1. OBJECTIVE
To lay
down a procedure for preparation, review, and approval of Performance
Qualification (PQ) and Re-Qualification (RQ) plan/ protocol, execution of the
qualification activity and post-execution approval of qualification report.
2. SCOPE
This
procedure is applicable to all performance / re-qualifications performed in
Pharma Ltd.
3. RESPONSIBILITY
3.1 Validation
Group:
3.1.1 Is
responsible for preparation of plan/ protocol. Also responsible for execution
of qualification activity as per the approved protocol, with required support
from cross functional groups (User, Engineering, QC).
3.2 Engineering
/ Instrumentation:
3.2.1 Is
responsible to review the protocol and support the qualification activity, wherever
applicable, and review the qualification data/ activity.
3.3 User
department:
3.3.1 User
is responsible to review the protocol, support the qualification activity,
wherever applicable, and review the qualification data/ activity.
3.4 Quality
Control:
3.4.1 Is
responsible to review the protocol, test the qualification samples and review
the report, wherever applicable.
3.5 Quality
Assurance:
3.5.1 QA designee is responsible to review
the plan/ protocol and report and verify the qualification activities, wherever
applicable.
3.6 Head-
QA:
3.6.1 Head-QA
is responsible to approve the protocol and report.
4. PROCEDUR
4.1 Protocol
Preparation And Approval:
4.1.1 Responsible
person in Validation group of QA shall prepare PQ/ RQ protocol, in coordination
with Production, Engg. QC and QA, in the prescribed Format – 1 for each
facility/ utility and process equipments.
4.1.2 The
contents used in the Format– 1 are only for guidance to the concerned
personnel. Any additions/ deletions, based on the scope of qualification and
design features/ requirements of the equipment, shall be considered while
preparation/ review of a protocol.
4.1.3 Expertise
of the competent personnel on system/ equipment, and knowledge gained during
the DQ, IQ and/ or OQ of the system/ equipment, shall be the basis for PQ.
4.1.4 The
philosophy defined in VMP shall be referred for qualification approach, while
preparation of PQ protocol, wherever applicable.
4.1.5 Below
mentioned attributes shall be considered, in determining the extent of tests to
be performed, as part of performance qualification:
· CGMP requirements/ current
industry practices.
· Criticality of the equipment/
system.
· Intended
use of equipment/ system, including the range of operating parameters and user
requirements.
· Risk
to product quality and/ or personnel safety
4.1.6 In
case of RQ protocol, the attributes which are qualified during the PQ shall be
considered. The qualification testing shall include repetition of PQ testing
(full/ partial) and/ or review of routine monitoring data, as per the
philosophy described in the VMP.
4.1.7 There
shall be qualification protocol for each equipment/ system and qualification
plan shall be in place for some systems, as described in 4.2, and protocol
shall be prepared based on this plan.
4.1.8 Draft
protocol for PQ/RQ of each equipment/ system shall prepare by VG (originator of
the protocol), and shall be submitted to QA, User, QC and/ or Engineering for
review, as applicable.
4.1.9 Responsible
personnel in applicable cross functions shall review and give comments on the
draft protocol. User requirements, design features and CGMP requirements shall
be considered, during the review.
4.1.10 VG shall make
corrections in electronic copy of the protocol based on comments and the
finalized electronic copy shall be submitted to QA documentation cell for final
printing and approval.
4.1.11 The protocol
number shall be allotted to protocol as described in SOP FU4-QA-GEN-007.
4.1.12 The printed
protocol shall be sent for signatures of applicable cross functions. Finally, a
responsible person in QA shall sign on the protocol and get the approval of
Head-Quality or his/ her designee.
4.1.13 The necessary
support shall be provided by User department, QC, Engineering/Instrumentation
and/ or QA for the preparation of protocol.
4.1.14 The electronic
copy and hard copy of approved protocol (masters) shall be archived in
documentation group of QA, for further distribution and control.
4.1.15 In case of any
additional PQ to be performed for already qualified equipment, the same shall
be carried out through Addendum/ Supplement Qualification documents. The
Format-I shall be used for same by keeping relevant headings/ contents.
4.1.16 Wherever PQ is
being performed by an external agency with their protocol, the same may be
accepted for the execution. The approval shall be done by representatives of
Aurobindo Pharma Ltd. in the prescribed Format – 2 of SOP FU4-QA-GEN-034, prior
to execution of the qualification. Aurobindo Pharma Ltd shall ensure the
compliance of protocol to defined quality systems of Aurobindo Pharma Ltd and
CGMP requirements.
4.1.17 The approved
protocol provided by supplier shall be considered as master protocol and
directly used for execution. This protocol shall have in house protocol
numbering as per the SOP FU4-QA-GEN-007. Executed protocol shall be approved in
the prescribed Format – 3 of SOP FU4-QA-GEN-034.
4.1.18 Supplier
Qualification documents used for Qualification activities must meet in-house
requirements. Any additional Qualification to be done shall be carried out
through in-house Addendum/ Supplement Qualification documents.
4.1.19 In case of
requalification, the approved protocol prepared for each equipment/ system
shall be used for multiple executions and/or revised with version number based
on the variables being covered in the respective requalification.
4.2 Preparation
and approval of Qualification plan:
4.2.1 Responsible
person in Validation group shall prepare qualification plan in coordination
with Production, Engineering, QC and QA, in the prescribed format for
applicable systems as per Format – 2.
4.2.2 The
contents used in the Format – 2 are only for guidance to the concerned
personnel. Any additions/ deletions, based on the scope of qualification and
design features/ requirements of the equipment shall be considered while
preparation/ review of plan.
4.2.3 Where
ever the system undergo qualification by considering wide range of attributes
and bracketing approach, a qualification plan shall be prepared specific to
each system (equipment/ utility).
4.2.4 The
following systems shall be considered for qualification plan, but not limited
to:
· HVAC
· Autoclave
· Tunnel
· DHS
· Filling / Washing machine
etc.,
4.2.5 VG
(originator of the plan) shall submit the draft plan to QA, User, QC and/ or
Engineering for review, as applicable.
4.2.6 The
qualification plan is a consolidated document to determine the extent of
qualification and various tests to be performed on risk based approach.
4.2.7 The
qualification matrix of the plan describes the variables for e.g. container
type, load type etc., and the input shall identify specific element of variable
i.e. capacity of the container etc.,
4.2.8 Responsible
personnel in applicable cross functions shall review and give comments on the
draft qualification plan.
4.2.9 VG
shall make corrections in electronic copy of the qualification plan based on
comments and the finalized electronic copy shall be submitted to QA
documentation cell for final printing and approval.
4.2.10 QA documentation
cell shall allocate number to each plan and print as described in SOP
FU4-QA-GEN-007.
4.2.11 The printed
qualification plan shall be sent for signatures of applicable cross functions.
Finally, a responsible person in QA shall sign on the qualification plan and
get the approval of Head-QA or his/ her designee.
4.2.12 The necessary
support shall be provided by User department, QC, Engineering/Instrumentation
and/ or QA for the preparation of qualification plan.
4.2.13 The electronic
copy and hard copy of approved qualification plan (masters) shall be archived
in documentation group of QA, for further distribution and control.
4.2.14 The qualification
plan shall be revised in each calendar year and/or for any changes to reflect
two year forward planning with status of execution after each study.
4.3 Execution
of Qualification Protocol:
4.3.1 Responsibilities
for the execution from each department shall be followed as described in
validation master plan and shall be mentioned in the protocol.
4.3.2 All
the sampling/ testing for PQ/ RQ shall be performed by trained personnel of
responsible departments. Responsible person in validation group shall witness
the qualification activities, wherever applicable.
4.3.3 All
the tests prescribed in IQ and OQ shall be completed, with post execution
approval of qualification report, prior to start of PQ.
4.3.4 In
the event where IQ/ OQ is not closed for any reason, and doesn’t have any
impact on the outcome of PQ, environment/ personnel safety and/ or CGMP
compliance, an interim approval shall be in place to proceed with PQ in the
prescribed Format – 4 of SOP FU4-QA-GEN-034.
Note: All the checks/ tests of IQ and OQ shall
be satisfactorily completed, with post execution approval, prior to approval of
PQ report.
4.3.5 Engineering
shall ensure the availability of utilities and preventive maintenance program
is in place, with required SOPs and updated PM schedule, wherever applicable.
4.3.6 QC
shall ensure the availability of SOPs, trained analysts, qualified equipments
and validated methods for timely testing of all the samples, wherever
applicable.
4.3.7 Before
start of PQ/ RQ testing, the execution team shall ensure the controlled state
of all the operations and documentation. Following attributes shall be verified
by execution team, but not limited to:
· Approved
SOPs are in place for operation and monitoring of equipments/ utilities.
· Established
cleaning/ sanitization procedures for area/ utilities and equipment are in
place.
· Approved
SOPs are in place for Entry/ exit and gowning, for area qualification.
· Calibration
validity of all the instruments of the equipment/ system.
· Applicable
recording forms/ log books are in place for documenting various operational
attributes.
· All
the concerned personnel are adequately trained on applicable procedures.
4.3.8 Re-qualifications
shall be performed in prescribed frequencies, as described in respective PQ
and/ or VMP. Responsible person in validation group shall maintain the annual
schedule for re-qualifications and coordinate with respective user/ engineering
personnel for timely completion of activities.
4.3.9 Typically
the tolerance of one month (at maximum) shall be considered for completion of
requalification, irrespective of the criticality and frequency of equipment/
system.
4.3.10 The
requalification date shall be calculated from completion date of initial
performance qualification, i.e. last test date irrespective of receipt of
results. This due date is mentioned in Annual Requalification Schedule
(Annexure-II of VMP) and maximum of one month tolerance is applicable.
4.3.11 However, the
subsequent requalification dates shall not be changed based on the current
requalification date. For e.g. the PQ of equipment/ system is completed on
15/07/12 and the subsequent requalification dates (considering 6 months as a
requalification frequency) shall be 14/01/13 and 13/07/13 respectively, with a
maximum tolerance of one month, i.e. 14/02/13 and 13/08/13 respectively.
4.3.12 Any deviation to
the prescribed schedule shall be handled through a PNC as per the SOP
CQA-CP-GEN-014.
4.3.13 Execution
personnel shall initiate qualification testing, as per the instructions of
protocol.
4.3.14 During the
qualification activity, execution team shall record the observations/ results
in approved Protocol. Wherever applicable, QC shall document the testing
results in analytical test record as per respective testing SOPs.
4.3.15 All the reports/
data sheets, generated during the execution shall be attached to the protocol.
Documentation practices shall be in consistence with the instructions of SOP
FU4-QA-GEN-005.
4.3.16 If any
qualification testing to be outsourced from an external agency (part/ full
testing), a representative of Aurobindo Pharma Ltd shall witness the activity
and ensure following, prior to start of any activity:
· Credentials
of agency (vendor), i.e. qualification, experience and training.
· Training
of external personnel on Aurobindo Pharma Ltd practices, i.e. Entry/ Exit,
gowning, documentation, safety etc as per respective SOP.
· Calibration
status, with adequate traceability, of all the measuring instruments.
· All
the requirements mentioned in this SOP are satisfactorily addressed in the
protocol.
· Unit
representative shall ensure the integrity of data/ reports, provided by the
external agency, by signing with date on each page.
4.3.17 All the deviations
observed during execution of performance qualification shall be recorded in the
discrepancies section provided in the protocol and impact of these deviations
shall be evaluated by User and QA. Necessary corrective and preventive actions
shall be implemented/ initiated by concerned personnel of the Unit, to address
such deviations prior to closure of the report.
4.3.18 If any deviations
observed during the requalification, same shall be handled through the SOP
CQA-CP-GEN-014 and thorough investigation shall be performed.
4.3.19 Necessary
conclusions shall be documented, including the impact of deviations and
corrective actions initiated/ implemented to address the deviations in the
protocol after completion of all the activities by VG.
4.3.20 Wherever the
outcome of qualification to be integrated to routine operations, for e.g.
incorporation of qualified load patterns into autoclave SOP, the responsible
person in user department shall prepare/ revise the applicable documents.
4.3.21 The completed
protocol shall be reviewed by Engineering, User and/ or QC (as applicable) and
shall be submitted to QA, with all the supporting data, for final review and
approval.
4.3.22 Responsible person
in QA shall review the executed protocol by ensuring the compliance of
qualification activity to operational attributes and documentation
requirements.
4.3.23 Finally, the PQ/
RQ protocol with conclusions shall be approved by head-QA or his/ her designee
by ensuring its compliance to CGMP requirements, inline with applicable
guidance and current industry practices.
4.3.24 All the applicable
testing of PQ shall be satisfactorily completed before taking any decision on
the quality of product, being manufactured by using such equipment/ utility.
4.3.25 If equipment/
system fail to meet the pre-determined acceptance criteria during any stage of
qualification, Head QA or his/ her designee shall take decision on the usage of
equipment, including disposition of the product being manufactured, with
adequate impact assessment, justification and corrective actions.
4.3.26 Post approval of
PQ/ RQ report by head-QA or his/ her designee, all the qualification documents
(i.e. Protocol with supporting data) shall be archived with QA documentation
cell in secured/ retrievable manner.
5. ENVIRONMENT,
HEALTH AND SAFETY
5.1 Identify
all the potential hazards during the qualification activity and list adequate
measures to be taken, to eliminate the hazards, while developing the
qualification protocol.
6. ABBREVATIONS
/ GLOSSAR
6.1 AHU : Air
Handling Unit
6.2 CGMP :
Current Good Manufacturing Practices
6.3 DQ :
Design Qualification
6.4 ID
No :
Identification Number
6.5 HVAC :
Heat Ventilation and Air Condition
6.6 IQ :
Installation Qualification
6.7 NA : Not
Applicable
6.8 OQ :
Operational Qualification
6.9 PM :
Preventive Maintenance
6.10 PQ :
Performance Qualification
6.11 PS :
Pure Steam
6.12 PW :
Purified Water
6.13 QA : Quality
Assurance
6.14 QC :
Quality Control
6.15 RQ :
Re-Qualification
6.16 SOP :
Standard Operating Procedure
6.17 VMP :
Validation Master Plan
6.18 VG :
Validation group
6.19 WFI : Water
For Injection
6.20 Performance
Qualification: To generate a documented evidence that the equipment /
system is performing consistently as per the design, to deliver intended
requirements in controlled state.
6.21 Re-Qualification: To
generate documented evidence that the equipment is consistently meeting the
intended requirements, set in the Performance Qualification (PQ), in prescribed
frequencies. Typically this is repetition of performance qualification in full
or partial and / or a formal documented review of various performance
attributes.
6.22 Clean
Utilities: These are critical systems and have direct impact on the
product quality, i.e. Water System (PW, WFI and PS), HVAC, Compressed Air and
Nitrogen gas.
6.23 Plant
Utilities: These are non-critical systems, which are supporting for clean
utilities or plant operations, i.e. plant steam generated from the boiler,
Chilled water from the chillers, pre-treatment water etc.
6.24 Process
equipment: All the equipments used in production/ quality control for
processing and/ or handling of a drug product/ component, including equipments
used for process support.
6.25 Analytical
Equipment: All the measuring instruments used in quality control/
production for testing of drug product/ component, including equipments used
for analytical support
7. REFERENCES
7.1 Numbering
and Control of Validation / Qualification
protocols - FU4-QA-GEN-007
7.2 Good
Documentation
Practices -
FU4-QA-GEN-005
7.3 Reporting
and monitoring of process non conformance in
automated quality management system
software -
CQA-CP-GEN-014
7.4 Installation/
Operational
Qualification -
FU4-QA-GEN-034
8. FLOWCHART
Not
Applicable
9. FORMATS
9.1 Format-1
: PERFORMANCE/ RE QUALIFICATION PROTOCOL
|
PERFORMANCE / REQUALIFICATION
PROTOCOL |
|
||||
|
|
|||||
|
Protocol No.: |
Equipment No.: |
|
|||
|
Details of
Equipment/ System |
|||||
|
User Department |
|
||||
|
System ID |
|
||||
|
Equip. Location/ Room No. |
|
||||
|
Equip. Make/ Model |
|
||||
|
Equip. Serial No. (Supplier) |
|
||||
|
Document Effective Date |
|
||||
|
Qualification
Start Date |
|
||||
|
Qualification
Completion Date |
|
||||
|
Requalification
due date |
|
||||
|
Table
of Contents |
|||||
|
S. No. |
Details |
Page No. |
|||
|
|
Pre-Approval |
|
|||
|
|
Scope |
|
|||
|
|
Objective |
|
|||
|
|
Abbreviations |
|
|||
|
|
Responsibility |
|
|||
|
|
Intended use of equipment |
|
|||
|
|
Equipment / system description |
|
|||
|
|
Safety Precautions |
|
|||
|
|
Training Record |
|
|||
|
|
Equipments/ Materials Required for
Qualification |
|
|||
|
|
Verification of calibration status |
|
|||
|
|
Verification of operational controls |
|
|||
|
|
Qualification requirements &
observations |
|
|||
|
|
Qualification Tests & Results |
|
|||
|
|
Requalification criteria |
|
|||
|
|
Details of Descrepancies |
|
|||
|
|
Summary / Conclusion |
|
|||
|
|
References |
|
|||
|
|
Annexure |
|
|||
|
|
Post Approval |
|
|||
ConversionConversion EmoticonEmoticon