Handbook of Polymer Applications in Medicine and Medical Devices || Regulations for Medical Devices and Application to Plastics Suppliers

14 Regulations for Medical Devices and Application toPlastics Suppliers: History and Overview

Vinny R. Sastri

O U T L I N E

14.1 History and Introduction 337

14.2 United States Regulations 338

14.2.1 FDA Master Files 340

14.3 ISO 13485 (European and Global

Standard) 34014.3.1 European Union Medical Device

Directive 341

14.4 Other Countries 34314.4.1 Japan 343

14.4.2 China 343

14.4.3 Australia 343

14.4.4 India 344

14.4.5 South America 344

14.5 Global Harmonization Task Force

(GHTF) 344

14.6 Applicability of the Regulations to Material

Suppliers 345

14.7 Conclusion 345

References 346

14.1 History and Introduction

Over the past 2000 years, many devices have

been developed and used in the mitigation and

diagnosis of diseases. The materials used in these

devices have ranged from stone, wood, metal, cera-

mics, and most recently plastics. Medical devices

have also evolved in sophistication and complexity

over time. With the formalization of the scientific

method in the seventeenth century such devices

became more prevalent [1]. Many medical devices

were manufactured by doctors or small companies

and sold directly to the public with no government

standards or oversight. With the explosion of medi-

cal technology in the early twentieth century, sev-

eral intermediaries had evolved between the

medical device industry and the public. In 1879, Dr

E.R. Squibb, in an address to the Medical Society

of the State of New York, proposed the enactment

of a national statute to regulate food and drugs [2].

It was not until 27 years later that the Food and

Drug Act of 1906 was introduced into the Congress

and signed into law by President Theodore

Roosevelt [3]. At that time, devices that were harm-

ful to human safety and health proliferated the

market but regulation of medical devices by the

Bureau of Chemistry (the precursor to the Food and

Drug Administration—FDA) was limited to chal-

lenging commercial products only after they had

been released into the market. Devices in the mar-

ketplace that were defective, adulterated, or mis-

branded were seized and the device manufacturers

were prosecuted in a court of law, but only after

the products were sold in the market and caused

harm to the end users. Thus, there was a strong

need for regulating the devices before they entered

the marketplace. An FDA report [4], issued in

September 1970, detailed as many as 10,000 inju-

ries and 731 deaths from ineffective medical

devices. The report recommended the formation of

a regulatory system and body that would enforce

the production and sale of safe and effective

devices to the public. All medical devices already

on the market would be inventoried and classified

into a three-tiered system based on their criticality

of end use. It also detailed requirements for records

and reports, registration and inspection of establish-

ments, and uniform quality assurance programs

called good manufacturing practices (GMP). After

much lobbying by the FDA, Senate bill SR 510,

337Handbook of Polymer Applications in Medicine and Medical Devices. DOI: http://dx.doi.org/10.1016/B978-0-323-22805-3.00014-1

© 2010 Vinny Sastri. Published by Elsevier Inc. All rights reserved. Reproduced from a chapter in: Sastri, Plastics in Medical Devices (2010).

http://dx.doi.org/10.1016/B978-0-323-22805-3.00014-1

“The Medical Device Amendments of 1973” was

introduced by Senator Edward M. Kennedy and

was passed by the Senate in 1975. House bill HR

11124, introduced by Representative Paul Rogers,

was passed by the House in 1976. These bills even-

tually became the Medical Device Amendments of

1976, and were signed into law by President Nixon.

The Medical Device Amendments of 1976 became

the basis for the medical device regulation in the

United States to control and regulate the production

of finished devices and thus the device manufac-

turers themselves.

The GMP requirements for medical devices came

into effect on December 18, 1978. This regulation

was designed to specify general requirements for all

manufacturers as well as special requirements for

what were termed “critical devices.” Yet, between

1978 and 1990 a number of studies and data from

recalls of medical devices [5,6] indicated that a sig-

nificant number of recalls were due to improper,

faulty, or ineffective designs. On November 28,

1990, Congress passed the Safe Medical Device Act

(SMDA), providing the FDA with the authority to

add pre-production design controls to the GMP regu-

lation. This meant that device manufacturers would

need to have controls over their design and develop-

ment processes including strict controls of the raw

materials and components used to manufacture the

finished device. It also incorporated a provision to

include the oversight of foreign countries selling

products into the United States. Quality System

Regulation 21 CFR Parts 820 [7] was then drafted.

Efforts were made to harmonize this regulation with

both the ISO 9001:1994 entitled “Quality systems:

Model for quality assurance in design, development,

production, installation and servicing” and with ISO

13485:1996 entitled “Quality Systems—Medical

Devices—Particular requirements for the application

of ISO 9001.” This new regulation removed the

term “critical devices” and allowed manufacturers to

tailor their quality systems commensurate with the

risk associated with their device during end use. For

example, an implantable device will need more strin-

gent (design, development, and production) controls

compared to a simple tongue depressor and these

will differ in the level of detail and complexity of

their respective quality system requirements.

The purpose of the regulations is to ensure that

manufacturers of medical devices have the appropri-

ate procedures and processes in place to design,

develop, and produce consistent, safe, and effective

devices for their intended use. The regulations are a

framework for manufacturers and are flexible enough

to allow them to formulate and implement those parts

of the regulation that are applicable to their products

and processes and the risk of their products.

14.2 United States Regulations

The design, development, production, distribu-

tion, and use of medical devices in the United

States of America are regulated by the Federal

Drug and Cosmetics Act in the Code of Federal

Regulations (CFR)—21 CFR Parts 820 [7]. This

regulation is entitled “The Quality System

Regulation.” To sell medical devices in the United

States of America, all (domestic or international)

finished medical device manufacturers must register

with the Federal Drug Administration (FDA), must

be willing to comply with the regulation, and must

be willing to let the FDA inspect their facilities.

The intent of 21 CFR Parts 820 is that “quality

must be designed and built into components

through the application of proper quality systems”

[8]. The regulation requires that medical device

manufacturers establish and implement an appropri-

ate quality system that encompasses the design,

manufacture, packaging, labeling, storage, installa-

tion, and servicing of the finished device intended

for commercial use and distribution in the United

States. Effective quality systems will ensure that

manufacturers are in a “state of control” and pro-

duce consistent, safe, and effective devices for their

intended use. The FDA monitors and inspects the

complaints, data, and records from both end users

and manufacturers to track and determine the safety

and efficacy of a device.

Table 14.1 details the various sections of the reg-

ulation with a brief description of each section.

This regulation pays particular attention to the

design controls that were added to the latest (1997)

version.

Suppliers of raw materials or components do not

have to comply with the regulations, but are subject

to the purchasing controls of the regulations.

Finished device manufacturers must establish

procedures and controls with their suppliers for

essential raw materials that include quality metrics,

material performance and purity specifications,

assurance of supply, and notification of any formu-

lation or process changes.

338 HANDBOOK OF POLYMER APPLICATIONS IN MEDICINE AND MEDICAL DEVICES

Table 14.1 FDA 21 CFR Part 820 and Its Subsystems

Section Title Description

Subpart A General requirements Defines the scope and applicability requirements for thequality system. Who needs to comply?

Subpart B Quality Systemrequirements

Outlines the methods of formulating, implementing aneffective quality system via management reviews, qualityaudits, and appropriate personnel.

Subpart C Design controls Describes the process and controls during the variousstages in design and development of a medical device fromdesign inputs, design outputs, design verification andvalidation, design reviews, and effective design transfers.

Subpart D Document controls Review, approval, retention, accuracy, and accessibility ofappropriate documents.

Subpart E Purchasing controls Controls and processes all raw materials, components,products, and services.

Subpart F Identification andtraceability

Documentation and process to identify and trace incoming,in process, and finished device products and components,especially those of high-risk devices.

Subpart G Production and processcontrols

The development, monitoring, and control of all processesused in production of the finished device.

Subpart H Acceptance activities Establishing and using acceptance criteria for the control ofincoming, in-process and finished device performance,quality, and consistency.

Subpart I Nonconforming product Developing and implementing procedures to assess andcontrol all products and processes that do not meetspecified requirements.

Subpart J Corrective andpreventive action

Establishing and implementing procedures and processesfor sustainable corrective and preventive action of identifiedissues.

Subpart K Labeling and packaging Ensuring that there are procedures and processes in placeto include the requirements, design, production, and controlof device packaging and labeling into the quality system.

Subpart L Handling, storage,distribution, andinstallation

Having procedures for the handling and storage of allincoming, in-process, and finished device products.Ensuring proper distribution procedures for finished devicesand if applicable, procedures and processes for theinstallation of finished devices at the end user’s facility.

Subpart M Records Documents specific to this regulation include the DesignHistory File (DHF), the Device Master Record (DMR), theDevice History Record (DHR), and complaint files.

Subpart N Servicing If needed, maintenance and servicing procedures andprocesses must be included to continue and to ensuresafety and efficacy of devices at the end user.

Subpart O Statistical techniques The regulation encourages the use of statistical techniques(like sampling, data analysis, design of experiments) whereappropriate.

33914: REGULATIONS FOR MEDICAL DEVICES AND APPLICATION TO PLASTICS SUPPLIERS

14.2.1 FDA Master Files

For the submission of a Premarket Approval

(PMA) [9], a 510(k) [10] for substantially equivalent

devices or an Investigational Device Exemption

(IDE) [11] a finished device manufacturer submits an

application to the FDA containing substantive data of

the finished device including performance, chemical

resistance, biocompatibility, toxicity, and clinical

data. In many cases, the finished device or compo-

nents are made from a supplier’s product or raw

materials. In order that a sound scientific evaluation

may be made of the PMA, 510(k) or the IDE, a

review of data and other information related to the

supplier’s product, facility, or manufacturing proce-

dures is required. While suppliers may be willing to

have the FDA review this information, they may not

want their proprietary information in the hands of

their customers (the finished device manufacturers).

A system for the submission of Master Files was

developed by the FDA to permit the suppliers of the

materials to provide confidential product information

directly to the FDA for its review without disclosing

the confidential information to the customer or manu-

facturer. If the same raw material is used in various

applications, components, or devices, only one Master

File is required.

There are various types of master files depending

upon the intended use.

• Device master files (MAF)—Supporting data

on material used in medical devices (informa-

tion for pre-manufacturing notices, 510(k)s

and Investigational Device Exemptions);

• Drug Master File (DMF)—Supporting data on

material used in drugs; (information for

Investigational New Drug Applications (IND),

New Drug Applications (NDA), and

Abbreviated New Drug Applications (ANDA));

• Biologics Master Files�Supporting data for

material used in applications contacting blood

or blood products (information for notices of

claimed Investigational Exemption for an

Investigational New Drug (IND) for biologics

and biologic licenses);

• Food Master Files (FMF)—Supporting data mate-

rial used in food applications (information for

Food Additive and Color Additive Petitions); and

• Veterinary Medicine Master Files—Supporting

data for materials used in animal drug and

devices (Investigational New Animal

Exemptions (INAD) and New Animal Drug

Applications (NADA)).

The content of a Master File includes the

following:

• Company Name,

• Product Name,

• Manufacturing Address,

• Statement of Commitment,

• Product Formulation,

• Product Specification, and

• Test methods and results (physical, chemical,

biocompatibility, and toxicity).

The information provided in the master file gives

the device manufacturer and the FDA a level of

comfort that the raw material being used in the

device will pass the specific physical, chemical,

biocompatibility, and toxicity tests. The FDA must

be notified of any changes to the formulation and

subsequent properties of the material and the

Master File must be updated. Failure to notify and

comply will render the finished device “adulter-

ated” and may not be subjected for sale or use.

MAFs may be submitted for various types of

operations and products and can be grouped by the

following types:

• facilities and manufacturing procedures and

controls;

• synthesis, formulation, purification, and specifi-

cations for chemicals, materials (e.g., an alloy,

plastic, etc.), or subassemblies for a device;

• packaging materials;

• contract packaging and other manufacturing

(e.g., sterilization);

• nonclinical study data; and

• clinical study data.

14.3 ISO 13485 (European andGlobal Standard)

The international standard for medical devices is

ISO 13485:2003 entitled “Medical devices—Quality


management systems—Requirements for regula-

tory purposes” [12]. Though geared specifically

toward medical device manufacturers, the ISO

13485 standard is harmonized with ISO 9001:2000

with some differences. ISO 13485:2003 includes

particular requirements for medical devices and

excludes some of the requirements of ISO

9001:2000 that are not appropriate as regulatory

requirements with respect to medical devices.

Thus, organizations which conform to ISO

13485:2003 cannot claim that they conform to

ISO 9001:2000 or vice versa unless their quality

management systems conform to all the require-

ments of ISO 9001:2000. Risk management is a

key part of ISO 13485 [13]. Terms like customer

satisfaction and continuous improvement have

been removed from this document (compared to

ISO 9001:2000). The regulation consists of the

sections as described in Table 14.2. An ISO tech-

nical report (ISO/TR 14699) [14] provides guid-

ance for the application of ISO 13485.

The primary objective of the regulation is to pro-

vide harmonized guidelines to organizations so that

they can consistently meet end user and regulatory

requirements. Compliance with ISO 13485 is recog-

nized as a first step in achieving compliance with

European regulatory compliance. Certification of

the Quality Management System allows the manu-

facturer to sell medical devices in the European

Union.

14.3.1 European Union MedicalDevice Directive

There are three directives for medical devices in

the European Union.

Table 14.2 ISO 13485:2003 Sections and their Descriptions

Section Title Description

1 Scope Defines the scope of the regulation, describes the requirementsfor exclusion to design and development where appropriate, andthe applicability of the regulations

2 Normative references References ISO 9001:2000

3 Terms and definitions Provides the terms and definitions used in the regulation

4 Quality managementsystem

Focuses on procedures and processes for the implementation ofan effective quality management system including the review,approval, and control of records and documents

5 Managementresponsibility

Emphasizes the involvement of management in the entireprocess, from customer needs, to product planning and productrealization. Use of effective reviews, communication to ensureimplementation and effectiveness of the quality system

6 Resource management Ensures that there are adequate resources that includepersonnel, infrastructure, and the work environment

7 Product realization A significant part of the regulation, includes product planning,product design and development, purchasing process andcontrols, production and service validation and controls, and, theidentification and traceability of all products and componentsused in the production of devices

8 Measurement analysisand improvement

A separate section is devoted to the importance of goodmeasurement systems, monitoring products and processes,controlling nonconforming products, analysis of data, andcorrective and preventive action

9 Annex A Differences between ISO 13485:2003 and ISO 13485:1996

10 Differences between ISO 13485:2003 and ISO 9001:2000

11 Bibliography References


• The Active Implantable Medical Device

(AIMD) Directive—90/385/EEC;

• The Medical Device Directive (MDD)—93/42/

EEC; and

• The In Vitro Diagnostic Directive (IVD)—98/

79/EC.

After June 14, 1998, medical devices could

not be offered for sale in the European Union

without “CE marking” and a “declaration of con-

formity.” The letters CE stand for “Conformite

Europeene” in French literally meaning “European

Conformity.” For many products CE marking and a

declaration of conformity may only be affixed with

proof of a certified quality system and/or product

testing based on its end use. The quality systems

certification, the CE marking, and the declaration

of conformity are provided by a “Notified Body”

which is an organization appointed by the national

accreditation authorities and which “notifies” the

European Commission to approve products covered

by the Medical Devices Directive. All medical

device manufacturers must designate a notified

body to certify and register their products. For

all classes of devices, a detailed technical file must

be submitted providing objective evidence demon-

strating compliance with the Medical Device

Directive’s essential requirements and with appro-

priate harmonized standards which include ISO

13485:2003 and ISO 10993 standards [8].

Products shipped must bear the CE marking to

show compliance with the directive (Figure 14.1).

If a Notified Body is involved in the approval, the

number of the Notified Body must also appear adja-

cent to the CE marking.

Additionally, the product must be shipped with a

Declaration of Conformity, an example of which is

shown in Figure 14.2.

Documentation can include the following:

• Evidence demonstrating compliance with

essential requirements detailed in the directive

for the particular product’s end use;

• Demonstration of design verification and

validation;

• Risk assessment and analysis;

• Clinical evidence demonstrating effectiveness

of the device;

• Procedures for post-market surveillance;

• Complete declaration of conformity;

• Technical information of the finished device—

including toxicity and biocompatibility

studies;

Figure 14.1 The CE mark.

EC Declaration of Conformity

Council Directive 93/42/EEC concerningmedical devices

We (Name and address of manufacturer)

Certify that the product described is in conformitywith the applicable provisions of Council Directive

93/42/EEC concerning medical devices.

(Name, type or model, lot, batch or serial no. etc.)

(Description)

(Name of Responsible Person) (Signature of Responsible Person)

(Date)

Figure 14.2 CE marking declaration of conformity.


• Accurate product identification, labels, proce-

dures, and user instructions; and

• CE mark or label on product or packaging.

14.4 Other Countries

14.4.1 Japan

The Japanese government, through the Ministry

of Health, Labor, and Welfare (MHLW), regulates

all medical devices, whether manufactured in Japan

or imported from other countries. In Japan, the

term “medical device” is used for any instrument,

apparatus, or material as designated by the

Japanese government that is used in diagnosing,

treating, and/or preventing diseases in humans or

animals and which can be used to affect the struc-

ture and functions of humans or animals. The

Pharmaceutical Affairs Law (PAL) is the primary

governing law for medical devices in Japan.

Medical devices must undergo thorough safety

examinations and demonstrate medical efficacy

before they are granted approval, or “shonin,” to be

sold in Japan. PAL regulations specify very

detailed requirements for companies that manufac-

ture or import medical devices for sale in Japan,

ranging from infrastructure and facilities to person-

nel and processes. For new medical devices for

which there are no equivalent products already

approved in Japan or for devices that have been

improved or modified that might affect device safety

and efficacy, clinical trials are required. Clinical trials

must be conducted to demonstrate the safety and

efficacy of the product under strict Good Clinical

Practice (GCP) standards, and must be followed by

standard Post-Marketing Assessment (PMA) reporting

and a follow-up program.

In April 2004, the Pharmaceuticals and Medical

Devices Agency (PMDA) was established in an

effort to create a more efficient and transparent

medical device registration review process. The

PMDA was formed by merging three already exist-

ing organizations: (1) the Pharmaceuticals and

Medical Devices Evaluation Center (PMDEC), (2)

the Organization of Pharmaceutical Safety and

Research (OPSR), and (3) the Japan Association for

the Advancement of Medical Equipment (JAAME).

Two of these three agencies (PMDEC and JAAME)

were previously involved in the medical device

approval process, including the review of product

registration applications and clinical trial consulta-

tions. Prior to the creation of the PMDA, the appli-

cation and review process for new devices could

take as long as 2 years. Over the next several years,

the PMDA intends to shorten this process, although

it has not had success in doing so thus far.

Under the New PAL, the Quality Assurance

Controller will be responsible for ensuring compli-

ance with the new Good Manufacturing Practice

(GMP) requirement, based on Japan’s own adapta-

tion of ISO 13845:2003, as well as Good Quality

Practice Ordinance (GQP) standards [15]. The

Standard Operating Procedures (SOPs) for GQP

include product storage controls, the release of pro-

ducts into the market, quality control at local

offices, ensuring the maintenance of all quality

assurance documents and reports, the handling of

product recalls, and audits.

Necessary Governmental Authorizations (for sale

of devices into Japan):

• Manufacturing (or import) approval (“Shonin”)

which guarantees the safety and efficacy of the

device, obligatory for every product;

• Manufacturing (or import) license (“Kyoka”) of

a device, which the Japanese manufacturer and

importer hold, renewable every 5 years; and

• Reimbursement listing approval.

14.4.2 China

There are two main agencies in China that regu-

late medical devices, the State Food and Drug

Administration (SFDA) and the Department of

Medical Devices. The State Food and Drug

Administration (SFDA) is the Chinese equivalent

of the FDA in the United States. All imported

medical devices must be registered with the

SFDA. The Department of Medical Devices under

the SFDA is responsible for the standardization,

product registration, safety, and supervision of all

imported devices into China. Some of the stan-

dards used by the agency are ISO 10993 (Biologic

Evaluation of Materials and Medical Devices),

ISO 14971 (Risk Management), and ISO 13485

(Medical Devices—Quality Management Systems).

14.4.3 Australia

The medical device legislation has been estab-

lished by the Therapeutic Goods Act 1989 as


amended by the Therapeutic Goods Amendment

(Medical Devices) Bill 2002 and the Therapeutic

Goods (Medical Devices) Regulations 2002. The

new framework also adopts the philosophies of the

Global Harmonization Task Force on medical

devices.

The new regulatory system has the following

features:

• a device classification scheme based on differ-

ent levels of risk for each class of device;

• essential principles for the quality, safety, and

performance of the medical device that must

be complied with before the product can be

supplied;

• options as to how compliance with the essen-

tial principles can be satisfied and assessed;

• manufacturer quality systems, type testing, and

design evaluation;

• the use of recognized standards to satisfy the

requirements of the essential principles;

• a comprehensive post-market surveillance and

adverse incident reporting program;

• appropriate regulatory controls for the

manufacturing processes of medical devices;

• the continued use of the Australian Register of

Therapeutic Goods as the central point of con-

trol for the legal supply of medical devices in

Australia; and

• chemical, physical, and biological properties.

14.4.4 India

The Central Drugs Standards Control

Organization (CDSCO) under the Ministry of

Health and Family Welfare regulates the licensing,

import, manufacture, and sale of medical devices

into the country. Approvals can be facilitated by

evidence of approval from the US FDA, the EU

MDD (CE certificate), and approvals from

Australia, Canada, Japan, and other countries. ISO

certification for specific manufacturing facilities

(ISO 13485) is also accepted. Device master files

must contain details of good manufacturing prac-

tices including components and materials used

in the device. It must also include the manufactur-

ing and quality assurance processes, risk assess-

ment, design verification, sterilization, stability,

biocompatibility, and toxicological data associated

with the materials and production of the finished

device.

14.4.5 South America

For most companies the access point to South

America is Brazil. Brazil has the second largest

healthcare market in the Americas (bigger than

Canada and second only to the United States). It is

a member of Mercosur—the South American Free

Trade Area that includes Brazil, Argentina,

Uruguay, and Paraguay. Separate submissions

have to be made in each country. Registration of

products or product families must contain informa-

tion on the manufacturer, the materials and com-

position used, and the intended use.

Mexico has patterned its regulations after the US

FDA and ISO requirements under the Secretarıa

de Salud.

14.5 Global Harmonization TaskForce (GHTF)

The GHTF was conceived in 1992 and is an

informal grouping that was formed to respond to

the growing need for the international harmoniza-

tion of regulations in medical devices. The mem-

bers of the GHTF include government and industry

officials from the European Union, Japan, Canada,

Australia, and the United States. These representa-

tives working with medical device manufacturers

and other organizations related to medical devices

try to harmonize global approaches to the safety,

efficacy, clinical performance, and quality of medi-

cal devices with the goal of protecting public

health, promoting innovation, and facilitating inter-

national trade. Global harmonization is the aligning

of the different regulatory systems of the world

making them globally on par with each other to

manufacture and sell safe and effective devices.

The GHTF is committed to developing guidelines

accepted in all GHTF countries and gives technical

guidance toward a more coherent approach on the

interpretation of technical and quality requirements

for medical devices. It has four study groups, deal-

ing with product approval-related issues, post-

market surveillance, quality system requirements,

and audits of quality systems.


14.6 Applicability of theRegulations to Material Suppliers

The regulations (FDA 21 CFR Parts 820 and

ISO 13485:2003) are applicable to the manufac-

turers of “finished devices.” Suppliers of raw mate-

rials are not expected to comply with these

regulations but must meet acceptable material

requirements set forth by the device manufacturers

(as per their purchasing controls). Finished device

or component manufacturers expect their material

suppliers to have consistently good quality and pro-

cess control in their facilities.

In July 1998 in the United States, the Biomaterials

Access Assurance Act—BAAA (HR 872) was signed

into law by President Bill Clinton. The purpose of

the act was to “establish rules governing product lia-

bility actions against raw materials and bulk compo-

nent suppliers to medical device manufacturers, and

for other purposes” [16]. This was a very important

bill, as it protects the suppliers of biomaterials or

components of implanted devices from liability if an

entire device results in injury or death, provided it

was not the fault of the material or component. This

act was in response to a very serious concern

expressed by suppliers following many expensive

lawsuits where it was found that the eventual cause

of the problem was not with the material but with

the finished device itself. Many plastics suppliers are

willing to supply materials as long as their materials

are used in devices that are in contact with the

human body for less than 29 days (minimal contact

with and minimal residence time within the body).

A few plastics suppliers are willing to recommend

their products for implants and devices that are in the

body for more than 29 days (implantable devices)

based on the extensive studies and data that show

their materials pass all physical, chemical, biocom-

patibility, hemocompatibility, and toxicity tests

required for implantable devices.

Finished device manufacturers are expected to

establish purchasing controls [17], providing mate-

rial suppliers with acceptance criteria and material

specifications and requirements needed for their

specific devices and applications. Such require-

ments might include the following:

• Raw material performance specifications,

• Biocompatibility,

• Sterilization requirements,

• Material purity,

• Chemical resistance,

• Toxicity requirements,

• Product quality and consistency,

• Notification of formula changes,

• Adherence to good manufacturing practices,

and

• Assurance of supply.

14.7 Conclusion

The purpose of regulations for medical devices

is to ensure that the products are consistent, safe,

and effective for their intended use. The two major

regulations are the 21 CFR Parts 820 Quality

Systems Regulations enforced by the Food and

Drug Administration in the United States and the

global standard by the International Organization of

Standards ISO 13485:2003 “Medical devices—

Quality management systems—Requirements for

regulatory purposes” enforced by the European

Union. Most countries have adopted modified ver-

sions of the ISO 13485 and/or the FDA regulations.

Finished device manufacturers need to comply with

the regulations. Suppliers of raw materials and

components do not need to comply with the regula-

tions, but are subject to the purchasing controls of

the finished device manufacturers. Finished device

manufacturers must have stringent supplier qualifi-

cation procedures that include supplier audits,

incoming raw material and component specifica-

tions, and quality metrics. Plastic material suppliers

must provide appropriate data and information

about their products that the regulatory bodies and

the finished device manufacturers can use to assess

the performance and viability of the raw materials

for their specific devices. This is only required for

high-risk devices. Such information includes the

formulation, the performance specifications, the

test methods and release criteria, the quality

metrics, material characteristics (physical, chemi-

cal, biocompatibility, and toxicity), the assurance of

supply, and the notification of any formulation

changes. This information is typically maintained

by the regulatory bodies in master files, is kept con-

fidential, and is accessible only to the regulatory

bodies but not to the finished device manufacturers

or the public at large.


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York: CRC Press: Marcel Dekker Inc; 1990.

[2] Squibb ER. The collected papers of Edward

Robinson Squibb, M.D., 1819�1900.

In: Porter D, Earl R, editors. Food labeling:

toward national uniformity. Washington DC,

USA: National Academies Press; 1992. p. 39.

[3] Federal food and drugs act of 1906 (The

“Wiley Act”) Public Law Number 59�384 34

Stat. 768 (1906) 21 U.S.C. Sec 1�15 (1934)

(Repealed in 1938 by 21 U.S.C. Sec 329 (a)).

[4] Study Group on Medical Devices. Medical

devices: a legislative plan. Washington, D.C.:

Department of Health Education and Welfare;

1970.

[5] FDA office of compliance and surveillance.

Device recalls: a study of quality problems.

HHS Publication FDA-90-4235: Washington

DC, USA; 1990.

[6] FDA medical device regulation from premarket

approval to recall—department of health and

human services inspector general’s study; 1990.

[7] 21 CFR Part 820—Quality Systems Regulation.

[8] 21 CFR Parts 808, 812, 820 Medical Devices;

Current Good Manufacturing Practices

(CGMP); Final Rule; October 7, 1996,

p. 52606, response #7.

[9] Premarket Approval (PMA)—is the FDA pro-

cess of scientific and regulatory review of

devices “that support or sustain human life,

are of substantial importance in preventing

impairment of human health, or which present

a potential, unreasonable risk of illness or

injury.”

[10] 510(k) application and submission—is the

FDA scientific and regulatory approval pro-

cess of devices that a manufacturer thinks is

“substantially equivalent” to a similar device

that was on the market prior to May 28, 1976.

This is less involved than the premarket

approval defined in reference 9.

[11] Investigational Device Exemption (IDE) is

issued by the FDA to allow the use of investi-

gational devices in human subjects for clinical

trials and investigation in order to evaluate the

safety and effectiveness of the investigational

medical device.

[12] ISO 13485:2003, Medical devices—Quality

management systems—Requirements for regu-

latory purposes.

[13] ISO 14971:2007, Medical devices—Application

of risk management to medical devices.

[14] ISO/TR 14969:2004, Medical devices—Quality

management systems—Guidance to the appli-

cation of ISO 13485:2003.

[15] Ministerial Ordinance on Standards for

Quality Assurance for Drugs, Quasi-drugs,

Cosmetics, and Medical Devices MHLW.

Ordinance Number 136; September 22, 2004.

[16] Public Law 105�230, sect. 1, 112 Stat. 1519

codified in 21 U.S.C. 1601�1606, 1999.

[17] Quality Management System—Medical

Devices—Guidance on the Control of Products

and Services Obtained from Suppliers.


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