Qualification in pharma
Purpose
To lay down the procedure to prepare, review, approve
and execution of equipment/ instrument/utility qualification protocol and
report.
Responsibility
Head/Designee of concern department Preparation of URS
for the respective equipment/Instrument/utility.
Preparation of FAT and SAT documents (protocols and
reports).
To execute the FAT activity for the respective
equipment/instrument/utility at vendor site.
To execute the SAT activity for the respective
equipment/instrument/utility at manufacturing site.
Preparation of Operational Qualification protocol and
report of respective equipment / instrument / utility in coordination with QA
and engineering department.
Review of URS, DQ, FAT, SAT, IQ, OQ, PQ and RQ
documents (protocol and report).
Head/Designee-ENG: Assistance in
qualification of equipment/instrument/ utility.
Preparation of design specification sheet and
installation qualification protocol and report of respective equipment /
instrument / utility in coordination with vendor and concern departments.
To execute the FAT activity for the respective
equipment/instrument/utility at vendor site with concern department.
To execute the SAT activity with concern department at
manufacturing site.
Review of URS, DQ, FAT, SAT, IQ, OQ, PQ and RQ
documents.
To provide necessary support and utility to execute
qualification activity.
Executive/Designee- QA: Preparation of
Performance qualification protocol and report of respective equipment /
instrument / utility in coordination with concern departments.
To execute the FAT activity for the respective
equipment/instrument/utility at vendor site with concern department.
To execute all qualification activity for the
respective equipment/instrument/utility at manufacturing site with concern
department.
Review of URS, DQ, FAT, SAT, IQ, OQ, PQ, RQ Protocols
and reports of respective equipment/instrument/ utility.
Preparation of qualification schedule of equipment/
instrument/utility.
Head/Designee- EHS: Review of URS and
other documents wherever applicable.
Head/Designee- QAD: Review and approval
of URS, DQ, FAT, SAT, IQ, OQ, PQ, RQ Protocols and reports of respective
equipment/instrument/utility.
Procedure:
Definition
Qualification: Qualification is
the act of planning, executing and recording of tests on equipment and
instrument, which form part of the validated process, to demonstrate that it
works correctly and leads to the expected results.
User Requirement Specification (URS): A requirement
specification that describes what the equipment or system is supposed to do,
thus containing at least a set of criteria or conditions that have to be met.
URS comprises a broad set of requirements or “wish list” that could be met in
order to satisfy equipment or a utility need.
Design Qualification (DQ): The initial phase of
qualification in which specifications and requirements are developed and
established. Design qualification is documented evidence that the proposed
design of the equipment and instrument are suitable for intended purpose. The
compliance of the design with various standards like cGMP, safety, etc., shall
be demonstrated and documented.
Factory Acceptance Test (FAT):
Pre-delivery equipment testing designed to establish confidence that the
equipment and ancillary systems will meet functional requirements, and is
capable of consistent operation. FAT is performed at the supplier site, and the
results are used to release the equipment for shipment.
Installation Qualification (IQ): Installation
qualification is a documented verification that the equipment and instrument as
installed or modified, comply with the approved design and manufacturer’s
recommendation. Documented verification that determines whether all necessary
equipment components were delivered and correctly connected, and installed in
an environment suitable for required operation based on the manufacturer’s
requirements (e.g., voltage, frequency, temperature, humidity, space, etc.)
Operational Qualification (OQ):
Operational qualification is a functional testing to ensure that each component
of a system perform as intended within the representative/ anticipated
operating range according to functional specification. Documented verification
which determines that equipment performs as expected throughout its entire
operating range.
Performance Qualification (PQ):
Performance qualification confirms that the system is capable and performing/
controlling activities of the process as intended according to URS in a
reproducible manner while working in specified operating environment.
Re-qualification (RQ): Equipment,
utilities and instrument should be evaluated at an appropriate frequency to
confirm that they remain in a state of control.
Preventative Maintenance: A maintenance system designed
to detect and prevent problems before they occur.
Qualification protocol: A written
procedure that states how qualification testing will be conducted, including
test parameters and acceptance criteria.
Qualification Approach:
The SOP is applicable to qualify the following:
Major manufacturing process equipment.
Analytical equipment/instrument.
Major supporting utilities.
Qualification shall normally be done in following
stages/phases (but not limited to):
URS
Design Qualification (DQ).
Factory Acceptance Test (FAT).
Site acceptance Test (SAT).
Installation Qualification (IQ).
Operational Qualification (OQ).
Performance Qualification (PQ).
Re-qualification (RQ)/Re-validation, as applicable.
User Requirement Specification (URS): User requirement
specification comprises a broad set of requirements or “wish list” that could
be met in order to satisfy equipment or a utility need.
URS includes the following wherever applicable, but not
limited to,
Desired operational requirement
Process controls
Technical specification of major components
Instrument and controls.
Safety features
MOC
Documents requirements.
URS shall be prepared. Content of URS shall be as per
format but not limited to and can be added or updated as per requirement.
After the approval of the URS the engineering
department shall prepare design specification sheet for respective equipment or
instrument.
Engineering department shall ensure safety requirements
during procurement and during qualification of the equipment.
Identification and selection of suppliers/
manufacturer/ vendor of the equipment/instruments by engineering or purchase
department.
Purchase Indent shall be raised by user department
which shall be approved by Head-concern department followed by
Head/Designee-QAD.
Purchase order shall be prepared by purchase
department.
After approval of Purchase order, a change control
system is in place to ensure that any proposed change is reviewed, before
implementation to assess their impact on validated systems.
Design Qualification:
The “next element is DQ” which serve to ensure the
compliance of the design with GMP and should be “demonstrated and documented”.
It also states the “requirements of the URS should also be verified during the
design qualification”.
Equipment especially if incorporating novel or complex
technology, may be evaluated, if applicable, at vendor site prior to delivery.
Design qualification shall be prepared by the
engineering department on the basis of vendor / supplier documents and
recommendation for protocol and for report but content is not limited to and
can be added or updated as per the requirement.
DQ shall be further reviewed by Engineering, User
department and Quality assurance and approved by Head/Designee-QAD.
DQ includes the following, wherever applicable, but not
limited to:
Basic design
Critical component
MOC
Safety features
Requalification criteria
Deficiency and corrective action
Change Control
Document requirement
Factory Acceptance Test (FAT): FAT
wherever applicable shall be done ABC Limited representative at vendor site.
For FAT, Engineering/QA/User department personal shall
visit vendor site for Factory Acceptance Test to confirm that the
equipment/instrument and fabrication as per design specification.
In case of any deficiency found during FAT, the same
shall be recorded in the FAT report with corrective action.
After approval of FAT report,
equipment/instrument/utility shall be transferred to ABC Limited site.
Site Acceptance Test (SAT):
Once the equipment/ instrument/Utility shall deliver at
the ABC Limited premises, then the Engineering/QA/User department personnel
shall perform SAT for verification of design specification at the site and any
damage to the equipment/instrument/utility during transport. Checklist can be
updated as per
the requirement.
In case of deficiency during SAT shall be recorded in
the SAT report with corrective action as per format.
Installation Qualification (IQ):
Installation qualification is defined as documented
verification that the equipment/instrument/utility, as installed or modified,
comply with the approved design, manufacturer’s recommendations and or user
requirements.
IQ shall be prepared by engineering department but the
contents shall not be limited to this and can be added or updated as per the
requirement.
A typical equipment/instrument/utility protocol and
report for Installation Qualification shall be under the following heads as
described (but not limited to):
Purpose: Give a clear and concise statement of the
objectives of the qualification study.
Scope: The scope of the protocol shall be mentioned
here.
Responsibility: Mention the individual responsible for
executing the installation as per protocol.
Equipment Description: This section gives
a brief description of the instrument/equipment. The details related to the
identification of the instrument/equipment shall also be provided.
Supporting Documentation: This section
provides a list of drawing, manuals including the list of spare parts for the
equipment etc.
Material of Construction: This section
identifies and provides the material of construction used for the contact as
well as non-contact parts. The verification of the MOC used is based on the
test certificates and manufacturer’s specifications, wherever available.
Installation verification of support Utilities: This
section shall list the specifications of the utilities installed. Utility
hook-up and the requirement of utilities of the equipment shall also be
verified.
Safety Features: This section shall
list and verify all safety features and alarms installed.
Identification of SOPs: This section shall identify and
list all the standard operating procedures(SOPs)/Preventive Maintenance Plan
associated with the equipment/instrument.
Installation Acceptance Criteria: This
section shall provide an overview of all pertinent information and data required
to qualify the installation of the equipment/instrument as acceptable and ready
for installation qualification.
Deviation and corrective actions: This section shall
also list the deviations and corrective actions taken if any to accept the
equipment.
Summary and conclusion: This section shall
provide the overview of the summarized data and observed results during
qualification and to verify with acceptance criteria. As summarized
qualification report the conclusion and recommendation shall be given.
Approval: After complete execution and
compilation of the protocol, report approval sheet shall be reviewed and
approved.
Installation certification: All the concerned
department personnel shall certify and sign off for qualifying the
installation.
Operational Qualification:
Operational qualification is defined as documented
verification that the equipment or each component of the system, as installed
or modified, performs as intended throughout the anticipated operating ranges.
OQ shall be prepared by user department. The contents
of the OQ protocol and report shall not be limited to format and can be added
or updated as per the requirement.
A typical protocol and report for OQ shall be under
various heads as described below:
Objective: The objective of preparing the
protocol shall be mentioned in brief in sub head.
Scope: The scope of the protocol shall be
mentioned here.
Responsibility: mention the persons responsible for
executing the protocol.
Equipment Description: This section gives a brief
description of the instrument/equipment.
Pre-requisite of Operation Qualification: Availability
of required documents like identified draft SOPs and calibration status shall
be verified prior to OQ.
Training of personnel: After approval of
the protocol, training shall be provided on protocol for execution to all
concern personnel and oral assessment shall be done.
Operational and functional test: This section shall
provide purpose, scope, equipment used, procedure, documentation and acceptance
criteria of the individual tests to be performed. The data sheets and test
results shall be attached to the Validation document.
Safety Features testing: This section shall verify that
all safety features and alarms installed functions when the required conditions
are simulated.
Operation acceptance criteria: This section shall
provide an overview of all pertinent information and data required to qualify
the operation of the equipment/instrument and data required to qualify the
operation of the equipment/instrument as acceptable. This section shall also
list the deviations and corrective actions taken, if any, to accept the
equipment.
Deficiency and correction action: This
section shall also list the deviations and corrective actions taken if any to
accept the equipment.
Summary and conclusion: This section shall provide the
overview of the summarized data and observed results during qualification and
to verify with acceptance criteria. As summarized qualification report the
conclusion and recommendation shall be given.
Approval: after complete execution and
compilation of the protocol, report approval sheet shall review and approved.
Certification: All the concerned
department personnel certify and sign off for qualifying the operation.
Performance Qualification (PQ):
PQ is defined as the documented verification that the
equipment/instrument/utility and ancillary systems, as connected together, can
perform effectively and reproducibly based on the approved process method and
meet the pre-established specifications.
PQ of the equipment shall be done after the successful
completion of OQ.
PQ can also be performed during the process validation
batches or taking dummy trial batches or commercial batches.
If PQ is performed using dummy batch the composition of
the dummy batch record shall be part of the PQ protocol.
A separate batch record shall be maintained for the
dummy batch and shall be attached with the qualification document of the
equipment/instrument. Quality attributes related to product, affected by
equipment performance shall be monitored.
PQ shall be prepared. The content of the PQ protocol
and report shall not be limited to format and can
be added or updated as per requirement.
Quality of the product shall meet the acceptance
criteria of approved product specification.
After completion of PQ, equipment/instrument shall be
certified as qualified and handover to user department for routine use.
A typical equipment/instrument/utility protocol and
report for Performance qualification shall be under various heads as described
below:
Purpose: The purpose of preparing the
protocol shall be mentioned in brief in this sub head. This is to document the
initial performance of equipment for defined process parameters.
Scope: the scope of the protocol shall be
mentioned here.
Responsibility: mention the responsibility of
individual responsible for executing the protocol.
Pre-requisite of PQ: Availability of
required documents like identified Sops, OQ report etc. shall be verified prior
to performance qualification.
Acceptance criteria: Product parameters shall meet the
desired specification. Equipment shall show the correlation between physical
and chemical parameters of product and equipment performance at identified
processing steps.
Deviation and corrective action: This
section shall also list the deviations and corrective actions taken if any to
accept the equipment. If a test fails or if it becomes necessary to modify the
test procedure or acceptance criteria during testing, the deviation shall be
investigated, justified and documented.
Summary and conclusion: This section shall
provide the overview of the summarized data and observed results during
qualification and to verify with acceptance criteria. As summarized
qualification report the conclusion and recommendation shall be given.
Approval: after complete execution and
compilation of the protocol, report approval sheet shall be reviewed and
approved.
Certification: All the concerned
department personnel certify and sign off for qualifying the performance after
reviewing the results and other supporting documentation. The performance
qualification for the equipment shall be considered acceptable.
Re-Qualification/Re-validation (RQ):
Equipment/instruments shall be qualify / evaluated as
per below mentioned table:
Sr. No. Re-Qualification/Re-Validation Re-Validation Period Frequency
1. QC/Micro/ARD Equipment/Instruments One year ±15
days
2. PLC/HMI Five years ±30 days
3. Major Equipment Five years ±30
days
HVAC shall be
evaluated as per below mentioned table:
Sr. No. Test
Parameter Re-Validation Period Frequency
1. Integrity test for HEPA filter Yearly ±30 days
2. Air flow pattern Yearly ±30
days
3. Velocity and air changes Six months ±15
days
4. Non-viable particulate count Six months ±15 days
5. Recovery test (non-viable particle
count) Yearly ±30 days
Equipment shall be re-qualified under following
conditions:
After major breakdown
Major modification of equipment
Design changes of spares that have impact on
performance of the equipment.
After re-location of critical equipment involving
various utilities.
As per scheduled re-qualification.
Situations arising out of unusual occurrences of
system/process.
Situations arising out of annual review of machine
history.
Change control procedure shall be followed for
re-qualification activities except scheduled qualification.
Re-qualification/re-validation shall be done to evaluate
the impact of changes on equipment/instrument/utilities, intentionally or
un-intentionally. The process is intended to ensure that the qualified
equipment/instrument continue to perform in accordance with the parameters
defined during the initial qualification.
PLC/HMI shall be verifying in every five years for
their input/output check.
Re-qualification/Re-validation shall not be done under
following conditions:
Routine preventative maintenance.
Repair/replacement with identical parts but not
impacting the product quality directly or indirectly.
Re-calibration
Adjustments within calibrated parameters
RQ shall be prepared. The content of the RQ protocol
and report shall not be limited to format and can be added or updated as per
requirement.
A typical equipment/instrument protocol and report for
re-qualification/Re-validation shall be under various heads as described below
but not limited to:
Purpose.
Scope.
Responsibilities.
System Description
Pre-requisite of Performance
re-qualification/re-verification.
Performance re-qualification procedure
Acceptance criteria
Deviation and corrective action report
Summary and conclusion
Approval
Qualification and Re- qualification Schedule:
Qualification and Re- qualification Schedule shall be
prepared QA equipment/instruments and for HVAC.
Qualification Documentation:
A written protocol shall be established to specify how
to conduct the qualification activity.
The first page contains the table defining necessary
details of the equipment/instrument and company logo and address below the
table.
The Header part contain the document name, Protocol
No., effective date and page number and its common for all pages.
DQ, IQ and OQ Protocol/Report received from the vendor
shall be considered for the qualification purpose.
System generated documents (protocols and reports)
shall not contain the effective date, prepared by, checked by and approved by
at the bottom.
