STRATEGIC FUTURE
(FY 1999-2004)

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 conduct of research, in concert with other HHS public health agencies, academia, and industry, to further development of new products and to provide sound scientific basis for their regulation.

The regulation of biologics has been significantly affected by reinvention initiatives. In 1995, the Agency responded to manufacturers' concerns with a series of measures that included the replacement of 21 application forms with one harmonized version; and allowed the use of small scale pilot facilities during the approval phase of biological products.

Recently, the Agency proposed a truly novel scientific framework for regulating therapies derived from human cells and human tissues. The key feature of this proposal is that the FDA interventions are proportionate to the degrees of risk. Under the proposed regulation, oversight will be commensurate with degree of public health risk. The Agency recently announced two proposed guidances that clarify the quantity and quality of evidence needed to approve a new or supplemental therapeutic indication.

Assumptions:

1. That CBER's PDUFA-related research will be phased out over three years (FY 1998-FY 2000). The reduction in PDUFA research activities will be largely offset by additional PDUFA review activities.

STRATEGIC GOAL AREA: PREMARKET REVIEW

FY 1999 Performance Goal Highlights Review 90% of standard original NDA/PLA/BLA submissions within 12 months of receipt (30% within 10 months); and 90% of priority original NDA/PLA/BLA submissions within 6 months of receipt. Review 90% of standard efficacy supplements within 12 months of receipt (30% within 10 months); and 90% of priority efficacy supplements within 6 months of receipt. Review 90% of manufacturing supplements within 6 months of receipt, and review 30% within 4 months of receipt. Review 90% of Class 1 resubmitted original applications within 4 months of receipt (50% within 2 months); and review 90% of Class 2 resubmitted original applications within 6 months of receipt.

Cluster 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 Food and Drug Administration (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.

Resources, Approaches, Processes, Skills, and Technology: 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 14.5 months in FY 1996.

FDA has met or exceeded its 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 (PLAs) are of better quality and there are fewer refuse-to-file decisions. The number of user-fee PLAs that were refused filing declined from three in FY 1994 to zero in FY 1997.

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.

The Quality Assurance Staff has oversight responsibility for both the Clinical Hold and the Refuse-to-File Oversight committees, thereby bringing a program management review and perspective to the process. Review of these actions by the respective committees ensures that high review standards and consistency of action are maintained. This program will be expanded to examine IND and PLA letters for consistency and quality. The assessments will be designed to enhance the Program's reviewer training programs and aid management to make corrections.

STRATEGIC GOAL AREA: PREMARKET REVIEW

FY 1999 Performance Goal Highlights Review and act on 70% of complete blood bank and source plasma PLA/BLA submissions and PLA/BLA Major supplements within 12 months after submission date. Review and act on 60% of complete blood bank and source plasma ELA Major supplements within 12 months after submission date.

Cluster 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 12 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.

Resources, Approaches, Processes, Skills, and Technology: FDA reviews and evaluates pre-marketing 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 biologics license application (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 revitalization and rewriting of blood regulations.

STRATEGIC GOAL AREA: POSTMARKET ASSURANCE

FY 1999 Performance Goal Highlights Assure that the domestic biologics manufacturers and repacking establishments inspected by the FDA achieve a 90% rate of conformance with FDA requirements. Increase compliance of plasma fractionator establishments to 80%.

Cluster Rationale: FDA is required by law to conduct biennial inspections of all licensed establishments to determine compliance with current good manufacturing practice (GMP) 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 under contract to a licensed establishment. FDA conducts biomedical research inspections to review pivotal clinical trial data and inspections of new tissue-cellular-based products.

Resources, Approaches, Processes, Skills, and Technology: 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; conducting training programs for inspectors to implement the new approaches; conducting workshops to clarify Agency expectations for industry; and evaluating 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 will 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 to assure that all policies are mutually consistent in guarding the safety of the nation's blood supply.

Strategic Goal Area:	PREMARKET REVIEW
Cluster:	Prescription Drug User Fee Act (PDUFA)
1. Review and act on 90% of standard New Drug Applications (NDA) and Product License Applications/Biologics License Applications (PLA/BLA) filed within 12 months after receipt (30% within 10 months of receipt); and review and act on 90% of priority NDA and PLA/BLA submissions within six months of receipt.
Agency Strategies:	Streamline application reviews.
Data Sources:	CBER's Biologics Regulatory Management System (BRMS).
Baseline Data:	Standard applications: FY 1993: 86% FY 1994: 100% FY 1995: 100% FY 1996: 100% Priority applications: Under development. Data showing percent reviewed within six month period will be available mid-FY 1998.
2. Review and act on 90% of standard efficacy supplements within 12 months of receipt (30% within 10 months of receipt); and review and act on 90% of priority efficacy supplements within six months of receipt.
Agency Strategies:	Streamline application reviews.
Data Sources:	CBER's Biologics Regulatory Management System (BRMS).
Baseline Data:	Standard applications: FY 1993: 55% FY 1994: 83% FY 1995: 100% FY 1996: 88% Priority applications: Under development. Data showing percent reviewed within 6 month period will be available mid-FY 1998.
3. Review and act on 90% of manufacturing supplements filed within six months of receipt, and review and act on 30% of manufacturing supplements requiring prior approval within four months of receipt.
Agency Strategies:	Streamline application reviews.
Data Sources:	CBER's Biologics Regulatory Management System (BRMS).
Baseline Data:	FY 1993: 53% FY 1994: 85% FY 1995: 94% FY 1996: 98%
4. Review and act on 90% of Class 1 resubmitted original applications within four months of receipt (50% within two months of receipt); and review and act on 90% of Class 2 resubmitted original applications within six months of receipt.
Agency Strategies:	Streamline reviews. Inform and assist product sponsors.
Data Sources:	CBER's Biologics Regulatory Management System (BRMS).
Baseline Data:	Under development. Data showing percent reviewed within 6 month period will be available mid-FY 1998.

Strategic Goal Area:	PREMARKET REVIEW
Cluster:	Blood, Tissues, and Other Biological Products
1. Review and act on 70% of complete blood bank and source plasma PLA/BLA submissions and PLA/BLA Major supplements within 12 months after submission date.
Agency Strategies:	Streamline reviews.
Data Sources:	CBER's Biologics Regulatory Management System (BRMS).
Baseline Data:	Complete submissions: FY 1993: 34% FY 1994: 43% FY 1995: 84% FY 1996: 95% Major supplements: Under development. Data showing percent reviewed within 12 month period will be available mid-FY 1998.
2. Review and act on 60% of complete blood bank/source plasma Establishment License Applications (ELA) Major supplements within 12 months after submission date.
Agency Strategies:	Streamline reviews.
Data Sources:	CBER's Biologics Regulatory Management System (BRMS).
Baseline Data:	Under development. Data showing percent reviewed within 12 month period will be available mid-FY 1998.

Strategic Goal Area:	POSTMARKET ASSURANCE
Cluster:	Biologics Compliance
1. 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 rate of conformance (at least 90%) with FDA requirements by the end of the fiscal year.
Agency Strategies:	Inform and assist firms to achieve compliance.
Data Sources:	Field Data Systems.
Baseline Data:	Prior compliance performance measures have been essentially counts of activities at various points along the enforcement continuum-i.e., number of inspections, violative inspections, warning letters, prosecutions, etc. This new measure strives to integrate the results of these activities into an end-of-the-year statement about the compliance of this specific industry sector. A prototype of the new measure will be generated in FY 1998.
2. Increase the percentage of plasma fractionator establishments in compliance with current good manufacturing practices (CGMPs) to 80%.
Agency Strategies:	Inform and assist firms to achieve compliance. Target high priority domestic and import risks. Maintain inspection visibility.
Data Sources:	ORA's PODS.
Baseline Data:	There are 26 foreign and domestic fractionator establishments. In FY 1996, 12 establishments were inspected and 9 were in compliance (75%).