Objective for Pharmaceutical Facility Qualification:
To describe the procedure for Qualification of Classified areas.To define a procedure for qualification of pharmaceutical Manufacturing, Packaging, Storage and Testing facility prior to manufacturing or testing of commercial pharmaceutical products.
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Scope:
This SOP is applicable to qualify and validate all the Pharmaceutical Facility/Areas where processing, storage, packaging and microbiological testing of pharmaceutical products are carried out and supporting areas such as change rooms, corridors, airlocks, etc. at your company.
Responsibility:
| Designation | Responsibilities |
| Officer/ Executive/ Designee of Quality Assurance Department | Responsible to prepare area qualification protocol and report. To execute qualification in co-ordination with other departments. Responsible for SOP Preparation, Checking, Distribution, Retrieval, Approval. Training and effective implementation of this SOP in all the applicable areas. Responsible to ensure Facility/Area is qualified as per the protocol. Responsible to be a part of qualification team and coordinate with representatives of other departments for qualification efforts. Responsible for checking of the raw data of the qualification. Responsible for the Issuance of number for qualification documents. |
| Officer/ Executive of Engineering department | Responsible for the Execution of Facility Qualification activity as per SOP. Responsible to assess the qualification requirement of Facility/Area. Responsible to be a part of qualification team and jointly share the efforts. Responsible to execute, record and certify the tests which needs engineering measurements. Responsible to provide inputs while the preparation of protocol. Responsible for checking & verification of the raw data and complies as per protocol. |
| Officer/ Executive of Production Department | Responsible to provide area as per qualification planner for Execution of Facility Qualification activity as per SOP. Responsible for checking possible impacts on process coming through facility qualification exercise. |
| Head/ Designee of Quality Control/ Microbiology Department | Responsible to assess the qualification requirement of Facility/Area. Responsible tobe a part of qualification team and jointly share the Quality aspects. Responsible to contribute by testing and record the results during Facility/Area qualification. Responsible to provide inputs while the preparation of user requirement. Responsible for providing microbiological analytical support to facility qualification review & exercise. |
| Head- Quality Assurance Department | Responsible for the Approval of area qualification protocol and report. Responsible to provide inputs while the preparation of protocols. Responsible to ensure implementation of procedure as per SOP. |
Procedure for Pharmaceutical Facility Qualification:
Definitions:
Qualification: Qualification is an act of planning, carrying out and recording of tests on Facility/Area which will form part of the validation process to demonstrate that it will perform as intended or designed.
Facility Qualification:Facility Qualification is the process by which the suitability of the facility in which the products are manufactured is examined and documented.
Area Qualification: It is the documented procedure to show that the Product/ Process, cGMP, regulatory guidelines, safety, security access, Environmental guidelines have been followed during the installation, or changes has been made in the area as per the URS.
User Requirement Specification (URS): It describes what the Facility/Area is intended to do and all essential requirements such as Dimension, location, surface finish, material of construction, environmental parameters etc.
Room Data Sheet: defines technical specifications for cleanrooms and areas, capturing construction, environmental, and utility parameters (e.g., room size, HEPA filters, temp/RH, pressure, air changes) for verification. It serves as a benchmark for installation (IQ) and operational (OQ) qualification to ensure GMP compliance.
Design Qualification (DQ): Establishing documented evidence that the user requirement, which include establishment of critical operating or operational parameters or specifications before the final design is agreed, have been met. It is performed after these requirements have been incorporated in to the detailed design document.
Installation Qualification (IQ): Establishing documented evidence that the Facility/Area is installed according to design documents.
Operation Qualification (OQ): Establishing documented evidence that the Facility/Area performs as intended throughout all specified ranges.
Performance Qualification (PQ): Establishing documented evidence that Facility/Area is capable of performing consistently (during multiple cycles or extended periods) to give an outcome that meets predetermined specifications.
Re-Qualification: Re-confirming that the Facility/Area are meeting the predetermined acceptance criteria after major change in the parameters.
Protocol: A written, approved plan stating how qualification/validation will be conducted. It includes design, requirements, specifications, test parameters, product characteristics, required Facility/ Area/ Equipment and procedures and relevant acceptance criteria.
General Procedures – Pharmaceutical Facility Qualification
For new Facility/Area, change request shall be initiated and impact assessment (if applicable) to be performed prior to initiation of the validation procedure.
The approach taken towards Qualification/Validation activity shall be based on rationale/risk assessment.
User shall prepare the qualification document using the formats provided in this procedure.
Acceptance criteria shall be adequately defined to enable confirmation that they are attained.
During preparation of Layout or requirement of design of Area, Area code number shall be allocated The documents shall be pre-approved by the Qualification team before being used for execution and also post approval will be done by the qualification team after execution.
The test execution during qualification shall be either carried out by or witnessed by qualification team.
A post execution review shall be done by the Qualification team to ensure that all the tests have been carried out, all deviations (if any) has been addressed properly and the Facility/Area qualification is successfully complete.
Any modification/ improvement in area is carried out after taking approval from Drug Regulatory authorities (if necessary).
Civil, electrical, mechanical, HVAC, flow of material and man is considered while making protocols for qualification. The specification, verification and challenge procedure for size, suitability is considered.
Nominate qualification team and draft the protocol for the area under modification/new area.
A qualification activity that centres on area is referred as area qualification. New Area qualification is divided into 5 parts that is User Requirement Specification (URS), Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ) & Performance Qualification (PQ).
User Requirement Specification (URS), Design Qualification (DQ), Installation Qualification (IQ) are prepared for one time in the life of area except PQ. PQ shall be repeated after scheduled interval throughout the life of the area. But if the area is modified/extended, then based on the modification requalification (IQ, OQ& PQ) shall be performed. User has to decide the criteria for requalification based on the criticality of occasion.
Qualification consists of following steps:
User Requirement Specification (URS)
Design Qualification (DQ)
Installation Qualification (IQ)
Operational Qualification (OQ)
Performance Qualification (PQ)
User Requirement Specification (URS) for Pharmaceutical Facility Qualification:
The User requirement specification shall be prepared by the user department in coordination with Engineering and QA department.
The URS shall describe the essential requirements such as dimension, location, surface finish, material of construction, environmental parameters etc. by considering regulatory cGMP requirements, safety, process and product requirements.
This is listing of requirements considering Good Manufacturing Practices (GMP),volume, flow etc.
Room Data Sheet (RDS):
Room data sheet shall be prepared after finalizing the area, which includes the general construction, environmental, and utility parameters (e.g., room size, HEPA filters, temp/RH, pressure, and air changes) for verification.
Design Qualification (DQ):
The Design Qualification protocol cum report shall be prepared by the user /QA department in coordination with Engineering, EHS and QA department.
For DQ first make the necessary diagrams or layouts if any required and write down the specification with the help of user requirement specification by considering regulatory requirements, cGMP requirements, architectural requirements, utilities requirement, accessories required, safety, process and product requirements.
The Design Qualification protocol shall be prepared for each Area based on user requirement.
Pre approvals of concerned persons mentioned in protocol shall be taken and then execute the protocol. The compliance of the design with cGMP and also with the specification shall be demonstrated and documented.
Once design qualification is over, purchase order shall be released to vendor/contractor along with the specification.
Civil Consideration: Dimensions of area, nature of constructions and finishes of wall, floors, and coving, doors (Size, type), view panel etc. Consider slope, types of floors, joint epoxy/ polyurethane (PU) of entire floor or joint filling.
Electrical Works:
Wiring, Lighting, Power, Switches.
Consider types of wire / cable, types of light (intensity, lux level, location) as per requirement.
Air Handling System: Consider room occupancy, classification, grade, heat load, pressure differentials, temperature, and humidity.
Service/ Utilities: Compressed Air consider volume, flow rate, pressure etc., Potable/ Purified/ Chilled water, Vacuum etc.
Sanitation:
Dust generation, method of cleaning, level of cleanliness etc.
Drains: Avoid drain, however if required decide number, size and design.
General Requirement: Man, movement and material flow, Environmental condition, pass box, Change room etc.
Installation Operation Qualification (IOQ)– Pharmaceutical Facility Qualification
Itconsists of Installation as well as operational qualification of area/facility.
Installation Qualification (IQ):
Installation qualification (IQ) shall be performed on new or modified Facility/Areas.
Installation of Facility/Area, piping, services and instrumentation shall be checked to current engineering drawings and specification.
Verify the construction and design criteria at this stage.
The installation qualification shall certify and demonstrate cGMP compliance and documented.
During Installation Qualification it shall be ensured that the Facility/Area and supporting utilities have been built & installed in compliance with their approved design specification (DQ).
Civil Considerations:
Dimension of area: Ensure that the air leakage through openings or penetration is kept to a minimum during construction.Ensure that area is designed as per design specifications.Check the dimension of the room (length, width, and height in meters/ metric system).
Walls: Verify the wall material used.Ensure that wall is free from cracks and crevices.Ensure that wall have smooth surfaces and easy to clean.Ensure usage of appropriate paint (Quality, colour, grade, number of coatings).
Floors: Verify the flooring material used.Ensure floor to wall corners have smooth coved surfaces.Ensure that no crevices are found on the floor.Ensure slope has easy flow of water towards drain where ever it is required.Ensure that floor surface in the area is easy to clean. Ensure stone joining epoxy or cement is used as per requirement.
Ceiling: Verify the ceiling material used.Ensure that no cracks/ gaps on ceiling, at light fixture. Check type of paint applied (Synthetic enamel/ Oil bound distemper).Ensure that ceiling to wall corner have smooth coved surfaces.
Coving: Ensure Polyurethane (PU) is used between floor and wall for coving. Ensure that skirting is flushed with wall (150 mm).
Doors: Ensure design and arrangement is such that minimize migration of particulate and other contaminants into the controlled process area. Material of construction, i.e. Aluminum frame with partly laminated bison and partly glazing. Requirements of number of doors as per area. Check that proper direction stickers are provided in all door, i.e. (Push and Pull).Ensure that no projection or crevices between frame and wall surface.
View Panel: Ensure that it is properly sealed to prevent dirt accumulation.Check the material of construction, as per design. Check single/ double glass, colour of glass, type of glass, type of glass as per requirement.Check the requirement of number of view panel as per area.
Electrical Works:
Wiring, Lighting, Power, Switches.
Consider types of wire / cable, types of light (intensity, lux level, location) as per requirement.
Make all drawings.
Wiring: Verify all the electrical cables present in the room are concealed. Ensure joints between electrical sockets and wall surface is cover.
Lighting: Number of light fixtures based on the area requirement. Check the unit of lux and compare with the standard for each room.
Power: Location of the connections and its voltage and phase.Check the location of plug point with the design specification.
Air Handling System: Check the number of inlets air grills required as per area. Hang the ducting with suitable support. Verify the insulation, joints, no leakage/ gap is visible. Ensure that all processing have negative pressure with respect to internal corridor.
Services/ Utilities:
Compressed Air: Check the number of points as per required area. Ensure the material of construction of pipe and verify the size.
Potable Water/ Purified Water/ Chilled Water: Check the number of points as per required area. Ensure the material of construction of pipe and verify the size. Ensure that no any leakage found.
Safety: Ensure that emergency door is accessible in the area and marked with separate label. Ensure that fire extinguisher is accessible in the area. Information regarding first aid box in the area.
Sanitization: Ensure that the area is cleaned.
Drains: Check number of drain points and type of drain trap as per area requirement. Check the slope for water draining.
General Requirement:
Man, movement and Material flow: Check the entry and exit for man and material flow.
Pass Box: Check number of pass box and its type static or dynamic as per requirement.
Operational Qualification (OQ):
Operational Qualification (OQ) shall be performed after completion of Installation Qualification along with the supportive documents such as drafted SOPs etc. (if any).
Tests that have been developed from knowledge of product, process, maximum manpower and equipment design/size/operation/cleaning/maintenance.
Tests to include conditions encompassing upper and lower limits of operation.
Development of operating and cleaning SOPs and maintenance schedule.
The successful operational qualification shall be well demonstrated and documented.
Proceed the following checks in Operation Qualification:
Civil Considerations
Electrical Works
Air Handling System
Services/ Utilities
Safety
Sanitation
Drain
General: Airborne Particle Count, Air Flow Velocity (unidirectional), Air Flow Rate (non- unidirectional), Room Air Change rates, Air Pressure Difference Test Each Day, Installed filter leak test, Airflow Direction/ Visualization, Temperature & Humidity Each Day, Recovery Test and Microbial Levels Each day.
Demonstrates and document that the area is ready as per the approved design.
Make protocol of IOQ accordingly, get approved. Challenge, verify and document in the form to report.
Performance Qualification (PQ) – Pharmaceutical Facility Qualification
Performance Qualification shall be performed after successful completion of Operational Qualification and effective SOPs and maintenance schedule etc. (If any).
Tests for environmental parameters/conditions (Physical and microbiological) and utility/services supply.
Tests to include a condition or set of conditions encompassing upper and lower operating limits.
Challenge tests if any shall be performed based on scientific rationale.
Perform the qualification of Facility/ Area as per approved protocol. Persons involved in performing the qualification and testing shall be trained prior to performing the qualification/tests.
Demonstrates by the execution of a series of tests that the area meets the predetermined specifications & ready for the intended use. The performance qualification will also include testing that demonstrates that all the set criteria can be met.
Note: The performance qualification protocol for area can only be executed after the Installation and Operational Qualification protocols have been completed and report concluded.
Test to be performed by External Agency: Viable Count, Pressure Differential & Temperature Monitoring, HEPA filter integrity test, Recovery Test, Air Flow Pattern & ACPH.
Performance Qualification of Facility/ area shall be done.
Re-Qualification – Pharmaceutical Facility Qualification:
Requalification after major changes in Facility/Area, change in critical attributes of HVAC.
Addition or removal of major equipment resulting in civil work of Facility/Area.
Re-qualification after major changes: Shall be carried out when any major changes in Facility/Area is done, when there is change in critical attributes of HVAC, when there is addition or removal of major equipment is done resulting in civil work of Facility/Area. The extent of Re-qualification after the change shall be justified based on risk assessment/scientific rationale of the change.
Note: For Re-qualification purpose use the protocol formats as specified in the annexure of this SOP for qualification.
Abbreviations:
SOP : Standard Operating Procedure
No. : Number
QA : Quality Assurance
DQ : Design Qualification
IOQ : Installation Operation Qualification
IQ : Installation Qualification
OQ : Operational Qualification
PQ : Performance Qualification
GMP : Good Manufacturing Practices
ACPH : Air Changes Per Hour
HEPA : High- Efficiency Particulate Air
HVAC: Heating Ventilation and Air Conditioning
URS : User Requirement Specification
EHS : Environmental Health & Safety
cGMP : current Good Manufacturing Practices
Change history:
| Effective Date | Nature of revision | Change Control No. | Reason for Revision |
Reference (s):
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