Abstract
The Center for Drug Evaluation and Research (CDER)/FDA web page, 〈http://www.fda.gov/cder〉, contains a wealth of information regarding development of pharmaceuticals and pharmaceutical information. We will focus this review primarily on nonclinical information.
The main CDER web page lists the most recent product approvals and other news of greatest interest, including the most frequently used links to Drug Safety and other topics, including the inactive ingredient database, and the orange book (approved drug products with therapeutic equivalence evaluations). A link to the Advisory Committee home page leads to lists of the Advisory Committees, the members, and upcoming meetings, as well as to staff contacts and minutes of past meetings.
〈http://www.fda.gov/cder/audiences/acspage/index.htm〉 is the general link for advisory committee information. Although the advisory committee meetings generally focus on efficacy issues, approval decisions are always a balance of safety and efficacy, and sometimes safety concerns based on pharmacology or toxicology data are an important part of a meeting. Also seen on the main page are tabs at the top, which allow easy access to information about CDER, drug information, regulatory information, the CDER calendar, information for specific audiences, and document archives.
The “About CDER” tab has links under “Who We Are” for key officials, organizational charts, and links to office and home pages. The Pharmacology/Toxicology contacts are listed at 〈http://www.fda.gov/cder/PharmTox/contact.htm〉. Under “What We Do” is a list of FDA and CDER facts and lists, news, and training information, as well as CDER history and regulatory authority. One example is 〈http://www.accessdata.fda.gov/scripts/cder/iig/index.cfm〉, an inactive ingredient database.
The “Drug Information” tab includes information on recent drug approvals at 〈http://www.fda.gov/cder/rdmt/default.htm〉. This tab also includes links to information on prescription and over-the-counter drugs, consumer drug information, drug safety and side effects, clinical trials, health alerts and warning letters, and reports and publications.
Under the “Regulatory Guidance” tab, there are links to regulatory and scientific guidance, the drug development and approval processes, policies and procedures, and guidance documents. The drug approval process is described at 〈http://www.fda.gov/cder/regulatory/applications/default.htm〉, including how to file an application for an investigational new drug or a new drug application. Under the “Manual of Policies and Procedures” (MaPPs) at 〈http://www.fda.gov/cder/mapp.htm〉 under “Pharmacology and Toxicology” is Chapter 7400, the collection of MAPPs that apply to pharmacology and toxicology, mainly management of various CDER Pharmacology/Toxicology Coordinating Committees. Two MaPPs of interest to persons outside of the FDA are 7412.1 Management of CDER Carcinogenicity Assessment Committee (CAC) and Executive CAC, and 7412.2 Distribution of Final Reports from the Carcinogenicity Assessment Committee (CAC) and the Executive CAC). Also included under the Regulatory Guidance tab are links to Freedom of Information and the electronic document reading room. The link at 〈http://www.fda.gov/cder/foi/index.htm〉 explains how to get more detailed information through freedom of information requests if the web page and its links do not lead one to sufficient details.
At the CDER/FDA Guidance document web page, 〈http://www.fda.gov/cder/guidance/index.htm〉, of particular interest are the International Conference on Harmonisation (ICH) and FDA Guidance documents. ICH Guidances are the product of agreements among the United States, the EU, and Japan. ICHM3 (R1) Nonclinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals discusses when in pharmaceutical development various nonclinical studies need to be conducted. The ICH S1 guidances discuss various aspects of carcinogenicity studies. The S2 guidances discuss genotoxicity. The S5 guidances discuss reproductive toxicity. Other ICH S series guidances discuss pharmaco/toxicokinetics, safety pharmacology, biotechnology-derived products, and immunotoxicity. The Q3 documents discuss when impurities need to be investigated and possible nonclinical studies needed.
On the Guidance document web page under Pharmacology/Toxicology 〈http://www.fda.gov/cder/guidance/index.htm#Pharmacology/Toxicology〉, CDER/FDA also has guidances on a variety of topics that include nonclinical issues:
Carcinogenicity Study Protocol Submissions
Content and Format of INDs for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-Derived Products
Developing Medical Imaging Drug and Biological Products: Part 1: Conducting Safety Assessments
Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers
Exploratory IND Studies
Format and Content of the Nonclinical Pharmacology/Toxicology Section of an Application
Immunotoxicology Evaluation of Investigational New Drugs
Nonclinical Pharmacology/Toxicology Development of Topical Drugs Intended to Prevent the Transmission of Sexually Transmitted Diseases (STD) and/or for the Development of Drugs Intended to Act as Vaginal Contraceptives
Nonclinical Safety Evaluation of Drug or Biologic Combinations
Nonclinical Safety Evaluation of Pediatric Drug Products
Nonclinical Studies for the Safety Evaluation of Pharmaceutical Excipients
Photosafety Testing
Recommended Approaches to Integration of Genetic Toxicology Study Results
Reference Guide for the Nonclinical Toxicity Studies of Antiviral Drugs Indicated for the Treatment of N/A Non-Life-Threatening Disease Evaluation of Drug Toxicity Prior to Phase I Clinical Studies
Single Dose Acute Toxicity Testing for Pharmaceuticals
The final tabs are for the CDER Calendar, and information for specific audiences. 〈http://www.fda.gov/cder/about/smallbiz/definitions.htm〉 contains many drug development and review definitions, including the pharmacology/toxicology review.
For additional links of interest to pharmacology see: 〈http://www.fda.gov/nctr/index.html〉, which describes nonclinical research efforts of NCTR/FDA, a number of which relate to issues or pharmaceuticals regulated by CDER or relate to methods that could be used by CDER. 〈http://www.fda.gov/cder/genomics/default.htm〉 describes initiatives in the area of “omics.”
In addition to copies of approved labeling, 〈http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm〉, gives information on genotoxicity, carcinogenicity, reproductive and developmental toxicity of drugs, and 〈http://www.fda.gov/cder/drug/DrugSafety/DrugIndex.htm〉 contains patient information for specific drugs. 〈http://www.fda.gov/cder/biologics/default.htm〉 contains information on therapeutic biological products. 〈http://www.fda.gov/cder/Offices/OTC/default.htm〉 delves into issues of over-the-counter drugs.
The Medwatch program, whose purpose is to promote and facilitate voluntary reporting of serious adverse events and product problems with drugs by health care practitioners is described at 〈http://www.fda.gov/cder/handbook/medwatch.htm〉. A special web site for Medwatch, outside the CDER web site, is at 〈http://www.fda.gov/medwatch/index.html〉. At this site, safety alert information is given, as well as instructions on how to report safety information.
From time to time specific safety issues arise, and information is provided on the CDER/FDA web page. 〈http://www.fda.gov/cder/livertox〉 on drug-induced liver toxicity is one such example.
Finally, since pharmacologist and toxicologist reviewers are always being sought, see 〈http://www.fda.gov/cder/career/default.htm〉 for career opportunities.