Biologics

1/ Includes Salaries & Expenses, Rent and PDUFA, where applicable.

EXPLANATION OF PROGRAM

The availability of safe and effective biological products for disease prevention and treatment, and the assurance of the safety of the nation's blood supply are essential elements of the nation's health-care-delivery system. 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 disease in humans are pure, potent, safe, and effective, as well as properly labeled for their intended uses.

FDA's 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 conduct of mission-related research, in concert with other HHS public health agencies, academia, and industry, to further the development of new products and to provide a sound scientific basis for regulation. FDA ensures that vaccines are safe and effective through evaluation of products, the manufacturing process, and by monitoring adverse events associated with immunization. The Agency seeks to facilitate the development of the safest and most effective childhood vaccines by sponsoring and conducting research toward their development.

FY 2001 BUDGET REQUEST

ASSURING SAFETY/STRENGTHENING SCIENCE INITIATIVES

PREMARKET INITIATIVES + $7.3 MILLION, 30 FTE

Bringing Products of New Technology to Market + $7.3 million, 30 FTE

In order to speed the availability of new products to the market, the Center for Biologics Evaluation and Review (CBER) has focused on developing mechanisms to most effectively and efficiently complete the review process. Resources are needed to address the following areas:

• Implement the Center's Managed Review Process, which is a system designed to most effectively and efficiently review all license applications and supplements. This process provides mechanisms to solve problems and address issues at key development and review stages, through interactions with CBER and the sponsor. This process substantially streamlines the entire review process from pre-pivotal trials in the Investigational New Drug Application (IND) phase through post marketing and results in a shorter review cycle for applications. (Biologics Performance Goals # 1, 2, 3, 4)

• Provide the necessary scientific expertise to expedite the review and approval of non-PDUFA biological product applications by recruiting, training, and retaining qualified application reviewers. Additional scientific review staff will facilitate the review of product applications, initiate opportunities for use of academia, the National Institutes of Health (NIH), and other entities to participate on the review of new, specialized products, and ensure evaluation of biological product applications is accomplished pursuant to a science-based approach. In addition, scientific review staff will ensure that regulatory decisions reflect a state-of-the-art scientific understanding through collaborations with NIH, the Centers for Disease Control and Prevention (CDC), and the Health Resources and Services Administration (HRSA) on emerging technology in areas such as xenotransplantation, cell and gene therapies, and tumor vaccines. Additional resources will permit the continuing professional development of the scientific review staff which is the foundation of the application review process.

• Improve the quality and safety of the nation's blood supply by improving or developing diagnostic tests and identifying validation criteria important to maintaining surveillance of blood and blood products. This will reduce the threat of emerging blood-borne infectious diseases being transmitted through blood and blood product transfusions.

• Improve our ability to ensure the safest and most effective vaccines. This can be accomplished through increased laboratory testing and evaluation of vaccine safety and purity; exploring new approaches for the fuller evaluation of vaccines before they are widely used; and developing new approaches to testing for the presence of unknown or previously undetected agents in vaccines. This will increase the safety of vaccines, and reduce the risk of disease transmission though vaccines. FDA will also pursue the use of IAGs, and CRADAs with outside organizations.

• Develop influenza vaccine strains with industry, CDC and NIH. The Agency reviews and approves annual influenza vaccines to address pandemic flu outbreaks. Resources are needed to improve the range of activities related to the availability of approved influenza vaccines on an annual basis. These activities include: producing influenza virus strains that can be used for large scale manufacturing; developing biological materials to assess potency; conducting research to improve vaccines and to understand how to produce safe and effective vaccines as quickly as possible; and evaluating reports of side-effects after marketing. This will increase the public health by reducing the incidence or severity of influenza.

• Enhance the availability of new products and ensure an increased level of safety against novel pathogens in blood and blood products, vaccines, novel therapies and products manufactured from transgenic plants and animals, and used in patients who are immuno-compromised, through the development of science-based standards and guidance to industry. This will make new and novel products available quicker. Resources will be used to conduct workshops with industry and academia on research-related issues and to collaborate with outside organizations and other government agencies.

• Expand bioresearch monitoring activities to assure the protection of human subjects, that clinical investigations are properly conducted and that premarket approval goals are met.

• Improve the consistency, quality and usefulness of inspections by developing and using computerized inspectional guidance software that provides investigators with specific program guidance, laws, and regulations necessary for them to conduct scientific risk based biologics inspections.

To make the Biologics application review process more efficient, and to make safe and effective emerging biotech biological products available as quickly as possible.²

POSTMARKET INITIATIVES + $4.8 MILLION, 20 FTE

Medical Errors + $2.8 million, 8 FTE

The Institute of Medicine's (IOM) 1999 report on medical errors emphasized the need for the American medical community to reevaluate practices and procedures that may lead to fewer deaths. Additional resources of $2.8 million in this area will be used in FY 2001 to do the following:

² We have attempted to align the budget request and performance plan goals. All italicized items represent performance goals in the Agency's performance plan, with the specific reference following. More information on these goals and past performance can be found in the performance plan.

To reduce the number of deaths attributable to medical errors by detecting products causing adverse reactions quickly and taking actions to reduce patient risks.

Inspectional Activities + $2.0 million, 12 FTE

FDA will increase the inspectional coverage rate of both domestic and foreign establishments while the overall inventory continues to expand. The request for $2.0 million, inspectional activities will be used to:

USER FEES

PREMARKET

Current Law User Fees +$0.8 million

Prescription Drug User Fee Act II (PDUFA II) + $1.5 million

FDA proposes to revise the distribution of projected spending of PDUFA fees for FY 2001 among the Human Drugs, Biologics, and Other Activities programs to reflect recent patterns of actual spending within the PDUFA program. This is similar to reallocations approved by the Appropriations Committees in both FY 1998 and FY 1999, and will not increase FDA's total spending for Other Activities. The net change for this reallocation is zero.

The reallocation within PDUFA is necessary to assure that PDUFA fee revenues are used to pay their fair share of the costs of FDA management (Other Activities). To make this change permanent, our FY 2001 budget request reflects our proposal to fully utilize these funds for Other Activities and possibly avoid a reprogramming later in the year. This $5 million of Salaries and Expenses funds will be made available to FDA operating programs (excluding Tobacco), as a partial alleviation of the cost impact of the recent 4.8 percent general pay raise.

The total PDUFA budget request for the Agency in FY 2001 is $149.27 million and 920 FTE, including $32.2 million and 204 FTE for the Biologics program. As a result of the proposal to reallocate PDUFA funds, the program will experience an increase of $1.5 million. The revenues generated from the fees paid by the pharmaceutical and biological prescription drug industries will be dedicated to continuing to improve and expedite the prescription drug application review and approval process. The fees collected in FY 2001 will enable the FDA to continue to meet its PDUFA II performance goals, which include the following:

• Review and act on 90 percent of standard original NDA and PLA/BLA submissions filed during FY 2001 within 12 months of receipt, and review and act on 70 percent within 10 months of receipt.

• Review and act on 90 percent of priority original NDA and PLA/BLA submissions filed during FY 2001 within 6 months of receipt. 

• Review and act on 90 percent of standard efficacy supplements filed during FY 2001 within 12 months of receipt, and review and act on 70 percent within 10 months of receipt. 

• Review and act on 90 percent of priority efficacy supplements filed during FY 2001 within 6 months of receipt. 

• Review and act on 90 percent of manufacturing supplements filed during FY 2001 within 6 months of receipt and review and act on 70 percent of manufacturing supplements requiring prior approval within 4 months of receipt. 

• Review and act on 90 percent of Class 1 resubmitted original applications filed during FY 2001 within 4 months of receipt, and review and act on 70 percent within 2 months of receipt. 

• Review and act on 90 percent of Class 2 resubmitted original applications filed within 6 months of receipt.

SPECIAL PROGRAM INITIATIVES

Countering Bioterrorism + $6.5 million, 14 FTE

FDA plays a critical role in the preparation for bioterrorist attacks by reviewing new drugs and vaccines to counter the effects of anthrax and other potential bioterrorism events. The Agency must also conduct Good Manufacturing Practice inspections of drug manufacturers whose products may be stockpiled as a part of the government's bioterrorist efforts. As part of the interagency effort FDA intends to:

• Expand efforts to test and produce DNA vaccines against the lethal factor and edema factor of anthrax and further develop an Ebola DNA vaccine. Explore the use of DNA vaccines for smallpox and the use of RNA vaccines against some of the encephalitis-causing alphaviruses. Expand efforts to develop non-DNA-based vaccines. This will increase the protection of the American public and the military against potential bioterrorist biological agents.

• Initiate or expand programs on pathogenesis and mechanisms of immunity for a variety of pathogens including anthrax, tularemia, plague, and viral hemorrhagic fever causing viruses. The development of vaccines is often facilitated by detailed knowledge of disease pathogenesis and mechanisms of immunity. This will increase the effectiveness of bio-defense vaccines. The Agency will utilize IAGs, CRADAs and contract fellows to participate in appropriate areas.

• Develop microarray technology to rapidly detect the presence of nucleic acids, oligonucleotides, and RNA fragments. Microarray technology is cutting edge technology using viral genomes to produce signals that rapidly screen for potential viruses. This will increase ability to identify the pathogenic organisms.

• Improve scientific expertise in monoclonal antibody therapies, new approaches in the use of biotherapeutics, animal and human derived immune globulins in the treatment of viral and bacterial diseases and in the area of emerging infectious diseases. Antibodies are immune-system proteins that attack foreign invaders like germs - or that neutralize substances the body is over-producing. Monoclonal antibodies are artificial, highly purified antibodies, made by combining animal and human genetic material, that work with exquisite precision in small doses. This will enhance our ability to identify, treat and test for previously unrecognized threats.

• Participate in the planning and coordination of public health responses to bioterrorist attacks.

• Prepare field staff to safely seize, remove, and dispose of contaminated products by developing procedures and providing appropriate facilities and equipment.

• Develop inspection methods and procedures to assure the safety of regulated products at manufacturers and other establishments. 

To contribute to the Nation's capabilities to respond to potential biological threats from bioterrorism, including the development of new vaccines and therapeutics.    

JUSTIFICATION OF BASE  

FDA will continue to ensure 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 disease in humans are pure, potent, safe, and effective, as well as properly labeled for their intended uses.

• 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 biological products from the market. 
• Development of necessary regulations, compliance programs and guidelines relating to biological products such as blood and blood products, vaccines and therapeutics. 
• Conduct of research, in concert with other DHHS public health agencies, academia, and industry, to provide a sound scientific basis for their regulation, and to further the development of new biological products. 
• FDA will continue its activities to ensure that vaccines are safe and effective through evaluation of products, their manufacture, and by monitoring adverse events associated with immunization.

Countering Bioterrorism - One-time Supplemental

In FY 2000, the Biologics Program received $7.5 million one-time funding from the Department's Public Health and Social Services Emergency Fund to begin the process of developing the necessary expertise and infrastructure to address regulatory activities for the Presidential Initiative to counter bioterrorism. The one-time funding will be used for activities to expeditiously develop and license new vaccines for anthrax and smallpox and the associated vaccinia immune globulin (VIG) products used to treat or prevent serious vaccinia infections brought on by the smallpox vaccine.

Biologics 

Selected FY 1999 Accomplishments

• Fast Track Designation. Published a guidance entitled that informs sponsors of new products intended for treatment of a serious or life-threatening condition, which demonstrate the potential to address unmet medical needs, and that may be eligible for designation as fast track.

Blood Safety and Availability

• Approved the first biologic for von Willebrand's Disease (vWD), the clotting disorder. The new indication for a plasma-derived product called Antihemophilic Factor/von Willebrand Factor Complex (Human), is marketed as Humate-P by Centeon L.L.C. of Kankakee, Illinois.  
• Continued to implement the Blood Action Plan, which is designed to increase the effectiveness of its scientific and regulatory actions, and to ensure greater coordination with FDA's Public Health Service (PHS) partners. The Action Plan addresses highly focused areas of concern such as emergency operations, response to emerging diseases, updating and reinvention of regulations, monitoring the blood supply, ensuring compliance of plasma fractionation establishments, and blood donor/recipient notification and lookback.  
• Completed the systematic update of the blood regulations. As a result, the number of outdated blood regulations was reduced; the number of guidance documents lacking enforceability have been reduced; and the blood industry's compliance with standards has increased. 
• Responded to challenges by blood-borne pathogens for which there are no vaccines or adequate therapies. Blood supplies are constantly exposed to the dangers posed by these pathogens, which include HIV, Hepatitis B and C, HTLV I & II, Cytomegalovirus (CMV), Transmissible Spongioform Encephalopathies (TSE) and others. Because most of these blood-borne contaminants have successfully evaded therapeutic and vaccine treatments, the current strategy for protecting the public health is to test and disqualify donors and blood donations found to be contaminated with known pathogens.

Developments in Vaccines

• Licensed the first vaccine to aid in the prevention of Lyme disease. Lyme disease is transmitted to people through the bites of ticks infected with the bacterium Borrelia burgdorferi. The new vaccine LYMErix, is approved for use in people 15 to 70 years of age who live or work in grassy or wooded areas where Lyme disease-bearing ticks are present. LYMErix is marketed by SmithKline Beecham Pharmaceuticals of Philadelphia, Pennsylvania. 
• Participated in the National Vaccine Advisory Committee (NVAC) - sponsored workshop on thimerosal for vaccines to examine ways to reduce or eliminate the use of mercury-based thimerosal as a preservative in childhood vaccines.

Cellular and Tissue-Based Products

• Licensed the first genetically engineered treatment for rheumatoid arthritis (RA). This incurable disease occurs when the body's immune system mistakenly turns against the joints. Etanercept, marketed under the trade name Enbrel by Immunex Corporation, Seattle, Washington, and Wyeth Ayerst Laboratories, Philadelphia, Pennsylvania, will offer an alternative to the more than two million Americans. 
• Approved Thymoglobulin, a drug used to aid in the treatment of acute rejection in renal transplant patients and is manufactured by Pasteur Meriex Serums of Lyon, France. 
• Initiated a Xenotransplantation Action Plan to address the risks of introducing infectious diseases into the human population from xenotransplantation procedures. Xenotransplantation is any procedure that involves the use of live cells, tissues, or organs including a non-human animal source transplanted or implanted into a human, or used with ex-vivo contact with human body fluids, cells, tissues or organs that are subsequently given to a human recipient.

Prescription Drug User Fee Act (PDUFA)

The PDUFA established performance goals for the evaluation of applications for marketing drug and certain biological products. Review performance monitoring is done in terms of fiscal year cohorts, e.g., the FY 1998 cohort includes applications received from October 1, 1997 through September 30, 1998. Fiscal year cohort performance is not immediately measurable at the end of the fiscal year. The measurable outcome will occur either 6 or 12 months after the last submission received during the fiscal year, depending upon the category of submission. FDA has met or exceeded all its performance goals.

The FY 1999 cohort review performance goals were:

• Review and act on 90 percent of standard original NDAs and PLAs/BLAs filed during FY 1999 within 12 months of receipt and review and act on 30 percent within 10 months or receipt. 
• Review and act on 90 percent of priority original NDA and PLA/BLA submissions filed during FY 1999 within 6 months of receipt. Review and act on 90 percent of standard efficacy supplements filed during FY 1999 within 12 months of receipt and review and act on 30 percent within 10 months of receipt. 
• Review and act on 90 percent of priority efficacy supplements filed during FY 1999 within 6 months of receipt. 
• Review and act on 90 percent of manufacturing supplements filed during FY 1999 within 6 months of receipt and review and act on 30 percent of manufacturing supplements requiring prior approval within 4 months of receipt. 
• Review and act on 90 percent of Class 1 resubmitted original applications filed during FY 1999 within 4 months of receipt, and review and act on 50 percent within 2 months of receipt. 
• Review and act on 90 percent of Class 2 resubmitted original applications received during FY 1999 within 6 months of receipt.

Biologics

Program Activity Data

¹ Total of approval, approvable, not approvable and complete decisions. Does not include refuse-to-file decisions or withdrawals.  

² Includes IND, IDE, Master File and license master files receipts.

³ An inspection is any visit to an establishment during which all or part of one or more phases of that establishment's operation is evaluated against appropriate agency requirements.

⁴ Includes MedWatch, Foreign reports and VAERS reports.

Edited 3/2/2000