Drug Disposal Labelingto Improve Safety

FDA Update on Drug Disposal Labeling Activities

James R. Hunter, R.Ph., MPHControlled Substance Staff

Center for Drug Evaluation and Research

Office of the Center Director

Food and Drug Administration

5th Annual Unused Drug Return Conference

November 11, 2008

The opinions and information in this presentation are those of the author and do not necessarily reflect the views and policies of the FDA

What I’ll Talk About Today…

• FDA roles related to prescription drug disposal

• Assessing and managing risks during the drug product lifecycle

• Disposal instructions in labeling as a risk mitigation strategy for certain drugs.

• New legal authorities to improve drug safety

• Update on related FDA activities

FDA’s Mission is to ensure that…FDA’s Mission is to ensure that…

Americans have access to safe and effective drug products

Foods are safe, wholesome, and properly labeled Blood used for transfusions and blood products are

safe & in adequate supply Medical devices are safe & effective Transplanted tissues are safe & effective Animal drugs and medicated feeds are safe &

effective, and food from treated animals is safe for human consumption

Radiation-emitting electronic products are safe Cosmetics are safe & properly labeled

FDA is an active Stakeholder in Drug Disposal Issues

• Federal/State Entities: – Environmental Protection Agency– Drug Enforcement Administration– Office of National Drug Control Policy– Substance Abuse and Mental Health Services Administration– U.S. Postal Service– U.S. Fish and Wildlife– State Regulatory Authorities

• Non-Government Organizations:– American Pharmacists Association– News media, press– Organizations representing local disposal initiatives

FDA Roles related to Drug Disposal

• Assessing environmental impact of new drug products – Part of the NDA approval process

– Exposure based on estimated drug use

• Prescription drug product labeling– Drug disposal information not routinely included

– Typically not required

– Usually included to improve products safety profile

"All substances are poisonous, there is none which is not a poison; the right dose differentiates a poison from a remedy"

Paracelsus, circa 1538

Benefits Risks

Drug Approval

• Safe and effective for use as described in product label

• Product’s benefit outweighs its risk

Pre-ClinicalTesting

R&D

IND

Clinical Research & Development

Post-MarketingSurveillance

Phase I

Phase III

Phase II

NDA

Phase IV

Risk Assessment During Product Lifecycle

Risk Management*

• The overall and continuing process of minimizing risks throughout a product’s lifecycle to optimize its benefit/risk balance

* From the Concept Paper on Risk Management Programs

Routine Risk Minimization

• Labeling (package insert) is the cornerstone of routine risk management efforts for most drugs approved by the FDA

Drug Disposal Instructions in FDA Drug Product Labeling

• Voluntary– not usually required

• Usually included to increase safety– Drug Product Specific– Comparison of risks and benefits suggests

product disposal instructions improve benefit-risk balance.

– When health care professional or patients must take special steps that are “unusual” for safety

• Required (New!)- If included in Risk Evaluation and Mitigation

Strategy

Types of Patient Information Labeling

• Package Insert (PI)– Practitioner to patient instruction

• Patient Package Insert (PPI)– May be part of PI or separate document – Voluntary distribution except for oral contraceptives

and estrogen products

• Medication Guide (MG)– FDA-approved patient labeling– Dispenser required to provide MG when product is

dispensed

FDAAA (New 2008!)

• FDA Amendments Act of 2007 gives New Authorities– May require:

• Postmarketing studies and clinical trials• Safety related labeling changes• Risk Evaluation and Mitigation Strategies

(REMS)

What is a REMS?

• A Risk Evaluation and Mitigation Strategy (REMS) is a required risk management plan that utilizes tools beyond routine labeling to ensure that the benefits of a drug outweigh its risks.– Always includes a medication guide which

may contain specific disposal instructions.

REMS• Scope

– Prescription drug and biologics only

• Before Approval REMS– FDA requires sponsor to submit a REMS– REMS needed to ensure that the benefits outweigh the risks of

the drug– Considerations

• Size of population likely to use drug• Seriousness of disease• Expected benefit of the drug

• Post-Approval REMS– New safety information shows REMS necessary to ensure that

the benefits outweigh the risks of the drug– FDA determines REMS is needed– FR Notice FDA-2008N-0174 (March 27, 2008): Identification of

Drug and Biological Products “Deemed” to have REMS, 16 drug products

Disposal Instructions for Controlled

Substances • Disposal instructions usually a part of a more

comprehensive risk mitigation strategy– Not included in all products containing controlled substances– Potency and formulation contribute to varying potential for

misuse, abuse, and accidental overdose• Dangerous amounts of residual drug after use (Fentanyl

transdermal patch)• High potency formulations (Extended release oxycodone, fentanyl

buccal tablets)• High likelihood of misidentification: Actiq (fentanyl citrate) looks like

candy and Xyrem (sodium oxybate) is clear liquid at bedside.

– Goal of disposal is to minimize exposure risk of potentially lethal drug to non-patients

• Make drug completely unavailable upon disposal• Disposal by Flushing• “Take-back” disposal option in FDA labeling limited by CSA

Fentanyl Buccal Tablet Disposal Instructions

Recent Activities• Identifying FDA approved drug product

labeling with drug disposal information– drug label review

• Assessing content and consistency of drug disposal information in product labeling – Sponsor-initiated labeling includes take-back disposal option

• Developing guidance for FDA reviewers and drug product sponsors– Actively assessing drug disposal labeling policy– Identifying and assessing sources of risk data to develop

evidence-based policy guidance

Office of National Drug Control Policyhttp://www.whitehousedrugpolicy.gov/drugfact/factsht/proper_disposal.html

FDA Consumer Health Information June 23, 2008

http://www.fda.gov/consumer/updates/drug_disposal062308.html

Store REYATAZ Capsules at room temperature, 59° to 86° F (15° to 30° C). Do not store this medicine in a damp place such as a bathroom medicine cabinet or near the kitchen sink.

Keep your medicine in a tightly closed container.Keep all medicines out of the reach of children and pets at all times.

Do not keep medicine that is out of date or that you no longer need. Dispose of unused medicines through community take-back disposal programs when available or place REYATAZ in an unrecognizable, closed container in the household trash.

FDA Supports Drug Take-Back Programs

Summary• FDA is focusing increased attention to drug disposal issues and

continues to work closely with our federal partners

• FDA supports the safe disposal methods as described in the Federal Drug Disposal Guidelines.

• For a limited number of higher risk products containing controlled substances, disposal instructions are necessary to improve safety.

• FDA has new authorities that could require sponsors to include drug disposal instructions as an added safety measure.

• FDA supports take-back programs, recognizing current limitations under in the CSA to collect controlled drug products.

• FDA is actively working to develop drug disposal labeling policies that account for the risk associated with products that are disposed of improperly.

Safety First!