| Total Program Resources (FY 2000): | $000 | FTEs | |
| Center | 115,532 | 819 | |
| Field | 22,582 | 248 | |
| Total | 138,114 | 1,067 |
FDA is responsible for assuring that blood and blood products, blood test kits, bacterial vaccines and antigens, viral vaccines, therapeutic agents, and other biological products intended for use in the prevention, diagnosis, and treatment of diseases in humans are pure, potent, safe, and effective, as well as properly labeled for their intended uses.
The Biologics Program includes registration and inspection of blood banks and other firms processing blood; licensing and inspection of firms collecting human source plasma; evaluating and licensing biologics manufacturing firms and products; lot release of licensed products; removal of ineffective, unsafe, or improperly labeled products from the market; development of necessary regulations, compliance programs and guidelines; and conducting research, in concert with other DHHS public health agencies, academia, and industry, to further the development of new products and to provide a sound scientific basis for their regulation.
| Resources: | $30,685,000 | 187 FTEs |
Performance Goals:
Rationale:
The Food and Drug Administration Modernization Act of 1997 (FDAMA), Public Law 105-115, authorized revenues from fees paid by the pharmaceutical industry to expedite review by the FDA of human drug applications. These revenues were directed by section 101(4) of this Act toward accomplishment of goals identified in the letters of November 12, 1997 from the Secretary of Health and Human Services to the Chairman of the Energy and Commerce Committee of the House of Representatives, and the Chairman of the Labor and Human Resources Committee of the Senate.
The FDA's Center for Biologics Evaluation and Research (CBER) continued to improve the speed of its processes while completing 38 major approvals covering a broad spectrum of new products, technologies, manufacturing methods, indications and premarket applications in 1998.
In 1998, the greatest acceleration was seen in 20 approvals, involving 11 PLAs and BLAs and 9 PLA and BLA supplements, which were part of the prescription drug user fee program. The PLA/BLA user fee approvals were completed in the median time of 15.19 months, or 16 percent faster than the corresponding median time of 18.06 months in 1996. The median time for the approval of PLA/BLA supplements for user fee products last year was 11.94 months.
Achievement of the performance goals will expedite the availability of safe and effective biological products for the prevention and treatment of disease.
Approaches, Skills, Technology, External Factors:
Resources are primarily devoted to application review, but also include pre-submission meetings and pre-approval inspections.
The FDAMA authorizes the collection of user fees to enhance the review process of new human drug and biological products through FY 2002. The Act establishes fees for applications, establishments and approved products. The user fees have enabled the Agency to improve its performance for drug review and approval times. The median user-fee PLA approval time decreased from 22.5 months in FY 1994, to 15.2 months in FY 1998.
FDA has met or exceeded its Prescription Drug Use Fee Act (PDUFA) performance goals thus far. Meeting with sponsors early in the drug development process makes the process more efficient for industry and the Agency. Product license applications are of better quality and there are fewer refuse-to-file decisions.
FDA has initiated programs designed to make the application review process more efficient. One such initiative is the Managed Review Process. The Managed Review Process incorporates concepts of project management with the goal of producing high quality reviews in a timely manner. The system includes establishing specific time frames with interim milestones for the evaluation of both establishment and product license applications.
Factors that affect the Agency's ability to achieve the performance goals are: quality and complexity of applications; the number of applications received; commitments which take researchers/reviewers away from their assigned review work, such as regulation/guidance writing; and the Agency's ability to hire and train qualified researchers/reviewers as needed. Interaction between FDA scientific reviewers and scientific experts in industry enhances the reviewers' expertise in current product science and technology. CBER scientists use applied research programs to gain experience and establish standards for new therapies.
Performance Goals, Data Sources, and Baselines:
Note about Baseline Data: In several years the program performance (Baseline Data) exceeds the projected FY 2000 performance goals. The projected performance goals are as the Secretary committed to in her letters to Congress. "NA" means the goal is not applicable in that fiscal year.
Goal Statement: Review and act on 90 percent of standard original New Drug Application (NDA), Product License Application (PLA) and Biologic License Application (BLA) submissions within 12 months of receipt (50 percent within 10 months); and review and act on 90 percent of priority original NDA/PLA/BLA submissions within 6 months of receipt.
Data Sources: CBER's Biologics Regulatory Management System
Baseline Data:
Standard Applications within 12 months:
FY 1993: 86%
FY 1994: 100%
FY 1995: 100%
FY 1996: 100%
FY 1997: 100%
FY 1998: 90% (estimate)
FY 1999: 90% (target)
Standard Applications within 10 months:
FY 1997: NA
FY 1998: NA
FY 1999: 30% (target)
Priority Applications within 6 months:
FY 1997: 100%
FY 1998: 90% (estimate)
FY 1999: 90% (target)
Goal Statement: Review and act on 90 percent of standard efficacy supplements within 12 months of receipt (50 percent within 10 months); and review and act on 90 percent of priority efficacy supplements within 6 months of receipt.
Data Sources: CBER's Biologics Regulatory Management System
Baseline Data:
Standard Applications within 12 months:
FY 1993: 55%
FY 1994: 83%
FY 1995: 100%
FY 1996: 88%
FY 1997: 100%
FY 1998: 90% (estimate)
FY 1999: 90% (target)
Standard Applications within 10 months:
FY 1997: 44%
FY 1998: NA
FY 1999: 30% (target)
Priority Applications within 6 months:
FY 1997: 100%
FY 1998: 90% (estimate)
FY 1999: 90% (target)
Goal Statement: Review and act on 90 percent of manufacturing supplements within 6 months of receipt, and review and act on 50 percent within 4 months of receipt.
Data Sources: CBER's Biologics Regulatory Management System
Baseline Data:
Within 6 months:
FY 1993: 53%
FY 1994: 85%
FY 1995: 94%
FY 1996: 98%
FY 1997: 98%
FY 1998: 90% (estimate)
FY 1999: 90% (target)
Within 4 months:
FY 1997: 26%
FY 1998: NA
FY 1999: 30% (target)
Goal Statement: Review and act on 90 percent of Class 1 resubmitted original applications within 4 months of receipt (review 50 percent within 2 months); and review and act on 90 percent of Class 2 resubmitted original applications within 6 months of receipt.
Data Sources: CBER's Biologics Regulatory Management System
Baseline Data:
The breakdown of resubmitted original applications into classes 1
and 2 is a new definition prescribed in the FDAMA beginning in
1998. FDA has not tracked the applications using the new
definitions in the past. Data showing the percentage reviewed
within prescribed time frames during FY 1998 will not be available
until mid-FY 1999.
Resubmissions within 6 months:
FY 1998: 90% (estimate)
Class 1 resubmissions within 6 months:
FY 1998: 90% (estimate)
FY 1999: NA
Class I resubmissions within 2 months:
FY 1998: 30% (estimate)
FY 1999: 50% (target)
Class I resubmissions within 4 months:
FY 1998: NA
FY 1999: 90% (target)
Class II resubmissions within 6 months:
FY 1998: NA
FY 1999: 90% (target)
| Resources: | $72,286,000 | 542 FTEs |
Performance Goal:
Rationale:
The mission of the Blood Program is to ensure that blood, blood products, biotechnology-derived hematologics, and devices associated with their manufacture and use are safe, effective, and adequately labeled.
The blood supply is critical to the nation's health care system, and the United States has the safest blood supply in the world. Each year approximately 14 million blood units are drawn from volunteer donors for use in more than 3.5 million Americans. FDA vigorously continues to strengthen its efforts to protect the nation's blood supply, and to minimize any risk to patients acquiring the human immunodeficiency virus (HIV), hepatitis, Creutzfeldt-Jakob disease (CJD), and other bloodborne diseases.
Achievement of the performance goals will facilitate the availability of safe and effective source plasma and blood bank products for the treatment of disease and injury.
Approaches, Skills, Technology, and External Factors:
FDA reviews and evaluates premarketing license applications for blood establishments and blood products. The Agency also conducts research of blood and blood products pertinent to its regulatory mission. FDA will continue to develop regulations to screen and test donors for infectious diseases. FDA will also extend its current blood oversight, and regulation revitalization and reinvention project. The major areas to be addressed include: development of the BLA as it applies to blood establishments; development of Agency-wide goals and direction; coordination of Agency-wide resources to protect the blood supply; and the revitalization and rewrite of blood regulations.
With FDAMA, resources need to be expended in the early product development stages for consultation. Additional resources are required to have meaningful dialogue between the sponsor and the appropriate FDA staff during early stages and to also perform the on-going application reviews. Otherwise, application review times will slip or the appropriate expertise will not be available for the sponsor meetings and commitments will be made to do studies that are not in the best interest of the public health. In addition, enforcement/compliance actions appear to be increasing. These also detract from application review resources.
Factors which affect the Agency's ability to achieve the performance goals are: the quality and complexity of applications, the number of applications received, and commitments which take researchers/reviewers away from their assigned review work, such as regulation/guidance writing.
The ability of FDA to protect the nation's blood supply is enhanced through scientific efforts to understand HIV, hepatitis, CJD, and other bloodborne diseases. The ability of CBER scientific reviewers to ensure the safety and efficacy of blood screening tests and other new technology is increased through applied regulatory research.
Performance Goals, Data Sources, and Baselines:
Goal Statement: Review and act on 85 percent of complete blood bank and source plasma Product License Application (PLA)/Biologic License Application (BLA) submissions, and 90 percent of PLA/BLA Major supplements within 12 months after submission date.
Data Sources: CBER's Biologics Regulatory Management System
Baseline Data:
Complete Submissions:
FY 1993: 34%
FY 1994: 43%
FY 1995: 84%
FY 1996: 95%
FY 1997: 83%
FY 1998: 70% (estimate)
FY 1999: 60% (target)
Major Supplements:
FY 1997: 98%
FY 1998: 90% (estimate)
FY 1999: 90% (target)
| Resources: | $ 35,143,000 | 338 FTEs |
Performance Goals:
Rationale:
FDA is required by law to conduct biennial inspections of all licensed establishments to determine compliance with Current Good Manufacturing Practice (CGMP) regulations and to ensure compliance with applicable product and establishment standards and license commitments. In addition, FDA inspects all manufacturing facilities, which are unlicensed and/or under contract to a licensed establishment. FDA conducts biomedical research inspections to review pivotal clinical trial data, and in inspections of new tissue-cellular-based products.
"Team Biologics," a plan to revamp FDA inspections of biologics facilities by relying on investigator teams led by the Office of Regulatory Affairs (ORA), began implementation in late FY 1997. By transferring the lead responsibility for biologics postmarket inspections from CBER to ORA, all FDA CGMP inspections will be standardized by having a single Agency unit conduct inspections using a consistent approach. A core team of inspectors lead the inspections. The inspectors receive special training in performing inspections of biologics facilities, such as blood banks and plasma establishments. CBER product experts are also part of Team Biologics. They will be key in providing advice to their field colleagues on the team. This allows CBER/ORA to focus specially trained field investigators on the activities under this high priority program.
By accomplishing the performance goals the Biologics Program will ensure that biologics establishments are in compliance with regulations and that the products produced in those establishments are pure.
Approaches, Skills, Technology, and External Factors:
In addition to enhancing quality assurance procedures in blood banks, FDA will be defining new strategies for blood bank inspections based on control processes for critical production points. The Agency will also provide training programs for inspectors to implement the new approaches; conduct workshops to clarify Agency expectations for industry; and evaluate the need for changes in the error and accident reporting requirements.
FDA will continue to improve donor-eligibility criteria and deferral programs. It will also continue studies to assess the effectiveness of donor interview and education programs, and coordinate a national effort to address concerns regarding donor-deferral registries.
FDA will continue to collaborate closely with other government and non-government regulatory organizations such as the National Institutes of Health, Centers for Disease Control and Prevention, state health agencies, the American Red Cross, and the American Association of Blood Banks to assure that all policies are mutually consistent in guarding the safety of the nation's blood supply.
Factors which affect the Agency's ability to achieve the performance goals are unanticipated crises such as product tampering, which require immediate investigative and enforcement actions and take inspectors/investigators away from their planned assignments.
The availability of qualified scientific personnel to review, evaluate and investigate postmarket adverse events affects the Agency's ability to make sound and timely decisions concerning recalls and withdrawals.
Performance Goals, Data Sources, and Baselines:
Goal Statement: Assure that FDA inspections of domestic biologics manufacturers and repacking establishments, in conjunction with the timely correction of serious deficiencies identified in these inspections, result in a high conformance rate with FDA requirements (at least 90 percent).
Data Sources: FDA Field Data Systems
Baseline data:
FY 1997: 92%
FY 1998: 97%
FY 1999: at least 90% (target)
Note about Goal: Conformance rates estimate the post-inspection status of the establishments inspected in the given year. They are based on the number of establishments inspected, the incidence of serious deficiencies detected (Official Action Indicated), and statistical data of deficiency corrections. Since firms inspected are not randomly selected form the entire population, the rates should not be applied across that population. However, as coverage of the inventory of firms is improved, the rates will better represent the overall status of the industry sector.
Goal Statement: Increase the percentage of plasma fractionator establishments in compliance with Current Good Manufacturing Practices (CGMPs) to 80 percent.
Data Sources: Field Accomplishment and Compliance Tracking System (FACTS)
Baseline Data:
There are 26 foreign and domestic plasma fractionator
establishments.
FY 1996:
12 establishments were inspected and 9 were in
compliance (75%)
FY 1997:
The Agency performed 25 inspections of 23 plasma
fractionator establishments. One of the
establishments was found not to be in production. Of
the remaining 22 establishments, 9 were classified as
being essentially in compliance (41%)
FY 1998:
13 of 24 plasma fractionator establishments were
considered in compliance (54%)
FY 1999:
Compliance rate of 70% (target)
Goal Statement: Meet the biennial inspection statutory requirement by inspecting 50 percent of registered blood banks, source plasma operations and biologics manufacturing establishments.
Data Sources: Program-Oriented Data System, Official Establishment Inventory
Baseline Data:
FY 1997: 46% of establishments inspected
FY 1998: 46%
FY 1999: 43% (target)
Note about Goal: This includes inspections done by FDA directly, or through state contracts or partnership agreements.
Note about Baseline Data: Fiscal year baseline data is an estimate derived from two-year coverage data. Two-year coverage is computed by dividing the number of establishments inspected in the last two years by the total number of registered establishments. The fiscal year baseline estimate is half this number.
The Biologics Program uses various databases to manage its diverse programs and to assess performance. The principal CBER database is the Biologics Regulatory Management System (BRMS). The BRMS is CBER's VAX-based, Oracle database that is used to track all PLA, BLA, and supplement submissions; provide information to facilitate the review process (product, application status, milestone tracking, facility, review committee, industry contacts, and other information); and produce a wide variety management reports. The BRMS records application review information on each license application and supplement received and filed by the Center. The BRMS records information about PDUFA and non-PDUFA license applications. The milestone tracking module is used to track and report on CBER's PDUFA goals. Data entry is done in each of the offices' application review divisions. The Regulatory Information Management Staff (RIMS) monitors and is responsible for maintaining data quality and integrity in BRMS.
The Biologics Investigational New Drug (IND) Management System (BIMS) is CBER's VAX-based, Oracle database that is used to track all Investigational New Drug Applications (IND), Investigational Device Exemption (IDE), and Master Files (MF) submissions (nearly 11,000 in 1997); provide product, application status, and other information to facilitate the review process; and produce a wide variety of management reports. The system also stores summaries of telephone conversations and meetings related to the submissions, as well as actually generating some of the correspondence to sponsors. Most data entry is done by the Document Control Center (DCC) or the Consumer Safety Officers in each office's application review division. There are numerous mechanisms established for quality control in DCC, the application review offices, the Regulatory Information Management Staff, and several built into BIMS itself.
The Blood Logging and Tracking System (BLT) is under development by the Office of Blood Research and Review (OBRR) to record and track the various applications reviewed by that Office. The OBRR receives and reviews a wide variety of application types. PLAs, ELAs (Establishment License Applications) and BLAs are tracked by the BRMS, discussed above. INDs are tracked by the BIMS, also discussed above. The Office utilizes the BLT to record and track data concerning new drug applications (NDAs) and NDA supplements, device premarket applications (PMAs) and PMA supplements, 510(k)s, and Abbreviated New Drug Application (ANDAs) and ANDA supplements.
The data retrieved from these systems are reviewed and validated by the RIMS and the application review offices. If errors are detected the errors are corrected.
Federal regulations (21 CFR, Part 600.14) require reporting of errors and accidents in the manufacture of biological products that affect the safety, purity, or potency of the product. The error and accident reporting process enables the Agency to evaluate and monitor establishments, to provide field staff and establishments with trend analyses of the reported error and accident types, and to respond appropriately to reported errors and accidents to protect the public health. The regulation applies only to licensed manufacturers.
In May 1995, the DHHS Office of the Inspector General issued a report recommending that the reporting requirements be expanded to include unlicensed blood banks and transfusion services. A proposed rule was issued on September 23, 1997, that expands the reporting requirement to all biological product manufacturers regulated by FDA.
In the past five years, the Agency has received an average of 12,000 error and accident reports annually. FDA estimates that over 116,000 error and accident reports would be received under the proposed regulation. FDA does not have a computer system to permit the electronic submission of error and accident reports. If the Agency is to comply with the intended goals of the error and accident reporting regulation, it will need a system that would allow it to receive electronic submission of reports; and to review, process, and analyze more than 100,000 reports annually.
The Biologics Program relies on the Office of Regulatory Affairs' Field Accomplishments and Tracking System (FACTS) to register and record biologics manufacturing establishment inspection and compliance data. FACTS versions 1 and 2 together will replace the several dozen applications that comprise the current Field Information System. The software development contractor delivered FACTS version 1 to the FDA on September 30, 1997. Version 1 functionality includes all sample collections; all sample tracking, accountability, and dispositions; sample analysis of pesticides, additives, colors, elements, mycotoxins and radionuclides; firms inventory, maintenance and registration; work assignments and work management; and other features.
Meanwhile, the design and development of FACTS version 2 is underway. Major features of version 2 include replacing the remaining FIS functions: remainder of lab analyses; rest of investigations including records and tracking; compliance functions; other core items including personnel management (MUS); and miscellaneous operations including recalls and audit checks. The delivery to FDA of version 2 is scheduled for October 31, 1998, to be followed by the same implementation scenario as is being used for version 1.
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