An FMS will typically include several monitoring devices: temperature, humidity, and pressure sensors or transducers, and perhaps velocity sensors and particle counters as well. It may also include digital devices for monitoring vacuum pumps or machine running states and feature digital outputs for alert/alarm indicators such as lights or sirens, and for other control functions.
Documentation
The most important document for any proposed system is the User Requirement Specification (URS). Without this document, it is impossible to validate a system. This may come as a surprise to some, but validation is defined as no more—or less—than the process of generating documented evidence to provide a high degree of assurance that a system will consistently fulfill its stated function.
The URS states the required functions of the system. It need not be lengthy, but it must state the functions the system is to fulfill. Despite its name, it is not necessary for the user to generate the URS; the supplier can generate the document, but the URS must be authorized by the user. Its purpose is to ensure that both the user and the supplier understand what is required. The document should have a list of must-haves, want-to-haves, and would-be-nice-to-haves. The supplier must provide all the must-haves, but not necessarily the want-to-haves and the nice-to-haves.
From the URS, all other validation documents and stages then follow. This progression is normally shown in the form of the practical Validation Model (V-model) described in this article. These documents and processes are referred to as the Life Cycle Documents.
After the URS, the next step is for the supplier to generate a Functional Specification (FS). This document, which must address all the user’s must haves, want to haves, and would be nice to haves, should be generated before order placement. If some requirements cannot be met, as will inevitably be the case, the non-compliances must be listed within the FS. Quite often the requirement can be fulfilled in a different way; sometimes, the requirement is not even essential. The FS should include a cross-reference matrix so that the user can easily see how the supplier proposes to meet each requirement.
Tuesday, July 6, 2010
Facility Monitoring Systems Validation: A Practical Approach 1
By Mike Gough
While most professionals working in the pharmaceutical industry have thorough understanding of process validation, the validation of computer systems in process applications is less widely understood.
The problem is, of course, that microprocessors are now built into equipment throughout the pharmaceutical facility. They’re in formulation, stock control, integrated manufacturing, environmental monitoring, laboratory analysis, vision inspection systems, and even in chart recorders and temperature controllers. To ensure process integrity, each one of these devices must be properly calibrated as part of the larger validation process.
Simply having an understanding of computers and software systems isn’t enough: it’s not only essential to fully understand the process, but the equipment being validated as well. This can be difficult because those who best understand the equipment are the manufacturers, but often they may know little or nothing about validation.
This article addresses only one critical aspect of computer-based systems validation: the validation of Facility Monitoring Systems (FMS).
FMSs are normally used only for cleanrooms and associated areas. Such systems cannot be used to classify an area or facility; they perform a monitoring function only, providing evidence that the environmental conditions in the monitored area have been maintained within specified limits. FDA and other regulatory bodies do accept, however, that for users of an FMS, the period of reclassification can be extended (see ISO 14644-2).
While most professionals working in the pharmaceutical industry have thorough understanding of process validation, the validation of computer systems in process applications is less widely understood.
The problem is, of course, that microprocessors are now built into equipment throughout the pharmaceutical facility. They’re in formulation, stock control, integrated manufacturing, environmental monitoring, laboratory analysis, vision inspection systems, and even in chart recorders and temperature controllers. To ensure process integrity, each one of these devices must be properly calibrated as part of the larger validation process.
Simply having an understanding of computers and software systems isn’t enough: it’s not only essential to fully understand the process, but the equipment being validated as well. This can be difficult because those who best understand the equipment are the manufacturers, but often they may know little or nothing about validation.
This article addresses only one critical aspect of computer-based systems validation: the validation of Facility Monitoring Systems (FMS).
FMSs are normally used only for cleanrooms and associated areas. Such systems cannot be used to classify an area or facility; they perform a monitoring function only, providing evidence that the environmental conditions in the monitored area have been maintained within specified limits. FDA and other regulatory bodies do accept, however, that for users of an FMS, the period of reclassification can be extended (see ISO 14644-2).
Validating Processes For Surface Preparation
Validation of processes for surface preparation is crucial to many industries, including pharmaceuticals, biomedical device and even food preparation. The effectiveness of the methods for surface preparation in these industries should be established, documented and monitored on an on-going basis.
Validation helps ensure that the surface has been cleaned to an acceptable contamination level. This maximum tolerable contamination level may be termed the target level. Sampling and analysis techniques must have the specificity, sensitivity, reliability and robustness to assure that contamination does not exceed the target limit. The areas of surface where contamination is most adherent or where the negative consequences of contamination are greatest must receive special attention. The nature of potential contaminants must also be considered. While much attention is paid to biological debris, microbes, and pyrogens, other organic and inorganic contaminants can potentially impact product quality.
As applied to processes for surface preparation, validation is a quantifiable, structured approach to demonstrate and document process effectiveness and process consistency. The following are suggestions for a comprehensive validation process.
Process efficacy must be evaluated prior to implementing the procedure. The procedure should require re-validation after changes to the processes that may significantly affect the types and amount of contamination left on the surface, or when significant changes are made to the cleaning process and result of re-validation must be documented.
The essence of process validation is documented, scientific proof of consistent successful process performance. Full, detailed documentation is an integral part of the validation process to show that the process consistently performs as expected and yields a result that consistently meets predetermined specifications. Predetermined specifications in this situation refer to the maximum acceptable level of contamination that can be tolerated on the surface. Written procedures must be established detailing the surface preparation processes. Those responsible for performing, approving and documenting the validation study and the acceptance criteria must be included, as should documentation of the frequency of process monitoring. Written procedures on how process changes will be validated and requirements for documentation of validation should also be developed.
Sampling and analysis methods must provide for sample collection and detection of levels of contamination relevant to the target limit. The technique must be suited to the types and the target level of contamination. The detection technique should be reviewed periodically for its effectiveness and relevance to the type and level of contaminants currently encountered. Prior to accepting and implementing a validation procedure, the analytical or surface testing technique itself should be evaluated and successfully replicated at least three times. Where possible, direct surface monitoring is desirable and may be preferred over indirect, extractive methods. Part configuration and test method sensitivity must be considered.
Establishing appropriate target levels of maximum acceptable contamination is a challenge. Generally, the main consideration should be as to how much surface contamination can be tolerated. There are many ways of establishing contamination limits. Cost must be considered in determining the target contamination level. For each level of surface contamination there is an associated cost of achieving that level. In addition, with each level of contamination there is a level of non-conformance or failures. The cost associated with each level of non-conformance must also be considered. The maximum acceptable level (Target Level) is the one where the incremental cost of removing more contamination is not offset by the corresponding reduction in the non-conformance or failure cost. If, however, the cost of non-conformance is a health threatening, or life threatening product failure, then the target contamination level must be adjusted to an appropriately low level.The situation is akin to extrapolating from animal studies to humans using the lowest dose of a drug or chemical at which no adverse effects are seen.The appropriate “safety factor” or risk factor will depend on the nature of the observed problem animals or the anticipated consequence in humans.
Some general considerations in establishing target levels include the effect of different levels of contamination on the success of subsequent operations; the detection capability of the various analytical techniques available; the anticipated end-use and performance requirement of the product; and the economic and social cost of non-conformance or failure.
Validation helps ensure that the surface has been cleaned to an acceptable contamination level. This maximum tolerable contamination level may be termed the target level. Sampling and analysis techniques must have the specificity, sensitivity, reliability and robustness to assure that contamination does not exceed the target limit. The areas of surface where contamination is most adherent or where the negative consequences of contamination are greatest must receive special attention. The nature of potential contaminants must also be considered. While much attention is paid to biological debris, microbes, and pyrogens, other organic and inorganic contaminants can potentially impact product quality.
As applied to processes for surface preparation, validation is a quantifiable, structured approach to demonstrate and document process effectiveness and process consistency. The following are suggestions for a comprehensive validation process.
Process efficacy must be evaluated prior to implementing the procedure. The procedure should require re-validation after changes to the processes that may significantly affect the types and amount of contamination left on the surface, or when significant changes are made to the cleaning process and result of re-validation must be documented.
The essence of process validation is documented, scientific proof of consistent successful process performance. Full, detailed documentation is an integral part of the validation process to show that the process consistently performs as expected and yields a result that consistently meets predetermined specifications. Predetermined specifications in this situation refer to the maximum acceptable level of contamination that can be tolerated on the surface. Written procedures must be established detailing the surface preparation processes. Those responsible for performing, approving and documenting the validation study and the acceptance criteria must be included, as should documentation of the frequency of process monitoring. Written procedures on how process changes will be validated and requirements for documentation of validation should also be developed.
Sampling and analysis methods must provide for sample collection and detection of levels of contamination relevant to the target limit. The technique must be suited to the types and the target level of contamination. The detection technique should be reviewed periodically for its effectiveness and relevance to the type and level of contaminants currently encountered. Prior to accepting and implementing a validation procedure, the analytical or surface testing technique itself should be evaluated and successfully replicated at least three times. Where possible, direct surface monitoring is desirable and may be preferred over indirect, extractive methods. Part configuration and test method sensitivity must be considered.
Establishing appropriate target levels of maximum acceptable contamination is a challenge. Generally, the main consideration should be as to how much surface contamination can be tolerated. There are many ways of establishing contamination limits. Cost must be considered in determining the target contamination level. For each level of surface contamination there is an associated cost of achieving that level. In addition, with each level of contamination there is a level of non-conformance or failures. The cost associated with each level of non-conformance must also be considered. The maximum acceptable level (Target Level) is the one where the incremental cost of removing more contamination is not offset by the corresponding reduction in the non-conformance or failure cost. If, however, the cost of non-conformance is a health threatening, or life threatening product failure, then the target contamination level must be adjusted to an appropriately low level.The situation is akin to extrapolating from animal studies to humans using the lowest dose of a drug or chemical at which no adverse effects are seen.The appropriate “safety factor” or risk factor will depend on the nature of the observed problem animals or the anticipated consequence in humans.
Some general considerations in establishing target levels include the effect of different levels of contamination on the success of subsequent operations; the detection capability of the various analytical techniques available; the anticipated end-use and performance requirement of the product; and the economic and social cost of non-conformance or failure.
Sunday, July 4, 2010
Process Validation
INTRODUCTION
The Quality System (QS) regulation defines process validation as establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications [820.3(z)(1)]. The requirement for process validation appears in section 820.75 of the Quality System (QS) regulation. The goal of a quality system is to consistently produce products that are fit for their intended use. Process validation is a key element in assuring that these principles and goals are met.The process validation requirements stated in the QS regulation and the guidance offered here have general applicability to manufacturing processes for medical devices. Many technologies are used in the production of medical devices. The details of process validation will vary according to the nature of the medical device (e.g., sterile or non-sterile) and the nature and complexity of the process being validated.
Processes are developed according to the design controls in 820.30 and validated according to 820.75. The process specifications, hereafter called parameters, are derived from the specifications for the device, component or other entity to be produced by the process. The parameters are documented in the device master record per 820.30, 820.40 and 820.181. The process is developed such that the required parameters are achieved. To ensure that the output of the process will consistently meet the required parameters during routine production, the process is validated.
The basic principles for validation may be stated as follows:
- Establish that the process equipment has the capability of operating within required parameters;
- Demonstrate that controlling, monitoring, and/or measuring equipment and instrumentation are capable of operating within the parameters prescribed for the process equipment;
- Perform replicate cycles (runs) representing the required operational range of the equipment to demonstrate that the processes have been operated within the prescribed parameters for the process and that the output or product consistently meets predetermined specifications for quality and function; and
- Monitor the validated process during routine operation. As needed, requalify and recertify the equipment.
TERMS AND DEFINITIONS
Terms other than those used herein may be found in the literature.Validation: confirmation by examination and provision of objective evidence that the particular requirement for a specific intended use can be consistently fulfilled.
Process validation: establishing by objective evidence that a process consistently produces a result or product meeting its predetermined specifications.
Installation qualification: establishing documented evidence that process equipment and ancillary systems are capable of consistently operating within established limits and tolerances.
Process performance qualification: establishing documented evidence that the process is effective and reproducible.
Product performance qualification: establishing documented evidence through appropriate testing that the finished product produced by a specified process(es) meets all release requirements for functionality and safety.
Prospective validation: validation conducted prior to the distribution of either a new product, or product made under a revised manufacturing process, where the revisions may affect the product's characteristics.
Retrospective validation: validation of a process for a product already in distribution based upon accumulated production, testing and control data.
Validation protocol: a written plan stating how validation will be conducted, including test parameters, product characteristics, production equipment, and decision points on what constitutes acceptable test results.
WHY VALIDATE PROCESSES
There are many reasons, in addition to the regulatory requirements, for validating processes. A manufacturer can assure through careful design of the device and packaging, careful design and validation of processes, and process controls, that there is a high probability that all manufactured units will meet specifications and have uniform quality. The dependence on intensive in-process and finished device testing can be reduced. However, in-process and finished product testing still play an important role in assuring that products meet specifications. A properly validated and controlled process will yield little scrap or rework, resulting in increased output. Consistent conformance to specifications is likely to result in fewer complaints and recalls. Also, when needed, the validation files contain data to support improvements in the process or the development of the next generation of the process.WHAT PROCESSES SHOULD BE VALIDATED
Where process results cannot be fully verified during routine production by inspection and test, the process must be validated according to established procedures [820.75(a)]. When any of the conditions listed below exist, process validation is the only practical means for assuring that processes will consistently produce devices that meet their predetermined specifications:- Routine end-product tests have insufficient sensitivity to verify the desired safety and efficacy of the finished devices;
- Clinical or destructive testing would be required to show that the manufacturing process has produced the desired result or product.1
- Routine end-product tests do not reveal all variations in safety and efficacy that may occur in the finished devices.2 [RETURN from footnotes]
- The process capability is unknown, or it is suspected that the process is barely capable of meeting the device specifications.
TYPES OF PROCESS VALIDATION
Process validation may be conducted at different points during the life cycle of a product. The types of process validation are defined in terms of when they occur in relation to product design, transfer to production and release of the product for distribution.Prospective Validation
Prospective validation is conducted before a new product is released for distribution or, where the revisions may affect the product's characteristics, before a product made under a revised manufacturing process is released for distribution.Concurrent validation is a subset of prospective validation and is conducted with the intention of ultimately distributing product manufactured during the validation study. Concurrent validation is feasible when nondestructive testing is adequate to verify that products meet predetermined specifications and quality attributes. If concurrent validation is being conducted as the initial validation of a new process or a process which has been modified, product should be withheld from distribution until all data and results of the validation study have been reviewed, and it has been determined that the process has been adequately validated.
Concurrent validation may be conducted on a previously validated process to confirm that the process is validated. If there have been no changes to the process and no indications that the process is not operating in a state of control, product could be released for distribution before revalidation of the process is completed. There is some risk to early release of product in that subsequent analysis of data may show that the process is not validated.
Retrospective Validation
Retrospective validation is the validation of a process based on accumulated historical production, testing, control, and other information for a product already in production and distribution. This type of validation makes use of historical data and information which may be found in batch records, production log books, lot records, control charts, test and inspection results, customer complaints or lack of complaints, field failure reports, service reports, and audit reports. Historical data must contain enough information to provide an in-depth picture of how the process has been operating and whether the product has consistently met its specifications. Retrospective validation may not be feasible if all the appropriate data was not collected, or appropriate data was not collected in a manner which allows adequate analysis.Incomplete information mitigates against conducting a successful retrospective validation. Some examples of incomplete information are:
- Customer complaints which have not been fully investigated to determine the cause of the problem, including the identification of complaints that are due to process failures;
- Complaints were investigated but corrective action was not taken;
- Scrap and rework decisions that are not recorded, investigated and/or explained;
- Excessive rework;
- Records that do not show the degree of process variability and/or whether process variability is within the range of variation that is normal for that process, for example, recording test results as "pass" or "fail" instead of recording actual readings or measurements results in the loss of important data on process variability; and
- Gaps in batch records for which there are no explanations. (Retrospective validation cannot be initiated until the gaps in records can be filled or explained.)
After a validated process has been operating for some time, retrospective validation can be successfully used to confirm continued validation of that process if no significant changes have been made to the process, components, or raw materials.
Statistical process control is a valuable tool for generating the type of data needed for retrospective analysis to revalidate a process and show that it continues to operate in a state of control.
PROCESS VALIDATION STUDIES
Planning the Process Validation Study
Careful planning of a validation study is essential to ensure that the process is adequately validated. The plan should include design reviews. The plan for the validation study is documented in the validation protocol. A copy of the protocol and validation results are placed in the Design History File (DHF) [820.30 (j)] or quality system record file (820.186). The operational, monitoring, and other production-related procedures are part of the device master record (DMR) (820.181). Planning for the validation should include the following elements as well as any other relevant issues that must be addressed to conduct the validation study:- identification of the process to be validated;
- identification of device(s) to be manufactured using this process;
- criteria for a successful study;
- length and duration of the study;
- assumptions (shifts, operators, equipment, components);
- identification of equipment to be used in the process [820.75(b)(2)];
- identification of utilities for the process equipment and quality of the utilities;
- identification of operators and required operator qualifications [820.75(b)(2)];
- complete description of the process {may reference the DMR [820.181(b)]};
- relevant specifications including those for the product, components, manufacturing materials, the environment, etc. [may reference the DMR and quality system files {820.181(a) and (b); 820.186};
- any special controls or conditions to be placed on preceding processes during the validation;
- process parameters to be controlled and monitored, and methods for controlling and monitoring [820.70(a); 820.75(b)(2)];
- product characteristics to be monitored and method for monitoring [820.70(a)(2); 820.75(b)(2); 820.80(c)];
- any subjective criteria used to evaluate the product;
- definition of what constitutes nonconformance for both measurable and subjective criteria;
- statistical methods for data collection and analysis (820.250);
- consideration of maintenance and repairs [820.72(a)];
- conditions that may indicate that the process should be revalidated [820.75(c)];
- stages of the study where design review is required; and
- approval(s) of the protocol.
Installation and Operation Qualification
After process equipment is designed or selected, it should be installed, reviewed, calibrated, challenged, and evaluated to ensure that it is capable of operating within established limits and tolerances as well as throughout all anticipated operating ranges. Installation and operation qualification studies establish confidence that all equipment used in the manufacturing process meets specified requirements and is appropriately designed, constructed, placed, and installed to facilitate maintenance, adjustment, cleaning, and use [820.70(g)].The installation and operation qualification phases of process validation include:
- examining equipment design and supplied documentation;
- determining installation requirements;
- establishing any needed environmental controls and procedures;
- assuring that the work area has sufficient space to perform the processing and associated activities;
- installing the equipment;
- verifying correct installation;
- establishing manufacturing procedures for the monitoring, operation, and control of the equipment including the minimum number of operators;
- determining calibration, cleaning, maintenance, adjustment, and expected repair requirements;
- identifying important elements of the equipment that could affect the output or finished device;
- verifying that the system or subsystem performs as intended throughout all anticipated operating ranges; and
- documenting the above information.
Installation and operation qualifications should include establishing pertinent methods, procedures, and schedules for calibration, cleaning, and maintenance, and establishing a repair parts list for each piece of equipment. Planning for eventual maintenance and repairs can reduce or prevent confusion during emergency repairs which could lead to improper repairs such as the use of the wrong replacement part. Post-repair cleaning, calibration, and re-start requirements should be established if necessary to prevent inadvertent manufacture of nonconforming devices. The objective is to assure that all repairs can be performed in a way that will not affect the characteristics of material processed or devices manufactured after repairs.
Process and monitoring equipment (instruments) should be calibrated at the beginning of the validation study, and the calibration should be checked at the end of the study to establish confidence in the validation of the process. Equipment found out of calibration at the end of a process validation study may indicate that the process has not been operating in a state of control and cannot be considered validated. More frequent calibration or more robust equipment may be necessary, or you may wish to use stand-alone instruments in parallel with the built-in process monitoring equipment.
It is important to document installation and operation qualification studies. Such documentation can substitute for part of the requalification of equipment in future process validation studies. When equipment is moved to a new location, installation and operation should be requalified. By comparing data from the original installation and operation qualification and the requalification, the manufacturer can determine whether there have been any changes in equipment performance as a result of the move. Changes in equipment performance should be evaluated to determine whether it is necessary to revalidate the process.
Process Performance Qualification
The purpose of process performance qualification is to rigorously test the process to determine whether it is capable of consistently producing an output or in-process or finished devices which meet specifications. In entering theprocess performance qualification phase of validation, it is understood that the:- device, packaging, and process specifications have been established, documented, and essentially proven acceptable through engineering, laboratory or other verification methods [820.30; 820.70(a)]; and
- process and ancillary equipment and the environment have been judged acceptable on the basis of installation and operation qualification studies [820.70(g)].
Process and product data should be analyzed to determine what the normal range of variation is for the process output. Knowing what is the normal variation of the output is crucial in determining whether a process is operating in a state of control and is capable of consistently producing the specified output.
Process and product data should also be analyzed to identify any variation due to controllable causes. Depending on the nature of the process and its sensitivity, controllable causes of variation may include:
- temperature,
- humidity,
- variations in electrical supply,
- vibration,
- environmental contaminants,
- purity of process water,
- light, and
- inadequate employee training.
After routine production begins, data derived from monitoring the process and output product can be analyzed for variation and compared to the normal range of variation. Such analyses can detect when the process output is shifting so that corrections can be made before, or soon after, nonconforming product is produced.
Product Performance Qualification
The purpose of product performance qualification is to demonstrate that the process has not adversely affected the finished product and that the product meets its predetermined specifications and quality attributes. Product performance qualification and design validation of initial finished devices are closely related. According to the design control requirements, design validation shall be performed under defined operating conditions on initial production units, lots, or batches, or their equivalents [820.30(g)]. Products used for design validation should be manufactured using the same production equipment, methods and procedures that will be used in routine production. Otherwise, the product used for design validation may not be representative of production units and cannot be used as evidence that the manufacturing process will produce a product that meets pre-determined specifications and quality attributes.Design validation can be conducted using finished products made during process validation studies and will satisfy the need for product performance qualification. Design validation shall ensure that devices conform to defined user needs and intended uses and shall include testing production units under actual or simulated use conditions [820.30(g)]. Original designs and design changes are subject to design control requirements [820.30(i)]. The results of design validation are subject to review under the design control review requirements [820.30(e)].
DOCUMENTATION
The requirements for process validation are described in section 820.75 and include documentation requirements for the process validation study phase as well as for routine production using a validated process. Records of validation activities and results must be maintained [820.75(a)]. Validation protocols and results may be filed in the DHF [820.30(j)] or in the QS files (820.186). Records must include the date and signature of the individual(s) approving the validation and, where appropriate, the major equipment validated [820.75(a)]. Procedures for monitoring and control of process parameters must be established and maintained for validated processes [820.75(b)]. Procedures for the operation, monitoring and control of processes are part of the DMR (820.181).When a validated process is used for manufacturing finished devices, the process must be performed by a qualified individual [820.75(b)(1)]. Records must be maintained of the monitoring and control methods and data; where appropriate, the individual(s) performing the process; the date performed; and major equipment used. The records should be maintained in the DHR (820.184).
REVALIDATION
As long as the process operates in a state of control and no changes have been made to the process or output product, the process does not have to be revalidated. Whether the process is operating in a state of control is determined by analyzing day-to-day process control data and any finished device testing data for conformance with specifications and for variability.When changes or process deviations occur, the process must be reviewed and evaluated, and revalidation must be performed where appropriate [820.75(c)]. Review, evaluation, and revalidation activities must be documented.
Processes may be routinely validated on a periodic basis; however, periodic validation may not be adequate. More important is appropriate monitoring so that if problems develop or changes are made, the need for immediate revalidation is considered.
REFERENCES
1. Guideline on General Principles of Process Validation, May 1987, FDA, CDRH/CDER2. Journal of Validation Technology, Vol. 1, No. 4, August 1995
Saturday, June 5, 2010
The Validation Process
Overview
Introduction | This chapter looks at the validation process. Note: This validation process is used to validate a specific computer system. It may be done on an existing computer system or on a new computer system. |
Purpose | The purpose of the validation process is to provide a high degree of assurance that a specific process (or in this case computer system) will consistently produce a product (control information or data) which meets predetermined specifications and quality attributes. |
The Validation Facets | The validation effort consists of 5 specific facets or processes, each alone, would not constitute a validation. However, depending on the specifics of the application, system or process, would depend on which facets would be required. There following facets are: · The Validation Master Plan (VMP) · The Project Plan · Installation Qualification (IQ) · Operational Qualification (OQ) · Performance or Process Qualification (PQ) |
Types of validation | The two types of validation are: · Prospective validation: the validation of a new system as it is developed · Retrospective validation: the validation of an existing system |
Validation process | The validation process and document references are shown below: | |
Step | Action | |
1 | Establish Team(s) | |
2 | Determine Validation Activities | |
3 | Write the Validation Protocol | |
4 | Specify the System Development Details | |
5 | Perform Qualification Activities | |
6 | Develop/Review Controls and Procedures | |
7 | Certify the System | |
8 | Review Periodically | |
Steps 1 to 8
Introduction | This topic provides an overview of the validation process. |
Step 1: | The first step in the validation process is to establish the System Validation Team and if required the System Validation Steering Team. These are the teams that will be responsible for the validation process. |
Step 2: | The second step in the validation process is to determine and record all of the validation activities that will be undertaken in order to validate the computer system. The validation activities are the exact details or activities that will be required for each of the steps in the validation process. The output from this activity will be the Validation Plan. Example: At step six of the validation process (Develop/Review Controls and Procedures) the exact controls and procedures that will be required to keep the computer system validated will be determined and recorded. Note: The type and number of validation activities will depend on the nature of the computer system that is being validated. |
Step 3: | The third step in the validation process is to write the Validation Protocol. The Validation Protocol describes the procedure and the steps within the procedure that will be followed in order to validate the system. The Validation Protocol must also provide a high level description of the overall philosophy, intention and approach. |
Step 4: | The fourth step in the validation process is to specify the system development details. You should specify to the supplier or developer of a system that they must have: · a good methodology in order to develop a system · a formal quality management system for the development, supply and maintenance of the system You may need to specify to the supplier or developer the types of items you want to see - this could be done in the form of a Quality Plan. These items will help you ensure that the supplier or developer has a good methodology and formal quality management system in place. Examples: Items that will help you ensure a good methodology and formal quality management system include: · quality management procedures · life cycle definition · specifications, for example user requirements specification and functional specification · documentation controls and various items of documentation, for example user manuals and administrator documentation · testing procedures If the computer system is a new one, then the system development requirements will be identified prior to system selection/development. If the computer system is an existing one, then the system development requirements will still be identified and used as a basis against which to evaluate the system. |
Step 5: | The fifth step of the validation process is to perform the qualification activities, which are comprised within the validation process. Some examples of these qualification activities include: · Supplier audit · Specification qualification · Design qualification · Installation qualification · Operational qualification · Performance qualification |
Step 6: | The sixth step of the validation process is to develop/review controls and procedures. If the computer system is a new one, then you will need to develop the controls and procedures, or check the suitability of existing generic procedures applicable to the site or department. If the computer system is an existing one, then you will need to review the controls and procedures and update them if required. |
Step 7: | The seventh step of the validation process is to certify the system. This step is where you certify that the validation deliverables have met the acceptance criteria that were described in the Validation Protocol. When you certify the system you should prepare a validation report. The validation report should outline the details of the validation process. Examples of details that should be outlined include: · what was done and the results that were obtained · any special considerations · whether the validation procedure (as described in the Validation Protocol) was followed · a summary of all documentation that was generated · the location of the validation documentation · the retention period for the documentation |
Step 8: | The eighth and final step of the validation process is to review the system validation periodically. The system should be reviewed periodically to provide additional assurance of validation. There should be documentation outlining the details of how the review is to be done and what the review should cover. The end result of a review should be a summary of the review and a recommendation as to what to do next. |
Timing and Documentation
 |
Introduction | This topic looks at the timing of the validation process and documentation. |
Timing | Ideally, the validation process begins at the inception of the system selection or design process. It then proceeds alongside the system development and is completed prior to implementation of the system. Many aspects of computer systems validation are just "Good Informational Resources (IR) Practice" and as such should occur anyway during the implementation of a system. For many reasons, a system may not have been validated until after it has been in use for some time. The basic validation process is the same as for a new system. The timing of some of the validation activities may, however, differ. Note: Retrospective validation is becoming increasingly unacceptable to regulatory inspectors. New systems should be validated before use. |
Timing for a new system | The steps in the validation process, and their associated validation activities are performed in parallel with the system development life cycle and reference the development documentation as it is produced. |
Timing for an existing system | For existing systems, the validation activities will still follow the development life cycle but will reference the development documentation retrospectively. |
Example | An example of the parallel between system development and validation activities is shown below. * Functional Specification can comprise mechanical, electrical and software functional specification for systems embedded in equipment ** Systems embedded in equipment with significant control and monitoring instrumentation *** Testing carried out by supplier can form part of subsequent qualification activities if adequately controlled. This can help reduce the amount of testing needed later, particularly at operational qualification. |
Documentation | Every step in the validation process, and the activities within the steps, requires documented evidence that the steps or activities have been completed. The table below shows the documents that must be generated at each step. Note: In some cases some of these documents may not be required. |
Step | Action | Documents Generated |
1 | Establish Validation Team(s) | · Team Charter · Terms of Reference · Role Definition · Team Organization Chart |
2 | Determine Validation Activities | · Validation Plan |
3 | Write the Validation Protocol | · Validation Protocol |
4 | Specify the System Development Details | · Systems Development Life Cycle documentation |
5 | Perform qualification activities | · Supplier Audit Report · In-house Audit Report · Source Code Review Report · Specification Qualification Report · Design Qualification Report · Installation Qualification (IQ) Protocol · IQ Results · IQ Summary Report · Operational Qualification (OQ) Protocol · OQ Results · OQ Summary Report · Performance Qualification (PQ) Protocol · PQ Results · PQ Summary Report |
6 | Develop/Review Controls and Procedures | · SOPs (Standard Operating Procedures) · Training procedures · Training records |
7 | Certify the System | · Validation Report · Validation Certification |
8 | Review the System Validation Periodically | · Periodic Review Procedure · Periodic Review Audit Report |
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