Standard Operating ProcedureTitle:Design Qualification Guidelines
responsibilities for both the technical and cGMP compliance review of the design should be clearlymandated.
It is crucial to start off with a User Requirement Specification (URS) for the project. It ensures thatthe user has defined exactly what is required, by specify operating and output requirements, anycritical control requirements and any internal and regulatory standards, which may apply. All
Requirement Specification documents should be approved by appropriate stakeholders including thequality group for GMP compliance, and used as primary referenced document in the design reviewprocess. SeeSOPVAL-030.
Once compiled, this information will provide the project team with a basis for discussions andclarification of the system through the design phase of the project and to enable functionalspecification to be drawn up and reviewed.
2.1.Design Qualification Process
The Design Qualification process should address the following points:
What will be reviewed? (Documented in Validation Plan or DQ protocol)
What methods or approach will be followed?(Documented in Validation Plan or DQ protocol)List of documents to be reviewed and consulted(Documented in Audits report or in design review
minutes)
List of members involved inthe DQ review session(Documented in Audits report or in design
review minutes)
Conclusions and actions required(Documented in DQ protocol)
The level of Design Qualification applied to any design should be based on a consideration of thecomplexity and novelty (to the user) of each system, and the impact of each system on the productquality. (SeeSOPVAL-045., section 3.1 and 3.2 for a list of questions assess whether anItem/Function has a “Direct or Indirect Impact” on the quality of a product/process).
SuiteFinishing LineRecorderSYSTEMIMPACT(sterile)Production HVAC(non sterile )Supply OF NOVELTYHighly complex, “Direct Impact” system, warrant a greater degree of scrutiny than simple, familiarsystem of no impact.2.2.
Selecting a Design Qualification Review Method
The Project Manager or Project Coordinator will determine the most appropriate review method,based on the system impact, complexity and novelty. Below are few approaches that may beapplied during the Design Qualification, but not limited to:
Review the Functional and Project Specifications against the URS and manufactureliterature.
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Standard Operating ProcedureTitle:Design Qualification Guidelines
Will an alarm system be activated if air pressure differentials are outside limits?Have dust and process extracts been considered in the air balance?Will the critical openings be protected by interlocked doors?
Do the specifications for the upper acceptable limit for particles of defined size meet cGMP?Do the specifications for the upper acceptable limit for viable organisms meet cGMP?Will ductwork be clearly identified?
Are the commissioning tests clearly explained?Will commissioning method statements be provided?Are the validation tests clearly explained?Will all instruments be calibrated?Will all instruments be calibratable?Will calibration certificates be provided?Will the design facilitate maintenance?Will the design facilitate cleaning?Will as-built drawings be provided?
Will manuals covering operation be provided?Will manuals covering maintenance be provided?
Will the cleaning method be clearly specified?
The responses to these aspects should be documented in detail and a list of deficiencies, remedialactions and issues for resolution produced.
5.Appendix 2– HAZOP
HAZOPrefers to a formal and structuredHazard andOperability study. It is a systematic anddetailed study following a preset agenda and involving a team with a variety of backgrounds andresponsibilities. It involves an examination of the possibility and consequences of deviations fromnormal or acceptable conditions in an attempt to ensure all possible EHS risks and risks to productquality are foreseen and addressed.
For each operation or activity associated with the system a list of possible deviations is considered.For each possible deviation, the severity and likelihood of the deviation is assessed and, if
warranted, the issue is listed as a problem to be solved. A list ofkeywords is used as prompts forthe HAZOP team. The key words used in a HAZOP will vary depending on the nature of the systemunder analysis. However, if a keyword is not relevant it will take little extra time to dismiss it.
Whereas, if a keyword is left out, the risk of missing a deviation is increased. Refer to section 5.2 foran HAZOP example.5.1.
KeywordsVariableTimingPositionDirectionSpeedFlowLevelPressureTemperatureHumidityCopyright©www.gmpsop.com. All rights reserved
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oo Close, Wrong OrientationGuide WordStandard Operating Procedure
Title: Design Qualification Guidelines
6.
Appendix 3– Failure Mode Effect Analysis (FMEA)
The principle of FMEA is to consider each mode of failure of each component in turn and determinethe effects. The FMEA can be undertaken from the perspective of system operation, product qualityor EHS but not all three at once. For example, a component whose failure will cause significantdowntime, but has little effect on the product, will have high severity consequences for systemoperation but not for product quality.The Table below is a sample Assessment.Function
Modes
Cause
DetectionMethodof thesecausesdetectable
Failure
Probability
Probability
Factor
Onefunction
failuremodes
causesfor eachmode?
/ severity offailure?
probable isthis failurecause?
can we beof detectingthe failurecause?(3-1)of risk doesthis
represent?
(1-3)(1-3)The severity factor score will highlight the major risks and the priority in addressing them. Forexample; a failure that has low severity consequences, that is unlikely to occur and has a high
probability of detection has a severity factor of 1 (1x1x1). Whereas, a frequent, undetectable failureof severe consequences has a severity factor of 27 (3x3x3).
7.Appendix 4- Risk Assessment on Product Quality
Risk Assessment on Product Quality evaluates the impact of the system on product quality on areasthat have a Direct and Indirect function. The key product quality attributes to be considered are:
IdentitySafetyEfficacyPurity
The risk assessment process allows for early actions to be implemented during the implementationphase to reduce and eliminate risk during the project life cycle.7.1.
Overall Approach1.
The first step is the determination of whether the system function or sub-function
represents a risk when assessed against a series of GxP criteria. (SeeSOPVAL-045.section 3.1 and 3.2.)
Having determined that a particular function or sub- functions may have a direct andIndirect GxP associated with it, the assessment should proceed to identify the variousrisk scenarios. It is useful to consider for each event what is the likely effect will be(note that each event may have more than one effect).
For each Event consider thelikelihood (frequency or probability) of it occurring. Assigna ranking to the likelihood of low, medium or high. Where the likelihood is unable to beestimated, assign a ranking of high. The GAMP4 suggested method of frequencyranking is
Low– The Frequency of the event occurring is perceived to be once per tenthousand transactions (1 in 10,000).
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2.
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