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 based on 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 human functions.

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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 of the device; design qualification/verification in the development step must be done in detail and process control by scientific parameters is important to assure quality.
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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

are 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 and metabolic action, are involved. In vitro diagnostic products also involved in this category.

2: Medical devices that are composed in batches and

Category

(part) for assembly in the manufacturing process, and constituted (assembled) and maintained at user site. Function of the medical device after assembly must be tested before release. Method verification for constitution should be one of the key factors, as well as qualification and validation in the manufacture of components (parts).Example: NMR Spectroscopy
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3: Medical devices are controlled with each component

 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

1.Development of (Design) Concept 1.1 Product 1.2 Manufacturing Equipment 2. Preparation of Design 2.1 Product 2.2 Manufacturing Equipment 3. Design Verification 4. Preparation of Equipment to manufacture Medical Device

9. Process Validation

8. Performance Qualification

7. Efficacy Trails (Development Stage)

5.Installation Qualification

6. Operational Qualification
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1.

2.

Validation is one method of assuring that the product manufactured satisfies the design required, the specification established, and the reproducibility of the results. 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 from micro-organisms. Preparation of design, which is for both product and the manufacturing (assembly) process and test method. Design preparation should satisfy the design concept.
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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
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6.

Operational qualification (or verification with the existing line) for each processing machine and assembled processing line. Operational qualification is required to confirm that all machines and equipment can be operated in the designed manner 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 assembled process 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 developed operational 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 to process 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, inprocess 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 each item, such as design verification and installation qualification. For example, the purpose of cleaning validation is to avoid any contamination.
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b) The protocol shall include the established methods to perform the study and also include the acceptance criteria for the operational parameters (temperature, electrical current, etc.) of the equipment and in-process product specifications as well as the product specifications. When the protocol does not include the fixed operating conditions with the acceptance criteria, the study is categorized in the development stage rather than the qualification stage. c) The study shall be carried out according to the method described in the protocol. When the method used in the study deviates from the protocol, it shall be shown that the method used is equivalent to the method in the product. d) All the operating conditions and in-process parameters must be recorded. e) The QC testing of the final product must be performed and results must be recorded.
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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, inprocess 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. 15 5/2/2012

2. The protocol must include development of the design of inprocess product as well as the design of final product based on the product concept. A program should thus be included to confirm that the design of the product satisfies the product concept. This program will be performed by using a checklist that includes the items such as size, shape, and nature of the materials. 3. The protocol must include the proposed tentative specifications of the in-process product with the acceptance criteria and directs the finalization of the specification at the end of the development stage. The specification should be proposed based upon the product design; that is, the specification includes the size, shape, impurities, and nature of the materials, such as viscosity and tension. Developing the specifications of the final product and parts for assembly must be performed to specify the product efficacy and product liability based on the design concept and scientific data, such as stability data.
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4. The protocol must include the proposed tentative manufacturing procedure that will be fixed at the end of the development stage. The tentative manufacturing procedure include what kind of manufacturing 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 end of the development stage. 5. The protocol must include directions on selecting or developing the maintenance program, including preventive and corrective action. The maintenance program includes the calibration program of measurement equipment and the replacement of equipment parts. 6. The study shall be carried out according to the method described in the protocol. When the method used in the study is changed from the protocol, it shall be justified in the document according to the established change control system. In general, however, the acceptance criteria of the specifications for the final product should not be changed without specific data relating to safety and functional 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 is necessary to finalize the specification of the products. 9. The results obtained for the specification testing shall satisfy 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.
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1.ISO/DIS 13485: The supplier shall establish, document, and maintain a quality system as a means of ensuring that product conforms 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.
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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:1. Concept of Product
Concept of products should include whether products are used in sterilized condition.

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2. Design of product with the tentative specification and design of process lines
When the products are used in sterilized condition design of materials of products and select ion of sterilization should be included.

3. Design Verification

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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4. Establishment of process line to manufacture product

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.

5.IQ/OQ
When the sterilization process is included , it may be recommended to use ISO requirements standard listed in the references for medical devices

6. Efficiency trails to develop inprocess parameter

Regarding sterilization process, in-process parameters should be developed to satisfy physical and microbiological criteria.
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When sterilization process is included. ISO requires performing the qualification in the worst case (product qualification)

7. Performance qualification and process validation

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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Risk assessment for medical devices is thus required to provide satisfactory goods to customers by controlling the manufacturing process and by testing inprocess product as well as final product

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1.

REFERENCES:ISO 13485. Quality SystemsMedical Devices: Particular Requirement for the Application of ISO 9001. Switzerland (1997). 2. U.S. Food and Drug Administration. Guidance on General Principles of Process Validation. (1987).

2.

3.

4. 5. 6.

ISO 9001. Quality SystemModel for Quality Assurance in Design, Development, Production, Installation and Servicing. Switzerland (1994). 4. Code of Federal Regulations (CFR), Title 21. Part 820.5: Quality Assurance Program; Part 820.20(a): Quality Assurance Program Requirements. Washington, DC: U.S. Government Printing Office (1996). 5. Global Harmonization Task Force. Guidance on Quality Systems for the Design and Manufacture of Medical Devices. (1994).

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QUERIES???

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