1. Public Health Issues Related to Mutually Conforming Labeling: CDRH Perspective Miriam C. Provost, Ph.D. Office of Device Evaluation Center for Devices and Radiological Health

2. FDA Mission Stated most simply, FDA's mission is to promote and protect the public health by helping safe and effective products reach the market in a timely way, To monitor products for continued safety after they are in use, and To help the public get the accurate, science-based information needed to improve health.

3. The Balancing Act Promotion of public health - expedite approval of innovative products that have potential for positive impact on public health Protection of public health – ensure that all medical products are adequately tested for safety, that labeling provides adequate directions for safe use

4. General Purpose Drug Delivery Systems CDRH has a long history of clearing unfilled general purpose drug delivery systems through 510(k) Examples: External infusion pumps 21 CFR 880.5725. “An infusion pump is a device used in a health care facility to pump fluids into a patient in a controlled manner. The device may use a piston pump, a roller pump, or a peristaltic pump and may be powered electrically or mechanically. The device may also operate using a constant force to propel the fluid through a narrow tube which determines the flow rate.” I.V. Administration Set 21 CFR 880.5440 “An intravascular administration set is a device used to administer fluids from a container to a patient`s vascular system through a needle or catheter inserted into a vein. The device may include the needle or catheter, tubing, a flow regulator, a drip chamber, an infusion line filter, an I.V. set stopcock, fluid delivery tubing, connectors between parts of the set, a side tube with a cap to serve as an injection site, and a hollow spike to penetrate and connect the tubing to an I.V. bag or other infusion fluid container.”

5. General Purpose Drug Delivery Systems (cont.) Nebulizer 21 CFR 868.5630 “A nebulizer is a device intended to spray liquids in aerosol form into gases that are delivered directly to the patient for breathing. Heated, ultrasonic, gas, venturi, and refillable nebulizers are included in this generic type of device.” Catheter 21 CFR 880.5200 “An intravascular catheter is a device that consists of a slender tube and any necessary connecting fittings and that is inserted into the patient`s vascular system for short term use (less than 30 days) to sample blood, monitor blood pressure, or administer fluids intravenously. The device may be constructed of metal, rubber, plastic, or a combination of these materials.”

6. General Purpose Drug Delivery Devices In general, mutually conforming labeling not an issue Not pre-filled with drug No indications or claims for delivery of a specific drug or biologic There are one or many drugs already approved by FDA that can be delivered by these devices by this route of administration Submitter of 510(k) needs to show adequate safety and performance as a tool for delivery of drugs or biologics, i.e., devices are substantially equivalent to a legally marketed predicate Submitter of 510(k) does not need to show that the combination of drug and device is safe and effective

7. Specific drug delivery systems CDER lead Pre-filled with drug Pre-filled syringes Metered dose inhalers Photodynamic therapy devices Drug/device only effective in combination Implanted infusion pumps Device design/use may affect drug stability

8. Drug Delivery systems: When do questions arise? Proposed indication for use for device would necessitate a change in the route of administration for approved drugs Devices indicated for infusion of therapeutic drugs into the neurovasculature Devices indicated for targeted delivery of chemotherapeutic agents

9. Drug Delivery systems: When do questions arise? Devices intended for enhancement of drug effects – combined use may have a different safety/efficacy profile Devices used to prepare skin prior to administration of lidocaine Use of device as labeled may necessitate a change in dosing of approved drugs Breath actuated nebulizers Patient controlled infusion pumps for pain medication

10. Mutually conforming labeling: helping to ensure patient safety By (sometimes) requiring that drug labels be changed to reflect changes to indication, route of administration or dosing that are facilitated by a new device, FDA helps ensure patient safety: Adequate information is provided to users on both the drug and device labels Postmarket safety information is collected on the combined use, labels updated accordingly New uses are thoroughly evaluated by FDA experts in both centers according to their respective regulatory authorities

11. Mutually conforming labeling: manufacturing concerns In the absence of mutually conforming labels (and an agreement between drug and device companies), changes to drug formulations or changes to device design are not communicated Example: changes to endotoxin level of IV drug, impact on device for intrathecal drug delivery Example: changes to laser output of photodynamic therapy device

12. Summary FDA regulations allow flexibility to clear devices as general purpose drug delivery systems when appropriate Questions arise when the device use requires an unapproved drug use (indication, route of administration or dose) Mutually conforming labeling helps to ensure safe and effective use of the combination product and helps FDA achieve our mission