medical device validation radha

8/3/2019 Medical Device Validation Radha

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FACILITATED BY:

Dr.T.M.Pramod Kumar

HOD

REGULATORY AFFAIRS GROUP

DEPT. OF PHARMACEUTICS

JSSCP, MYSORE

PRESENTED BY:RadhaDevi.N

1ST M. PHARMA

RA GROUP

JSSCP, MYSORE


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Medical devices for human may also be classified basedon whether and how long the device is in contact with

tissue or cells and on the degree of disjunction induced

by the device when in a disabling situation.

The term covers various categories, such as scissors

and tweezers, with small risk to human function, to

central venous catheters, artificial dialysis (human

kidney), and pacemakers, with high risk to humanfunctions.

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The ISO (International Standard Organization)

Standard (ISO 13485 [1]) for medical devices, Quality

Assurance System for Medical Devices, has been

implemented globally.

GMPs are clearly required for the manufacture of

medical devices, including process control, quality

control, and appropriate facilities and equipment.

GMP also play a role in maintaining the quality of

medical devices.

Performing only a specification test of the final

product for release may not guarantee high quality ofthe device; design qualification/verification in the

development step must be done in detail and process

control by scientific parameters is important to

assure quality. 5/2/2012 4


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To achieve appropriate quality control status, medical devices

may be categorized under design, manufacturing method,

assembly method, and quality control testing.

Category 1: Medical devices that are controlled by in-process

tests, with critical specifications designed for both individual

products and a group, but not implemented in human and

animals.

Qualification of equipment to test critical product specifications

and validation of test methods should be key factors.

Example:- Scissors, Tweezers and pair of glasses.

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Category 2: Medical devices that are composed in batches andare tested with representatives in a batch.

Process validation should be a key factor in manufacturing

uniform products. Example;- Sterile products, such as central venous catheters and

ophthalmic viscosugical solutions without pharmacological andmetabolic action, are involved. In vitro diagnostic products alsoinvolved in this category.

Category 3: Medical devices are controlled with each component(part) for assembly in the manufacturing process, and constituted(assembled) and maintained at user site. Function of the medicaldevice after assembly must be tested before release.

Method verification for constitution should be one of the keyfactors, as well as qualification and validation in the manufactureof components (parts).Example: NMR Spectroscopy

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Category 4: Medical devices that are controlled by in-process

tests, with critical specifications designed for individual products

or a group of products and are implanted in human and animals

for the long term.

The compatibility of product material with tissues and cells, the

stability of product in the implanted site, and the sterility of

product should be key factors to assure the product safety.

Example:- Intraocular lenses and Pacemakers .

Items required for validation of Medical Devices;-

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1.Development of (Design)Concept

1.1 Product 1.2Manufacturing Equipment

2. Preparation of Design2.1 Product 2.2

Manufacturing Equipment

3. DesignVerification

4. Preparation of Equipmentto manufacture Medical

Device

5.InstallationQualification

6. OperationalQualification

7. Efficacy Trails (Development Stage)

8. Performance

Qualification

9. Process Validation


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Validation is one method of assuring that the productmanufactured satisfies the design required, the specification

established, and the reproducibility of the results.

1. Development of the (design) concept, which is for both the

product and the manufacturing (assembly) process and test

method. The design concept for the product should include

factors of function as well as safety factors. The design concept

for the manufacturing (assembly) process and test method

should include accuracy for manufacture and testing, and

safety for preventing contamination, such as occurs frommicro-organisms.

2. Preparation of design, which is for both product and the

manufacturing (assembly) process and test method. Design

preparation should satisfy the design concept.5/2/2012 9


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3. Design verification, which is for both product and the

manufacturing (assembly) process . Design verification

should reflect design preparation.4.Preparation of equipment for manufacture and testing,

which is performed when equipment is necessary.

5.Installation qualification (or verification with the

existing line) for each processing machine, and

assembly according to the processing line. Installation

qualification is required to confirm that all machines

and equipment are instilled with all functional parts at

the specific sites intended. Preventive and corrective

maintenance programs should be established.5/2/2012 10


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6. Operational qualification (or verification with the existingline) for each processing machine and assembled processing

line. Operational qualification is required to confirm that all

machines and equipment can be operated in the designedmanner within the intended range . Preventive and corrective

maintenance programs are established.

7. Efficiency trails, which means developing specific operational

conditions of the machinery and equipment in the assembledprocess line to manufacture the intended product. When

needed, process control parameters for monitoring and

acceptance criteria must be developed. Operational conditions

and the end point must be developed to satisfy the approved

specification of the products. To satisfy the developedoperational conditions and end point, master records for the

products and SOPs relating to processing must be developed

and established with appropriate approval

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8. Performance qualification, which includes the equipment

qualification operated under loaded conditions. Performance

qualification is carried out with individual equipment based

on the information obtained in efficiency trails prior toprocess validation under the complete assembled condition.

In the case of environmental qualification and utility

qualification, performance qualification is generally carried

out under the operating condition for 1 year to confirm there

is no deviation by season.

9. Process validation (product qualification), which is

performed on each intended product, even when

manufactured in the same manufacturing line. According to

the master record, the manufacturing must be carried out, in-process control parameters must be monitored, and

specification testing of the product must be performed. The

result of specification testing must satisfy the requirements.

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Validation is classified in two categories: The

Development Stage (rectangle) and the Establishment Stage

(oval).

The Establishment stage includes verification, qualification,

and individual validation, including process validation,

computer validation, method validation, and cleaning

validation.

In practical terms, the verification, qualification, analytical

validation, cleaning validation, and process validation need to

satisfy certain requirements.

a) The protocol must include the clarified purpose of eachitem, such as design verification and installation

qualification. For example, the purpose of cleaning

validation is to avoid any contamination.

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f.) The results obtained shall satisfy the criteria of the operating

parameters and the specifications of the in-process products

as well as the final product.

g) The written study report shall be prepared.

h) The documents shall be verified, approved, and filed; the

necessary documents are protocol, records for operation, in-

process parameters, specification test as quality control, and

final report.

Studying the development stage works (design steps and

efficiency trails steps) is necessary for designing the product.

Development stage works must satisfy the fallowing:

1.The protocol must include the product concept as well as

the purpose. The product concept must be comprehensively

simplified for designing the next step and should describe the

effective role of the medical device against the disease.5/2/2012 15


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2. The protocol must include development of the design of in-process product as well as the design of final product based onthe product concept. A program should thus be included toconfirm that the design of the product satisfies the productconcept. This program will be performed by using a checklistthat includes the items such as size, shape, and nature of thematerials.

3. The protocol must include the proposed tentative

specifications of the in-process product with the acceptancecriteria and directs the finalization of the specification at theend of the development stage. The specification should beproposed based upon the product design; that is, thespecification includes the size, shape, impurities, and nature of

the materials, such as viscosity and tension. Developing thespecifications of the final product and parts for assembly mustbe performed to specify the product efficacy and productliability based on the design concept and scientific data, suchas stability data.

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4. The protocol must include the proposed tentative manufacturingprocedure that will be fixed at the end of the development stage.The tentative manufacturing procedure include what kind ofmanufacturing equipment will be used, how the manufacturing

equipment will be assembled, and how to operate the equipment.The operational condition of the equipment will be fixed at the endof the development stage.

5. The protocol must include directions on selecting or developingthe maintenance program, including preventive and corrective

action. The maintenance program includes the calibration programof measurement equipment and the replacement of equipmentparts.

6. The study shall be carried out according to the method describedin the protocol. When the method used in the study is changed from

the protocol, it shall be justified in the document according to theestablished change control system. In general, however, theacceptance criteria of the specifications for the final product shouldnot be changed without specific data relating to safety andfunctional assessment.

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7. All operating conditions and in-process parameters must

be recorded. This is important to provide the scientific

and/or statistic rationale to fix the operating conditions at

the end of the development stage.

8. The specification testing of products that are manufactured

in the trial run and stored according to the proposed

conditions must be documented, because all information isnecessary to finalize the specification of the products.

9. The results obtained for the specification testing shallsatisfy the acceptance criteria that assure the efficacy and

safety of the product.

10.The study report shall be prepared as development of

product in a written document.11. The documents shall be verified, approved, and filed;

essential documents are the protocol, records for operation,

in-process control parameters, change control document,

specification test as quality control, and final report.5/2/2012 18


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1.ISO/DIS 13485: The supplier shall establish, document, and

maintain a quality system as a means of ensuring that productconforms to specified requirement. The supplier shall prepare

a quality manual covering the requirements of ISO 9001. The

quality manual shall include or make reference to the quality

system procedures and outline the structure of the

documentation used in the quality system.

2. CFR21 Section 820.5 Quality System: Each manufacturer

shall establish and maintain a quality system that is

appropriate for the specific medical device(s) designed or

manufactured, and that meets requirements of this section.

3. Global Harmonization Task Force (GHTF), which was

formed to harmonize regulatory requirements for the medical

device may recommend referring to ISO 10013 for general

guidance on the content of a quality manual. 5/2/2012 19


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1. 21CFR Section 820.72 and 820.75 states the

requirements.

AN APPROACH TO THE VALIDATION OF

MEDICAL DEVICES AND CRITICAL ISSUES IN

EACH STEP OF THE PROCESS:-

Concept of products should include whether products are used in

sterilized condition.

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1. Concept of Product


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When the products are used in sterilized condition design of

materials of products and select ion of sterilization should be

included.

When sterilization process should be included, the selection of

material and the process should be verified from the point of

physical and microbiological integrity of product.

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2. Design of product with

the tentative specification

and design of process lines

3. Design Verification


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It should be established whether use of terminal sterilization

or in-process sterilization with aseptic operation. When terminal

sterilization is adapted for medical devices ISO standard listed in

references shall be referred.

When the sterilization process is included , it may be

recommended to use ISO requirements standard listed in the

references for medical devices

Regarding sterilization process, in-process parameters should be

developed to satisfy physical and microbiological criteria.

4. Establishment of process line to

manufacture product

5.IQ/OQ

6. Efficiency trails to develop in-process parameter


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When sterilization process is included. ISO requires performing thequalification in the worst case (product qualification)

RISK ASSESMENT FOR VALIDATION;- Because validation is required to establish the quality of

the medical device, including reproducibility, each process

shall undergo risk assessment. Risk assessment includes

two criteria: (1) how the process can avoid the appearance

of rejected goods or other unsatisfactory goods in each

process, and (2) how the in-process parameters, including

in-process product specification, can detect goods to be

rejected or otherwise unsatisfactory goods.

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7. Performance qualification and

process validation


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Risk assessment for medical devices is

thus required to provide satisfactory goodsto customers by controlling themanufacturing process and by testing in-process product as well as final product

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REFERENCES:-1. ISO 13485. Quality SystemsMedical Devices: Particular

Requirement for the Application of ISO 9001. Switzerland(1997).

2. 2. U.S. Food and Drug Administration. Guidance on GeneralPrinciples of Process Validation. (1987).

3. ISO 9001. Quality SystemModel for Quality Assurance inDesign, Development, Production, Installation andServicing. Switzerland (1994).

4. 4. Code of Federal Regulations (CFR), Title 21. Part 820.5:Quality Assurance Program;

5. Part 820.20(a): Quality Assurance Program Requirements.Washington, DC: U.S. Government Printing Office (1996).

6. 5. Global Harmonization Task Force. Guidance on QualitySystems for the Design and Manufacture of Medical

Devices. (1994).

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QUERIES???

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medical device validation radha

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