Validation Master Plan 2024 Updated

HMA MEDICAL LTD Page 1 of 64
Plot 9, Block 4, Transit Camp Road, Ilorin, Kwara State, Nigeria.

ESTABLISHMENT DOCUMENT
Title: Validation Master Plan
Department: Quality Assurance Issued Date: 6th June, 2023
Mandatory Review Date: 12th June, 2025 Effective Date: 13th June, 2023
SOP NO: HMA/QAD/VMP001-00 Supersede: Nil
VALIDATION MASTER PLAN
SR. NO. CONTENTS PAGE NO.
1 APPROVAL
2 INTRODUCTION
3 VALIDATION POLICY
4 OBJECTIVE
5 SCOPE
6 VALIDATION RESPONSIBILITIES
6.1 Validation Team Constitution
7 FACILITY DESCRIPTIONS AND DESIGN
7.1 General Description and Design Concept
7.2 Description of Products
7.3 Description of Process

7.4 Description of Equipments
8 VALIDATION PROGRAM AND SUPPORTING SYSTEMS
8.1 Fundamentals of Validation Program
8.2 Supporting systems for validation program
9 VALIDATION CONCEPT AND TYPES
10 ACCEPTANCE CRITERIA
11 RISK MANAGEMENT STRATEGY
12 STANDARD OPERATING PROCEDURES
13 CHANGES AND MODIFICATIONS
13.1 Changes and modification to the validation systems
13.2 Changes and modification to the validated systems
14 VALIDATION SCHEDULE
15 ANNEXURE
16 GLOSSARY
1.0 VALIDATION APPROVAL SECTION

This Validation Master Plan has been initiated, checked, approved and authorized for implementation
by the undersigned.
DESIGNATION NAME SIGNATURE DATE

Quality Assurance Executive

(Validation)
INITIATED BY:
Quality Control Manager
Production Manager
Maintenance Manager
CHECKED BY:
APPROVED BY:

Quality Assurance Head
General Manager
AUTHORIZED BY:
Group Managing Director
VALIDATION MASTER PLAN DATE: JUNE, 2023

2.0 INTRODUCTION
2.1 Project Description:
 HMA Medical Limited is an indigenous, state of the art, medical devices manufacturing company
which uses specialized automated manufacturing equipment for the production of syringes, and
disposable hypodermic needle set of various pack sizes under the trademark “Deleject”. It is
situated at Plot 9b, Block 4, Transit Camp Road, Lubcon Avenue, Ilorin Kwara state, Nigeria.
 The facility was designed in the year 2017 to meet national regulatory and cGMP requirements.
The manufacturing facility is supported by Maintenance/Engineering, Warehouse, and Quality
Assurance departments with all these departments covered under the relevant validation activities.
 The Validation Master Plan is a dynamic document which provides complete overview of the
validation program.
 It describes the overall objective, intention and approach for establishing performance adequacy of
equipment, utilities, processes and systems.
 It identifies the scope of validation, applicable validation protocol reports, procedures and
frequency of validations.

3.0 VALIDATION POLICY
3.1 The organization HMA Medical Limited is committed to the concept of validation and all
processes, facilities, equipment, machines, instruments, control systems, utilities, and analytical
methods are put through appropriate qualification and validation cycles before being accepted
for use. Performance qualification shall be carried out for all critical equipment used for
manufacturing, engineering and quality control.
3.2 All systems are subject to ongoing validation to evaluate the impact of changes in process,
systems, environment, equipment directly or indirectly on the product.
3.3 Three validation studies are carried out as per protocol prepared by nominated team members
from various departments
3.4 For certain equipment/instruments in case-by-case basis, the manufacturer’s qualification
document shall also be taken as inputs for qualification activities this includes pre delivery,
inspection and FAT.

4.0 OBJECTIVE
4.1 This Validation Master Plan is a document, which describes HMA Medical Limited intentions
and the methods which are related to validation of the equipment, instruments, systems, utilities,
facilities, materials, analytical methods and processes.
4.2 Validation Program is designed to demonstrate that the facility for the production up to the final
stage of production of different pack sizes of finished product and intermediate components is
capable of meeting the process parameters in a repeatable and controllable manner.
4.3 Validation Master Plan ensure that validation activities are carried out as per respective protocols
and after completion will determine whether the equipment, systems, process and methods,
 Meets the specification of its design
 Suitable for its intended applications
 Conform to the basic cGMP design criteria
 Will satisfy the regulatory requirements

 Meets safety requirement as applicable
 Is capable of consistently producing a product that is fit for use.
4.4 The critical utilities, equipment and process validation programme are established in accordance
with the methods and procedures maintain by the product requirements which are based on the
currently available products information and the current Good Manufacturing Practices,
guidelines and other regulations.
4.5 Validation Master Plan helps:
 The management to know and access what the validation program involves and
understand its necessity.
 The validation team members to understand their tasks and responsibilities.
 To understand the company’s approach towards validation and the setup of organising
validation related activities.
5.0 SCOPE
5.1 The scope of this document is to describe the system and methodology used in executing the
various phases of the validation program.
5.2 It encompasses all critical equipment, instruments, procedures and processes, utilities, facilities,
and other quality supporting system used for manufacturing, processing, testing, labelling and
packaging which may affect the quality of product directly or indirectly.
5.3 Validation Master Plan applies methodology of validation program to the following,
 Facilities
 Equipments/ Instruments/ System (Qualification)
 Utilities (e.g. HVAC, Water system and Compressed Air)
 Control Systems (e.g. Computer hardware and software)
 Manufacturing processes
 Cleaning processes
 Analytical methods
 Environmental (Physical & Microbiological)
 Personnel (e.g. Analysts, checkers on inspection or packing line)
 Revalidation or Requalification
6.0 VALIDATION RESPONSIBILITIES
6.1 Validation Team Constitution
6.1.1 The overall validation process is coordinated by a team, which is a working group comprising of
qualified personnel as required for the specific validation activities.
6.1.2 The validation team is made up of representatives from the following areas:
 Quality Assurance
 Production
 Maintenance
 Quality control
6.1.3 Validation team is responsible for:
 Preparation of Validation Master Plan
 Determination of the equipment, instruments, systems, facilities and utilities to be
validated
 Preparation of validation and qualification protocols
 Execution of the validation and qualification protocols
 Determining the suitability of the established protocol to qualify a system
 Approving all validation protocols and report each validation from respective functional
department heads
 Reviewing each protocol and reports content to assure compliance with current
regulations and guidelines
 Verifying the adequacy of the tests used for the verification of the system as established
by the validation protocols
 Determine the extent of revalidation necessity in case of changes in a validated system
 Document control
6.1.4 Other personnel will be utilised, as necessary, by the members of the validation team to assist in
the assessment of the special equipment, system, utilities where their area of expertise will
facilitate the development and execution and assure the quality of the validation efforts
6.1.5 Individual responsibilities of different departments are as follows:
6.1.5.1 Production: it is responsible for,
 Describing the production process in collaboration with Quality Assurance
 Preparation of the batch records in collaboration with Quality Assurance
 Transferring the processes to the production facility in collaboration with Quality
Assurance
 Providing all current and approved standard operating procedures to be used as part of
manufacturing process
 Providing personnel and materials as required for the execution of validation
protocols, equipment trials and process trials.
 Training of all manufacturing personnel in technical, validation and GMP aspects
 Sampling and execution of process controls
 Preparing reports on any deviation that occurs during process
 Participating in preparation of draft validation protocols
 Executing DQ, IQ, OQ, and PQ with validation team members as per validation
protocols
 Tracking for validation requirements
 Operating and maintaining plant, facilities, equipment, support systems and the
specific manufacturing process within its design limits.
6.1.5.2 Maintenance: it is responsible for,
 Instrument list
 Building
 Maintenance requirements
 Spare part list
 Calibration requirements and procedures
 Equipment design, installation and system construction procedures
 Operational recommendations
 Coordination of calibration activities for all critical instruments as defined by the
validation team
 Executing DQ, IQ, and OQ tasks and assisting in the execution
 Preparing and maintaining calibration records for all critical instruments
 Executing the installation and maintenance of production facilities and laboratories
 Training of all engineering personnel in technical, validation and GMP/GEP aspects
NOTE: Critical instruments are those which have direct impact on the product quality, i.e.,
instruments which measure, monitor, or control manufacturing, processing and testing
parameters.
6.1.5.3
Quality Control: it is responsible for,
 Training of all Quality Control personnel in technical, validation and GMP/GLP aspects
 Testing of validation samples as per validation protocols and specifications.
 Preparing laboratory reports by collecting data and verified summaries of findings and
conclusions
 Ensuring that the laboratory systems, instruments, devices and equipment to be used in
6.1.5.4 the course of validation studies have been qualified, validated and calibrated
Quality Assurance: it is responsible for,

 Coordinating and organising the validation team
 Coordinating the preparation of the validation protocols for each area, system, facility,
utility, equipment, instrument
 Coordinating the process validation by monitoring, sampling, testing and challenging the
specific manufacturing processes
 Coordinating all change control approvals, organising the changes required to approved
protocols resulting from specification changes or changes in operating parameters
 Training of personnel involved in validation activities
 Collecting and organising the validation data
 Tracking of all validation requirement based on the review of guidelines or literatures
 Preparing the final validation summaries and certification statements
7.0 FACILITY DESCRIPTIONS AND DESIGN
7.1 General description and design concept of facility

7.1.1 HMA Medical Limited have provided manufacturing facility for medical device (Needle and
Syringe) of different pack sizes.
7.1.2 The plant is functionally divided into different blocks, Administration block, which houses the
Account, HR/Admin; Maintenance block which houses the generator room, service floor, and its
personnel office; Manufacturing block which consists of raw and packaging material store,
production area, Quality Assurance and In process/ Quality Control Laboratory inside the
production area, Microbiology Laboratory, Change Rooms, Air Handling Unit and few offices.
There is an extension of the manufacturing arena which is under construction. The Gate house is
separate and likewise the Canteen, there is also a separate area for the storage of inflammable
substances.
7.1.3 The production area has infrastructure to manufacture needle and syringe of different pack sizes
7.1.4 The production and supporting areas are made of concrete blocks, high tensile steel
reinforcements and rafters, aluminium roofing, concrete plaster, and non-flaking paint wall
finishing, metal doors and aluminium frame glass panel window.
7.1.5 The clean areas are enclosed within the manufacturing building with pre-fabricated cork
filled/insulated aluminium wall and ceiling panels, pre-fabricated cork filled/insulated
aluminium door panels, non-laminated hard clear glass fittings, sealed window panels, high
quality PVC plastic finished concrete flooring, epoxy flooring in some areas like the needle
assembly, all manufacturing areas and corridors of the new extension, Injection Moulding.
7.1.6 Air locks and pass boxes are also installed in the new extension.
The return air risers of the HVAC system are concealed within the wall to avoid recesses, the
7.2 terminal filter and lighting feature are recess type and ceiling mounted.
Description of Products
7.3 As per attached Annexure
Description of Process flow
7.4 As per attached Annexure
List of equipment
As per attached Annexure
8.0 VALIDATION PROGRAM AND SUPPORTING SYSTEMS
8.1 Fundamentals of Validation Program
8.1.1 The validation programme shall be divided into five phases as follows:
 Phase I- Preparation and Approval of the Validation Master Plan
 Phase II - Preparation and Approval of the Validation Protocol
 Phase III- Execution of Validation protocols, tests laid down in Validation Protocols and
data collection.
 Phase IV – Preparation of Validation Report, Compilation of data collected during
Validation, review, recommendations and Approval of validation Report.
Document shall be kept under the custody of the Quality Assurance.
 Phase V - On going evaluation, review, Change Control, Deviations and Revalidation.
8.1.2 The Validation Master Plan (VMP) shall be prepared by the Validation Executive.
The document shall be checked by the Heads of all Functional area.
8.1.3 The document shall be approved by the Quality Assurance Manager and General Manager and
authorized by the Group Managing Director.
8.1.4 There shall be separate protocols for DQ, IQ, OQ, PQ (where ever applicable), Environmental
Control, Analytical method validation, facility, Utility, Process Validation, and Cleaning
Validation etc. All the protocols shall be numbered as per SOP for the numbering of reports and
protocols.
8.1.5 The protocols shall consist of the objective, scope, responsibilities, procedures for conducting
the tests for validation. The results observed during the validation studies, summary, conclusion
and final approval shall be included in the reports.
8.1.6 Validation Executive and Concerned department Executive shall initiate the Validation
Protocols. Concerned HOD and HOD of production, Engineering/Maintenance shall
check/verify, Quality Assurance Manager and General Manager shall Approve while the Group
Managing Director finally authorize the validation protocol.
8.1.7 The approved Master Copies of protocol shall be kept in the custody of the Quality Assurance
Manager. During execution of validation protocol, validation report shall be prepared as par
protocol and attach the collected data of the same to the reports.
8.1.8 Summary and Conclusion Report and Approval
 After the execution of the protocols, a validation task report shall be reviewed,
summarize, concluded and recommendations made by the team carrying out the
validation activity and approved by the involved team members.
8.2 Supporting systems for validation program:
8.2.1 Protocol and Documentation System

The system shall be designed to assure that all validation documentation shall be prepared
according to validation policies established by a validation team, which shall be responsible for
coordinating of the validation program and approving all validation activities.

8.2.2 Documentation control system:
The system shall be designed to manage all documents generated during validation process,
including that from the change control program. The system will include a numbering system to
identify each protocol and an index to list of all approved protocols. It assures that all
documentation shall properly be stored and controlled so as to maintain its integrity.
8.2.3 Protocol execution system:
This system shall assure that all requirements outlined in the approved validation protocol are
met
and thus, system shall be considered valid. To comply with these requirements this system shall
establish the procedure to be followed for the coordination of the validation tasks through the
validation team. This system shall also provide assurance that information collected is timely,
8.2.4 correct and properly reviewed and shall be approved by the validation team members
Change control system: refer to the SOP for Change Control
9.0 VALIDATION CONCEPT AND TYPES
9.1 Definition:
9.1.1 The collection and evaluation of data, beginning at the process development stage and
continuing through the production phase, which ensures that the facility, equipment, equipment,
manufacturing process, control systems utilities and personnel and materials are capable of
achieving the intended results on a consistent and continuous basis and thus is capable of
consistently producing a product that meets the established products specification.
9.1.2 Validation is documented evidence which can confirm predetermined critical parameters
9.2 Validation Types

9.2.1 Facility Validation:
 Room no. and Location
 Purpose of Area for use
 Dimension of Area: Height (Meter), Width (Meter), Length (Meter), Area (M2or Ft2),
Volume (M3 or Ft3),

 Area Details:
 Walls: Wall to floor, wall to false ceiling, Wall to return air riser, Wall to door frame
 Ceiling: Type, Finish, Painting Shade and Jointing
 Door: Type, Dimension (W x H meter), No of doors, Location, Painting, No and type of
door closer, No and type of handle, Size of glass view panel, Door interlocking.
 Windows: Type and No of windows, Dimensions (W x H meter), Door Jointing.
 Drainage: Type of trap. No and location, Material of construction
 Electrical work: Wiring type, no. of computer points, no. of power sockets, no. of single
phase sockets and type illumination level in Lux.
 Building Management system: Indication box, size, Location indication, pressure
Indication, temperature indication, humidity and Door status.
 Other facilities: Insectocutor, Air curtain, PVC strip door, SS corner angle, SS fenders,
Fan safety, pass box.
9.2.2 Analytical Method Validation:

This is a type of validation that is usually done at the R & D research Laboratory
9.2.3 Vendor Qualification:

Vendor qualification shall be carried out for all the vendors o f raw and packaging materials to
9.2.3.1
ensure that the components of the product consistently meet predetermined specifications.
Vendor evaluation shall be done on the basis of questionnaire, pre-shipment samples, machines
9.2.3.2 trials and/or vendor audit.
The supplied materials shall be checked /analysed with reference to the in-house specifications.
9.2.3.3
Control system Validation:

9.2.4
Computer software
 Computer software
9.2.4.1  The objective of the computer system validation is to demonstrate that the computer
system performs (Create, modify, archive and retrieve) as it is supposed to
 This shall be based on following:
 Specification for software depending on intended use
 Computer and manual modes of data validation giving similar results.
 Accessibility, durability and accuracy of stored data
 Levels of authority for data entry and change.
 Accuracy and reliability of data entered.
 Security system to ensure any alteration or pilferage of data.
Qualification (DQ/ IQ/ OQ/ PQ) of Computer Software:
 To control the equipment/ instrument/ system, computer hardware and software systems
used as a part of equipment or instrument or system must be validated. Design qualification,
Installation qualification and operational qualification shall be executed prior to
performance qualification of associated equipment/ instrument/ system.
 To expedite the process of validation, the computer system validation shall be done as a part
of equipment/ instrument/ system validation.
 The following are the contents for computer hardware and software validation:
1. Detail description of control system
 Control panel
 Power supplies
 Temperature sensor (Wherever applicable)
 Humidity sensors (Wherever applicable)
 Smoke detectors (Wherever applicable)
 CPU
 Location
 Manufacturer
 Model
 Processor
 Capacity
 Disk type
 Floppy disk drive

 Hard disk drive
 Ports
 Monitor
 Manufacturer
 Model
 Type
 Size
 Software
 Operating system version
 Application program version
 Password control
 Input devices
 RAM
 CDROM
2. Computer Software
 Software
 Verification that software prevents unintentional access.
 Verify back up procedures.
 Verification of restart of software procedures after system failure.
 Verification of software change control procedures.
 Verification whether the controller operates as a stand alone device or as part of a
distributed system. If the controller operates as part of a distributed system, verify
that the program is written to prevent unauthorised access between the system.
 Verification that the following phases of software life cycle have taken place ,
o Requirements
o Design phase
o Installation and check out phase
o Operation and maintenance phase
o Performance phase
 Verification that supplier has provide the following
o Logic flow diagram
o Operating manual
o Software description
o Where does memory reside (RAM, Tape Disk)
3. Controlled devices:
 Verification that the controlled devices for the system as per approved drawings,
specifications and authorised change orders.
 Verification that all the controlled devices have been installed and tagged as per ,
o Manufacturer
o Model
o Location
o Description
o Function
o Calibration date
o ID number
 Verification that all the wiring done as per specifications. Execution of point to point
verification between the control panel. Confirm the correct identification of wires
and / or air control lines.
 Evaluate the controlled functions for their potential effect on the quality strength,
purity and safety of the final product.
Equipment validation (Qualification):
1. Design Qualification
2. Installation Qualification
3. Operational Qualification
4. Performance Qualification
1. Design Qualification (DQ)

The following sections are to be included in design qualification:
 User requirement specification (U.R.S.):
 The following sections are to be included in User Requirement Specification:
1.0 Description
2.0 Overview
3.0 Operational Requirements
3.1 Capacity
3.2 Specifications
3.3 Functional Requirements
3.4 Environment
3.5 Maintenance
4.0 Life Cycle
4.1Prefered vender list
4.2Development
4.3Testing
4.4 Delivery
4.5 Support
5.0 Glossary
6.0 References
7.0 Approval
Note: Numbering system as per SOP of User requirement specification
 Functional Requirement specification ( FRS): Specification provided by the supplier

end is to be attached to the report.
 Factory acceptance test procedure (F.A.T.):
 Remark of team of selector on F.A.T.
 Approval
2. Installation Qualification (IQ)

 Installation Qualification is documented check that all key aspects of the installation
adhere to appropriate codes, approved design intentions and that manufacturer’s
recommendations are suitably considered.
 To qualify, the specifications of the new equipment received, must match with the URS.
Any exceptions to the original Purchase order or Functional specification shall be
documented and justified. Attribute inspection of the equipment/ Instrument/ System
shall be carried out, documented and proper installation shall be verified.
 All modifications in existing Equipments shall be properly documented through a change
control procedure.
 It may not be possible to inspect and verify every feature associated with a piece of
equipment. In such cases, a certificate of conformance shall be considered, obtained from
the equipment manufacturer.

 The following sections are to be included in Protocol of Installation Qualification
protocol:
 Approval
 Objective
 Scope
 Responsibility
 Procedure
 Re-qualification criteria
 Abbreviations
 Reference
3. Operational Qualification (OQ)
 OQ demonstrates that the equipment/ Instrument/ System can operate throughout it’s
dynamic range of operation, within limits and tolerances as per specified in the operating
manual or instructions.
 This demonstration of equipment’s basic operation shall involve all control parameters of
the equipment.
 OQ shall be carried out for equipment/ Instrument/ System that will be used routinely in
manufacturing, testing or in critical utilities.
 The following sections are to be included in Operational Qualification protocol:
 Approval
 Objective
 Scope
 Responsibility
 Procedure
 Abbreviations
 Reference
4. Performance Qualification (PQ)

 Performance qualification is documented verification of performance of equipment/
Instrument/ System as intended for the process under specified operating ranges.
 All critical equipment / Instrument/ System are qualified for performance verification.
 The study shall involve the challenging of the system to simulated worst case situations,
and establishment of operating variables.
 The following sections are to be included in performance qualification protocol:
 Approval
 Objective
 Scope
 Responsibility
 Procedure
 Acceptance criteria
 Abbreviations
 Reference
NOTE: All equipment, Instrument and system shall have required separate qualification protocol
and report.
Process validation:
 Process validation is established documented evidence which provides a high degree of
assurance that a specific process will consistently produce a product , meeting its
predetermined specifications and quality characteristics.
 If a new product is duplicasy of the existing product then its validation shall be bracketed
with the existing product.
 The purpose of process validation is to demonstrate the reliability and reproducibility of
manufacturing process, within established parameters and to assure batch uniformity and
integrity of drug products. A process validation program shall establish a documented
evidence of three full-scale production batches.

 The validation protocol shall be a written document that defines and gives the detail of
critical steps of manufacturing process. It shall state, how the validation program will be
conducted and lists acceptance criteria for successful validation.
The process validation batches shall be taken for packing after completion of 30 days hold time
study for the initial batches manufactured, Provided the product meets the Finished product /
release specification/ upon re analysis.
 There are four types of the process validation.
 Prospective validation
 Concurrent validation
 Retrospective validation
 Revalidation
1. Prospective validation:
 Prospective Validation shall be carried out on the small scale or R & D batches during
development stage.
 These validations were carried out to identify the processing steps, equipment settings and
process timings, which can prove to be critical in overall impact of product quality. All
these steps, equipment setting and process timing are evaluated to finalise the setting
parameter. Limits of all critical parameters shall put tentatively.
 This draft form of study can lead towards the finalisation of Batch Manufacturing Record /
Batch Packing Record for large scale batches.
 The prospective validation shall take care of following:
1. Process description
2. Investigation summary of critical processing steps
3. Finished product release specification
4. Calibration of equipment
5. Appropriate analytical methods
6. Proposed in process control with acceptance criteria
7. Sampling plan
8. Method for recording and evaluating results and responsibilities.
2. Concurrent validation:
 This validation comprises of determination and evaluation of process parameters
applicable from scale up to large scale batches.
 Process validation for establishing the predetermined limits of all critical parameters
by conducting three consecutive commercial or large scale batches.
 Validation carried out during routine production or products manufacturing for sale.
 The tests are finalised based on evaluation of the results of these batches. These
batches were monitored for stability and quality trends.
 Matrix approach can be applied to process validation. The matrix approach means that
a plan to conduct process validation on different strength of same product,
manufactured by the same process and similar type of equipment. e.g. validation on
one strength (preferably smallest) as a representative amongst the multiple strength of
the same product. This approach should be in accordance with cGMP and should
demonstrate that the process is consistent for all the strength.
Note: The batches will not be dispatched unless and until the analysis of the validation sample is
completed.
3. Retrospective validation:
 Historical trending of all critical parameters obtained from analytical results and / or
IPQC results observed after testing of physical, chemical and microbiological parameters
of product manufactured by same process. To ensure that all the parameters shall be in
the limit and in uniform range.
 Retrospective validation shall done yearly of products or batches manufactured in
previous year.
 Minimum first 20 batches shall consider for retrospective validation. If less than 20
batches were manufactured in one year then batches of previous years were consider for
trending.
4. Revalidation:
 Periodic revalidation: This type of revalidation shall be done on periodic basis as per
specified frequency. The revalidation shall be governed by the Change Control
procedure.
 Revalidation after any change: All validated equipment, systems, processes, products etc.
shall be continuously monitored for any change, to be considered for revalidation of the
same.
 Revalidation / Requalification [Verification of validation] shall be considered in the case
of :
 Equipment / Instruments / System:
1) Substitution of existing equipment with a new equipment /instrument/System.
2) Change of site /location of the equipment / instrument / System from qualified existing
place to other place.
3) Any major modification in the existing equipment / instrument /System since purchase
which can have an adverse effect on the quality and efficacy of the finished product.
 Manufacturing Process:
A change in the validated manufacturing process that has an effect on the quality and
efficacy of the finished product, which includes a change in the following:
1) Master formula or manufacturing process.
2) Raw Materials
3) Equipment
4) Batch Size
5) Change in manufacturing site or location.
1. Cleaning validation:
Definition:
· Validation of the process by which the equipments are cleaned is called as cleaning
validation.
Objective:
 Cleaning validation is an important mechanism to protect the pharmaceutical products
from cross contamination. A pharmaceutical product can be contaminated by previous
product residues, traces of cleaning agent, micro-organisms or any foreign particle as
borne particles, dust, raw materials etc.
 This should be performed to provide a documented evidence that the procedure being
followed for cleaning of equipment and accessories is effective and removes residues of
previous batch / product up to a predetermined acceptance level, using a well defined
protocol and acceptance criteria.
 For equipments which are not product specific, cleaning procedure for such equipment
should be able to ensure that it can consistently remove residues to the predetermined
level.
Procedure:
 There are two methods employed for sampling during cleaning validation. These are Rinse
and Swab method. Rinse method will be applicable when swabs are not practically
possible.
 Cleaning procedures for products and processes, which are very similar are do not need to
be individually validated. Representative of similar range can be selected to justify the
validation programme, which addresses the critical issues relating to selected products and
processes.
 A single validation study under consideration of the “worst case” can be carried out on
the basis of the maximum strength, potency, solubility and LD50. The cleaning validation
can be evaluated,
1. For highest strength product in multi strength products or all products.
2. For highest potency product in all products.
3. For least solubility in common cleaning solvent i.e. Water.
This “worst case” term can also be referred as “bracketing”. And such approach is called as
matrix approach.
 Three cleaning validations exercise shall be performed and shown to be successful in order
to prove that the method is validated.
 The documentation of cleaning validation shall include validation protocol, cleaning
procedures, sampling plans, surface area calculations, testing procedures and executed
record of the cleaning event, a record of the sampling and testing events and a validation
report which contains clear conclusions against acceptance criteria.
 This validation shall covers sanitation, microbiology as well as removal of external
agents like detergents, using sampling techniques capable of detecting and measuring to
very low levels wherever applicable.
 There are two criteria’s for the cleaning validation, one is dose criteria and second is 10
PPM criteria.
 Validated analytical methods used for cleaning validation shall have sensitivity to detect
residues or contaminant of previous product. The detection limit for each analytical
method should be sufficiently sensitive to detect the established acceptance level of
residues or the contaminant
 Equipment surface area calculation:
1. The product contact surface area for each equipmenshall be calculated by
theoretically breaking down the equipment in to basic geometric shapes
[cylindrical, cubical, cone, rectangle etc.] and then apply to relevant area
calculation formulae.
2. Amount of contaminant, mix from previous product to next product, depend on
the common surface area of equipment used for both previous and next product.
Responsibility:
 Quality Assurance:
Generation of validation protocol
Sampling during validation
Review and compilation of validation data & certification
 Production:
Ensuring cleaning of equipment

1. Utilities Validation:
 Equipments / Machineries used for plant utility as,
1. HVAC system
2. Water system
3. Pure steam generator
4. Compressed air system
1. HVAC system:-
 Air Handling Unit system, ventilation system, and evaporating system are the part of
HVAC system which is one of the utility have directly or indirectly impact on products.
 Total ____ number of independent air handling units, _____ number of ventilation systems
with supply and exhaust duct have been provided in the facility. Each critical operational
area has a dedicated air-handling unit (AHU) and has temperature and humidity controls.
Each room is provided with terminally filtered air, as per the requirement of operation, to be
carried out in the room. Total ___ number of evaporating units in service floor are provide
 The core corridors are provided with controlled environment. Pressure balancing of
each room has been done to avoid any cross contamination, by any ingress of air /
drug product from adjacent areas.
 There is provision to automatically control and record temperature and percentage
relative humidity & monitor and record the pressure differential across Rooms, by
means of a computer interface.
 This system is qualified initially, monitored at regular intervals and revalidated once
in a year in oral dosage form area.
 Initially Temperature control test, Humidity control test, Air velocity & number of air
changes test, Differential Pressure Control test, Air borne Particle Count test,
Microbial count test, Air flow direction test shall be conduct to perform the system.
 Limits for each test shall mentioned in the validation protocol as acceptance criteria.
2. Water system:-
 Water system is one of the utility which have directly or indirectly impact on
products. There are mainly three types of water system as follows,
Raw water system [Potable water]
DM water system [Deionised water]
Purified water system
 New water system shall be established and use for regular purpose after one year
validation study includes the results of chemical and microbiological quality of the
water.
o For qualifying the DM water system & purified water system, Chemical and
Microbiological Test shall be conduct mentioned as follows.
o Temperature, PH, Conductivity, Colour, Total hardness, Total dissolved solids,
Turbidity, Alkalinity and presence of ions or minerals, Microbial counts, pyrogens
and endotoxins. Test method for each tests shall be mentioned in the protocol.
o Location of sampling points shall be done as per specified in Validation protocol or as
per SOP.
o Frequency for all above mentioned tests shall be mentioned in the individual
validation protocol.
o Validation of water system shall divide in to three different phases as follows.
Frequency of sampling, number of samples taken and no. of sampling locations are
reduces from phase I level to next phase level
Phase – I –
Phase – II –
Phase – III –
 Following acceptance criteria:
1. Raw water circulation and its storage shall be requalified if microbial load is
if,more than 500 CFU / ml and chemical water quality shall confirms to In-house
standards.
2. Demineralised water circulation and its storage shall be qualified if microbial load
is if, more than 100 CFU / ml and chemical water quality shall confirms to In-
house standards.
3. Purified water circulation and its storage shall be qualified if microbial load is
if,more than 10 CFU / ml and chemical water quality shall confirms to In-house
standards.
4. For acceptance criteria of chemical and microbiological tests of purified
water,USP – 41 [NF – 36] shall be refer.
 Sanitization of purified water system shall be done after 15 days
 Water system shall be revalidate if there is any major change, replacement or
modification in existing system. It shall be periodically revalidate or verified once
in a year on the basis of monthly, weekly or daily testing data as per scheduled
trend.
4. Compressed air system:-
 Compressed air system is one of the utility which have directly or indirectly impact on
the quality of the product.
 Sampling locations shall be mentioned in the validation protocol. Sampling method of
Compressed Air shall be carried out as per respective Standard Operating Procedure.
 Following test shall conduct to qualify compressed air system. Limits or Acceptance
criteria for each tests shall defined in the validation protocol.
1. Water vapour: Dew point and moisture content in air shall identify.
1.1 Pressure Dew point : 0 to + 3° c.
1.2 Atmospheric Dew point : – 15 to – 20° c.
2. Compressed Air must be oil free so during the course of generation it
does not comes in contact with Oil.
3. Hydrocarbons should be less than 5 mg / m3.
4. Micro organisms should be less than 3 CFU/ m3.
5. Particulate matter such as fibres and metal particles should be NMT 100 particles of 0.5
mper cubic feet of air.
6. Compressed air system should meet the class 100 requirement.
 Frequency of different tests of different frequency should be specify in to the validation
protocol.
 Data of chemical and microbiological analysis collected monthly or quarterly shall be
reviewed and trend shall be prepared for year.
 Based on the trend data of the year summary report shall be prepared and shall be
approved at unit levels.
 Compressed Air System shall be revalidate if there is any major change, replacement or
modification in existing system. It shall be periodically revalidate or verified once in a
year on the basis of monthly and yearly testing data as per scheduled trend.
Note: During validation program of above described utilities some tests were conducted by
external party and some tests were in-house, specified in validation protocol.
10.0 ACCEPTANCE CRITERIA

10.1 The specific acceptance criteria for the experimentation results, during validation, shall be
defined in detail in the respective validation protocol. Recognised national or international
standards shall be cited for reference.
11.0 RISK MANAGEMENT STRATEGY
11.1 Risk: It is defined as the combination of like hood and consequences of specified hazardous
event occurring.
11.2 Hazards: It is defined as the source or situation with potential for harm in terms human
injury or ill health, damage to property, damage to work place, damage to environment, or a
combination of these.
11.3 Any aspect of the operation that can affect the quality attributes i.e. Identity, purity,
strength, safety of the product directly or indirectly, obviously that can affect the health of
customer, that’s why, assessment of impact of risk requires.
11.4 This shall be based on the comprehensive understanding of the product, process, system and
components. Where possible this assessment of impact shall be defined in the user requirement
specification & process validation.
11.5 Risk and issue management strategy:-
Sources of risks: Risk sources are broadly categorized into,
 New project
 Introduction of new equipments in to the existing facility
 Changes in the existing facility or utility or equipments
 Introduction of new product
 Change in the approved vendor.
11.6 Method of Risk identification and Evaluation:
Impact assessment: The risk is identified and categorized in to impact and no impact.
Identify the system
Develop system boundaries
Does the system have an direct impact on product quality
Is it linked with direct Direct impact
impact system
No impact system Indirect Impact Develop supporting rational
11.7 Based on the findings, if the impact of the risk is direct or indirect one, then the extent of
validation is decided i.e. whether it requires a process, equipment, analytical method, cleaning
process or vendor qualification.
11.8 Risk categorization, validation priorities, schedule preparation, depth of

validation including timelines shall be determined by the functional team members from the
production, QA, QC and Engineering.
11.9 When a new product is introduced in to the existing system, the risk is assessed by using
matrix vs. does form which is evaluated in the product development plan for the process
validation and cleaning validation.
11.10 Impact assessment: The applicability of any thing of the following criteria was taken as an
indication that the system has direct impact or indirect impact on the product. Systems such
provides Utility which has direct contact with the product are compressed air, purified water,
Pure stem and HVAC system
Name of System /
Description Equipment / Direct impact Indirect impact Remark
Instrument
Area — Y — —
HVAC System Y — —
Compressed air Y — —
Utilities Purified water Y — —
Potable water N Y —
Pure steam Y Y —
All equipments
used in the
Equipments Y — —
manufacturing
processes
All equipments N Y —
or machineries
used for storage
12.0 STANDARD OPERATING PROCEDURES
12.1 The Standard Operating Procedures relevant to the equipment, process,and analytical
methods shall be available at individual site.
13.0 CHANGES AND MODIFICATIONS:

13.1 Changes and modification to the validation systems:
Any changes or modifications to the validation protocol, test reporting formats and other related
documents must be approved by the validation team prior to becoming effective through a
‘Change Control’ system.
13.2 Changes and modification to the validated systems:
All changes or modifications to a validated systems must be evaluated and approved by
following ‘Change control system’. A supplement to be attached to the revised protocol to
reflect the approved changes as it may be deleted part or additional part in the validation
protocol.
14.0 VALIDATION SCHEDULE
14.1 The Validation for equipment, instruments, systems and processes which requires to be
periodically revalidated at defined frequency as per individual validation protocol within ± 1
month of the due date.
15.0 GLOSSARY
1. Acceptance criteria:
The product, equipment, and /or process specifications and limits, such as acceptable
quality level and unacceptable quality level, that is necessary for making a decision to
accept or reject.
2. Calibration:
Demonstrating that a measuring device produces results within specified limits of those
produced by a reference standard device over an appropriate range of measurements. This

process results in corrections that may be applied if maximum accuracy is required.
3. Change control:
A formal system by which qualified representatives of appropriate discipline reviewed proposed
or actual changes that might affect a validated status. The intent is to determine the need for
action that would ensure and document that the system is maintained in the validated status.
4. Certification:
Documented testimony by qualified authorities that a system qualification, calibration, validation
or revalidation has been performed appropriately and that the results are acceptable.
5. Critical variable study:
A study that serves to measure variables or parameters , critical to the satisfactory operation of a
piece of equipment or plant and to assure their operation within monitored and controlled limits.
Examples of variables are pressure, Temperature, Flow rates , Time etc.
6. Limit of detection:
The lowest amount of analyse in a sample which can be detected but not quantitiated as an exact
value. The limit of detection is mostly a parameter of the limit test.
7. Limit of Quantitation:
The lowest amount of analyse in a sample which can be quantitatively determined with defined
precision and accuracy under the stated experimental condition. The limit of detection is mostly
a parameter of the limit test.
8. Inspection:
The process of measuring, testing or otherwise comparing the item to requirement.
9. Installation Qualification:
Documented verification that all key aspects of the installation adhere to appropriate codes and
approved design intentions and that manufacturer’s recommendations are suitably considered.
10. Operational Qualification:
Documented verification that the system or subsystem performs as intended throughout all
anticipated operating ranges.
11. Quality control:

The regulatory process through which industry measures actual quality performance, compares it
with standards and acts on the difference.
12. Quality function:
The entire collection of activities from which industry achieves fitness for use, no matter where
these activities are performed.
13. Revalidation:
Repetition for verification of the validation and qualification process or a specific portion of it.
14. SOP: Standard Operating Procedure.
15. State of control:
A condition in which all operating variables that can affect performance remain within such
ranges that the system or process performs consistently and as intended.
16. Validation change control:
A formal monitoring system by which qualified representatives of appropriate disciplines review
proposed or actual changes that might affect validated status and cause corrective action to be
taken that will ensure that the system retains its validated state of control.
17. Validation task report:
A scientific report of the results derived from executing a validation protocol A brief summary
of conclusions from a specific task conclusions report, usually indicating validation success
and designating proven acceptable ranges that have resulted. The conclusions are formally
approved.
18. Validation Master Plan:
A document providing information on the company’s validation activities. It should be define
details of and time scales for the validation works to be performed. Responsibilities relating to
the plan should be stated.
19. Worst case:
A condition or set of conditions encompassing upper and lower processing limits and
circumstances within standard operating procedure, which pose the greatest chance of product or
process failure when compared to ideal conditions. Such conditions do not necessarily induce
product or process failure.
18. Critical Part:
Part of an equipment which can affect the quality of product directly is known as critical part.
Retrospective Validation: -
Retrospective Validation shall be used for facilities, processes, and process controls in operation
use that have not undergone a formal document validation process. Validation of these facilities,
processes and process controls is possible using historical data to provide the necessary
documentary evidence that the process is doing what it is believed to do.
In each case of retrospective validation, it shall be decided which elements of the above fig.3.2.1.
Shall be used.
In general, the Design Qualification (DQ) shall be left out of the retrospective life cycle and
Requalification will have to be done.
3.2.3 Concurrent Validation: -

Validation Master Plan
DQ
Revalidation
IQ
Monitoring OQ
Maintenance
Change Control
PQ
Cleaning Validation Process Validation

In certain circumstances it may not be possible to compete validation programme before routine used. In
These cases it shall be known in advance that the product. Process and equipments shall be used for routine
use.
Each concurrent validation step shall be described in Qualification/Validation documents. In these
documents,
the test methods for validation and acceptance criteria for the results are specified, except for the
Validation
Master Plan and the Validation report.

3.3 Elements of Qualification / Validation
3.3.1 Design Qualification (DQ):
The purpose of the Design Qualification is to establish documentary evidence that the equipment design
meets the process requirement for the manufacturing of Pharmaceuticals formulation at HMA MEDICAL
Limited, Ilorin (Nigeria). The design qualification contains the design of equipment required for
manufacturing of product and should agree with the design specification of customer.
In the design qualification process, all qualified personnel from various departments of the company shall
be involved.
3.3.1 Design Qualification (DQ): - (Continue...)
The Design Qualification is divided into the following sections:
1) Protocol: -
 Introduction & Protocol Approval
 Overview: -
o Objective
o Purpose and scope
o Responsibility
o Qualification team
o Process requirement vs design specification
o Specification provided supplier and given by supplier
o Vendor selection
2) Design qualification report (report shall be prepared as per content provided in IQ-Protocol)
3) Approval procedure
The person responsible from project department shall do the DQ and it shall be reviewed and
checked by person responsible from production and maintenance department respectively.
Finally, design Qualification docket shall be approved by QA Manager.
3.3.2 Installation Qualification (IQ): -
The purpose of the installation qualification is to establish documentary evidence that all parts of
equipment are installed according to the process requirements for the manufacturing in HMA
MEDICAL Limited, Ilorin (Nigeria). It is documented that the operating criteria for the equipment,
as installed are in compliance with the plant functional specifications.
The IQ refers to as possible engineering documents (e.g., equipment drawing, calibration of

equipment, plant functional specifications etc.) To avoid redundant documentation and to minimize
overheads of updating.
The Installation Qualification is divided into the following sections:

1) Protocol: -
 Introduction and protocol approval
 Overview: -
o Objective
o Purpose and scope
o Responsibility
o Description of equipment
o Equipment details
o Design parameters
o Installation checks
o Utility services (if available)
o Procedure
o Acceptance criteria
2) Installation Qualification report (report shall be prepared as per content described in the IQ-
Protocol)
3.3.3 Operational Qualification (OQ): -
The purpose of the operational qualification is to establish documentary evidence that the
equipment and its accessories are capable of operating as per stated ranges and designed criteria.
To start the OQ process for given equipment, it is necessary that the IQ process for same equipment
has been completed. The witness shall be available by signature to ensure that the test procedure
carried out by the operating person is in accordance with their test specifications.
The operational qualification is divided into the following sections:
1) Protocol: -
 Overview: -
o Objective
o Purpose and scope
o Responsibility
o Description of equipment/system
o Procedure
o Qualification methodology
o SOPs of operation, calibration, maintenance, training, cleaning etc.
o Utilities services
o Calibration of measuring instruments
2) Operational Qualification report (report shall be prepared as per content described in the OQ-
Protocol)
3.3.4 Performance Qualification (PQ): -
The purpose of the performance qualification is to establish documentary evidence that the product
manufacturing by using the equipment shall give consistent quality of product that meets the
predetermined specifications.
The PQ includes critical process parameters and critical quality attributes. To start the PQ process
for given equipment, it is necessary the OQ process for same has been completed. The witness shall
be available by signature to ensure that the operating and test procedure carried out by the operating
person is in accordance with their teat and operating specifications.
The performance qualification is divided into the following sections:

1) Protocol:
 Overview: -
o Objective
o Purpose & scope
o Responsibility
o Procedure
o Critical parameters
2) Performance Qualification Report (report shall be contain certificate of analysis, yield of product,
critical parameters etc.)
3) Approval procedures
3.3.5 Process Validation (PV): -
The Purpose of Process Validation Is to Provide Documentary Evidence That the Process within
their Specified design parameters Is capable to produce consistent quality product of predetermined
Quality.
All Qualification Procedures for Equipment and Services of the Manufacturing Process Must Be
Completed Before Starting Process Validation Process.
 The Process validation plan shall cover the following features:

 Which manufacturing process must be validated (Product matrix)
 Which kind of validation (Prospective, or concurrent) must be done
 Schedule of the validation of product process
 Number of batches that must be used for validation (normally 3batches shall be taken for
Prospective and Concurrent validation)
 Responsibilities
 The Process validation program shall also contain the following key aspects:
 History of development and a description of the product (if available)
 A manufacturing procedure and flowchart of the manufacturing process
 A list of Raw material
 A list of all equipment required for production.
 Utilities
 A list of production stages that may be critical for product quality
 A list of quality parameters
 A schedule for Process validation test procedures
 Sampling procedures
 Specification finished product
 Acceptance criteria
Process validation protocol shall be prepared before starting of Process validation, covering all
above points. Process validation report shall be prepared as per content described in protocol. After
completion of Checking and Reviewing procedure, Q.A Manager shall state his conclusion in the
document.
3.3.6 Cleaning Validation (CV): -
The purpose of cleaning validation Is to provide documentary evidence that ensures that the cleaning
procedure being used is suitable and delivers consistently, results for cleaning of equipment to
obtain an acceptable level of cleanliness.
The Acceptance criteria for the Cleaning Validation:
No Residue Shall Be Visible, On The Equipment Surface, After Cleaning Procedures Are
Performed.
No More Than the Limit Specified of the Residue Shall Remain, As Residue In Any Equipment,
After Cleaning Procedures Has Been Done. Total Residue of All Equipment Observed in Rinse
Sample Shall Be Less Than the Specified Limit.
Total Residue of All Equipment Observed in Swab Sample Shall Be Less Than the Specified
Limit.
First Batch of the Next Product, Taken After The Cleaning Procedures Are Performed, Shall Pass
Predetermined Specifications.
At Least Three Consecutive Cleaning Runs / Opportunities Shall Meet the Above Mentioned
Acceptance Criteria, Before The Cleaning Procedures Can Be Considered as Validated.
For Multi-Purpose/Dedicated Equipment, It Is Acceptable to Visually Confirm that The Equipment Is

Clean After Batch-To-Batch Cleaning Procedures. Therefore, Following Consideration Towards
Cleaning Validation for Such Equipment May Not Be Necessary.
 The Cleaning Validation Plan Shall Contain, For Example,

 Which Manufacturing Processes Must Be Validated
 Which Kind of Validation (Prospective, Or Concurrent) Must Be Done
 Schedule of the validation of Product Processes
 Number of batches that must be sued for validation (normally 3 batches shall be taken for
prospective and concurrent validation)
 The following points shall be included in the cleaning validation program.
 Purpose of validation
 Contents of sops and Cleaning procedure
 Method validation of test procedure
 Methodology of Cleaning validation
 Sampling Procedure
 Acceptance Criteria
3.3.7 Validation Report: -
The validation report refers following sub-sections:

 Qualification : Includes DQ, IQ, OQ, PQ

 Process validation : PV
 Cleaning validation : CLV
Contents: A detailed discussion of the following points shall be included in validation report
 Changes and deviations of the qualification /validation activities from the documentation shall be
listed. The measures taken instead must be justified and incomplete measures must be listed.
 Critical points found during qualification/validation shall be listed and the measures taken
described.
 The validation report shall include overview of all documentation including annexure.
 At the end of the validation report, a conclusion shall be given as to whether or not the equipment
and the process have the status “qualified /validated”.
3.3.8 Change of Documents
If it is necessary to edit or remove test specifications from the documentation, this shall be done
according to the following procedure. The version number of the test specification shall be
increased by one after specification is edited.
 The results of the test shall be updated.

 The history shall be updated
 The table content shall be updated
The changes shall be approved by qualified personnel by signature on a new coversheet. (The approval is
valid for the changes only
4.0 REVALIDATION
The purpose of Revalidation is to maintain the validated status of plan, equipment and manufacturing
process.
The reason for starting of revalidation include:
 The transfer of a product from one plant to another: -
For the transfer of a product from one plant to another qualified production plant, it is essential to
revalidate the entire manufacturing process in the new plant. Several new critical or non-critical
parameters must be determined during revalidation.
 Revalidation shall be necessary for any of the following reasons:
 Change in the plant

 Change in the manufacturing process
 Change in the raw material
 Change in the vendor of critical raw material
 Change in the packaging material
 Change in the cleaning processes or agents
 Change which can affect the quality and effectiveness of product
The scope of the revalidation procedures shall depend on the extent of the changes and the effect upon
the product.
5.0 FACILITY DESCRIPTION
HMA MEDICAL Limited, Ilorin (Nigeria) is a Medical Device Manufacturing company having its
product marketed to accredited distributors.
Quality Assurance Department:
 Quality Assurance
 Quality Control
Technical Department:
 Production
 Engineering
Human Resource/Administration Department:
 Marketing
 Personnel
 Accounts
 Procurement
 Warehouse
 Dispatch
6.0 BUILDING DESCRIPTION
The design and material used for the construction of building is according to cGMP regulations. All walls,
ceilings, and flooring inside the production area are designed as per cGMP regulations.
The building is divided into two floors:

1) Production area (ground floor)
2) Service floor for utilities.
Fig 1.0 process flow chart
Supplied Barrel Moulding Barrel Printing

Raw Materials Moulded Barrels
QC Analysis Q.C.
In-Process Check Q.C.
QC Passed Printed Barrels
Raw Material
Plunger Moulding Moulded Plungers

Syringe Assembling
Dispensing of Raw
Materials Q.C.
In-Process Check
Assembled
Hub/Cap Moulding Needle Assembling
Assembled Needles Syringes
Q.A.
Verification Check
Q.C. Blister Packing
In-Process Check
Quarantine Product Sterilisation by E.O. gas Packaging of Finished
products
QA Sampling
Physicochemical Analysis of samples Sterility test of product samples
Rejection of failed product Release of passed product


6.1 EQUIPMENT DESCRIPTION
S. Name of Equipment No of Location Make
No Equipment
1. Injection Moulding 14 Production Area China

Machines
2. Barrel Printing Machines 5 Production Area China
3. Needle Assembly Machines 2 Production Area China
4. Syringe Assembly 4 Production Area China

Machines
5. Blister Packing Machines 5 Production Area China
6. Ethylene Oxide 2 Production Area China

Sterilization Machines
7. 150 grams Weighing Scale 4 Production Area China
8. 250 KVA Generator 1 Maintenance
11. Medical Needle 1 Quality Assurance China

Penetration Force Tester
12. Medical Needle Bond 1 Quality Assurance China

Strength Degree Tester
13. Medical Plunger Actuation 1 Quality Assurance China

Force Tester
14. Medical Syringe Liquid 1 Quality Assurance China

Leakage Tester
15. Ultrasonic Cleaning 2 Quality Assurance China

Machine
16. Laboratory Auto clave 2 Quality Assurance China
17. Water Distiller Machine 1 Quality Assurance China

18. PH Meter 1 Quality Assurance China
19. Anemometer 1 Quality Assurance China
20. Dust Particle Counter 1 Quality Assurance China
21. Air Sampler 1 Quality Assurance China
22. Air flow Rate meter 1 Quality Assurance China
23. Lux meter 1 Quality Assurance China
24. Son meter 1 Quality Assurance China
25. Unified Thermometer 1 Quality Assurance China
26. Analytical Weighing 3 Quality Assurance China

Balance
27. UV-VIS 1 Quality Assurance China

Spectrophotometer
28. Incubator 5 Quality Assurance England
29. Conductivity meter 1 Quality Assurance China
30. Ovens 1 Quality Assurance China

7.0 VALIDATION PROGRAM OVERVIEW
7.1 Validation responsibilities:
The validation team shall be responsible for validating the facility. The QA Manager shall be
responsible for approval of all validation protocols, final reports, SOPs, chemical and
microbiological testing, as well as other critical cGMP documentation.
7.2 Design and validability review:
The validation of company’s facility shall start with the initial conceptual design.
Design review include,

 Architectural layout
 Civil work execution
 HVAC system
 Water system
 Personnel and material flow
 Equipment
 Material receipt, storage and dispatch
 Quality assurance/control testing and inspection
 Maintenance and calibration
7.3 Installation Qualification protocols
The installation qualification (IQ) verifies that the equipment or system and/or corresponding
utilities are installed in accordance with design specifications, manufacturer’s recommendations,
and cGMP. The IQ shall confirm that critical instruments are calibrated and that system
components are properly identified. Any exceptions shall be documented, corrected and/or
justified.
Typical installation qualification test functions include, but are not limited to the following:
 Manufacturer specification
 Purchase order specification
 Piping and installation drawing
 Construction and installation
 Test equipment calibration
 Required spare parts
 Cleaning
 System installation compliance to cGMP
The IQ shall be performed in accordance with a reapproved written protocol.

7.4 Operational Qualification Protocols
The operational qualification (OQ) verifies that the system or equipment operates in
accordance with design specification, manufacturer recommendations, and cGMPs. OQ testing
is designed to stimulate the full range of operating conditions to establish a system capabilities
baseline and to ensure that the system operates as intended.
Typical Operational Qualification test functions include, but are not limited to the following:
 General operational and control verification

 Functional testing of computer-related systems
 Specific operational testing
 Utility system
 Calibration of test equipment
 Standard operating procedures (SOP)
 Cleaning procedures etc.
The Operational Qualification shall be performed in accordance with a reapproved written protocol.
7.5 Performance Qualification Protocols

The performance qualification (PQ) verifies that the performance of critical utility systems or
processes is in accordance with the process requirements. Critical utility system such as
purified water, air, shall be challenged throughout proposed operating ranges for extended
periods of time, while an extensive program of quality monitoring shall be performed. At least
three consecutive batches shall be taken for the performance qualification.
Performance qualification shall be carried out in accordance with a reapproved written

protocol. The specific PQ protocol shall be developed from the finished product specifications,
cGMP requirements, and other specific documents.
7.6 Process Validation Protocols

Process Validation verifies the performance of the overall product manufacturing process.
Process validation shall be performed on the entire product manufacturing process, which shall
include all support, processes, packaging and labelling, critical process parameters, critical
quality parameters, utilities etc.
During process validation, three consecutive batches shall be manufactured and all in-process
and finished product specification shall be verified. Critical parameters shall be set at different
ranges during the manufacturing process to verify that the product consistently meets its
predetermined quality specification over the range of critical parameter settings. All equipment
processes, and testing procedures must be validated prior to the start of process validation.
Process validation shall be performed in accordance with a pre-approved written protocol.

The specific PV protocol shall be developed from finished product specification, the
manufacturing process capability, cGMP requirements and other specific documentation. These
along with the acceptance criteria shall be approved by Head QA.
7.7 Validation master report

The final report shall summarize the result of the validation process and provides an analysis
of the test data in support of the conclusion that the equipment or system demonstrates
consistent performance within the established acceptance criteria.
Deviations and/or exceptions to approved protocols, along with suitable explanations and
justifications, shall be documented in the final report.
7.8 Validation package

The final reports, completed protocols, and all supporting documentation shall be placed into
final report package for checking, reviewing and approval.
Deviations and/or exceptions to approved protocols, along with suitable explanations and
justifications, shall be documented in the final report.
7.9 Certification for use in manufacturing

Validation of a system /equipment/process shall be considered complete when its respective
protocols identified in the validation master plan have been successfully implemented and the final
report has been approved.
A system /equipment/process shall be certified for use in manufacturing upon completion of the
following:
 Applicable protocols have been successfully completed and the final report has been approved.
 Applicable SOPs have been approved.
 Validation shall be completed for all utility systems that support the equipment or process, and
for all equipment that supports a process
 All system /equipment/process shall be under calibration criteria
7.10 Required protocol and procedures for production

S.No System /Equipment Protocols SOP’s
DQ IQ OQ PQ CL FR OP PM CL CA
L
01 √ √ √ √ √ √ √ √ √
02
03
04
Here, DQ: Design Qualification IQ: Installation Qualification.
OQ: Operational Qualification PQ: Performance Qualification
CL: Cleaning Procedure CAL: Calibration Procedure

FR: Final Report OP: Operating Procedure
CV: Computer Validation PM: Preventive Maintenance Procedure
8.0 Calibration program summary

Calibration is defined in related SOPs
 All process and facility instruments are classified to their calibration status into one of the three
following categories:
1. Calibration
2. Preventive Maintenance
3. No calibration/ no preventive maintenance
 All instruments providing critical process information necessary to make a quality
documentation shall be calibrated with the available standards.
 User department is responsible for scheduling, tracking and maintenance of standards, record,
etc.
 All instruments providing critical process information shall be calibrated before performing the
validation studies.
List of equipment accordingly:
1. Calibration:
2. Preventive maintenance:
9.0 PREVENTIVE MAINTENACE PROGRAM SUMMARY

An appropriate preventive maintenance program shall be defined for the equipment that shall be
checked at the time of validation
The in-charge of the related area and the engineer concerned shall sign the register and verify if
repairs are required.
10.0 KEY STANDARD OPERATING PROCEDURE (SOPs)
List of key procedures for process operations and maintenance are as follows:
 Raw material issuing system
 Packaging material issuing system
 Manufacturing procedures
 Batch packing record system
 Equipment operating procedures
 Equipment calibration procedure

 Equipment maintenance procedure
 Product release procedure
 Handling out of specification result
 Complaints handling system
 Change control system
11.0 VALIDATION OF BUILDING

11.1 Civil work
Test functions:
 Inspect the facility as per approved layout
 Inspect floors in each room
 Inspect painted surface in each room
 Perform dimensional testing for each room
 Inspect lights in each room
 Inspect utilities into each room
 Inspect all drains
 Inspect all doors and interlocks
Acceptance criteria:
 The facility is constructed in accordance with design specifications and cGMP.
 Doors are opened/closed properly, and interlocks operates in accordance with design
specification
 Floor surfaces are smooth, and free of holes and soft spots
 Painted surfaces have full and smooth coverage
 The length, width, and height of each room conforms to design specification
 All light switches and light should be adequate at all work stations
 All utilities penetration are to be correctly installed, labelled and sealed
 All drains are located according to the design specification
11.2 Drainage system
Test functions:
 Inspect the drainage system as per the approved layout
 Inspect floors drain locations as per the approved layout
 Check that process drains are segregated from the sanitary waste
 Ensure that process drains are provided with deep-seal traps
 The system is constructed and installed in accordance with design specification, manufacturer
recommendations and cGMP.
 Open floor drains are not to be located at core areas

 Process drains are to be separated from sanitary waste drainage
 Process drains have adequate back-flow preventive devices
12.0 VALIDATION OF UTILITY SYSTEMS

This part of validation master plan provides a summary of the key validation test functions and
acceptance criteria for each utility system.
12.1 Water system (DM Water Plant)
Test functions:
 Test the water produced by the system to ensure adequate conductivity
 Check that the holding tank water quality does not change adversely during storage holdings in
tanks.
 The system should be installed in accordance with design specifications, manufacturer

recommendation, and cGMP
 Instruments should be calibrated, identified and entered into the calibration program
 General controls and alarms should be operated in accordance with design specification
 The system should be operated in accordance with design specification throughout the
operating range or range of intended use
 System regulators must operate within predetermined operating pressure
 The system capacity must be sufficient to operate all systems at peak demand periods.
12.2 Compressed air

Test functions:
 Perform installation qualification

 Perform general operational controls verification testing
 Operate system throughout the range of operating design specification or range of intended use
 Verify that the compressed air system is capable of supplying pressurized compressed air to all
use points, perform an operational test of the distribution system and pressure regulators by
monitoring the pressure output at the respective use points
 Perform a capacity test to verify that the system is capable of supplying the required pressure,
and flow rate at each use point
 Verify that in-line filters are integrity tested. Confirm that all documentation clearly indicates
acceptable test result
 Perform viable particulate count and microbiological testing
 The system should be installed in accordance with design specification, manufacturer

recommendation and cGMP. Instruments should be calibrated, identified, and entered into the
calibration program
 General controls should be operated in accordance with specification design
 The compressed air distribution system must consistently deliver pressurized compressed air to
the use point at the design pressure as specified
 All in-line filters should be integrity tested and qualify per manufacturer’s operating
specifications.
12.3 Purified water

Test functions:
 Perform installation qualification
 Perform general operational controls verification testing
 Verify that the purified water system is capable of supplying water to all use points, perform an
operational test of the distribution system and pressure regulators by monitoring the pressure
output at the respective use points
 Perform a capacity test to verify that the system is capable of supplying the required water,
pressure, and flow rate at each use point
 Verify that filters are integrity tested. Confirm that all documentation clearly indicates
acceptable test result
 Perform water analysis chemical as well as microbiological
 Check bio-burden if necessary
 The system should be installed in accordance with design specification, manufacturer

recommendation and cGMP. Instruments should be calibrated, identified, and entered into the
calibration program
 General controls should be operated in accordance with specification design
 The purified water distribution system must consistently deliver water to the use point as per
the design specified
 All filters should be integrity tested and qualify per manufacturer’s operating specifications.
 The microbiological test result must meet the approved specification requirements
PROCESS FLOW. CONTROL VARIABLES, AND MEASURED RESPONSES
Flow chart for Syringe and Needle Parts (Barrel, Plunger, Cap and Barrel Printing
Barrel Moulding
Hub) Moulded Barrels
Q.C.
Q.C.
In-Process Check In-Process Check
Printed Barrels
QC Analysis Supplied
Raw Materials
Plunger Moulding Moulded Plungers

Syringe Assembling
QC Passed Q.C.
Raw Material In-Process Check
Assembled
Hub/Cap Moulding Needle Assembling Syringes
Dispensing of Raw Assembled Needles
Materials
Q.C. Blister Packing
In-Process Check
Q.A.
Verification Check
Quarantine Product Sterilisation by E.O. gas
Packaging of
Finished products
QA Sampling
Physicochemical Analysis of samples Sterility test of product samples
Rejection of failed product Release of passed product

14.0 QUALITY CONTROL LABORATORY VALIDATION
The quality control laboratory serves one of the most critical functions in HMA MEDICAL Ltd.
Consequently, a comprehensive validation program shall be initially performed for procedures
and equipment used for testing of all products, as well as any analytical procedures. Thereafter,
the analytical methods requirements and resulting validation shall be evaluated and performed
as required for each new product.
14.1 Laboratory equipment qualification
Laboratory equipments such as incubators, refrigerators, polar meter, etc. Shall be qualified using the
same approach as that used for process equipment and utility systems.
Validation of Facility/Equipment/Systems to be carried out:
 Validation of Facility/Equipment/Systems includes designs, installation, and operational

qualification
 Performance qualification carries through process validation for an individual product
INSTALLATION QUALIFICATION:
Test functions:
 Checks for the fulfilment of the manufacturer’s recommendations (utilities such as electricity,
water and environmental conditions such as humidity, temperature, vibration level and dust)
and allow sufficient shelf space for the equipment, SOPs, operating manuals and software.
 Describe vendor selection, instrument design parameter and its capacity in validation docket
 Compare equipment, as received, with its purchase order (including software accessories, spare
parts)
 Check documentation for completeness (operating manuals, maintenance instructions, standard
operating procedures for testing, safety validation certificates)
 Checks equipment for any damages
 Switch on the instruments and ensures that all modules power up and perform an electronic
self-test.
 Install software on computer following the manufacturer’s/supplier’s recommendation
 Verify correct software installation, e.g., are all files loaded. Utilities to do this should be
included in the software itself
 Make back up copy of the software and configure peripherals, e.g., printers and equipment
modules
 Identify and make a list with a description of all hardware, include drawings where appropriate
 List equipment manuals and SOPs
 Prepare an installation report
 The system should be installed in accordance with design specifications, manufacturer’s

recommendations, and cGMPs. Instruments should be calibrated, identified, and entered into
the calibration program
 The safety device should operate as specified in the manual
OPERATIONAL QUALIFICATION:
Test functions:
 Calibrate the parameters like temperature, rpm, gauges, dimension etc.
 Check functional parameters of operation
 If calibration and functional operation is not satisfactory, get it rectified from the engineer and
recheck the instrument
 If calibration and functional operation is satisfactory, proceed for performance qualification.
 The system should operate as per testing requirement
 Calibration and function operation must give satisfactory result
PERFORMANCE QUALIFICATION:
Test function:
 Carryout the performance of instrument as per standard calibration procedure of the respective
instrument
 Measure performance characteristic of instrument and compare with the document preset limit
 If performance is satisfactory, instrument may be released for use
 If performance is not satisfactory, call service engineer/vendor for necessary corrective actions
 Record all the result and get approved
 All the documents like purchase order, supplier’s validation certificates, list of manuals etc., to
be attached with the report of performance qualification
 The system should perform in accordance with manufacturer recommendation

 Instrument should be calibrated, identified and entered into calibration program
CALIBRATION:
 Each equipment of quality control should undergo calibration program
 Each equipment should be calibrated before use
 Analytical weighing balance should be calibrated with standard weights daily

 Prepare the calibration format for each instrument. All records should be stored in calibration
file
 If calibration results are not acceptable, rectify the error if any
 Calibration frequency of QC is as follows:
METHOD VALIDATION:
 Each analytical method should be validated before use
 Method validation should contain following performance parameters.
 Precision
 Accuracy
 Selectivity & specificity
 Limit of detection
 Limits of quantification
 Linearity and range
 Ruggedness or robustness
 Stability of analytical solution
 Check following parameters during quantitative analysis of active ingredients and finished
product
 Accuracy
 Precision
 Specificity
 Linearity
 Range
 Check following parameters during quantitative analysis of impurities in RM & finished
products
 Accuracy
 Precision
 Specificity
 Check following parameters during quantitative analysis of finished products before cleaning
validation.
 Blank interference
 Stability of analytical solution
 Linearity
 Range
 Limit of quantification
 Limit of detection
CLEANING VALIDATION:
 Cleaning procedure used to clean the equipment should be validated

 Analytical method used for testing of cleaning validation samples should be validated
 Perform the test and sampling as described in cleaning validation protocol and specific SOP for
the cleaning of such equipment
 Equipment should be cleaned up to acceptance level of cleaning
 Perform both rinse and swab sampling method
 Prepare the cleaning validation report.
14.2 Computer related systems used in quality control laboratory
 Computer related systems used in the laboratory should be validated

 Data entry authorisation (e.g. password protected)
 Security of the data base should be maintained.
15.0 Validation criteria and qualification frequency

S.N System /Equipment Protocols Frequency of Validation
D IQ O P C CL PQ O CAL
Q Q Q L P
01
02
03
04
05
06
07
08
09
10
11
12
13
14
15
16
17
18
19
20
21
22

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HMA MEDICAL LTD Page 1 of 64

Plot 9, Block 4, Transit Camp Road, Ilorin, Kwara State, Nigeria.

VALIDATION MASTER PLAN

SR. NO. CONTENTS PAGE NO.

6.1 Validation Team Constitution

7 FACILITY DESCRIPTIONS AND DESIGN

7.1 General Description and Design Concept

7.2 Description of Products

7.3 Description of Process

7.4 Description of Equipments

8 VALIDATION PROGRAM AND SUPPORTING SYSTEMS

8.1 Fundamentals of Validation Program

8.2 Supporting systems for validation program

9 VALIDATION CONCEPT AND TYPES

11 RISK MANAGEMENT STRATEGY

12 STANDARD OPERATING PROCEDURES

13 CHANGES AND MODIFICATIONS

13.1 Changes and modification to the validation systems

13.2 Changes and modification to the validated systems

1.0 VALIDATION APPROVAL SECTION

DESIGNATION NAME SIGNATURE DATE

Quality Assurance Executive

DESIGNATION NAME SIGNATURE DATE

Quality Control Manager

DESIGNATION NAME SIGNATURE DATE

Quality Assurance Head

DESIGNATION NAME SIGNATURE DATE

Group Managing Director

VALIDATION MASTER PLAN DATE: JUNE, 2023

VALIDATION MASTER PLAN DATE: JUNE, 2023

VALIDATION MASTER PLAN DATE: JUNE, 2023

 Will satisfy the regulatory requirements

Quality Assurance: it is responsible for,

7.1 General description and design concept of facility

8.2.1 Protocol and Documentation System

coordinating of the validation program and approving all validation activities.

9.2 Validation Types

Volume (M3 or Ft3),

9.2.2 Analytical Method Validation:

9.2.3 Vendor Qualification:

Control system Validation:

Qualification (DQ/ IQ/ OQ/ PQ) of Computer Software:

 Floppy disk drive

1. Design Qualification (DQ)

 Functional Requirement specification ( FRS): Specification provided by the supplier

2. Installation Qualification (IQ)

the equipment manufacturer.

4. Performance Qualification (PQ)

evidence of three full-scale production batches.

Ensuring cleaning of equipment

10.0 ACCEPTANCE CRITERIA

customer, that’s why, assessment of impact of risk requires.

11.8 Risk categorization, validation priorities, schedule preparation, depth of

Utilities Purified water Y — —

used for storage

12.0 STANDARD OPERATING PROCEDURES

13.0 CHANGES AND MODIFICATIONS:

14.0 VALIDATION SCHEDULE

produced by a reference standard device over an appropriate range of measurements. This

11. Quality control:

3.2.3 Concurrent Validation: -

Cleaning Validation Process Validation

Each concurrent validation step shall be described in Qualification/Validation documents. In these