Need of Qualification
- To manufactured a quality product
- Proof “suitability for intended use”
- Regulatory requirements
- Cost effective
To Initiate the qualification of pharmaceutical equipment a frame work before startup is required:
- Defining User Requirements (URS) Defining Functional Requirements for given User requirements (FRS)
- Defining Design based on URS & FRS (DQ)
- Factory Acceptance Test at the site of manufacturer (FAT)
- Site Acceptance Test at the site of user (SAT)
- Installation Qualification (IQ)
- Operational Qualification (OQ)
- Performance Qualification (PQ)
User Requirement Specification
User Requirement Specifications consist of Design Specifications and Functional Specifications. Design Specifications provide explicit information about the design requirements for equipment e.g. the dimensions, material of construction, layout, etc. Functional Specification denotes how each feature of the equipment/system must function.
User Requirement Specifications, which consist of design and functional specifications for the equipment, verified with the actual equipment details (design and functional) offered by the Supplier. This is called Design Qualification and this is a documentation activity and recommended to be completed before the PO is placed.
Factory Acceptance Test (FAT)
- Checks for completeness of installation.
- Verification of URS with the actual.
- Proof of functionality, by either a conventional function test or by simulation.
- Verification of documents (availability and quality).
- Overall Review/Inspection.
The Factory Acceptance Test is to be conducted to:
- Ensure that the equipment/instrument/system operates correctly and is of high quality and integrity.
- Establish confidence that the equipment/instrument/system performs as expected under the full range of foreseeable conditions.
- Ensure that the initial set of out-of-the box failures have been eliminated prior to shipment.
- Eliminate the need to modify, adjust, and replace faulty components without fabrication shop support.
Site Acceptance Test (SAT)
- Verification of equipment design
- specifications of received equipment at the site of User by received documents/drawings from Manufacturer / vendor
- Physical verification
Installation qualification test consist of checking of:
- Presence of all components of the equipment against the specification described in Design Qualification and/ or manufacturers’ specification.
- Damages to the component.
- Design features of all critical component e.g. dimension, make, model, Material of Construction etc. against the Design Qualification specification and/ or manufacturer’s claim.
- List of Instruments requiring qualification
- Utility connection against applicable specification.
- Availability of required documents i.e. instruction manual, drawings etc.
- Verification of drawings
- Assembly of components against the manufacturer’s recommendation.
Installation Qualification to be re-qualified incase of:
- Shifting of the equipment from one location to another(excluding portable type).
- In case of major modification or to address the qualification of newly added component
IQ is to be executed typically against a pre-approved protocol, and all the results are to be compiled and summarized.
- OQ specifically tests each function of the system e.g., unit operational functions, specific equipment functional testing, etc.
- To ensure that the intended tasks will be performed when the system is adjusted and operated throughout the recommended operating ranges.
- The OQ execution process provides an assessment of the system operation.
- The OQ phase includes calibration/testing of the instruments.
- For instruments such as dial type gauges, load cells, etc., where there is possibility of malfunctioning due to improper installation/transportation calibrated at site during OQ.
- The IQ protocols have a provision to identify such instruments, which requires calibration.
- The other goal of OQ is to confirm that the system can sequence through its operating steps, and that key process parameters or functions are checked, to ensure that they are in compliance with the operating specifications. Once the results of the IQ execution have been reviewed and approved, the OQ execution can begin.
- During OQ, if any calibration activities are undertaken by an external agency, the calibration reports of such activity reviewed by site representative for compliance to laid down specifications.
- Such external agency reports/ data from the part of calibration data and qualification report.
- Any change(s) made to the system/equipment during the OQ documented in the OQ report. Any changes proposed after the OQ (During PQ or routine manufacturing) managed through change control SOP.
- A draft Standard Operating Procedure for operation & preventive maintenance (wherever applicable) of the equipment, instrument & system prepared before/during the Operational Qualification. The draft Standard Operating Procedure for operation approved and effective before the performance qualification is initiated.
Operational Qualification to be re-qualified incase of:
- Shifting of the equipment from one location to another (excluding portable type).
- In case of major modification or to address the qualification of newly added component RQ be initiated (RQ is referred in a separate section).
OQ is executed against a pre-approved protocol, and all the results are to be compiled and summarized.
The PQ integrates procedures, personnel, systems, and materials to verify that the pharmaceutical grade utility, environment, equipment, or support system produces the required output. This output may be Product or product contact utility (clean compressed air, Purified water, etc.) or environment (HVAC system).
The testing philosophy, during designing of protocols, are governed by following principles, and explanations enumerated here under,
- Each system, and equipments in particular have many variables, and they have relationship w.r.t. to equipment, process (unit operation) and formulation / Product. This relationship that can be strong to weak, or not applicable from the basis for PQ verification steps.
- Variables related to equipment investigated during PQ as specific tests or Load Trials as designed in the protocol.
- The process measures, which are actually dependent on the formulation characteristics, and combination of interactions of process and formula, tested as a part of process validation exercise. For example achieving of Blend Uniformity (BU) of Blend in Qualification of the Blender is more a process and type of formulation variables having strong relation to process and formula.
- Further as applicable, capacity and occupancy also determined to cover edge failure cases.
- All equipments coming in to direct contact with product(process steps and primary packing), can contribute adversely, if cleaning procedures are not adequate, hence during PQ, the fundamental elements of base line data, required for Cleaning Validation program, like Total Contact surface area, established. Also equipment cleaned as per the SOP, and verification done, for cleanliness by visual criteria. This ensures that basic, elements verification during PQ, and builds a “Procedures to obtain base line/input data, for the cleaning validations program matrix.
Pre-requisites to PQ execution are:
- Availability of approved OQ Report
- Availability of effective SOPs for operation, calibration, cleaning, maintenance of the said equipment
- Training of relevant personnel
- Updation of Calibration & PM Schedules
- Completion of PLC Validation
- Training on GDP for external vendor, if vendor is executing the protocol
Acceptance criteria should be clearly indicated within the PQ document.
The PQ is the final stage of qualification, which demonstrates how equipment/system will perform under simulated or actual production or operating conditions. This series of tests is designed to demonstrate that the equipment/system is capable of consistently operating and manufacturing product of specified quality in the worst case. This phase can only be undertaken once the operating parameters have been defined and approved.
Performance Qualification to be re-qualified incase of:
- Replacement of existing instrument / component in the equipment with a new one, which can have a direct impact on the performance of the equipment.
- Any major modification to the existing Equipment/System, which can affect the performance of the equipment.
- If system is found to be malfunctioning during performance qualification.
PQ executed in a pre-approved protocol
Re-Qualification is an activity involving complete or portions of ‘elements’ of qualification activities, like IQ, OQ and PQ.
Re-Qualification carried out for one or more of the following reasons:
- To address deficiencies observed in an executed qualification
- Need for additions in qualification test criteria
- To qualify changes done in the equipment or a process involving the equipment
- Findings/Recommendations from Inspections/Audits/ PQR, etc.
- Inputs from Preventive Maintenance/Calibration Program
- Equipment Up-gradation
In addition to testing the elements impacted by the changes or qualification parameters found to be deficient, all critical components of the equipment verified for functionality during Re-Qualification.