U.S. Food and Drug Administration
Performance Plan
2002

2.3 HUMAN DRUGS (continued)

4. Protect human research subjects who participate in drug studies and assess the quality of data from these studies by conducting approximately 780 on-site inspections and data audits annually. (12032)

• Context of Goal: FDA approves drug products only after the manufacturers/sponsors provide adequate and reliable information on which FDA can base its decision. Manufacturers/sponsors generate, collect, and report data from both clinical (human subjects) and non-clinical (animal and other) studies in support of their applications. Under FDA's Bioresearch Monitoring (BIMO) Program, FDA inspects sponsors, clinical investigators, contract research organizations, monitors, institutional review boards, and non-clinical/analytical laboratory facilities to ensure that the rights and welfare of human subjects who participate in research are protected, and to verify that data collected by the regulated industry are accurate and reliable. FDA is the only government agency with an active program of on-site inspections and the necessary expertise to evaluate the conduct of these studies. PDUFA mandates specific deadlines for review of manufacturers'/sponsors' submissions.
• Data Source and Issues: COMIS, Field Accomplishments and Compliance Tracking System (FACTS), and ACCESS databases are used to track assignments and results of inspections/data audits.
• Performance: The Agency completed 683 BIMO inspections in FY 1999, 697 in FY 2000, and 553 in FY 2001. The number of inspections conducted and completed each year is dependent on the number of applications received.

5. Publish guidance for Industry on developing antimicrobial drugs for inhalational anthrax (post-exposure). (12033)

• Context of Goal: Issuance of a Guidance for Industry on inhalational anthrax post-exposure prophylaxis will facilitate drug manufacturers' ability to expeditiously develop new drugs or already marketed drugs for this indication.
• Data Sources and Issues:
• Performance:

6. Facilitate the initiation of research in a non-human primate model of pneumonic plague. (12034)

• Context of Goal: At present, only streptomycin and doxycycline are FDA-approved for the treatment of plague. However, no drug is specifically approved for inhalational pneumonic plague. Animal models are needed to address whether certain drugs are effective (or ineffective) in the treatment of human pneumonic plague.
• Data Sources and Issues:
• Performance:

7. Expeditite the review of protocols for investigational new drugs (INDs) to treat organophosphorous nerve agents in the event of chemical attack. Encourage sponsors of these new drug application (NDAs) to update current labling for Antidote Treatment Nerve Agent, Autoinjectors (ATNAA). (12035)

• Context of Goal: In the event of a nerve agent attack, a vulnerability to the public health exists if limited drugs options are available. Increasing the number of drugs approved for this specific usage improves the Nation's preparedness including the CDC's National Pharmaceutical Stockpile (NPS).
• Data Sources and Issues:
• Performance:

8. Identify and begin to address labeling gaps in the therapeutic armamentarium for the prevention, mitigation, and treatment of illnesses cases by chemical and biological attacks, including the needs for special populations, such as pregnant women, pediatric, and geriatric populations. (12036)

• Context of Goal: In the Federal Government's response to various agents of mass destruction, drugs will be mobilized from the CDC's National Pharmaceutical Stockpile (NPS). However, not all drugs in the NPS are FDA-approved for counter-terrorism uses. Identification of these deficits including development of a plan to address these deficits will move the Public Health Service closer to a goal of labeling all drugs that reside in the NPS for counter-terrorism uses.
• Data Sources and Issues:
• Performance:

9. Develop guidance for Industry on developing antiviral drugs for the mitigation of complications associated with vaccinia immunization. (12037)

• Context of Goal: In the event that the public receives vaccinia immunization as protection against a smallpox threat, it is estimated that some vaccine recipients will experience serious complications due to the vaccine. Drug therapies are needed to mitigate the risks associated with vaccinia immunization. No drug is currently FDA-approved to mitigate the complications associated with vaccinia immunization.
• Data Sources and Issues:
• Performance:

10. Facilitate human clinical trials in pneumonic plague for antimicrobial drugs that are not yet labeled for this treatment indication. (12038)

• Context of Goal: At present only streptomycin and doxycycline are FDA-approved for the treatment of plague. However, no drug is specifically approved for inhalational pneumonic plague. Human clinical trial data experience is needed to demonstrate safety and efficacy for this specific treatment indication and to identify new therapeutic drug options.
• Data Sources and Issues:
• Performance:

11. Develop guidance for Industry on developing antiviral drugs for the treatment of smallpox. (12039)

• Context of Goal: If smallpox was intentionally released on the American pubic, the effects could be devastating. One response to this threat includes mass vaccinia immunization. However, depending on the patient population, safe and effective drug therapies may be preferred to vaccinia immunization. No drug is currently FDA-approved for the treatment of smallpox.
• Data Sources and Issues:
• Performance:

12. Publish a final rule which allows the agency to approve new drug and biological products for the treatment of chemical, biological, radiological, or nuclear substances based on animal efficacy studies when adequate and well-controlled studies in humans cannot be ethically conducted and field studies are not feasible. (12040)

• Context of Goal: To date FDA approvals of drugs and biological products require that prior to licensing, safety and efficacy must be substantiated in adequate and well-controlled human clinical trials. Issuance of a final "animal rule" (Evidence Needed to Demonstrate Efficacy of New Drugs When Efficacy Studies in Humans are not Ethical or Feasible) will permit the Agency's determination of substantial evidence for efficacy be based on animal surrogates. This is particularly germane for drugs to prevent, mitigate, or treat the effects of a bioterrorist agent that can't be ethically studied in humans today (e.g., smallpox infection).
• Data Sources and Issues:
• Performance:

13. Expedite the review of protocols for investigational new radioprotectant drugs (including heavy metal chelators) for use in the event of a radiation emergency. (12041)

• Context of Goal: Although potassium iodide (KI) is FDA approved as a thyroid blocking agent in a radiation emergency, it's protective effects are limited to the thyroid gland. Additional drug options (e.g., heavy metal chelators) are needed to mitigate the effects of an intentional radiation emergency.
• Data Sources and Issues:
• Performance:

Strategic Goal 2:
Prevent unnecessary injury and death to the American public caused by adverse drug reactions, injuries, medication errors and product problems.

A. Strategic Goal Explanation

FDA cannot determine everything about a drug's safety before it is approved. FDA assures safe products are marketed by continued surveillance for adverse events and use problems, increased inspectional coverage of both foreign and domestic producers, increased enforcement efforts to prevent fraudulent activities involved with the sale of approved and unapproved prescription drugs over the Internet, and increased educational programs that address the interests of medical professionals, patients and consumers. FDA also must be vigilant to protect Americans from injuries and deaths caused by unsafe, illegal, fraudulent, substandard or improperly used products.

A comprehensive safety system for medical products is a critical priority. FDA's current systems are not intended to, and cannot, uncover the incidence of adverse events, their preventability, or the overall health and economic impact on Americans. A DHHS partnership to promote patient safety and prevent medical errors is being developed, with FDA taking the lead on a national critical event reporting system. This program is designed for broader monitoring and prevention of adverse events involving both new and already marketed products and would substantially reduce preventable injuries and death from the use of FDA-regulated products.

FDA uses a number of postmarketing risk assessment approaches to ensure the continued safe use of drug products. The Agency's current adverse event database for drugs and therapeutic biological products, AERS, contains approximately 2 million adverse event reports from health care professionals (see goal 12007). In calendar year 2000, over 275,000 individual safety reports (ISRs) were received into entry into AERS of which over 30% represented serious and unexpected events. The first quarter data for calendar year 2001 projects over 300,000 reports for the full year. FDA evaluates spontaneous reporting data from AERS to identify any serious, rare, or unexpected adverse events or an increased incidence of events. Based on its evaluation, FDA may decide to disseminate risk information, such as Dear Healthcare Professional letters, and may initiate regulatory action. Through a program called MedWatch, the FDA Medical Products Reporting Program, healthcare professionals and consumers are encouraged to report serious adverse events and product problems to FDA, the manufacturer, or both. FDA's Drug Quality Reporting System (DQRS) receives reports from pharmacists of deviations from Good Manufacturing Practices that occur during the manufacturing, shipping, or storage of prescription or OTC drug products. FDA receives medication error reports from pharmacists on marketed human drugs and maintains a central database within the DQRS and AERS for all reports involving a medication error or potential medication error. The Agency puts substantial effort into reviewing medication error case reports to identify serious or potentially serious outcomes that might be avoided by modifying the labeling or packaging. Manufacturers of human drugs must register their establishment(s) with the FDA and also submit a listing of every product they market in the US. The Agency uses this information to swiftly communicate with these manufacturers in cases of product emergencies.

B. Summary of Performance Goals

C. Goal-by-Goal Presentation of Performance

14. Expedite processing and evaluation of adverse drug events through implementation of AERS which allows for electronic periodic data entry and acquisition of fully coded information from drug companies. (12007)

• Context of Goal: AERS is an Oracle based computerized information system designed to support the Agency's post-marketing safety surveillance program for all approved drug and therapeutic biologic products. The structure of the database is in compliance with the international safety reporting guidance (ICH E2B), including content and format for electronic submission of the reports from the manufacturers. Features include on-screen review of reports, searching tools, and various output reports in support of postmarketing drug surveillance and compliance activities. AERS contains approximately 2 million individual safety reports (ISRs). FDA evaluates spontaneous reporting data from AERS to identify any serious, rare, or unexpected adverse events or an increased incidence of events. When a signal of a potential adverse reaction is detected, safety evaluators consult with product reviewers, medical officers, and epidemiologists to review available data and consider further options. FDA may decide to disseminate risk information, such as Dear Healthcare Professional letters, and may initiate regulatory action.
  In FY 2003, the Agency will conduct additional risk management and risk communication research, including pilot initiatives to minimize preventable adverse drug reactions and medication errors. The Agency will also implement a regulation related to Bar Coding of pharmaceutical products.
• Data Sources and Issues: AERS
• Performance: AERS has been operational for nearly four years. In calendar year 99, over 275,000 ISRs were received for entry into AERS of which over 82,000 (30%) represented serious and unexpected events (30%). In calendar year 2000, over 270,000 individual safety reports (ISRs) were received for entry into AERS with almost 3000 electronic submitted test reports. To date, AERS has received 105,000 ISRs, and it is anticipated that AERS will receive over 280,000 for the calendar year 2001, which will include electronic submitted reports (over 10%).
  AERS version 2.1, completed in February 2001, enhanced the compliance and Freedom of Information portions of AERS by making it more accessible to compliance staff and improving compliance-related search capabilities. CDER implemented an Electronic Submission Product Test Pilot for AERS in October 2000. This pilot provided a mechanism for companies to test and send electronic submissions of expedited reports via physical media or gateway directly into AERS. Over 11,000 individual case safety reports were submitted electronically under the pilot program in FY 2001 (see Figure 3 below).

Figure 3

AERS version 2.2 was implemented in May 2001, enhancing the ability of the system to accept electronic submissions. Also in May 2001, a draft guidance for industry, "Providing Regulatory Submissions in Electronic Format - Postmarketing Expedited Safety Reports" was released.

The Electronic Submission Product Test Pilot for AERS is part of a step-level implementation program for the electronic submission of postmarketing surveillance information. The pilot allows FDA to identify and resolve several process issues while regulatory and infrastructure changes are implemented. Electronic submissions provide CDER, FDA, and the public with several tangible benefits. Specifically, automating the receipt and processing of safety reports will allow FDA to: be more responsive to public health issues, reduce resources associated with data management, and apply better data and better science to the drug regulatory process. The proposed rule on ADR reporting and guidance on electronic submissions is in the process of being finalized.

15.CDER will conduct laboratory research on at least three projects identified and approved by the Product Quality Research Institute. (12016)

• Context of Goal: The Product Quality Research Institute (PQRI) is a first-ever collaboration among FDA, academic, and industry scientists to conduct research in the areas of pharmaceutical chemistry, biopharmaceutics, and science management. The purpose of this research is to establish better testing methods, standards, and controls for assessing product quality and manufacturing and management processes. This knowledge aids the Agency in developing consistent and reasonable requirements for product quality information in regulatory filings. Leveraging scientific expertise in this way contributes to streamlining the drug development and approval processes for industry and the FDA while ensuring the highest level of product quality.
• Data Sources and Issues: Office of Testing and Research (OTR) Research Plan; "A Proposal - PQRI;" Memorandum of Understanding between FDA and the American Association of Pharmaceutical Scientists; "Proposed Operating Principles for the PQRI"; PQRI Technical Committee, Steering Committee, and Board of Directors meeting minutes.
• Performance: In FY 2001, FDA initiated three laboratory research programs and performed the corresponding research in connection with the mission of PQRI: Oral Biopharmaceutics, Drug Product, and Drug Substance. The Oral Biopharmaceutics program completed the validation of the BCS system suitability of a cell culture system, performed two food effect clinical studies, established the Biopharmaceutics Classification System database (initial phase), and developed novel models of using in vitro methods to predict in vivo bioavailability and bioequivalence. The Drug Product program accomplished the design, manufacturing, and characterization of over 40 furosemide tablet formulations. The Drug Product program also evaluated the regulatory acceptability of using Near-IR to monitor the blend uniformity and assessed particle size technology. These programs are expected to contribute to developing/revising bioavailability/bioequivalence, SUPAC, and drug substance regulations for product quality.

16. Inspect 20% of registered human drug manufacturers, repackers, relabelers and medical gas repackers. (12020)

• Context of Goal: This goal measures performance for the statutory inventory of drug establishments for which inspections are required biennially. The total drug inventory is 19,749, of which 33 percent, or 6,509, are statutory. Inspections to accomplish this goal may be done by FDA directly, or through state contracts or partnership agreements. Achievement of this goal relies on the willingness and ability of the states to contract with FDA to inspect a large portion of the medical gas repacker industry. To implement these contracts, FDA's experience predicts that a significant investment in training and time is necessary to ensure quality and uniformity of inspections. In addition, the Human Drugs program has shifted its emphasis away from inspecting medical gas establishments to establishments in other risk categories. Since medical gas inspections represent a large portion of the statutory inspection workload, the statutory inspection coverage will be adversely affected.
• Data Sources and Issues: Program-Oriented Data System, Official Establishment Inventory
• Performance: The FY 2001 goal of 26% was not met. Due to a few problems resulting from the transition to a new database (FIS to FACTS) in FY 2000, some adjustments in counting the inventory and inspectional coverage were necessary. It is expected that any inconsistencies will be corrected when the FY 2002 actuals.

17. Assure that FDA inspections of domestic drug manufacturing and repacking establishments, in conjunction with the timely correction of serious deficiencies identified in these inspections, result in a high rate of conformance (at least 90%) with FDA requirements. (12006)

• Context of Goal: (Goal dropped for FY 02 and 03) In previous FDA performance plans, goals were established for maintaining the level of industry conformance to FDA requirements at 90% or above for each of the Agency product-oriented programs. This year we are recommending that these goals be deleted from the Plan. This is our rationale: Inspections are the Agency's method for determining whether an establishment is in or out of compliance with FDA requirements. Because of resource constraints, the Agency must allocate a significant proportion of its inspections to high risk situations, such as food firms who are producing high risk foods, or to emergency situations such as BSE. The number of remaining inspections each year is not adequate to draw a statistically valid inference about the compliance status of an entire industry at a reasonably high level of confidence. It is the Agency's professional judgement that the majority of firms in the regulated industries are in conformance with FDA's requirements. Based on the Agency's experience over several years, that percentage in general, has remained at 90% or above. Thus, establishing a performance goal that simply describes the stable state of the industry does not provide useful new information; nor does it serve as a management tool to drive the overall industry to a higher level of conformance.
• Data Sources and Issues: FDA Field Data Systems
• Performance: FY 99: 95%; FY 98: 96%; FY 97: 95%. Conformance rates for FY 97, FY 98 and FY 99 have been adjusted to reflect the observed average correction rate for each year.

18. Make available to consumers and health professionals more easily-understandable information on choosing and taking prescription and OTC drugs to prevent and reduce their misuse, take more of an activist role in how consumers use these drugs, and improve drug risk management, analysis, and communication procedures. (12027)

• Context of Goal: (Dropped for FY 02 and 03) There is increasing public recognition that marketed drugs can lead to harm as well as benefit. Drug-related injuries and deaths can be reduced by creating a more educated public through expanded outreach activities and collaborative efforts with academia, professional societies and health organizations. This goal has been dropped for FY 2002 and 2003 because performance goals that can be verified-- either through quantitative measures or milestones -- have not been specified. As specific goals are developed, this goal may be reinstated.
• Data Sources and Issues: Approval Letter for new and generic drugs and the Labeling Text or Final Printed Label (FPL) for new drugs; Consumer Drug Information Sheets for New Molecular Entities (NMEs); Availability of FDA's reviews of new and generic drugs via the internet; Prescribing Information Sheet for NMEs. Report to the FDA Commissioner--Managing the Risks from Medical Product Uses, An Assessment of FDA's Approval and a Look to the 21st Century.
  The program indicated that the following information on the processing procedures for this data is reliable and of sound quality. The information demonstrates that the appropriate quality control practices are in place.
  The project manager copies the approval letter and final labeling text to a secured drive. The Freedom of Information (FOI) component completes necessary redaction and transfers them to another secured drive. FOI then notifies the web team that they are ready to post. Posting is verified by FOI. There are time limits for each of these steps as stipulated in a Center policy.
  Consumer Drug Information Sheets for NMEs are prepared by Center pharmacists using information from the approved label and other sources and then cleared by the appropriate components. The information is then posted on the internet to a site for "Consumer Drug Information".
  It was determined that these data are valid based on the logical assumption that once this information is disseminated, the American public would benefit positively due to reduced drug misuse. A detailed assessment of the quality control process will be conducted in the coming year to ensure that performance data are reliable.
• Performance: In cooperation with its leveraging partners in FY 2001, FDA continued to develop the Over-the-Counter Medicine Label Campaign in anticipation of full implementation by manufacturers in FY 2002. FDA also addressed other emerging and high-priority risk-management issues for consumers such as those surrounding bioterrorism. Additional outreach for the Over-the-Counter Medicine Label Campaign resulted in an ad for movie theaters that reached six million viewers, refrigerator magnets distributed to 20,000 marathon runners and a grocery bag stuffer used by a large West Coast grocery chain. The Agency developed a consumer friendly brochure on medication risk management called "Be a Member of Your Health Care Team." The accompanying print public service announcement appeared in 212 newspapers nationwide with a combined readership of 30 million. A public service announcement outlining the risks and benefits of buying medications online has appeared in 646 newspapers with a readership of 27 million and aired on 233 radio stations with six million listeners. A risk management outreach program to reduce and eliminate death and injury from medical gas mixups used leveraging with professional societies and health organizations as well as public health advisories and printed posters, flyers and stickers.
  The Agency worked on expanding the prototype Dockets Comments Management System for the proposed regulation to improve the format and content of prescription drug labeling to allow easy electronic public comments linked with an internal networked comments review system. An outreach campaign to individual physicians was launched to gain their input and opinion about the proposed rule.
  Also in FY 2001, the Agency posted consumer-oriented risk management information on its Web site on these specific topics: the new risk-management plan for Accutane to reduce fetal exposure to the drug; the withdrawal of Baycol for safety concerns; the counter terrorism recommendations on using three specific drugs to treat exposure to anthrax; and strengthened warnings and precautions about the pain medication Oxycontin. The Agency's Web site has more than 38,000 drug information pages and documents plus three Web-enabled databases (Orange Book, National Drug Code Directory, and Oncology Tools). FDA has begun focusing on user-focused "sense-making" and content management by designing Web pages that pull information together in a way that will help solve users information problems. All pages are tested for both accessibility compliance and for usability. In FY 2001, FDA's Web site increasingly focused on consumer information, building sense-making introductory pages on drug safety, bioterrorism drugs, and risk management. An initial step in synchronizing the Agency's consumer information campaigns with Web sites included Over-the-Counter labeling and food-drug interactions. Development was begun on a one-stop catalog of drug information that will link a drug's labeling, its reviews, MedWatch alerts, and other information such as shortages. The one-stop catalog is being designed to replace four existing tables and indexes on the current site. FDA began obtaining cost estimates on Web casting drug advisory committee meetings with piloting expected in FY 2002. Public use of the Agency's drug information Internet site averaged more than half a million visitors each month, and each visitor viewed on average 17 pages of information including menus. The FDA's Consumer Drug Information Sheets received an average of more than 200,000 hits a month.
  In FY 2001, the Agency responded to more than 31,000 individual inquiries from consumers about their medications and nearly 8,000 similar inquiries from physicians and other health care professionals.

19. Finalize rulemaking to establish a web-based electronic drug registration and listing database to allow for complete and up-to-date data on all regulated drug products, and follow this finalization with launch of the electronic database. (12042)

• Context of Goal: In the event of a terrorist attack, various drugs may be utilized in response to the attack. Rapid access to accurate and timely information pertaining to the manufacturers and their respective drugs is critical to surge manufacturing production needs and to reduce the risk of drug shortages.
• Data Sources and Issues:
• Performance:

20. Publish a Notice in the Federal Register on doxycycline and penicillin G procaine dosing recommendations for inhalational anthrax. (12043)

• Context of Goal: At the time of the anthrax attacks, only one drug, ciprofloxacin, was approved for inhalational anthrax post-exposure prophylaxis. Issuance of this notice effectively approves two other drug options for this indication.
• Data Sources and Issues:
• Performance:

21. Issue guidance on the use of potassium iodide (KI) as a thyroid blocking agent in radiation emergencies. (12044)

• Context of Goal: In the event of an intentional radiation emergency, in addition to evacuation, potassium iodide would be indicated to decrease the risk of thyroid cancer. Issuance of a final KI dosing guidance will provide clear dosing recommendations to the public and facilitate Federal, State, and local preparedness.
• Data Sources and Issues:
• Performance:

2.3.3 Verification and Validation

A preliminary assessment for data completeness, accuracy, and consistency and related quality control practices was done for each performance goal. The purpose of the assessment was to determine if the data was of a sufficient quality to document performance and report program results, whether the data was appropriate for the performance measure and if it was considered sound and convincing. The Center obtained from its programs a description of the means that are used to verify and validate measured values for each performance goal. CDER has a number of quality control processes in place to ensure that performance data is reliable. Below are descriptions of several data systems used by CDER.

Adverse Event Reporting System (AERS)

The Adverse Event Reporting System (AERS) is an Oracle based computerized information system designed to support the Agency's post-marketing safety surveillance program for all approved drug and therapeutic biologic products. The structure of the database is in compliance with the international safety reporting guidance (ICH E2B), including content and format for electronic submission of the reports from the manufacturers. Features include on-screen review of reports, searching tools, and various output reports in support of postmarketing drug surveillance and compliance activities. The ultimate goal of AERS is to improve the public health by providing the best available tools for storing and analyzing safety reports.

Currently, reports are received either on paper as MedWatch forms or electronically. AERS assigns an individual safety report (ISR) identification number for each report. Paper submissions are scanned and stored in retrieval software. All data elements are entered and undergo data entry quality control to ensure completeness and accuracy. All reported adverse event terms are coded into a standardized international terminology, MedDRA (the Medical Dictionary for Regulatory Activities). This process is also subjected to coding quality control. After data entry, the reports are routed directly to assigned clinical reviewers in the postmarketing office. The reports are assessed individually and in aggregate for safety concerns.

The functions and tools developed in AERS provide the ability to easily customize queries; such queries are performed by multiple users on a daily basis for any drug and/or adverse event of interest. Standardized report outputs from AERS provide useful postmarketing information to many users within and outside FDA. These functions, combined with appropriate management and processes developed by the FDA, make AERS an effective tool for pharmacovigilance. There is an ongoing process in place to further improve the performance and functionality of AERS. Because pharmacovigilance is a constantly changing field and the volume of postmarketing safety information continues to increase annually, AERS will need modifications and improvements to maintain its usefulness to the FDA users.

AERS was designed to allow for electronic submission of individual case safety reports. Electronic submissions provide CDER, FDA, and the public with several tangible benefits. Specifically, automating the receipt and processing of safety reports will allow CDER to be more responsive to public health issues, greatly reduce resources associated with data management, and apply better data and better science to the drug regulatory process.

However, there are FDA regulatory and infrastructure changes needed for full-scale implementation of electronic submissions. The full-scale implementation requires CDER to develop processes for both electronic data management and pharmacovigilance. Accordingly, CDER has proposed a step-level implementation that will allow CDER to identify and resolve several process issues while the regulatory and infrastructure changes are implemented. This step-level implementation includes a pilot program. This program allows CDER to work with manufacturers who voluntarily submit safety reports electronically. Besides AERS resources being used for the users, AERS resources are used for this pilot program to work with the manufacturers for the implementation of the electronic submissions program of the safety reports. In conjunction with the pilot, proposed rulemaking is being written to require that manufacturers submit suspected adverse drug reaction reports electronically.

As we gain more experience with the pilot electronic submissions program with the manufacturers, maintenance and improvements will be needed to make it more functional and successful. AERS was designed to accommodate electronic submission of adverse event reports from the manufacturers based on ICH specifications. Periodically, these specifications are modified and updated. Therefore some of the AERS maintenance will be due to changing ICH specifications. For example, currently, there is a new version that needs to be implemented. The manufacturers' participation in the pilot program is delayed until the new version is in place. This maintenance also includes MedDRA version upgrades in AERS. This is to assure that the electronic submissions utilizing the current version of MedDRA from the manufacturers are compatible with the version utilized in AERS.

The ultimate goal of the electronic submissions program is to be able to exchange safety reports with other regulators and manufacturers. Currently, we are only able to receive reports electronically. Some of the pilot program manufacturers are able to send reports electronically and are working with their affiliates to be able to receive reports too. We need to be able to share and send reports electronically with other regulators and industry.

In summary, the AERS database in the FDA assures that postmarketing adverse event reports are completely and accurately entered, quality controlled and reviewed to monitor product safety and to protect the public health. The data are valid for this goal because they measure the required performance indicator of expediting the process and evaluation of adverse drug events.

Pediatric Exclusivity Database and the Pediatric Page database (Database enhancements required to meet goal)

The Pediatric Exclusivity Database tracks all data regarding pediatric exclusivity as mandated by FDAMA. Specifically, this database tracks the number of Written Requests issued and the number of products for which pediatric studies have been submitted and for which exclusivity determinations have been made.

The document room enters the date on which a Proposed Pediatric Study Request (PPSR) is received and when the Agency issues a Written Request (WR). Then the pediatric team enters the information pertaining to the types of studies to be conducted. Once the final pediatric studies are submitted to the Agency, the document room enters the receipt date into the database. The project manager for the Pediatric Team enters any additional information pertaining to the granting or denial of exclusivity. The data is quality controlled each month by the pediatric team when they complete their monthly statistics update.

The major strength of this database is that it captures all data relative to exclusivity. Maintaining the database is time consuming for the pediatric team, i.e., entering the data on the studies. However, the document room staff are not trained to recognize what types of studies are requested in the WRs so it is not feasible for them to enter this data themselves.

The Pediatric Page Database was redesigned, piloted, and implemented in July 2000. This database was designed to capture data pertaining to the Pediatric Final Rule, i.e., whether or not pediatric studies required under the rule were completed, the number of waivers and deferrals granted, and the age ranges that may be waived, deferred, or have actually been completed. The project managers consult with the medical officers to determine whether pediatric studies are necessary, waived, or deferred and what ages should be included in the study. Then the project manager enters the information into the database. This information must be entered prior to the approval of an NDA or supplement. The pediatric page, with all relevant pediatric data, is then printed from the database and included with the action package. The action package is then forwarded to various people, i.e., the appropriate reviewer, project managers, team leader, deputy division director, division director, and office director (for NDAs only) who verify the pediatric data and sign off on the package.

The previous version of the database required a password and was not user friendly. Therefore, many project managers did not use the system resulting in incomplete data for a number of applications. The database has been updated, no longer requiring a password, and is now web-based. Training has been provided to the divisions on the new version. The number of pediatric patients being requested to be involved in studies and the types of studies being requested are tracked manually and maintained by individuals in separate databases on their computers or on common drives. Alternatives are being considered to make this an electronic process as well.

The Pediatric Inpatient Database is still being negotiated. Once this information is available to the pediatric team it will be able to determine exactly what drugs are being used in the pediatric population for unlabeled indications and then focus on requesting the studies that are necessary in order to get the products properly labeled.

This information demonstrates that the data in the Pediatric Exclusivity Database and the Pediatric Page Database are complete and accurate and that appropriate quality control practices are in place. The data are valid for this goal because they measure the required performance indicators.

Center-wide Oracle Management Information System COMIS

The Center-wide ORACLE Management Information System (COMIS) is CDER's enterprise-wide system for supporting premarket and postmarket regulatory activities. It consists of multiple applications, or components, that store and retrieve data in a single integrated database. COMIS is the core database upon which most mission-critical applications are dependent. The new drug evaluation (NDE) and abbreviated new drug application (ANDA) portions of COMIS contain information about investigational new drug applications (INDs), new drug applications (NDAs), abbreviated new drug applications (ANDAs), supplements, and amendments, and it tracks their status throughout the review process. The type of information tracked in COMIS includes status, type of document, review assignments, status for all assigned reviewers, and other pertinent comments.

CDER has in place a quality control process for ensuring the reliability of the performance data in COMIS. Document room task leaders conduct one hundred percent daily quality control of all incoming data done by their IND and NDA technicians. Senior task leaders then conduct a random quality control check of the entered data in COMIS.

The task leader then validates that all data entered into COMIS are correct and crosschecks the information with the original document. Once the data are saved in COMIS, the document room staff no longer have the capability to change certain document fields. If a data entry change is necessary on any restricted field, the task leader or senior task leader must send a written change request to the Records Management Team (RMT), Office of Information Technology (OIT). Once the change has been made, the document room is notified and the senior task leader/task leader rechecks the data for accuracy.

The Records Management Team (RMT) has three Technical Information Specialists (TIS) assigned to the document rooms in Parklawn, Woodmont II, Corporate Boulevard, Metro Park North II and Wilkins Avenue who oversee the daily activities within their building document rooms. Quality control checks are done on application jackets, outgoing letters, memoranda and reviews, procedure and programming changes and all other activities that take place in their document rooms.

Overall, the data in COMIS are complete and accurate, and appropriate quality control practices are in place. A limited number of people in RMT and the Division of Applications Development Services (DADS), OIT, have authority to input data into COMIS, which helps to protect the integrity of the data. Once entered into the system, data are immediately accessible to users..

Meetings are held on a weekly basis to discuss any and all issues related to COMIS data entry, document rooms, and procedure changes to ensure that COMIS reflects changes in policy and legislative requirements. Attendees at these meetings include two members of the Document Control Room contract management staff in RMT, a Chief Project Manager review division representative from Parklawn, WOCII and Corporate Boulevard, a programmer from DADS, and representatives from the Division of Drug Marketing, Advertising, and Communications, the Office of Generic Drugs, and the Reports and Data Management Team, ORM.

The data obtained from COMIS are valid for this goal because they measure the required performance indicators, e.g., the numbers and types of submissions, receipt dates, and review times. Preliminary discussions have taken place to alleviate system weaknesses and redesign the system in phases over the next few years to improve efficiency. These weaknesses include a manual, paper-driven quality control process, inflexibility of the system to reflect policy and legislation changes in a timely manner, slow or unavailable network connections impeding a user's ability to acquire requested data, and unrecognizable codes requiring tracking to be done manually.

Contact Information:
Planning Staff, Office of Planning, FDA
Phone: 301-827-5210

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