Bsi bs en 00724 1995 (1998)

www bzfxw com BRITISH STANDARD BS EN 724 1995 Guidance on the Application of EN 29001 and EN 46001 and of EN 29002 and EN 46002 for non active medical devices The European Standard EN 724 1994 has the[.]

This British Standard, having

been prepared under the

direction of the Health and

Environment Sector Board, was

published under the authority

of the Standards Board and

comes into effect on

15 April 1995

© BSI 11-1998

The following BSI references

relate to the work on this

standard:

Committee reference HCC/66

Draft for comment 92/52898 DC

The preparation of this British Standard was entrusted to Technical Committee HCC/66, Quality systems for the manufacture of medical devices, upon which the following bodies were represented:

Association of British Certification BodiesAssociation of British Health-care IndustriesAssociation of Contact Lens ManufacturersAssociation of X-ray Equipment Manufacturers (BEAMA Ltd.)British Anaesthetic and Respiratory Equipment Manufacturers’ AssociationBritish In Vitro Diagnostics Association

British Orthopaedic AssociationBritish Surgical Trades AssociationDental Laboratories Association LimitedDepartment of Health

Electro Medical Trade Association LimitedGAMBICA (BEAMA Ltd.)

Guild of Hospital PharmacistsInstitute of Physical Sciences in Medicine (ISPM)Institute of Quality Assurance

Medical Sterile Products AssociationSurgical Dressings Manufacturers’ Association

Amendments issued since publication

This British Standard has been prepared by Technical Committee HCC/66 and is

the English language version of EN 724:1994 Guidance on the application of

EN 29001 and EN 46001 and of EN 29002 and EN 46002 for non-active medical devices, published by the European Committee for Standardization (CEN).

BS EN 724 provides guidance on the operation of quality management systems used in the manufacture of non-active medical devices A similar standard,

BS EN 501031), covers guidance for the manufacture of active medical devices including active implantable medical devices In addition another standard,

BS EN 928, which will provide guidance on quality management systems used in the manufacture of in vitro diagnostic devices, is in preparation

Cross-references Publication referred to Corresponding British Standard

BS 5750 Quality systems

EN 29001:19872) Part 1:1987 Specification for design/development,

production, installation and servicing

EN 29002:19872) Part 2:1987 Specification for production and installation

EN 29004:19872) Part 0: Principal concepts and applications

Section 0.2:1987 Guide to quality management and

quality system elements

EN 46001:1993 BS EN 46001:1994 Specification for application of

EN 29001 (BS 5750-1) to the manufacture of medical devices

EN 46002:1993 BS EN 46002:1994 Specification for application of

EN 29002 (BS 5750-2) to the manufacture of medical devices

A British Standard does not purport to include all the necessary provisions of a contract Users of British Standards are responsible for their correct application

Compliance with a British Standard does not of itself confer immunity from legal obligations.

1) In preparation.

2) For information, since the ratification of this European Standard, EN 29001:1987,

EN 29002:1987 and EN 29004:1987 have been superseded by EN ISO 9001:1994,

EN ISO 9002:1994 and EN ISO 9004-1:1994 The corresponding British Standards are

Guide d’application des EN 29001 et

EN 46001 et des EN 29002 et EN 46002 pour

les dispositifs médicaux non actifs

Anleitung zur Anwendung von EN 29001 und

EN 46001 und von EN 29002 und EN 46002 für nicht-aktive Medizinprodukte

This European Standard was approved by CEN on 1994-10-27 CEN members

are bound to comply with the CEN/CENELEC Internal Regulations which

stipulate the conditions for giving this European Standard the status of a

national standard without any alteration

Up-to-date lists and bibliographical references concerning such national

standards may be obtained on application to the Central Secretariat or to any

CEN member

This European Standard exists in three official versions (English, French,

German) A version in any other language made by translation under the

responsibility of a CEN member into its own language and notified to the

Central Secretariat has the same status as the official versions

CEN members are the national standards bodies of Austria, Belgium,

Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy,

Luxembourg, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland and

Foreword

This European Standard was prepared by the

Technical Committee CEN TC 205, Non-active

medical devices, the Secretariat of which is held by

BSI

This European Standard has been prepared under a

Mandate given to CEN by the European

Commission and the Secretariat of the European

Free Trade Association, and supports essential

requirements of EC Directive(s)

This European Standard shall be given the status of

a National Standard, either by publication of an

identical text or by endorsement, at the latest by

April 1995, and conflicting national standards shall

be withdrawn at the latest by April 1995

Annexes designated informative are given only for

information In this standard annexes A, B and C

are informative

According to the CEN/CENELEC Internal

Regulations, the following countries are bound to

implement this European Standard: Austria,

Belgium, Denmark, Finland, France, Germany,

Greece, Iceland, Ireland, Italy, Luxembourg,

Netherlands, Norway, Portugal, Spain, Sweden,

Switzerland, United Kingdom

4.8 Product identification and traceability 9

4.11 Inspection, measuring and test

4.13 Control of nonconforming product 12

Annex B (informative) Features of job descriptions of key individuals 20Annex C (informative) Bibliography 21

Introduction

This European Standard has been written to give

guidance to organizations providing a non-active

medical device who wish to ensure that they will

comply with EN 29001/EN 29002 and the particular

requirements given in EN 46001/EN 46002 It is

also intended to provide guidance for certifying and

regulatory bodies The guidance in this standard for

the fulfilment of requirements should always be in

relation to the products being manufactured and

interpreted accordingly

This standard needs to be read in conjunction with

the EN 29000 series of standards with which

compliance is sought This standard is not intended

as a replacement for EN 29004 which has its own

very distinct relationship with the EN 29000 series

of standards

The combination of EN 29001/EN 46001 and

EN 29002/EN 46002 embraces the principles of

Good Manufacturing Practices (GMP) which have

been in operation in the manufacture of non-active

medical devices for a number of years

This document seeks to assist in the transition

from GMP to quality systems by presenting familiar

concepts under the relevant paragraphs of

EN 29001/EN 46001 and EN 29002/EN 46002

The references which have been made to EN 29004

are not necessarily exhaustive but seek to identify

sections of EN 29004 with particular relevance to

the guidance in this document Consideration of this

document alone is not an alternative to

understanding EN 29004 and it is therefore

recommended that EN 29004 is first read and

understood in its entirety For ease in the use of this

standard, references to clauses in EN 29004 have

been cited within the framework of EN 29001 and

EN 29002

Annex A to this European Standard provides

additional guidance on those elements of quality

systems to which particular emphasis should be

placed for medical devices which are supplied either

sterile or to a defined standard of microbial or

particulate cleanliness The guidance in annex A is

intended to be considered in addition to that

provided in the body of the standard

1 Scope

This European Standard provides guidance on the

establishment and maintenance of the quality

systems specified in EN 29001/EN 46001 or

EN 29002/EN 46002 for the manufacture of

non-active medical devices It does not add to, or

otherwise change, the requirements of those

standards and is not intended to be used for the

assessment of a manufacturer’s quality system

This European Standard provides examples of how

to meet the requirements, recognizing that other methods which achieve the same ends are equally acceptable; gives general advice on how to meet the requirements; and draws attention to aspects of requirements that may not be readily apparent to those unfamiliar with quality systems for non-active medical devices

Annex A to this European Standard provides guidance on the elements of quality systems which are relevant to the manufacture of medical devices which are to be supplied either sterile or at a defined level of microbiological or particulate cleanliness

The adoption of systems other than those described

in this European Standard is not to be regarded as

a non-compliance with EN 29001 and EN 29002 and/or the specific requirements in EN 46001 and

EN 46002

2 Normative references

This European Standard incorporates, by dated or undated reference, provisions from other

publications These normative references are cited

at the appropriate places in the text and the publications are listed hereafter For dated references, subsequent amendments to or revisions

of any of these publications apply to this European Standard only when incorporated in it by

amendment or revision For undated references the latest edition of the publication referred to applies

EN 29001:1987, Quality systems — Model for

quality assurance in design/development, production, installation and servicing.

EN 29002:1987, Quality systems — Model for

quality assurance in production and installation.

EN 29004:1987, Quality management and quality

system elements — Guidelines.

EN 46001:1993, Quality systems — Medical

devices — Particular requirements for the application of EN 29001.

EN 46002:1993, Quality systems — Medical

devices — Particular requirements for the application of EN 29002.

3 Definitions

For the purpose of this standard the definitions given in EN 46001 and EN 46002 apply, together with the following:

3.1 contract

any agreement between the supplier and the purchaser concerning the supply of product

NOTE A contract may be in writing, verbal, or a combination of both.

any of the following apply:

a) requirements prescribed by the purchaser and

agreed by the supplier in a contract for product;

b) requirements prescribed by the supplier which

are perceived as satisfying a market need; or

c) regulatory requirements

3.5

validation

exercise of carrying out a programme designed and

documented to demonstrate that a process,

operating within specified limits, will consistently

produce product or services complying with

predetermined requirements

NOTE Validation is considered as a total process which consists

of:

a) obtaining and documenting evidence that the installation of

equipment follows design intentions and that the equipment

as installed will perform consistently within predetermined

limits (commissioning); and

b) obtaining and documenting evidence that the equipment as

installed and operated in accordance with process

specifications will function reliably, produce acceptable

product or services, and that key process variables are known

Guidance for clauses 4.1.1 of EN 29001 and

EN 46001 and for clauses 4.1.1 of EN 29002 and

EN 46002.

When defining and documenting the supplier’s

quality policy, commitment and objectives, the

management should express the policy in language

that the staff can understand The policy should be

specific to the product supplied and to the staff

employed

Management should be seen to demonstrate

commitment to their quality policy both actively and

on a continuing basis

For general guidance see 4.1, 4.2, 4.3 and 4.4.4 of

EN 29004

4.1.2 Organization

4.1.2.1 Responsibility and authority

Guidance for clauses 4.1.2.1 of EN 29001 and

EN 46001 and for clauses 4.1.2.1 of EN 29002 and

a) product meets specified requirements;

b) documented quality systems, standards and specifications are maintained; and

c) regular internal quality audits are performed

The responsibility for quality assurance and production should be assigned to separate individuals Annex B to this European Standard provides an example of the features of a job description for these individuals

Particular guidance on responsibility and authority for the manufacture of sterile products, or other products for which the microbiological cleanliness is

of significance, is provided in annex A

Deputies for the key individuals identified above should be nominated and be capable of assuming the responsibilities when necessary

For general guidance, see also 5.2.1, 5.2.2 and 5.2.3

of EN 29004

4.1.2.2 Verification resources and personnel

Guidance for clauses 4.1.2.2 of EN 29001 and

EN 46001 and for clauses 4.1.2.2 of EN 29002 and

EN 46002.

The resources which need to be provided may include personnel trained in specific disciplines, for example materials science, microbiology or

statistics

For general guidance, see also 5.2.4 and 18.3 of

EN 29004

4.1.2.3 Management representative

Guidance for clauses 4.1.2.3 of EN 29001 and

EN 46001 and for clauses 4.1.2.3 of EN 29002 and

EN 46002.

If the management representative (see also 4.1.2.1)

who has the responsibility for the quality system

has other functions to perform, there should be no

conflict of interest

4.1.3 Management review

Guidance for clauses 4.1.3 of EN 29001 and

EN 46001 and for clauses 4.1.3 of EN 29002 and

EN 46002.

For general guidance, see 5.5 of EN 29004.

4.2 Quality system

Guidance for clauses 4.2 of EN 29001 and EN 46001

and for clauses 4.2 of EN 29002 and EN 46002.

The main document in the quality system is usually

a quality manual This documents quality policy

and describes the quality system The quality

manual is usually supported by detailed procedures,

work instructions and specifications for product and

processes Such supporting documents themselves

are generally not within the quality manual because

of the frequency at which they may be subject to

change

EN 46001 and EN 46002 require that

documentation supporting the quality manual is

organized in a file for each product type Such files

may be referred to as “Device Master File” or

“Device Master Record” This can contain, or give

reference to the location of, documentation relevant

to the manufacture of that product Examples of

such documentation may include:

— specifications for raw materials, labelling,

packaging materials, intermediate and finished

products;

— drawings;

— work instructions, including equipment

operation;

— sterilization process details, if applicable;

— inspection procedures and acceptance criteria

Such files may also contain quality records

(see 4.16) such as:

— design verification records;

— process validation records

All this documentation forms part of the quality

system and should be subject to document control

— product description, quantity and price;

NOTE The relationship between the supplier and the

sub-contractor is covered by 4.6 of EN 29001 and this standard. 4.4 Design control

4.4.1 General Guidance for clauses 4.4.1 of EN 29001 and

EN 46001; not applicable to EN 29002 and

EN 46002.

The design phase takes a product from concept to production and is an important phase in the life cycle of a medical device The essential quality aspects of safety, performance and reliability of a device are established during this phase Therefore, adequate design controls should be established and implemented to ensure these aspects are met prior

to production One of the major causes of quality problems leading to device recalls and failures is deficient design

For general guidance see also 8.1 and clause 19 of

For general guidance, see also 8.2.1, 8.2.2 and 8.2.3

of EN 29004

4.4.2.1 Activity assignment

Guidance for clauses 4.4.2.1 of EN 29001 and

EN 46001; not applicable to EN 29002 and

EN 46002

For general guidance, see 8.2.1 and 8.2.2 of

EN 29004

4.4.2.2 Organizational and technical interfaces

Guidance for clauses 4.4.2.2 of EN 29001 and

EN 46001; not applicable to EN 29002 and

EN 46002.

When input to the design is from a variety of

sources, such as from personnel from different

functions and/or disciplines within or external to the

supplier’s organization or from individuals with

specialist expertise, the inter-relationship or

interfaces should be clearly understood and

controlled

For general guidance see also clause 7 of EN 29004.

4.4.3 Design input

Guidance for clauses 4.4.3 of EN 29001 and

EN 46001; not applicable to EN 29002 and

EN 46002.

Design input is typically in the form of a

performance specification and/or a product

description Design input should be specified to the

level of detail necessary to permit the design activity

to be carried out effectively, and to provide a

consistent basis for design decisions, design

verification and design changes

Design input data may include a product brief and

performance requirements, together with

requirements of regulations, harmonized European

Standards and other published technical standards

Design input data may also include advice from an

appropriately qualified practitioner For example,

consideration may need to be given to anatomical

and physiological implications of the intended use of

the product

For general guidance, see also clauses 7, 8.2.4

and 8.2.5 of EN 29004.

4.4.4 Design output

Guidance for clauses 4.4.4 of EN 29001 and

EN 46001; not applicable to EN 29002 and

EN 46002.

The design output documents include typically:

— product specifications and drawings;

— manufacturing specifications and drawings

They should:

— be able to be related to the design input and

permit design verification;

— identify aspects which affect safety,

performance and reliability;

— be maintained as quality records

(see also 4.16).

4.4.5 Design verification Guidance for clauses 4.4.5 of EN 29001 and

EN 46001; not applicable to EN 29002 and

EN 46002.

Design verification should be a formal procedure A detailed, documented description of the design verification programme should be established, including organizational functions involved, procedures and methods to be used, documentation required, and variables to be considered and evaluated

The extent of design verification required is a function of the safety, performance and the reliability requirements for the item under consideration, the complexity of the design, the existence of published technical standards, the state

of the art and the similarity with previously proven designs Should the person(s) responsible for design verification decide that certain aspects or

parameters related to safety, performance and reliability do not need to be verified, the decision should be properly reasoned and recorded

Upon completion of design verification activities, the final design configuration is documented and manufacturing specifications established prior to release to production For any subsequent design

design review meetings are retained (see 4.16)

and usually identify those present and decisions reached

b) Qualification tests and demonstrations

Once the design is translated into physical form, its safety, performance and reliability should be verified by testing under simulated use

conditions Such verification may include in vitro and/or in vivo testing

Clinical evaluation may be required as part of the design verification activities The general guidance presented here also embraces any clinical evaluations within the quality system

The conduct of the clinical investigation of medical devices is the subject of a harmonized European Standard (EN 540)

c) Alternative calculations

The appropriateness of any alternative calculation method should be reviewed

d) Design comparison

Design comparison may be applicable when:

— a new application is identified for a proven

Guidance for clauses 4.4.6 of EN 29001 and

EN 46001; not applicable to EN 29002 and

EN 46002.

Design changes may be necessary as a result of:

— experience in use;

— change in market requirements;

— change in regulatory or safety requirements;

— corrective action (see 4.14).

Any changes to design inputs should be identified

and reviewed by the supplier to determine whether

they affect previously approved design verification

results Design changes in one component of a

product should be evaluated for their effects on the

whole Improving one characteristic may have

unforeseen effects on another The design and

verification procedures should also be reviewed and

modified as necessary where a significant design

change arises because of an incorrect design

For general guidance, see also 8.8 of EN 29004.

4.5 Document control

Guidance for clauses 4.5 of EN 29001 and EN 46001

and for clauses 4.4 of EN 29002 and EN 46002.

For general guidance, see 17.1 and 17.2 of

EN 29004

4.5.1 Document approval and issue

Guidance for clauses 4.5.1 of EN 29001 and

EN 46001 and for clauses 4.4.1 of EN 29002 and

EN 46002.

Care and attention to detail should be taken in

preparing all documents, particularly in ensuring

that the information given is unambiguous and can

be understood by the persons who are going to use

them

Document control procedures may be assisted by the

adoption of a consistent structure for the documents

within the quality system Each document should be

paginated to ensure that the total document is

available and should state:

— title and scope;

— date of issue;

— revision status;

— the originator;

— the person(s) approving it;

— the person(s) issuing it

The document control procedure should:

— include periodic review of documents;

— assign responsibilities for preparation, check, release and issue;

— require review of all quality-related documents for accuracy, completeness and correctness before approval and issue;

— identify recipients of controlled copies of documents;

— ensure that documents which are not controlled are clearly marked indicating that these are not subject to updating;

— ensure prompt withdrawal of obsolete copies of

controlled documents (see 4.5.2 of this standard);

— define the method for recording the implementation date of a document change

4.5.2 Document changes/modifications Guidance for clauses 4.5.2 of EN 29001 and

EN 46001 and for clauses 4.4.2 of EN 29002 and

in accordance with the defined approval and issuing procedure For example, a raw material

specification change could apply to a number of different products

The date of the implementation of the change should

be recorded

The master copy of withdrawn documents should be clearly marked and retained by storage in a secure location Other copies of withdrawn documents should be disposed of The object of retaining a single copy of obsolete or superseded documents is to provide a full picture of the product at various stages of its life, from first design considerations through development to present status

4.6 Purchasing

4.6.1 General

Guidance for clauses 4.6.1 of EN 29001 and

EN 46001 and for clauses 4.5.1 of EN 29002 and

EN 46002.

A supplier may purchase, from a number of sources,

products and services which may include:

— raw materials;

— components or sub-assemblies manufactured

by others using equipment owned by, and/or

materials provided by, the supplier;

— components or sub-assemblies available as

standard items from other sources;

— components or sub-assemblies manufactured

by others to the supplier’s specifications;

— completed product bearing the mark and/or

name of the supplier; this may be ready for sale or

require some further processing such as

packaging and/or sterilization;

— services, e.g sterilization, calibration, testing,

pest control, waste disposal, cleaning,

environmental monitoring, laundry, transport,

installation

EN 29001 and EN 46001 use the term

“sub-contractor” to include all providers of

materials, components, sub-assemblies, finished

products or services However, a broad division can

be made between purchase of materials or services

to the supplier’s specification and the purchase of

standard commercially available items This can be

useful in deciding on the type and extent of control

to be applied to purchased materials or services

For general guidance, see also 9.1, 9.5 and 9.6 of

EN 29004

4.6.2 Assessment of sub-contractors

Guidance for clauses 4.6.2 of EN 29001 and

EN 46001 and for clauses 4.5.2 of EN 29002 and

EN 46002.

The selection of providers of products or services

consists of establishing criteria, making an initial

selection, and subsequent formal assessment of

capability; sub-contractors should be subjected to an

on-going surveillance and monitoring of

performance

All providers of products and services should be able

to meet the needs of the supplier The criteria which

form the basis for the assessment of potential

candidates should be established

The supplier should be able to demonstrate that the system provides for:

— formal consideration of the extent of assessment required;

— selection based on a sufficiently structured appraisal appropriate to the product or service procured;

— periodic reassessment of performance;

— due account of the results of surveillance when re-ordering

Surveillance may consist of one or more of the following activities

a) For a provider of standard, commercially available, products or services:

— periodic inspection of products or services received;

— monitoring of inspection results;

— accepting certification of the sub-contractor’s quality system by third parties;

— accepting certificates of conformance and/or

of analysis from the sub-contractor

b) For a provider of products or services to the specification of the supplier:

— auditing of the quality system by the supplier, in addition to the items listed in a) above

For general guidance, see also 9.3 of EN 29004 4.6.3 Purchasing data

Guidance for clauses 4.6.3 of EN 29001 and

EN 46001 and for clauses 4.5.3 of EN 29002 and

EN 46002.

For general guidance, see 9.2 and 9.4 of EN 29004 4.6.4 Verification of purchased product

Guidance for clauses 4.6.4 of EN 29001 and

EN 46001 and for clauses 4.5.4 of EN 29002 and

EN 46002.

This requirement of EN 29001 applies when the purchaser is the customer for the product which the

supplier manufactures (see clause 3).

4.7 Purchaser supplied product

Guidance for clauses 4.7 of EN 29001 and EN 46001 and for clauses 4.6 of EN 29002 and EN 46002.

This subclause applies when the purchaser provides items to the supplier to be incorporated by the supplier into the completed product or service For example, the purchaser may provide items to the supplier for inclusion into a kit or set In such cases, the supplier should not knowingly incorporate nonconforming parts into the product or service

4.8 Product identification and traceability

Guidance for clauses 4.8 of EN 29001 and EN 46001

and for clauses 4.7 of EN 29002 and EN 46002.

a) Identification

Identification of raw materials, components and

finished products is important for a number of

It is usual for finished products to be identified

by a batch/lot number or serial number The

extent to which raw materials and components

need to be identified and related to the finished

product batch/lot or serial number will depend

upon a number of factors including:

— the material involved;

— the type of finished product;

— the effect of failure of finished product or

materials used therein;

Batch/lot or serial numbers on products permit

traceability in two directions: forward to

purchasers and backward to raw materials,

components and processes used in manufacture

The former is important if it is necessary to trace

products to the user, e.g patients or hospitals,

and the latter enables investigation of quality

problems and feedback for the prevention of

nonconforming product

Where in-plant traceability of raw materials and

components is important to quality, appropriate

identification should be maintained throughout

the production process to ensure traceability to

original material identification and quality

status

The supplier should establish and maintain a

forward traceability system up to the point when

products leave the suppliers’ possession

For general guidance, see also 11.2 of EN 29004.

Particular guidance on process control for the manufacture of sterile products, or other products for which the microbiological cleanliness is of significance, is provided in annex A

For general guidance, see 10.1.1, 10.1.5, 10.2, 10.3, 11.3 , 11.5, and 11.6 of EN 29004.

a) Production processes

Manufacture begins with the issue of raw materials and provision of equipment and continues through all subsequent stages of production until the finished product is released for sale

A documented procedure should be agreed for each stage of manufacture This may include:

— equipment and materials to be used;

— precautions to be taken;

— step by step instructions;

— any in-process quality checks conducted by production personnel;

— the procedure to be followed in the event of quality problems;

— the disposition of accepted or rejected products

Before and during the introduction of a new

design of product (see also 4.4 of this standard)

the manufacturing process, including any new manufacturing and test methods, should be fully evaluated The key variables and acceptance limits should be identified and validated for processes, test methods and sampling plans Similar procedures should be followed where any significant change in processing occurs The results of validation exercises should be documented and processes should undergo a regular critical appraisal to ensure that they remain capable of achieving the intended results