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A Presentation On

Validation of Medical Devices

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Rahul SagarM. Pharm IInd semPharmceutics-DRA

PRESENTED BY

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Contents Medical devices and categories Medical device validation in quality systems Regulatory requirements of validation for

medical devices Validation for medical devices Process validation for medical devices Validation of medical devices and critical

issues Risk assessment for validation

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Medical devices and categories

A medical device is an implant and equipment to be used either to achieve disease diagnosis, medical treatment, or disease prevention for human and animals, or to influence the physical structure and function of human and animals.

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Contin….

Medical devices for humans 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.

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Categories

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.

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

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

Category 4: Medical devices that are controlled by in-process tests, with critical specifications designed for both individual products or a group, and are implemented in human and animals for the long term.

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Medical device validation in quality systems

1. ISO 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.

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.

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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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Regulatory requirements of validation for medical devices

Validation includes the design concept (design of product developed), design verification, each qualification for manufacturing, and assay/test equipment, including the establishment of a maintenance program, the development stage of manufacturing operation conditions and test methods, and individual validation (process validation and analytical method validation).

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Contin….

Validation is thus required to ensure the establishment of product specifications, how the manufacturer maintains the quality of a product in the manufacturing process, and what factors are critical in assuring the proper functioning of the medical device.

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Validation for medical devices

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Process validation for medical devices

Validation in quality systems includes establishment of procedures on how to qualify the equipment and machinery, how to verify the design of products, how to verify the process designed, how to verify the achievement of production procedures, how to validate the process developed, and how to validate the methods for measurement and assay.

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Contin…..

Validation also requires verification of specifications or acceptance criteria of in-process parameters relating to both raw materials and intermediate (in-process product) and finished products, and verification of acceptance criteria for in-process parameters relating to operating conditions of machinery and equipment.

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Validation of medical devices and critical issues

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Risk assessment 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

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2. How the in-process parameters, including in-process product specification, can detect goods to be rejected or otherwise unsatisfactory goods. Risk assessment for medical devices is thus required to provide satisfactory goods to customers by controlling the manufacturing process and by testing in-process product as well as final product.

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In Vitro Diagnostics Validation

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Validation of in vitro diagnostic tests

Validated Diagnostic Test should:

“Provides test results that identify positive or negative for an analyze or process (e.g. antibody, antigen or in duration at skin test site) with a degree of statistical certainty”

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Development and validation of in vitro diagnostic tests

Outline:

1) Analytical Validation

2) Clinical Validation

3) Regulatory Perspectives

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Analytical validation

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Analytical validation

Development Stage:

1. Feasibility Studies

- determine or identify a method for a particular use

- determine if the selected reagents and protocol have the capacity to distinguish between a range of antibody concentrations to an infectious agent while providing minimal background activity

- Give initial estimates of repeatability, and of analytical sensitivity and specificity

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Development/Validation Stage:

2. Assay Development and Standardization Selection of optimal reagent concentrations Determine the optimal temporal, chemical, and

physical variables in the protocol, e.g. incubation temperatures and durations; pH, molarity of diluent, washing, and blocking buffers

Repeatability – preliminary estimates (agreement between replicates within and between runs)

Determination of analytical sensitivity (the smallest detectable amount of the analyte) and specificity (the degree to which the assay does not cross-react with other analytes)

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Validation Stage:

3. Determining Assay Performance Characteristics Determine diagnostic sensitivity and specificity Precision- a measure of dispersion of results for a

repeatedly tested samples Repeatability- the amount of agreement between replicates Reproducibility- the amount of agreement between results

of samples tested in different laboratories Accuracy- the amount of agreement between a test value

and the expected value for an analyte in a standard sample of known activity (clinical samples; compare to cleared or gold standard method )

Selection of the cut-off/reporting threshold/LOD for qualitative/LOQ for quantitative

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Clinical Validation

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Considerations: Purpose – assess clinical sensitivity,

specificity and reproducibility Studies should be performed in a

representative sample of the intended use population

Common components – Precision, Reproducibility, and non-specificity of the investigational assay

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Regulatory Perspectives

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Regulatory perspectives

FDA guidelines – 21 CFR 809.3(a)

In vitro diagnostic products are those reagents, instruments, and systems intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequel. Such products are intended for use in the collection, preparation, and examination of specimens taken from the human body. These products are devices as defined in section 201(h) of the Federal Food, Drug, and Cosmetic Act (the act), and may also be biological products subject to section 351 of the Public Health Service Act.

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Regulation by Risk Risk defined by possible harm to patient of

unrecognized incorrect result Three classes from low to high risk (Class I, II

&III) - Regulatory control increases from Class I to Class III

Class I – most exempt from Premarket Notification 510(k)

Class II – most require Premarket Notification 510(k)

Class III – most require Premarket Approval (PMA)

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– A 510(k) is a premarketing submission made to FDA to demonstrate that the device to be marketed is as safe and effective, that is, substantially equivalent (SE), to a legally marketed device that is not subject to premarket approval (PMA).

– A PMA is an application submitted to FDA to request approval to market, or continue marketing, a class III medical device. PMA approval is based on scientific evidence providing a reasonable assurance that the device is safe and effective for its intended use or uses. PMA process is more involved and includes the submission of clinical data to support claims made for the device.

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Question time……

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Thanks for your attention…