# Presentation: 793916

## State of the U.S. Drug Regulatory System

- Janet Woodcock, M.D.
- August 17, 1998

## Purpose of this meeting:

**Input from stakeholders**
** **
**Purpose of this talk:**
**Scope of drug regulatory activities**
**Sense of current priorities and issues**

## Agenda

**Current drug regulatory system & public expectations**
**Scope of activities and resources available**
** **
**Current level of performance & issues**
**Summary**

## U.S. Drug Regulatory System

**In evolution over much of the 20th Century**
**Mission:  Promote and protect public health by assuring that safe and effective drugs are available to Americans.**
**Most recent modification:  FDA Modernization Act of 1997**

## Components of System

**FDA**
**Center for Drug Evaluation and Research**
**Office of Regulatory Affairs (FDA Field)**
**Office of Chief Counsel**
**Office of the Commissioner**

## Components of System (cont.)

**State and Local Officials**
**State Licensing Boards**
** **
**Institutional Review Boards**
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**DEA**

## Expectations for the System

**All marketed drugs are effective and safe in the context of their use.**
**Human drugs are of high quality**
**Generic competition keeps drug prices reasonable**
**All advertising and promotion of drugs is informative and is not false or misleading**

## Expectations for the System (cont.)

**Patients who lack alternatives have access to investigational drugs**
** **
**High quality information on how to use drugs is available including information on children, elderly patients and other groups**

## Expectations for the System (cont.)

- Robust drug development programs, that thoroughly protect human subjects, flourish and are productive

## Drug Regulatory System: Processes

- Application Review
- IND, New Drug Application
- ANDA
- Standard Setting
- OTC Monographs
- Standards for Marketing
- Technical Standards
- Quality Standards
- Format and Content

## Drug Regulatory System: Processes (cont.)

- Post-marketing safety surveillance (Pharmacovigilance)
- Post-marketing trials, registries
- Spontaneous reporting system
** **

## Drug Regulatory System: Processes

- Compliance /Enforcement
- Inspections
- Surveillance
- Drug sampling
- Advertising
- Education
- Regulatory Actions
** **
** **
** **

## Drug Regulatory System: Essential Supporting Activities

- Research
- Laboratory
- Regulatory Science
- Policy Development
- Policy Development
- International Collaboration/Outreach

## Essential Supporting Activities

- Communication
- Drug information/education
- Freedom of information process
- Dispute resolution
- CDER Ombudsman
- Citizen Petition process
- Stakeholder feedback - ORA

## Essential Supporting Activities:

- Information Management
- Information technology
- Medical library
- Electronic submissions
- Intra- and Internet - use

## Essential Supporting Activities:

- Training
- Internal
- Policies
- Procedures
- External

## FDA Drug Regulatory Program: 1998  Resources*

- 2,561  People
-  	1,708  CDER
- 	  853  ORA (field)
- $283,953.00	Budget
- 		206K	CDER
- 		11.5K	Orphan Products
- 		66 K	Field
- *Including User Fee Funding

## Factors Affecting Resource Distribution

- Historical
- Direct statutory mandates
- PDUFA dictates baseline level of effort in premarket review
- Advocacy:  Orphan Drugs,  AIDS

## Application Review:  IND Process

- Current Performance Level
- Process well managed and timely
- First-time-in-human trial issues resolved
- “Clinical holds” oversight

## IND Process:  Standards

- International Conference on Harmonization of Technical Requirements for Pharmaceuticals (ICH) Standards
- Good Clinical Practices (GCP)
- Toxicology protocols
- Clinical Testing Guidance
- Indication - specific guidance not updated

## Investigational New Drug Process: Issues

**1.**	Performance:  Extensive performance goals under
-      “PDUFA II”
- 2.	Access to Investigational Drugs
- 3.	Status of Institutional Review Boards
- 4.	Pediatric Drug Development
- 5.  Research:  Shorten drug development time & improve quality   (CDDI)

## New Drug Review:  Performance

- Timeliness:  Meeting all PDUFA goals
- Openness:  Over 50 Advisory Committee Meetings yearly
- Efficiency”  Moving toward electronic submission

## New Drug Review:  Standards

- Requirements to study children, women, elderly, ethnic groups
- Antibiotic resistance
- Over-the-Counter Switches
- Chronically used drugs:  patient follow-up

## New Drug Review:  Issues

- Standards
- Drug Safety
- Number of patients studied prior to marketing
- Benefits to many  Vs  risks to few
- Drug - drug interactions
- Radiopharmaceuticals and PET drugs

## Application Review:  Generic Drugs

- Current Performance Level
- Over 50% ANDA’s reviewed in 180 days
- Time to marketing has dropped from
-     40 months (1993) to 19 months (1997)
- Additional streamlining occurring

## Generic Drug Review:  Issues

- Manufacturers calling for further shortening of review times
- Congressional interest:  Barriers to generic competition
- Research:  Non-oral dosage forms

## Application Review:  Supplemental NDA’s (New Uses)

- FDA “New Use Initiative”
- Guidance “Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products”
- Guidance “FDA Approval of New Cancer Treatment Uses for Marketed Drug and Biological Products”

## Product Quality Assurance:  Performance

- Marketed drugs are of high quality
- Efficiency gains: “SUPAC” Process
- Not meeting every two year requirement for facility inspections

## Product Quality Assurance:  Issues

- Maintaining adequate inspectional coverage in U.S.
- 3rd party audit?
- 1st party audit?
- Inspection of foreign establishments
- Mutual recognition agreements

## Product Quality Assurance:  Issues (cont.)

- Manufacturing standards for bulk pharmaceuticals
- Standards for Pharmacy Compounding

## Surveillance/Compliance

- Health Fraud
- Dietary Supplements
- Marketed unapproved drugs

## Surveillance:  Drug Marketing and Advertising: Issues

- Direct-to-Consumer Advertising
- Disseminating of Reprints:  FDAMA
- Consumer information on prescription drugs
- Pharmaceutical firm’s role in managed care

## Surveillance:  Human Subject Protection

- Audits of clinical trials
- Audits of IRB’s
- Training IRB’s and clinical investigators
- International clinical trials
- Electronic data capture

## Safety of Marketed Drugs

- Premarket testing will not detect all problems/toxicity's
- Rare events
- Events caused by use outside approved parameters
- Medication errors

## Safety of Marketed Drugs (cont.)

- CDER is upgrading spontaneous reporting system (passive surveillance)
- Active surveillance of various kinds has been suggested

## Communications

- Effective communication linked to drug safety
- Prescription and OTC labeling
- Drug development statistics
- Communications research

## Summary

- Drug regulatory system in U.S. is very effective and performing well
- Many expectations for improvement and competing priorities
- We need to hear from stakeholders