ISO/DIS 16038

Male condoms -- Guidance on the use of ISO 4074 and ISO 23409 in the quality management of natural rubber latex condoms and synthetic condoms

Préservatifs masculins -- Directives sur l'utilisation de l'ISO 4074 et de l'ISO 23409 dans le management de la qualité des préservatifs en matières synthétiques et en latex de caoutchouc naturel

Standards Content (sample)

DRAFT INTERNATIONAL STANDARD ISO/DIS 16038
ISO/TC 157 Secretariat: DSM
Voting begins on: Voting terminates on:
2009-05-11 2009-10-11

INTERNATIONAL ORGANIZATION FOR STANDARDIZATION • МЕЖДУНАРОДНАЯ ОРГАНИЗАЦИЯ ПО СТАНДАРТИЗАЦИИ • ORGANISATION INTERNATIONALE DE NORMALISATION

Male condoms — Guidance on the use of ISO 4074 and
ISO 23409 in the quality management of natural rubber latex
condoms and synthetic condoms

Préservatifs masculins — Directives sur l'utilisation de l'ISO 4074 et de l'ISO 23409 dans le management de la

qualité des préservatifs en matières synthétiques et en latex de caoutchouc naturel

[Revision of first edition (ISO 16038:2005)]
ICS 11.200

In accordance with the provisions of Council Resolution 15/1993 this document is circulated in

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Conformément aux dispositions de la Résolution du Conseil 15/1993, ce document est distribué

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ISO Central Secretariat work of editing and text composition will be undertaken at publication

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THEY ARE AWARE AND TO PROVIDE SUPPORTING DOCUMENTATION.
International Organization for Standardization, 2009
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ISO/DIS 16038
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ISO/DIS 16038
Contents Page

Foreword............................................................................................................................................................ iv

Introduction ........................................................................................................................................................ v

1 Scope ..................................................................................................................................................... 1

2 Normative references ........................................................................................................................... 1

3 Terms and definitions........................................................................................................................... 1

4 Quality of design................................................................................................................................... 2

5 Quality of manufacture......................................................................................................................... 3

6 Quality in procurement......................................................................................................................... 4

7 Quality in testing................................................................................................................................... 5

8 Important parameters to be considered when using ISO 4074 and ISO 23409.............................. 5

9 Sampling.............................................................................................................................................. 11

Bibliography ..................................................................................................................................................... 12

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ISO/DIS 16038
Foreword

ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies

(ISO member bodies). The work of preparing International Standards is normally carried out through ISO

technical committees. Each member body interested in a subject for which a technical committee has been

established has the right to be represented on that committee. International organizations, governmental and

non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the

International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization.

International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.

The main task of technical committees is to prepare International Standards. Draft International Standards

adopted by the technical committees are circulated to the member bodies for voting. Publication as an

International Standard requires approval by at least 75 % of the member bodies casting a vote.

Attention is drawn to the possibility that some of the elements of this document may be the subject of patent

rights. ISO shall not be held responsible for identifying any or all such patent rights.

ISO 16038 was prepared by Technical Committee ISO/TC 157, Non-systemic contraceptives and STI barrier

prophylactics.

This second edition cancels and replaces the first edition (ISO 16038:2005) of which has been technically

revised.
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ISO/DIS 16038
Introduction

Condoms are medical devices used for contraception and for prevention of sexually transmitted infections.

ISO 4074 is a quality standard for natural rubber latex condoms and ISO 23409 for condoms made from

synthetic condoms. They are reference documents for standardized end-product quality test protocols and a

baseline specification for critical attributes that affect condom safety and effectiveness. They are applied by

manufacturers, procurement agencies, regulatory bodies and testing laboratories.

The use of ISO 4074 and or ISO 23409 does not by itself ensure consistency in quality; consistent high quality

at the lowest possible cost is attained ONLY through a regime termed quality management, through which,

quality is built into the product and assured at every point in the design, planning, production and procurement

processes. This International Standard should lead to continuous improvement in manufacturing, procurement

and testing processes. The special requirements of buyers and consumers should also be given due

consideration when applying ISO 4074 or ISO 23409, as ISO 4074 and ISO 23409 are general by design, and

will not cover completely all circumstances.

This International Standard is a guidance document providing manufacturers, buyers, and third-party test

laboratories guidance to implement and apply ISO 4074 in the manufacture of condoms and for purchasers to

apply ISO 4074 or ISO 23409 as a technical specification and to verify that condoms delivered, comply with

the specification, as appropriate.

In order to be acceptable, condoms need to meet or exceed the minimum requirements specified in ISO 4074

or ISO 23409, as applicable.

It is not possible, nor is it required, to subject condoms to user trials on a batch-by-batch basis. For this reason,

certain evaluations are carried out only in the case of a pre-market validation; for example for new or

significantly modified designs.

Design validation requirements normally include all the GMP validation requirements and the validation

requirements of ISO 9001 and ISO 13485; these are not currently covered by ISO 4074 and ISO 23409, but

are generally included by regulatory authorities as prerequisites for registering new designs of medical

devices. Design considerations such as stability testing, etc. are however covered in ISO 4074 and evaluation

of barrier properties by clinical trials and determination of burst properties are covered in ISO 23409.

ISO 4074 and ISO 23409 are mainly concerned with finished product testing carried out to monitor or to verify

that the condoms have been manufactured with adequate level of consistency in quality. For this purpose,

tests have been designed that can be carried out rapidly and economically. The requirements in ISO 4074 and

ISO 23409 are based on those properties which, based upon current knowledge, are believed to be relevant

to the performance of condoms in normal use.

Some important properties of condoms are nevertheless difficult to define in quantitative terms because of

lack of controlled studies, the absence of practical and economical tests, and the need for different

specifications to suit different users. ISO 4074 and ISO 23409 are therefore focused on the essential

properties where limits can be clearly defined. Other properties are addressed only in general terms and are

meant to be augmented through appropriate manufacturing records, certification by the manufacturer or by

buyers' specifications.

This International Standard also addresses how to deal with other important issues not covered by ISO 4074

and ISO 23409.

It is meant to help the user of ISO 4074 and ISO 23409 to understand any risks that may be associated with

the use of condoms. It also helps in deciding whether such risks are acceptable when weighed against the

benefits to the user. ISO 4074 and ISO 23409 also help in assessing whether the products are demonstrably

safe and offer protection to health. Good communication between the buyer and the manufacturer will result in

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ISO/DIS 16038

the delivery of satisfactory and safe products, thus avoiding unnecessary testing or inappropriate

specifications, thereby minimizing compliance testing costs.

It should also be noted that in many countries condoms being medical devices are subject to appropriate

regulations.

The requirements for quality management are given in standards such as ISO 9001 and ISO 13485. ISO 9001

is based on the approach of achieving business excellence through quality management. For condoms, being

medical device, it is appropriate that ISO 13485 is applied for quality management as part of compliance to

regulatory requirements.
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DRAFT INTERNATIONAL STANDARD ISO/DIS 16038
Male condoms — Guidance on the use of ISO 4074 and
ISO 23409 in the quality management of natural rubber latex
condoms and synthetic condoms
1 Scope

This International Standard provides guidance on using ISO 4074 and ISO 23409 and addresses quality

issues to be considered during the development, manufacture, quality verification and procurement of

condoms. It encompasses the aspects of quality management systems in design, manufacture and delivery of

condoms with emphasis on performance, safety and reliability of condoms. Male condoms are either made

from essentially natural rubber latex, in which case the requirements of ISO 4074 are applicable; or when

male condoms are made from synthetic materials and or blends of synthetic materials and natural rubber latex,

the requirements of ISO 23409 are applicable. This International Standard outlines the aspects applicable to

both types of condoms with specific clarifications where appropriate.
2 Normative references

The following referenced documents are indispensable for the application of this document. For dated

references, only the edition cited applies. For undated references, the latest edition of the referenced

document (including any amendments) applies.
ISO 31-0:1992, Quantities and units – Part 0: General principles

ISO 2859-1, Sampling procedures for inspection by attributes – Part 1: Sampling schemes indexed by

acceptance quality limit (AQL) for lot-by-lot inspection
ISO 4074, Natural latex rubber condoms – Requirements and test methods
ISO 9000, Quality management systems – Fundamentals and vocabulary

ISO 13485, Medical devices – Quality management systems – Requirements for regulatory purposes

ISO 14155, Clinical investigation of medical devices for human subjects
ISO 14971, Medical devices – Application of risk management to medical devices

ISO/IEC 17025, General requirements for the competence of testing and calibration laboratories

ISO 23409: – Male condoms – Requirements and test methods for condoms made from synthetic materials

3 Terms and definitions

For the purposes of this document, the terms and definitions given in ISO 4074, ISO 9000, ISO 13485 and

ISO 23409 apply.
1) To be published.
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ISO/DIS 16038
4 Quality of design
4.1 General

The condom is a single-use medical device, the performance and safety of which depends upon the design

and the manufacturing process. New designs of condoms may require clinical testing, several other tests and

analysis ‘on a limited basis' for validation purposes such as shelf-life determination (type testing) and risk

assessment. These requirements are generally prescribed by licensing authorities and the data generated

become part of the master file for the product. Guidelines are available in ISO 13485 and the GMP

requirements. When new products are developed, their design should conform to the requirements of design

control as laid down in ISO 13485 and GMP requirements.

The design control principles should be applied to parameters such as shape of condoms; dimensions; critical

components in formulation such as base materials, antioxidants, vulcanizers, stabilizers, colorants, etc.;

lubricants and additives such as flavour, additional lubricants etc.; and packaging materials. The safety of the

materials used should be reviewed and ensured in accordance with appropriate regulatory requirements such

as Medical Device Directive. Design control activities should be documented as part of the quality

management system documentation, reviewed and updated, when regulatory agency and/or customer needs

warrant changes. Whenever significant changes are made to the formulation or process that may substantially

affect the performance and/or safety of the condoms, these changes should be evaluated, validated and

documented (e.g. changes in types of formulation, changes in lubricant, changes in primary (individual)

packaging material, changes in leaching process).

Design of synthetic condoms and their materials are arrived at considering the variety of materials possible

and the need to meet the requirements of efficacy, adequate barrier properties and mechanical strength. The

efficacy is evaluates by using surrogate virus tests using bacteriophage Phi-X174, followed by clinical trials by

comparison against natural rubber latex condoms as reference.

Design validation should be used as the basis for ensuring that design parameters such as dimensions,

formulation, components, stability and shelf-life claims, packaging and dressing materials, etc., are

appropriate. When appropriate or necessary, such as when there has been a significant change in the

formulation, skin irritation studies and safety evaluation should be performed and documented as part of

design control activities.

Purchasers including procurement agencies, in addition to assuring that condoms comply with the ISO 4074

or ISO 23409, should interact with manufacturers in specifying the parameters such as dimensions, type and

amount of lubricant, type of packing, configuration of secondary and tertiary packaging, specific labelling, etc.

The shape, colour and additional features, if any, should also be stated by the procurement agency and

agreed upon with the manufacturer. Any additional specifications should be communicated to the testing

laboratories also so that the correct specifications are applied while testing the products.

4.2 Clinical investigation

Since condoms are medical devices, it may be appropriate to carry out clinical trials when significant changes

are made to the design, type of lubricant, etc. rather than relying on laboratory data. Clinical trials may also be

conducted to compare specific characteristics of different products. These characteristics might include

donning, slippage and breakage studies, and other parameters that could affect the efficacy and safety of the

condoms. Clinical trials should be conducted under a written protocol, to monitor the objectives clearly stated

in accordance with ISO 14155 and ISO 29943. Due consideration should be given to the inclusion of

appropriate reference condoms. The risk management should be carried out as specified in ISO 14971.

ISO 16037 is a guidance document that recommends physical parameters that should be measured before

conducting clinical trials. The clinical data thus generated should be reviewed as required to ensure continued

safety and compliance with performance requirements of the condoms.
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ISO/DIS 16038
4.3 Risk management
4.3.1 Risk analysis and risk management

The manufacturers should carry out risk management as specified in ISO 14971 and make the management

report available to purchasers and regulatory agencies upon request. Any claims of additional features should

have definite substantiated performance and safety data should be duly documented (e.g. extra-strength

condoms).

As an important component of risk management, the manufacturer needs to inform the user, through labelling,

of any properties of the product or substances contained in it that may cause irritation, sensitization or allergic

reaction. Guidelines for labelling have been set by several regional and national regulatory authorities and

also specified in ISO 4074 and ISO 23409, as applicable. Attention should be given to right choice of colours

and additives, which are approved by regulatory agencies or certified to be safe for use in human beings. The

consumer should be advised of potential of allergy in rare cases due to latex or other chemicals present in the

formulation.
4.3.2 Latex allergy

Condoms made from natural rubber latex or its blend release smaller amounts of protein than latex gloves as

they have thinner films and have shorter duration of usage. However latex condom manufacturers should

strive to keep the latex-protein level minimal. Control of extractable proteins is a quality management issue,

and the manufacturer needs to know about and control the content and release of allergenic substances, such

as extractable proteins, by appropriate process steps and controls; the process steps and controls should be

part of the manufacturer's quality management system. The methods for determining protein levels in latex

gloves are given in EN 455-3 and ASTM D5712-99.

These methods may be adapted to determine protein levels in condoms. Protein levels may also be

determined by the ELISA method given in ASTM D6499-03.
No limits for protein levels have been established in ISO 4074 and ISO 23409.
4.3.3 Bioburden

Although condoms are non-sterile medical devices, care should be taken during manufacturing operations, to

minimize microbiological contamination, particularly specific pathogens which affect the skin and mucosa, for

example various species of pseudomonas, streptococcus, staphylococcus and E. coli. The potential causes of

contamination should be identified, controlled and monitored through the quality management system. No

limits for bioburden are specified in ISO 4074 and ISO 23409. Reference is available in other standard such

as ISO DIN 4074. Biological evaluation can also be carried out using the test method specified in ISO 10993-1.

4.3.4 Nitrosamines

Condoms made from natural rubber latex are subject to considerations regarding nitrosamines. Though the

level of nitrosamines depend upon the formulation used by different manufacturers, the level of nitrosamines

released by condoms are considered generally safe. No regulatory specification has been arrived as yet for

this parameter. Manufacturers are conscious of this development and are advised to monitor the levels of

nitrosamines in their condoms. A method for determination of nitrosamines migrating from natural rubber latex

condoms into various media is given in ISO 29941.
5 Quality of manufacture
5.1 Quality management

The principle behind quality management is that quality cannot be achieved effectively and consistently

through end product testing alone. Rather, it needs to be built into every stage of the process and related

activities that have direct impact on the quality of the product. The manufacturer should apply the

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ISO/DIS 16038

requirements of ISO 9001, ISO 13485 or other similar standards as the basis for quality management system

and for its Good Manufacturing Practices for medical devices. These documents help to put into operation the

principles of quality management in the design and manufacture of products, and are generally required and

emphasized for production of health-related products throughout the world. They ensure that products are

manufactured with clear and appropriate quality objectives and require that the quality management systems

of manufacturers are subject to regular audits to ensure the effectiveness and continual improvement of the

systems. Procurement agencies and regulatory bodies should encourage and support manufacturers who

implement a quality management system as described above.
5.2 Lot testing (finished-product testing)

Manufacturers should establish appropriate procedures to ensure that each lot complies with requirements of

ISO 4074 or ISO 23409, as applicable and any additional requirements agreed with the purchaser.

Manufacturers may test every lot or establish appropriate statistical control procedures to ensure compliance.

Because testing is destructive, tests shall be conducted on samples drawn according to ISO 2859-1 or

equivalent. Sampling plans and compliance levels are given in ISO 4074 and ISO 23409 and these need to be

incorporated into the manufacturers' quality systems. While applying the sampling plan, it should be

emphasized that switching rules as specified in ISO 2859-1 should be implemented to offer necessary

customer protection. Manufacturers are advised to improve their production facilities to the stage where they

can establish more stringent internal compliance levels than those in ISO 4074 and ISO 23409, to maximize

acceptance by purchasers and third-party testing laboratories. Trends in lot quality can be used by

manufacturers to monitor their quality, and to give early warning that corrective action is needed to keep the

product quality within acceptable limits. Regulatory authorities and large purchasers can also examine trends

and long-term performance of suppliers to get a better assessment of the quality of product supplied by

particular manufacturers. Manufacturers are advised to establish more stringent internal compliance levels to

maximize yields. Trends in lot quality can be used by manufacturers or purchasers to further assess the

quality management of the individual manufacturer. Regulatory agencies and purchasers may employ certified

or accredited third party laboratories for testing lots of products in addition to periodic audits of manufacturer's

quality management system.

In cases of dispute where manufacturers and purchasers have agreed to retest a lot, it is recommended the

appropriate sampling plans given in Annex B of ISO 4074 or ISO 23409.

Alternate plans, if used should be according to the agreed plans between the supplier and purchaser as part

of the contract, where applicable.
5.3 Rounding-off values

The results obtained during testing of samples are to be rounded off as given in relevant clauses of ISO 4074

and ISO 23409. Where not specified in ISO 4074 and ISO 23409, follow the rounding-off rules specified in

ISO 31-0:1992, Annex B.
6 Quality in procurement

While procuring condoms, the institutional purchasers should define the specifications for condoms

considering the population to which the condoms are sold or distributed. It is necessary for the procurement

agencies to validate the source from which condoms are procured by pre-qualification assessment, by

periodic audit of the facilities and quality management system by an auditor familiar with condom

manufacturing and type testing of samples.

Traceability of the materials and the process used in manufacture of condoms is important and should be

implemented and monitored as required by ISO 13485, as part of manufacturer's quality management

systems.

If condoms are to be purchased from a distributor rather than a manufacturer, it should be ensured that there

is traceability of product to the manufacturer and that there is traceability within the manufacturer's production

systems. While selecting the sources, the quality and reliability of manufacturers should be reviewed with

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ISO/DIS 16038

additional weight given to manufacturers who exceed the basic requirements of ISO 4074 or ISO 23409, as

applicable by addressing additional measures such as implementation of quality managements, and special

issues such as stability of products, safety of products, control of bioburden, etc. The reliability of

manufacturers should also be assessed further on the basis of continuous supplies confirmed by end product

testing and adherence to delivery schedule, price and technical support services rendered by the

manufacturers. The objective of ensuring undisrupted timely supply of quality condoms can be achieved only

by selecting the right sources followed by continuous monitoring of supplies from those sources in addition to

end product testing. The results of lot-by-lot testing should be monitored for each manufacturer. Any dispute in

lot-by-lot testing should be reviewed considering all the relevant aspects and making use of advice as outlined

in a document by WHO publication [11].

Appropriate design and packaging specifications should be obtained while procuring condoms, considering

the need of population and logistics of procurement, promotion, storage, handling and distribution. Due

attention should be given for storage of condoms in cool places adequately protected from other deleterious

weather conditions, direct heat, sunlight and mechanical damage. It is necessary to ensure that condoms are

procured with shelf life claims duly supported by stability data and manage distribution in such a way that the

stocks are utilized well before their expiry date, by effective inventory management. Batch identification and

traceability are important aspects of quality management systems, which are relevant during handling, storage

and distribution of condoms.

While procuring condoms, marginal issues on specifications and disputes on testing should be handled on the

basis of technical expertise and guidelines, rather than by mere administrative provisions. The purchaser

should seek advice from technical experts on condoms and make a balanced decision weighing the risks and

availability of safe and reliable condoms.
NOTE The WHO offers a helpline service.
7 Quality in testing

In procurement of condoms and regulatory monitoring, third party laboratories are widely used. Third party

laboratories should be selected on the basis of their having certified quality management system (e.g.

ISO 9001) or by their being accredited in accordance with ISO/IEC 17025 by a recogn

...