FDA management on the following:

Potentially significant drug risks and safety issues;

Effective communication of drug safety information to healthcare professionals, patients, and the general public;

Establishment of general policies regarding drug safety issues and approaches to resolving internal FDA policy differences and disagreements; and

Disputes between a sponsor and CDER concerning Risk Evaluation and Mitigation Strategies (REMS) that occur after approval of a prescription product, if the sponsor requests DSB review.

FDA’ s SOP for the board is available (www.fda.gov). In fact, almost all of FDA’s policies and procedures are available on their website. The FDA has an extensive, useful website, although the information tends to be scattered and difficult to find. There is a search engine that is somewhat useful. The website has extensive information on how the FDA works, its history, drug availability, counterfeits, Internet purchases of drugs, labeling and medication guides for drugs on the market, signals, REMS, guidance, laws and regulations covering pharmaceuticals (as well as devices, biologics, radio-logic agents, over-the-counter (OTC) products, nutraceuticals, and more). The main CDER website lists late news and provides a jumping off point to other CDER information, including:

FDA Basics: This provides fundamental information on the various divisions, functions, and leaders at FDA.

Drug-Specific Information: This is an alphabetical list of drugs that have an information sheet, Early Communication about an Ongoing Safety Review, or other important information.

Development and Approval Process for Drugs: This provides information on how drugs are developed and approved.

Guidance, Compliance, and Regulatory Information: For industry, this key page for pharmacovigilance (PV) professionals has links to information on laws, acts, rules, good review practices, enforcement activities, surveillance, post-marketing commitments requirements, warning letters, enforcement actions, new guidance documents, cyber letters, and the CDER manual of policies and procedures.

Information for Industry: This is a page for the pharmaceutical industry with links to guidance, post-marketing information, the Prescription Drug User Fee Act (PDUFA, which is renewed every 5 years), industry fees, warning letters, electronic submissions, the Orange Book (approved drug products with therapeutic equivalence evaluations), abbreviations, and types of applications.

JumpStart: This is a tool for FDA reviewers to gain insights on data fitness in an application and which analytical tools might be appropriate for use in the review. This was spawned by CDER’s 21st Century Review Process, which is an integrated review process that partitions work into IT functions and scientific analysis. JumpStart is intended to be applied to electronic data between submission of a marketing application by industry and filing of the application by CDER.

MedWatch: See below for more detailed information.

Drugs at FDA: This is a link to the page that has an alphabetical list and search engine to find approved drugs by name, active ingredient, or application number.

openFDA: This is a software tool designed to facilitate public access and use of public FDA data.

Recalls, Market Withdrawals and Safety Alerts.