FDA Guidance Document Comments

FDA Guidance Document Comments

Total Product Life Cycle: Infusion Pumps – Premarket Notification [510(k)] Submissions

07/09/2010

Executive Summary

This document is prepared to provide a feedback to the FDA Guidance Document, ‘Total Product Life Cycle: Infusion Pump – Premarket Notification [510(k)] submissions, presented to the Infusion pump industry dated April 23, 2010. The feedback provided in the attached sections discusses simplification of the guidance document for the Non-electrically Driven Pumps. The Non-electrically Driven Pumps such as an Elastomeric Pump are simpler by design as there is no Software and Electrical Signals. Hence, we are recommending a specific section for the Non-electrically Driven Pumps within the context of overall guidance document. The benefits of this section will be as follows:

·  Simplification of the guidance document for the simpler Non-electrically Driven Pumps through a separate section.

·  Address product specific items such as applicable ISO standard for Non-electrically Driven Pumps.

·  Minimize or eliminate references to Software, Alarms and other non applicable items.

·  The benefits to the FDA will be a simpler evaluation with these pumps eliminating redundancy of non applicable electromechanical system requirements.

·  Preserve integrity of the overall guidance document and retain all the elements of applicable items of the guidance document.

Rationale for the proposal

·  FDA indicates that there are numerous infusion pump types and the Guidance Document appropriately addresses the various safety issues connected with infusion pumps. However, the document does not segment the differences in the inherent designs of these pumps which leads to fundamentally different risks and design requirements. ISO 28960 was created to distinguish the unique design parameters and requirements associated with non-electronic infusion pumps from electrically powered pumps. The existing standards could not be appropriately used to evaluate the designs of this class of pumps therefore the Guidance Document should also give the same consideration to segmenting the basic pump groups.

·  Overall complaint rates and failure modes are different for the elastomeric pump products compared to electromechanical pumps. The data is from 01/01/2005 to 12/31/2009 of the FDA guidance document. The comparison is as shown below:

Overall MDR Rate, All pumps / Elastomeric Pumps (% of Total)
Deaths reported / 710 / 4 (0.6%)
Serious Injuries / 19,040
Malfunctions / 34,720
Total MDRs / 56,000 / 1,568 (2.8%)
Total units sold

·  Overall # of MDRs for elastomeric pumps is quite low (2.8%).

·  Elastomeric pumps represent a potentially safer product by design. Basic design makes a simpler product configuration and is easier to use. The key differences are as follows:

Risk Factors

/

Electromechanical Pumps

/

Elastomeric Pumps

System Performance Requirement / A drug reservoir, a flow control module, and tube set to deliver the drug. / A drug reservoir, a flow control module, and tube set to deliver the drug.
Product Components / Hardware, User Interface, Mechanical Systems and Software systems / Mechanical delivery system
User Interface / Complex system with S/W, H/W and Disposable Set integration. / System is simple to use, portable and completely disposable. Strain of membrane provides pressure. No software or electromechanical components.
Disposable tubing set has Luers for connections for filling and patient access. / Closed system. Pre-attached tubing Simple Luers for connection to filling and patient access.
Patient Interface / The system has lot of push buttons and S/W requiring the skills to use the pump. / Patient friendly: no complicated programming. In-line flow control orifice controls infusion rate. Eliminates run-away infusions and reduces programming errors.
Patients have to learn about H/W, S/W and Disposable system. There are three major systems vs. one system. / Elastomeric pumps have become standard of care in Home Infusion for over 20 years primarily for antibiotics and chemotherapy. Acute pain management applications for the past 12 years. .
Multiple systems increase probability of failure. / No malfunction due to battery or S/W or H/W issue.
Alarms: Multiple alarms including occlusion, battery life, fluid presence etc. / Alarms: No alarms that distract the patients. The device is simple in nature and a visual review is a good indicator.
Pharmacist Interface / Aseptic fill. / Aseptic fill.
Life Sustaining Drugs / Yes / No - contraindicated
Operating Clinician/Nurse Interface / -  Need to have expertise in mounting the disposable set.
-  Need to know S/W and operating principles of the pump.
-  Need to confirm the environment of use.
-  Need to understand the basic pump function and patient access methods. / -  Need to understand the basic pump function and patient access methods.
Maintenance / -  Pump needs to be serviced periodically
-  Pump needs to be cleaned between users / -  Generally, they are Disposable, and Single use devices. Therefore, no PM or additional cleaning required

Recommendations

·  Considering the fundamental differences in technologies , we propose that the guidance document be separated into two sections: 1. Electromechanical Infusion Pumps, and 2. Non-electrically Driven Infusion Pumps.

Key Changes Proposed

·  Eliminated references to alarm and software errors.

·  Deleted references to specific applicable hazards and deleted references not related to the non-electrically powered pumps.

·  Added reference to ISO28620:2010 because of its direct applicability and relevance.

·  Eliminated references to ISO60601-1-8 as it is not directly applicable.

·  In labeling, deleted references to electrical systems such as alarm limits and ranges, RF wireless technologies.

Proposed Changes: Guidance for Non-electrically Driven Infusion Devices

New Section Proposed

1a. Introduction

For the purpose of this document, the non-electrically driven infusion device refers to a simple disposable ambulatory infusion pump that is made up of a drug reservoir, a non-electrical power source (mechanical, elastomeric, vacuum, etc), a flow controlling mechanism, and connection to patient. This type of infusion pumps can be used in healthcare setting, home care and in transit.

2a. Background

Overall, the MDRs broken down by different types of infusion pumps is as follows: LV, Insulin, Elastomeric Pumps, Enteral Feeding Pumps, PCA pumps, from the data between January 1, 2005 and December 31, 2009.

Total MDR / 56,000 (100%)
Large Volume Infusion Pumps / 26,320 (47%)
Insulin Pumps / 25,200 (45%)
Enteral Feeding Pumps / 2,184 (3.9%)
Elastomeric Pumps / 1,568 (2.8%)
PCA Pump / 896 (1.6%)

The most frequently reported infusion pump device problems related to non-electrically driven infusion pumps are: human factors (which include, but are not limited to, use error), broken components, over infusion and under infusion. In some reports, the manufacturer was unable to determine or identify the problem and reported the problem as “unknown”. Subsequent root cause analyses revealed that many of these design problems were foreseeable and, therefore, preventable. (Note: Eliminated references to alarm and software errors)

The FDA has evaluated a broad spectrum of infusion pumps across manufacturers and has concluded there are numerous, systemic problems with device design, manufacturing, and adverse event reporting. FDA has structured this guidance document to address these device problems prior to clearance of the premarket notification and in the postmarket context.

3a. Scope

The scope of this sub-section is related to the non-electrically driven infusion pumps. All the products with MEB classification are included within the scope. Any other therapeutic products such as an Enteral Feeding pump that is Non-electrically Driven Infusion Pump is within the scope of this sub-section. A completely disposable device that is not powered electrically, such as an elastomeric pump will be treated as part of the Infusion Pump system.

For purposes of this document, FDA defines the infusion pump system to include the:

Infusion pump;

·  Fluid infusion set for the complete fluid pathway from, and including, the drug reservoir or fluid source container (e.g., bag, cassette, vial, syringe), infusion set, extension set, filters and valves, clamps, up to and including the patient connection;

·  A non-electrically driven infusion pump system can be comprised of the Fluid Storage Reservoir and Power Source (e.g. Spring, Elastomeric Bladder, Vacuum) , infusion set or tubing, filters and valves, clamps, up to and including the patient connection (e.g. an elastomeric pump system).

·  Components and accessories (e.g., PCA)

·  Patient;

·  Environment of use (e.g., clinical setting, temperature, humidity); and

·  User (physician or lay user).

4 a. Device Description, Non-electrically Driven Infusion Pump

We recommend you identify your device by the regulation and product code MEB (or FRN) described in section 3, scope. You must provide information on how your device is similar to and/or different from other products of comparable type in commercial distribution, accompanied by data to support the statement as required by 21CFR 807.87(f). Side by side comparisons, whenever possible, are desirable,

You should include the following descriptive information about your device:

·  A clear statement of the intended use of your device, including:

-  The intended use environment

-  The intended route(s) of administration for infusion

-  Any specific uses for the infusion pump (e.g., PCA is a generally accepted specific use);

-  Whether the infusion pump is contraindicated for a specific use of for the delivery of a specific therapy.

·  If the infusion pump is labeled for use with a specific device, drug, or biologic, you should provide information demonstrating that this use is consistent with the FDA approved labeling for that device, drug, biologic.

·  For each route of administration identified in your statement of intended use, you should identify an FDA approved drug or biologic to demonstrate that at least one such product is approved for infusion through the proposed route of administration. (Note: dosage and drug libraries are not applicable to these pumps).

·  The non-electrically driven infusion pumps are also generally intended for ambulatory use, you should describe how the device has been designed to be safely and effectively used by the alternate site (e.g. homecare) population, which often have limited or no clinical background and may receive limited training with your device.

·  Provide a detailed description (including, where appropriate, engineering drawings and schematics) of the pump components. The components may include:

o  The infusion delivery mechanism including the power source and flow control mechanism

o  The drug reservoir

o  Pump tubing and connectors

·  You should describe the principle of operation of the infusion pump (i.e. the scientific principles behind how the device achieves its intended use).

·  You should describe the user interface components of the pump, including catheters, PCA modules/Bolus Buttons, Flow Rate Controllers, tubing or other components of the physical pump that may be manipulated.

·  You should describe how you will market the device (e.g. sterile, single use, home use or combination healthcare facility/home use).

To support substantial equivalence, we recommend that you provide a table comparing your device to a legally marketed predicate device. This table should include the following:

·  The intended use for each device, including the patient population for which the devices are intended (i.e. neonate, infant, pediatric, adult) and the intended use environment.

·  The specification for the device (e.g. flow rate accuracy specifications).

·  The technological features of the devices (e.g. flow rate control mechanism)

You should describe how any differences in technology may affect the comparative safety and performance of the device from the predicate device.

5 a. Risks to Health

In the table attached as Appendix Aa, FDA has identified the risks to health generally associated with the use of the devices addressed in this guidance document. If you elect to use an alternative approach to address a particular risk identified in this document, or if you have identified risks additional to those in this document, then you should provide sufficient detail to support the approach you have used to address the risks.

Note: Simplify the appendix A to relevant risks. Eliminate the following categories: 1. Air embolism, 2. Trauma, 3. Electric Shock, 4. Exsanguinations. In the non-electrically driven elastomeric industry, we have not observed any failures related to the above categories and the likelihood is remote.

6a. Assurance Case Report, Non-electrically Driven Infusion Pumps

As discussed in the main body of the guidance document, the three main elements of an assurance case are:

1.  Claim: Statement about a property of the system or some subsystem.

2.  Evidence: Information that demonstrates the validity of the claim. This can include facts (e.g. based on observations or established scientific principles), analysis research conclusions, test data, or expert opinions.

3.  Argument: Links the evidence to the claim. Arguments can be deterministic, probabilistic, or quantitative. The argument will describe what is being proved or established (i.e. the claim(s)), identify the items of evidence is adequate to satisfy the claim. Arguments may also introduce sub-claims or assumptions which require further exposition.

Note: Certain hazards are not present with the non-electrically powered infusion pumps, so the relevant hazards are as described below:

Section 6Aa: Operational Hazards

Section 6Ba: Environmental Hazards

Section 6Fa: Mechanical Hazards

Section 6Ga: Biological and Chemical Hazards

Section 6Ha: Use Hazards

We recommend that you conduct your own hazard analysis for your particular infusion pump to identify any hazards particular to your device. Your premarket notification should clearly describe the method used to analyze the hazards and each hazardous event mitigation. If you elect to use an alternative approach to address a particular hazard, or categorization of hazards, identified in this document or if you have identified a hazard additional to those in this document, you should provide sufficient detail to support the approach you have used to address that hazard.

Note: ISO60601-1-8 will not be applicable to our systems. There are limited alarms and no electromechanical interfaces. Hence, it may be a significantly simplified Assurance Case Report. Human Factors is a new section and the assessment will be provided.

[Note: There is a new ISO28620:2010, Medical Devices – Non-electrically driven portable infusion devices, which has references to the associated hazards. Those are as follows:

·  Operational Hazards: Flow rate impacts during use

·  Environmental Hazards: Resistance to drop, resistance to pressure, resistance to traction.