Foreword

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This document was prepared by Technical Committee ISO/TC 84, Devices for administration of medicinal products and catheters.

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Introduction

Current industry standards cover the quality of performance, e.g. dose accuracy or injection depth, of different types of drug delivery systems (DDS). These standards require the use of statistical tolerance intervals to quantify this quality of performance for each individual primary function.

The term “reliability” is commonly used to refer to such quantification, i.e. a tolerance interval based on a probability content and confidence level.

For at least two decades this approach has proven to be appropriate for many types of DDSs and continues to do so.

Today these DDSs are used across a broad range of therapeutic areas to deliver medicinal products treating chronic diseases of low immediate risk as well as potentially life-threatening acute illnesses.

Such DDSs not only need to meet the individual quality of performance for each primary function. They also need to successfully execute a sequence of functions necessary for delivery of the medicinal product.

In this document, the terms ‘capability’ and ‘system reliability’ are introduced to differentiate between the quality of performance of a primary function and the probability of each DDS to successfully deliver a medicinal product respectively.

Based on the severity of potential harm of not delivering the medicinal product this document suggests five reliability levels. Each of those is linked to minimum capability and system reliability values in line with current industry practice.

Due to the more severe consequences of some DDSs failing to deliver the medicinal product, requirements for demonstrating system reliability for the two highest reliability levels have also been added, as well as more stringent requirements for challenging the DDSs based on the environmental conditions they are intended to withstand and how these environmental conditions might need to be combined for testing purposes.

The document also emphasises that while both capability and system reliability must be demonstrated at the conclusion of development (as demonstrated by design verification), they also need to be maintained throughout manufacture of the DDS. In addition, the two highest reliability levels require additional effort to ensure these expectations are met.

The establishment of a system reliability is not intended to change the testing for devices that are already adequately addressed by the current standards (e.g. ISO 11608, ISO 20072 and ISO 21649). Specific detailed considerations for these standards are addressed in Annex B.

Demonstration of system reliability is not limited to (verification) testing. The entire process of developing the product and the application of control strategies ensures the DDS continuously meets the system reliability requirements.

The concept of system reliability is a special case of reliability engineering that pertains to “out of box” failures for all disposable single use DDSs for which there is a single opportunity to deliver a single dose of a medicinal product. In contrast, reliability engineering is a collection of techniques to ensure performance of durable or reusable DDSs over a long period of time and through multiple, successive actuations to ensure consistent performance possibly over many years.

There can be examples of single-use devices which are built to have on-board a second (or “backup”) dose. This document can be helpful in the development of such devices, but the reader should be aware that multi-dose or reusable DDSs are outside the scope of this document (see Annex B for further details).

Figure 1 illustrates the document structure and its relation to risk management.

1 Scope

This document addresses the specification and demonstration of capability and system reliability to successfully deliver a medicinal product as part of design verification and manufacture, utilizing empirical methods as well as modelling. This includes risk-based techniques to establish and demonstrate the required reliability level for all disposable single use drug delivery systems (DDSs) for which there is a single opportunity to deliver a single dose of a medicinal product.

DDSs covered by this document include, but are not limited to:

needle-based injection systems (ISO 11608-1);
needle-free injection systems (ISO 21649);
aerosol drug delivery systems (ISO 20072).

This document does not cover:

DDSs with containers that can be replaced;
DDSs intended for dental use;
finished needles;
empty syringes;
catheters;
DDSs for multi-patient use;
pumps [IEC 60601-2-24 (if electronic) or ISO 28620 (if non-electronic)];
stand-alone prefilled syringes defined by ISO 11040-8.

In this document system reliability is limited to assessing functional performance of the DDS and does not address human factors or user interface considerations. These will be covered by a usability engineering program in accordance with IEC 62366-1.

NOTE DDSs not in scope of this document can still benefit from elements in this document but provisions of this document might not completely fulfil the basic safety and effectiveness of such DDSs.

2 Normative references

3 Terms and definitions

4 Specification of system reliability and capability

4.1 General

4.2 Reliability level

4.3 Reliability level matrix

5 Requirements for demonstration of system reliability

5.1 General

5.2 Reliability levels 1, 2 and 3

5.3 Reliability levels 4 and 5

6 Design verification

6.1 General

6.2 Establishing conditions

6.3 Environmental and physical conditions

6.4 Combining conditions for testing

7 Maintaining system reliability

Bibliography