Download - Medical Device Validation Radha
-
8/3/2019 Medical Device Validation Radha
1/27
5/2/2012 1
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
-
8/3/2019 Medical Device Validation Radha
2/27
5/2/2012 2
-
8/3/2019 Medical Device Validation Radha
3/27
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.
5/2/2012 3
-
8/3/2019 Medical Device Validation Radha
4/27
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
-
8/3/2019 Medical Device Validation Radha
5/27
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.
5/2/2012 5
-
8/3/2019 Medical Device Validation Radha
6/27
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
5/2/2012 6
-
8/3/2019 Medical Device Validation Radha
7/27
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;-
5/2/2012 7
-
8/3/2019 Medical Device Validation Radha
8/275/2/2012 8
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
-
8/3/2019 Medical Device Validation Radha
9/27
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
-
8/3/2019 Medical Device Validation Radha
10/27
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
-
8/3/2019 Medical Device Validation Radha
11/27
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
5/2/2012 11
-
8/3/2019 Medical Device Validation Radha
12/27
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.
5/2/2012 12
-
8/3/2019 Medical Device Validation Radha
13/27
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.
5/2/2012 13
-
8/3/2019 Medical Device Validation Radha
14/27
-
8/3/2019 Medical Device Validation Radha
15/27
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
-
8/3/2019 Medical Device Validation Radha
16/27
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.
5/2/2012 16
-
8/3/2019 Medical Device Validation Radha
17/27
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.
5/2/2012 17
ll d d
-
8/3/2019 Medical Device Validation Radha
18/27
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
-
8/3/2019 Medical Device Validation Radha
19/27
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
-
8/3/2019 Medical Device Validation Radha
20/27
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.
5/2/2012 20
1. Concept of Product
-
8/3/2019 Medical Device Validation Radha
21/27
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.
5/2/2012 21
2. Design of product with
the tentative specification
and design of process lines
3. Design Verification
-
8/3/2019 Medical Device Validation Radha
22/27
5/2/2012 22
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
-
8/3/2019 Medical Device Validation Radha
23/27
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.
5/2/2012 23
7. Performance qualification and
process validation
-
8/3/2019 Medical Device Validation Radha
24/27
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
5/2/2012 24
-
8/3/2019 Medical Device Validation Radha
25/27
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).
5/2/2012 25
-
8/3/2019 Medical Device Validation Radha
26/27
QUERIES???
5/2/2012 26
-
8/3/2019 Medical Device Validation Radha
27/27
5/2/2012 27