Part 2: Performance Plan and Report--Biologics

U.S. Food and Drug Administration
Performance Plan
2002

2.3 BIOLOGICS

2.3.1 Program Description, Context, and Summary of Performance

Total Program Resources:

	FY 02 Budget Estimate	FY 01 Current Estimate	FY 00 Actual	FY 99 Actual
Total ($000)	155,507	140,251	140,717	124,365

The mission of the Biologics Program is to ensure the safety, purity, potency, and effectiveness of biological products (primarily vaccines, blood products, and therapeutics) for the prevention, diagnosis, and treatment of disease or injury. The products that the Biologics Program regulates are on the leading edge of technology. Rapid scientific advances in biochemistry, molecular biology, cell biology, immunology, genetics, and information technology are transforming drug discovery and development, paving the way for unprecedented progress in developing new medicines to conquer disease.

The number of Investigational New Drug Applications (INDs) and Investigational Device Exemptions (IDEs) received by the Biologics Program has increased 44% from FY 96 to FY 2000. INDs and IDEs are an indication of future workload. Sponsors submit INDs/IDEs prior to beginning clinical trials to determine the safety and efficacy of the product in humans.

While scientific advances of new biological products promise great health benefits for U. S. consumers, FDA must ensure that these products are safe. FDA is also responsible for ensuring the safety of the nation's blood supply by minimizing the risk of infectious disease transmission and other hazards, while maintaining an adequate supply of whole blood and blood products. These challenges are represented by the Program's two strategic goals for the 21st century:

Ensure the expeditious availability of safe and effective biologics, for the prevention, diagnosis, and treatment of disease or injury.
Reduce the risk of biologics products on the market through assuring product quality and correcting problems associated with their production and use.

FDA is responsible for ensuring that vaccines and related products (such as botulinum toxin, skin test reagents for tuberculosis, and allergenic products) are safe and effective and adequately labeled. Vaccines against diseases such as Hepatitis B, polio, Haemophilus influenzae type b, mumps, measles, rubella, diphtheria, tetanus, pertussis, and chicken pox are recommended for all U.S. children, and vaccines against influenza and pneumococcal infections are recommended for all adults more than 65 years of age. Periodic tetanus and diphtheria booster vaccinations are recommended for all adults. The use of influenza vaccine among adults has, in recent years, increased markedly (to a current use of about 80 million doses/year). Additional vaccines are recommended for special groups (for example, persons with Hepatitis A) or for travelers to particular areas of the world (for example, Salmonella typhi or Japanese encephalitis virus vaccines). Many additional vaccines are in various stages of investigation (for example, HIV or Herpes simplex virus vaccines), and their INDs are being reviewed.

FY 2000 Performance Highlights

Blood and Blood Products

Approved ReFacto, a biological product for the treatment and prevention of hemorrhagic episodes in patients with hemophilia A. Hemophilia A is a genetically inherited blood clotting disorder caused by a deficiency in specialized proteins instrumental in promoting the normal clotting process. ReFacto is a product of Genetics Institute, Incorporated of Andover, MA.

Vaccines

Approved Prevnar, the first vaccine to prevent invasive pneumococcal diseases in infants and toddlers - diseases that can cause brain damage and, in rare cases, death. The vaccine prevents invasive diseases caused by the organism Streptococcus pneumonia (also known as pneumococcus) including bacteremia (an infection of the bloodstream) and meningitis, an infection of the lining of the brain or spinal cord. Prevnar is a product of Wyeth-Ayerst Laboratories, a Division of American Home Products Corporation in Philadelphia, PA.

Each year public health experts collaborate to determine the strains of virus to be used to manufacture the influenza vaccine that will be administered that fall. The recommendations are based on the data provided from laboratories worldwide as the strains are continuously evolving or mutating. As soon as the strains are recommended, manufacturers begin to grow virus strains in fertile hen's eggs. The parent strains of vaccine, know as "seed strains," used by each manufacturer are tested by CBER to assure they are the same as the recommended strains. CBER pre-approves seed strains, conducts tests for potency, sterility, and endotoxin as well as other tests to assure the safety and efficacy of the vaccine. CBER also performs lot release on each lot of vaccine manufactured prior to distribution of the product. Lot release consists of CBER's review of the manufacturer's test results, including tests on the lots of monovalent virus strains and tests on the final trivalent product. CBER also performs additional testing as appropriate to assure the safety and efficacy of these products.

Therapeutic Products

Approved a new indication for Actimmune that delays the time to disease progression of severe, malignant osteopetrosis in children. Osteopetrosis is a life-threatening, congenital disorder in which an overgrowth of bony structures leads to blindness, deafness and increased susceptibility to infections. In the most serious form of the disease, most patients become blind or anemic by six months of age and die within the first ten years of life, frequently in the first two years. The disease is an orphan indication. Actimmune is a product of InterMune Pharmaceuticals, Incorporated of Palo Alto, California.

2.3.2 Strategic Goals

Strategic Goal 1:

Ensure the expeditious availability of safe and effective biologics, for the prevention, diagnosis, and treatment of disease or injury.

A. Strategic Goal Explanation

The FDA is responsible for reviewing and approving biologics covered under the Prescription Drug User Fee Act (PDUFA). These products are primarily vaccines and therapeutics. FDA is also responsible for reviewing and approving biologic products not covered by PDUFA. The non-PDUFA biological products are primarily blood and blood products, biotechnology-derived hematologics, allergenic products, and devices associated with their manufacture.

To provide the U.S. public with quicker access to new biologics, FDA consults closely with product sponsors early in product development, and makes prompt decisions on important new biological product applications. FDA will continue to make timely decisions in reviewing PDUFA product license applications (PLAs), Biologic License Applications (BLAs), and New Drug Applications (NDAs) and their supplements (performance goals 13001-13004). FDA will also continue to make timely decisions in reviewing non-PDUFA biologics, primarily blood and plasma products (performance goal 13005).

PDUFA Products: The Food and Drug Administration Modernization Act of 1997 (FDAMA), Public Law 105-115, amended the Prescription Drug User Fee Act (PDUFA) of 1992, and extended PDUFA through September 30, 2002. The PDUFA authorized revenues from fees paid by the pharmaceutical industry to expedite review by the FDA of human drug applications, including biologics. These revenues were directed by section 101(4) of this Act to accomplish 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.

Fees that FDA collected from drug and biologic firms are used to reduce the evaluation time for certain human drug, including biologics, applications without compromising review quality. FDA primarily spent these PDUFA funds to hire personnel to review applications and update the information technology (IT) infrastructure supporting the review process. PDUFA II will provide FDA with the resources necessary to sustain the larger application review staff. It will also provide FDA with additional funds to acquire the resources needed to achieve the more stringent performance goals.

The PDUFA time frames and performance goals are the result of in-depth negotiations between the drug industry and FDA. Industry and FDA determined that both the time frames and the percentage goals are realistic, achievable with the additional user fee resources, and desirable. The PDUFA time frames for drug applications differ in some cases from the Food, Drug and Cosmetic Act (FD&C) statutory requirements. Biologics applications are covered by the Public Health Service Act, which does not have any statutory time frames. Industry is pleased with the certainty of timely action and response from the FDA review process and the net result of a higher percentage of applications being approved faster. Patients benefit by having more therapies available more quickly. Performance goals for PDUFA applications are based on the PDUFA time frames. Some of the more stringent PDUFA II goals are phased in over several years.

Non-PDUFA Products: The Biologics Program also reviews and approves license applications for products not covered by PDUFA. 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 of acquiring the human immunodeficiency virus (HIV), hepatitis, Creutzfeldt-Jakob disease (CJD), and other blood-borne diseases.

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.

B. Summary of Performance Goals l

Performance Goals	Targets	Actual Performance	Reference
1. Review and act on 90% of standard original PDUFA NDA/PLA/BLA submissions within 10 months; and review and act on 90% of priority original PDUFA NDA/PLA/BLA submissions within 6 months of receipt. (13001)	Standard Applications within 12 months: FY 02: NA FY 01: 90% FY 00: 90% FY 99: 90%	Standard Applications within 12 months: FY 01: FY 00: 11/01 FY 99: 100% FY 98: 100% FY 97: 100%	1999 Update
	Standard Applications within 10 months: FY 02: 90% FY 01: 70% FY 00: 50% FY 99: 30%	Standard Applications within 10 months: FY 02: FY 01: FY 00: 09/01 FY 99: 80%
	Priority Applications within 6 months: FY 02: 90% FY 01: 90% FY 00: 90% FY 99: 90%	Priority Applications within 6 months: FY 02: FY 01: FY 00: 04/01 FY 99: 100% FY 98: 100% FY 97: 100%
2. Review and act on 90% of standard PDUFA efficacy supplements within 10 months; and review and act on 90% of priority PDUFA efficacy supplements within 6 months of receipt. (13002)	Standard Applications within 12 months: FY 02: NA FY 01: 90% FY 00: 90% FY 99: 90%	Standard Applications within 12 months: FY 01: FY 00: 11/01 FY 99: 100% FY 98: 100% FY 97: 100%	1999 Update
	Standard Applications within 10 months: FY 02: 90% FY 01: 70% FY 00: 50% FY 99: 30%	Standard Applications within 10 months: FY 02: FY 01: FY 00: 09/01 FY 99: 100%
	Priority Applications within 6 months: FY 02: 90% FY 01: 90% FY 00: 90% FY 99: 90%	Priority Applications within 6 months: FY 02: FY 01: FY 00: 04/01 FY 99: 100% FY 98: 100% FY 97: 100%
3. Review and act on 90% of PDUFA manufacturing supplements within 6 months of receipt, and review and act on 90% of PDUFA manufacturing supplements requiring prior approval within 4 months of receipt. (13003)	Within 6 months: FY 02: 90% FY 01: 90% FY 00: 90% FY 99: 90%	Within 6 months: FY 02: FY 01: FY 00: 04/01 FY 99: 100% FY 98: 99% FY 97: 98%	1999 Update
	Within 4 months: FY 02: 90% FY 01: 70% FY 00: 50% FY 99: 30%	Within 4 months: FY 02: FY 01: FY 00: 02/01 FY 99: 93%
4. Review and act on 90% of Class 1 resubmitted original PDUFA applications within 2 months; and review and act on 90% of Class 2 resubmitted original PDUFA applications within 6 months of receipt. (13004)	Class 1 resubmissions within 2 months: FY 02: 90% FY 01: 90% FY 00: 70 % FY 99: 50%	Class 1 resubmissions within 2 months: FY 02: FY 01: 12/01 FY 00: 100% FY 99: 100% FY 98: 100%	1999 Update
	Class 1 resubmissions within 4 months: FY 02: NA FY 01: NA FY 00: 90% FY 99: 90%	Class 1 resubmissions within 4 months: FY 00: 02/01 FY 99: 100%
	Class 2 resubmissions within 6 months: FY 02: 90% FY 01: 90% FY 00: 90% FY 99: 90%	Class 2 resubmissions within 6 months: FY 02: FY 01: FY 00: 04/01 FY 99: 100%
5. Review and act on 90% of complete blood bank and source plasma PLA/BLA submissions, and 90 percent of PLA/BLA supplements within 12 months after submission date. (13005)	Complete Submissions: FY 02: 90% FY 01: 90% FY 00: 85% FY 99: 60%	Complete Submissions: FY 02: FY 01: FY 00: 11/01 FY 99: 100% FY 98: 85% FY 97: 83%	1999 Update
	Supplements FY 02: 90% FY 01: 90% FY 00: 90% FY 99: 90%	Supplements FY 02: FY 01: FY 00: 11/01 FY 99: 99% FY 98: 97% FY 97: 98%
TOTAL FUNDING ($000)	FY 02: 118,959 FY 01: 108,357 FY 00: 111,968 FY 99: 98,032

C. Goal-By-Goal Presentation of Performance

Note about Baseline Data: In several years of the program, performance (Baseline Data) exceeds the projected performance goals. The PDUFA II goals were set forth in letters from the Secretary of Health and Human Services to Congressional Committee Chairmen on November 12, 1997. FDA developed these goals in consultation with the pharmaceutical and biological prescription drug industries. "NA" means the goal is not applicable in that fiscal year.

1. Review and act on 90% of standard original PDUFA NDA, PLA, and BLA submissions within 10 months; and review and act on 90% of priority original PDUFA NDA/PLA/BLA submissions within 6 months of receipt. (13001)

Context of Goal: The Prescription Drug User Fee Act authorizes the FDA to collect fees from the prescription drug and biologic drug industries to expedite the review of human drugs and biologics so they can reach the market more quickly. Standard original PLAs or BLAs, are license applications for biological products, not intended as therapies for serious or life-threatening diseases. A priority PLA/BLA is a license application for a therapy to treat serious or life-threatening diseases.
Data Sources: CBER's Regulatory Management System
Performance: CBER has met or exceeded these performance goals since 1994. These applications are tracked by year of receipt, which is the cohort year. The cohort-year review performance is not available until the prescribed review time, i.e., 12 months after receipt, is expired. The FY 2000 data for standard applications within 12 months will be available after November, 2001. The FY 2000 data for standard applications within 10 months will be available after September, 2001. The FY 2000 data for priority applications within 6 months will be available after April, 2001.

2. Review and act on 90% of standard PDUFA efficacy supplements within 10 months; and review and act on 90% of priority PDUFA efficacy supplements within 6 months of receipt. (13002)

Context of Goal: The PDUFA authorizes the FDA to collect fees from the prescription drug and biologic drug industries to expedite the review of human drugs and biologics so they can reach the market more quickly. A supplement is a change to an approved licensed product. An efficacy supplement provides information to FDA to modify the "approved effectiveness" in the labeling of a product such as a new indication, and normally includes clinical data.
Data Sources: CBER's Regulatory Management System
Performance: CBER has met or exceeded these performance goals since 1994. These applications are tracked by year of receipt, which is the cohort year. The cohort-year review performance is not available until the prescribed review time, i.e., 12 months after receipt, is expired. The FY 2000 data for standard applications within 12 months will be available after November, 2001. The FY 2000 data for standard applications within 10 months will be available after September, 2001. The FY 2000 data for priority applications within 6 months will be available after April, 2001.

3. Review and act on 90% of PDUFA manufacturing supplements within 6 months of receipt, and review act on 90% of PDUFA manufacturing supplements requiring prior approval within 4 months of receipt. (13003)

Context of Goal: The PDUFA authorizes the FDA to collect fees from the prescription drug and biologic drug industries to expedite the review of human drugs and biologics so they can reach the market more quickly. A supplement is a change to an approved licensed product. A manufacturing supplement provides FDA information relating to a proposed expiration date change, formulation revision, manufacturing process change, packaging change, or controls change.
Data Sources: CBER's Regulatory Management System
Performance: CBER has met or exceeded these performance goals since 1994. These applications are tracked by year of receipt, which is the cohort year. The FY 2000 data for review of manufacturing supplements within 6 months will be available after April, 2001. The FY 2000 data for review of manufacturing supplements within 4 months will be available after February, 2001.

4. Review and act on 90% of Class 1 resubmitted original PDUFA applications within 2 months; and review and act on 90% of Class 2 resubmitted original PDUFA applications within 6 months of receipt. (13004)

Context of Goal: PDUFA authorizes the FDA to collect fees from the prescription drug and biologic drug industries to expedite the review of human drugs and biologics so they can reach the market more quickly. A resubmitted original application is a complete response to an action letter addressing all identified application deficiencies. Class 1 resubmitted applications are applications resubmitted after a complete response letter that include one or more of the following items: final printed labeling; draft labeling; safety updates; stability updates; commitments to perform Phase IV (postmarketing) studies; assay validation data; final release testing; a minor re-analysis of data; other minor clarifying information; or other specific information requested by the Agency. Class 2 resubmissions include any other items.
Data Sources: CBER's Regulatory Management System
bThese applications are tracked by year of receipt, which is the cohort year. FDA's FY 2000 performance for review of class 1 resubmissions within 2 months was 100%. The FY 2000 data for review of class 1 resubmissions within 4 months will be available after February, 2001. The FY 2000 data for review of class 2 resubmissions within 6 months will be available after April, 2001.

5. Review and act on 90% of complete blood bank and source plasma PLA/BLA submissions, and 90% of PLA/BLA supplements within 12 months after submission date. (13005)

Context of Goal: Blood bank and source plasma applications are not covered by PDUFA. The non-PDUFA review resources in CBER are not protected from cuts as the PDUFA resources are by the PDUFA legislation. CBER's non-PDUFA review resources have been cut in recent years to meet unfunded pay raises, increased current service costs, and other budget actions.
Data Sources: CBER's Regulatory Management System
b These applications are tracked by year of receipt, which is the cohort year. The cohort-year review performance is not available until the prescribed review time, i.e., 12 months after receipt, is expired. The FY 2000 data for review of complete submissions and for major supplements will be available after November, 2001.

Strategic Goal 2:

Reduce the risk of biologics products on the market through assuring product quality and correcting problems associated with their production and use.

A. Strategic Goal Explanation

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.

By accomplishing the performance goals 13007 and 13012, the Biologics Program will ensure that biologics establishments are in compliance with regulations and that the products produced in those establishments are safe and pure. The Biologics Program also ensures that high-risk plasma fractionator establishments are in compliance (performance goal 13008).

Factors which affect the FDA'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.

B. Summary of Performance Goals

Performance Goals	Targets	Actual Performance
6. Assure that FDA inspections of domestic biologics manufacturing, repacking and blood banks establishments result in a high rate of conformance (at least 90%) with FDA requirements (13007)	FY 02: at least 90% FY 01: at least 90% FY 00: at least 90% FY 99: at least 90%	FY 02: FY 01: FY 00: 96% FY 99: 98% FY 98: 98% FY 97: 98%
7. Maintain the percentage of plasma fractionator establishments in compliance with CGMPs at 80%. (13008)	Currently 26 foreign and Domestic Plasma Fractionator establishments
	FY 02: 80%	FY 02:
	FY 01: 80%	FY 01:
	FY 00: 80%	FY 00: 69%, 18 out of 26 in compliance
	FY 99: 80%	FY 99: 62%, 16 out of 26 in compliance
		FY 98: 54%, 13 out of 24 in compliance
8. Meet the biennial inspection statutory requirement by inspecting 50% of registered blood banks, source plasma operations and biologics manufacturing establishments. 1 (13012)	FY 02: 50% FY 01: 50% FY 00: 50% FY 99: 43%	FY 02: FY 01: FY 00: 57% FY 99: 64% FY 98: 46% FY 97: 46%
TOTAL FUNDING ($000)	FY 02: 36,548 FY 01: 31,894 FY 00: 28,749 FY 99: 26,333
1 Some adjustments in counting inventories and inspectional coverage were necessary due to a few problems resulting from the transition to a new database (FIS to FACTS) in FY 2000.

C. Goal-By-Goal Presentation of Performance

6. Assure that FDA inspections of domestic biologics manufacturing, repacking and blood banks 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%) (13007)

Context of 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 on deficiency corrections. This is due to FDA's selection of high-risk firms. Since firms inspected are not randomly selected from 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.
Data Sources: FDA Field Information System (FIS)
Performance: Performance for this goal in FY 2000 was 96%. Conformance rates for FY 97 through FY 2000 have been adjusted to reflect the observed average correction rate for each year.

7. Maintain the percentage of plasma fractionator establishments in compliance with CGMPs at 80%. (13008)

Context of Goal: There are 26 foreign and domestic plasma fractionator establishments. It was discovered that very few of these establishments were in compliance with CGMP regulations. In an effort to bring the majority of the plasma fractionator establishments into compliance with CGMPs, the Agency transferred the responsibility for plasma fractionator inspections to the Field. Additionally, the Agency developed program guidance and conducted training for FDA inspectors to bring the establishments into compliance.
Data Sources: Field Information System (FIS)
Performance: Currently, there are 26 foreign and domestic plasma fractionator establishments. In FY 2000, 69%, or 18 establishments of 26 were in compliance. There has been steady compliance improvement. However, inspections continue to find compliance discrepancies. Due to the small number of plasma fractionator establishments, the non-compliance of a few establishments with GMPs skews the percentage adversely.

8. Meet the biennial inspection statutory requirement by inspecting 50% of registered blood banks, source plasma operations and biologics manufacturing establishments. (13012)

Context of Goal: This includes inspections done by FDA directly, or through state contracts or partnership agreements. The law requires FDA to conduct inspections of certain manufacturing facilities once every two years. There are currently 2,790 establishments in the Biologics Program inventory covered under this statute. There are 2,898 additional establishments in the Biologics Program inventory not covered under this statute.
Data Sources: Program-Oriented Data System, Official Establishment Inventory.
Performance: In FY 2000, FDA inspected 57% of the establishments in the Official Establishment Inventory, exceeding the goal of 50%. The drop in inspection coverage from 64% in FY 1999 to 57% in FY 2000 is attributed to changes in risk priorities. Some resources were re-allocated to other high-priority areas such as tissues. 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 2001 performance is reported.

2.3.3 Verification and Validation

The Biologics Program uses various databases to manage its diverse programs and to assess performance. The principal CBER database is the Regulatory Management System (RMS). The RMS is CBER's new VAX-based, Oracle database that is used to track all 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 of management reports. The RMS records application review information on each license application and supplement received and filed by the Center. The RMS 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 RMS.

The Biologics Investigational New Drug 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 (over 12,000 in 1999); 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 RMS, discussed above. INDs are tracked by the BIMS, also discussed above. The Office utilizes the BLT to record and track data concerning device premarket applications (PMAs) and PMA supplements, 510(k)s, and Abbreviated New Drug Application (ANDAs) and ANDA supplements. The Office also has an NDA tracking system.

The data retrieved from these systems are reviewed and validated by the RIMS and the application review offices. If errors are detected, they are corrected.

Federal regulations (21 CFR, Part 600.14) require reporting of deviations in the manufacture of biological products that affect the safety, purity, or potency of the product. The Biological Product Deviation Reports (BPDRs) (previously called error and accident reports) enable 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 pubic health. The regulation applies to licensed manufacturers, unlicensed registered blood establishments, and transfusion services which had control over the product when a deviation occurred to report to FDA the biological product deviation if the product has been distributed.

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 requirements to all biological product manufacturers regulated by FDA.

In the past five years, the Agency has received an average of 12,000 biologics product deviation reports annually. FDA estimates that over 116,000 biologic product deviation reports would be received under the proposed regulation. FDA does not have a computer system to permit the electronic submission of biologic product deviation reports. If the Agency is to comply with the intended goals of the biologic product deviation reporting regulation, it will need a system that would allow it to receive electronic submission of reports; and to process, analyze and evaluate more than 100,000 reports annually.

The Biologics Program relies in 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 (FIS). 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; inspections; rest of investigations including records and tracking; compliance functions; other core items including personnel management (MUS); and miscellaneous operations including recalls and audit checks.

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