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Effective Medical Device Validations

JWM Associates can provide your company with validation services to meet current FDA expectations and requirements in accordance with the Quality System Regulation (QSR).
Why is validation so important to your product development process? You will want to ensure that the device(s) will function as intended every time. It is apparent that validation and new product development are unequivocally linked together in this process.

JWM Associates Validation Services

• Documentation: Master Plans, Protocols, Validation Reports.
  
  
• Validation GAP Analysis.
  
  
• Analytical Methods Validation.
  
  
• QC Methods Validation.
  
  
• Analytical Instrument IQ/OQ/PQ Protocol Development.
  
  
• Cleaning Validation and Disinfectant Consultation.
  
  
• Equipment: Installation Qualification.
  
  
• Process: Performance Qualification.
  
  
• Product: Performance Qualification.
  
  
• Assistance in Systems to Assure Timely Revalidation.
  
  
• Retrospective Process Validation.

What is Validation?

Validation, according to the FDA's definition (Quality System Regulation section 820.3(z)) is confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use can be consistently fulfilled.

Linked with this general description is Process Validation, which means establishing by objective evidence that a process produces a result or product, meeting its predetermined specifications.

The following is a summary of The Ten Commandments of GMPs (QSR)… and how they are tied to validation. If these sound familiar, it's because validation, just like GMPs, are expected and required in the manufacturing facility. The Ten Commandments of GMP's were observed in an article published by The GMP Institute several years ago.

1. Procedures must be written;
2. Written procedures must be followed;
3. Work must be recorded or documented;
4. All work must be validated;
5. Proper facilities and equipment must be designed and/or available;
6. Facilities and equipment must be maintained;
7. Competence must be maintained as a result of education, training and experience;
8. Cleanliness levels must be defined and observed;
9. Quality must be controlled throughout all processes; and
10. Audits must be performed to assess compliance.

1987 Guidelines on General
Principles of Process Validation

The FDA published the Guidelines on General Principles of Process Validation on May 11, 1987. The guideline outlined general principles that FDA considered acceptable elements of process validation for the preparation of human and animal drug products and medical devices.

This guideline was issued under Section 10.90 (21 CFR 10.90) and was applicable to the manufacture of pharmaceuticals and medical devices. It stated principles and practices of general applicability that were not legal requirements but were acceptable to FDA.

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How Process Validation can be implemented throughout the product life:

During the R&D phase, the desired product should be carefully defined in terms of its characteristics, such as physical, chemical, electrical, and performance characteristics. It is important to translate the product characteristics into specifications as a basis for description and control of the product.

Documentation of changes made during development provides traceability that can later be used to pinpoint solutions to future problems.

The product's end use should be a determining factor in the development of product (and component) characteristics and specifications. All pertinent aspects of the product that impact safety and effectiveness should be considered. These aspects include performance, reliability, and stability. Acceptable ranges or limits should be established for each characteristic to set up allowable variations. These ranges should be expressed in readily measurable terms.

The validity of acceptance specifications should be verified through testing and challenge of the product on a sound scientific basis during the initial development and production phase. Once a specification is demonstrated as acceptable, it is important that any changes to the specification be made in accordance with documented change control procedures.

Validation Glossary

Validation terminology has been standardized in part by the FDA's QSR section 820.3 (Definitions). The Validation Glossary is provided below for your convenience.

Acceptance Criteria - The standards a product or process must meet to successfully complete a test phase or to meet delivery requirements.
Accuracy - The degree of freedom from error, the degree of conformity to a standard, or the closeness of test results obtained by that method to the true value; the agreement between a measured value and an accepted or true value.
Action Levels - A specific set of operating parameters which, when reached, signal variations from normal operating conditions and require documented action in order to return the system or process to a state of control.
Action Limits - Maximum (microbial, particulate, etc.) limits established with a specific course of action to be taken when samples are found to exceed those limits.
Alert Levels - A specific set of operating parameters which, when reached, signal potential variations from normal operating conditions. This level is within the proven acceptable range and, therefore, does not necessarily mean that product quality is threatened. However, the monitoring frequency of operation and maintenance should increase on the system or process.
Alert Limits - The concentration of viable or nonviable particulates in an environment that, when exceeded, signal a potential drift from normal operating conditions. A review of recent monitoring data and manufacturing practices should be conducted following such excursions to ensure that the manufacturing environment is still in control.
Calibration - Documented comparison, by written and approved procedures, of a traceable measurement standard, of a known accuracy, with another measuring device to respond to, detect, correlate, report or eliminate any variation in the accuracy of the item being compared over an appropriate range of measurements.
Change Control - A formal monitoring system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect a validated status. This is done to determine the need for corrective action to ensure that the system retains its validated state.
Characteristic - A physical, chemical, visual, functional, or other identifiable property of a product, component or raw material, also known as an attribute or parameter.
Concurrent Validation - Establishing documented evidence, based on an approved validation protocol, that a process does what it purports to do. This is based on information generated during the actual operation and implementation of the process to make marketable product.
Controlled Environment - Any area in an aseptic process system for which airborne particulate and microorganism levels are controlled to specific levels appropriate to the activities conducted within that environment.
Critical Component - Any component of a critical device who's failure to perform can be reasonably expected to cause the failure of a critical device or to affect the device's safety or
effectiveness.
Critical Device - A device intended for surgical implantation into body or used to support or sustain life. The failure of the device to perform, when used in accordance with instructions for use provided in the labeling, can be reasonably expected to result in significant injury to the user.
Critical Process Parameter - A control parameter that has a direct relationship to the quality, safety, effectiveness, or performance of the intermediate or final product.
Design History File - A compilation of records that describes the design history of a finished device.
Design Input - The physical and performance requirements of a device that are used as a basis of a finished device.
Design Output - The results of a design effort at each design phase and at the end of the total design effort. The finished output design output is the basis for the device master record.
Design Review - A documented, comprehensive, systematic examination of a design to evaluate the adequacy of the design requirements, to evaluate the capability of the design to meet these requirements, and to identify problems.
Design Validation - Establishing by objective evidence that device specifications conform with user needs and intended use(s). It should be performed under defined operating conditions and on the initial production units, lots, batches, or their equivalents to ensure proper overall design control and proper design transfer.
Device History Record - A compilation of records containing the production history of a finished device.
Device Master Record - A compilation of records containing the procedures and specifications for a finished device.
Environmental Monitoring Program - A documented program implemented through SOPs that describes the procedures and methods used for monitoring particulates and microorganisms in controlled environments (air, surface, operator's gear). The program includes sample sites, frequency of sampling, and investigative and corrective actions that must be followed if Alert or Action Levels are exceeded.
Final Validation (Technical) Report - A document summarizing the results derived from the execution of a protocol. The report should include a conclusion, which indicates validation success or failure and designated proven acceptance ranges for all critical process parameters as determined by the execution of the protocol.
Finished Device - Any device or accessory to any device that is suitable for use or capable of functioning, whether or not it is packaged, labeled, or sterilized.
Inspection - The process of measuring, examining, testing, or otherwise comparing a unit of product with the requirements for it.
Installation Qualification (IQ) - The performance of documented verification that an equipment/system installation adheres to approved contract specification and achieves design criteria. Documented verification that all key aspects of hardware installation adhere to appropriate codes and approved design intentions and that the recommendations of the manufacturer have been considered. The IQ is developed from drawings, purchase orders/specifications, equipment operating manuals, and other necessary documentation. The IQ precedes the OQ (Operation Qualification).
Manufacturing Material - Any material used to facilitate a manufacturing process (e.g., a cleaning agent, mold-release agent, cleaning fluids, etc.) which is not intended by the manufacturer to be included in the finished device.
Manufacturing Process - Manufacturing operations including, but not limited to, materials handling, product processing, fabrication and formulation, product filling, packaging, sampling, testing, and inspection support functions.
Method Validation - The documented demonstration that a test method is scientifically sound and serves its intended purpose.
Non-Conformity - A departure of a quality characteristic from its intended level or state that occurs with a severity sufficient to cause an associated product or service not to meet a specification requirement.
Objective Evidence - Information that can be proven to be true based on facts obtained through observation, measurement, test, or other means.
Operational Qualification (OQ) - The documented verification that the equipment/system performs per design criteria over all defined ranges. The OQ includes qualification of operating and maintenance records. The OQ precedes the Performance (or Process) Qualification (PQ). Documented verification that a system performs as intended throughout representative or anticipated operating ranges.
Performance Qualification (PQ) - Documented verification that equipment, systems, or processes operate the way they are purported to do. This operation must be reliable and reproducible within a specified, predetermined set of parameters under normal production conditions and must be in a state of control. Establishing documented evidence that operating characteristics and product are in conformance with the limits defined in the specifications. Critical parameters must be stable over time under both normal and worst-case conditions.
Precision - The degree of agreement among individual test results when a procedure is applied repeatedly to multiple samplings of a homogeneous sample; the degree of two or more measurements that are obtained under identical conditions using the same test method.
Process - The controlled system; a set of interrelated resources and activities which transform inputs into outputs.
Process Development - Establishing evidence that all process control parameters and all control parameter ranges are validated and optimized.
Process Validation (Process Performance Qualification) - Establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications.
Prospective Validation - Establishing documented evidence that a system does what it purports to do based on a written and approved preplanned protocol. The validation is conducted prior to the manufacture of marketable product, and the product is not sold until the equipment, system, and process meet the validation acceptance criteria.
Protocol - The written and approved document of an experimental sequence of tests that, when executed as prescribed, are intended to produce documented evidence that the equipment or system does what it is designed or claims to do reproducibly. The protocol will address all elements of the validation sequence relevant to the process, equipment, or system being challenged.
Protocol Addendum - A document explaining a change or addition to an original protocol. It must include the reason for the change or addition and approvals from responsible representatives.
Qualification - Used to describe the testing and review of a piece of equipment, system, or subsystem of a process to ensure its fitness for use. The qualification is associated with components or elements of a process, e.g., a molding tool, etc. The qualification procedure is determined by a written and approved protocol.
Quality System - The organizational structure, responsibilities, procedures, processes, and resources for implementing quality management.
Requalification - The approved written procedure used to return a process, piece of equipment, or system to a validated or qualified state after maintenance or minor changes have been made to it.
Retrospective Validation - Establishing documented evidence that a system does what it purports to do based on historical data and information obtained during the production of clinical or marketable product.
Robustness - The capacity to remain unaffected by small but deliberate variations in method parameters and provide an indication of its reliability.
Special Process - Any process whose results cannot be completely verified by subsequent inspection and testing.
Specification(s) - An approved, quantitative value and the document that prescribes the requirements to which a device, component, production or servicing activity, or quality system must conform.
Standard Operating Procedure (SOP) - A written procedure describing operations, testing, sampling, interpretation of results, and corrective actions that relate to the operations that are taking place in a controlled environment and auxiliary environments.
Statistic - An estimate of a parameter.
Validation - Confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use can be consistently fulfilled. The action of proving that any material, process, activity, equipment or mechanism used in manufacture or control can, will, and does achieve the desired or intended result.
Validation Master Plan - The establishment of a dynamic written plan that defines the overall approach to a validation Project. It will define the terminology to be used in all subsequent documentation, outlining descriptions of the facility site, the manufacturing processes, and the scope and implementation of the validation sequence. The VMP can be used as an executive summary to the management group, signifying the project description, risk category (low, medium or high), who will assume ownership, and the projected due date.
Verification - Confirmation by examination and provision of objective evidence that specified requirements related to a product or process have been met. The process of examining the results of an activity to determine conformity with the stated specifications for that activity and ensuring that a device is adequate for its intended use.
Worst-Case Condition - A set of conditions encompassing the upper and lower processing limits which pose the greatest chance of process or product failure when compared to ideal conditions. Such conditions do not necessarily induce product or process failure.

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