1.0 Purpose
1.1 To provide a clear overview of the validation program including schedule and responsibilities to those performing the validation studies and the Regulatory Authorities
2.0 Scope
2.1 This Master Validation Plan is applicable to the validation exercise to be carried out at “NAME” Pharmaceuticals Ltd.
3.0 Responsibility
3.1 Validation representative/ team member are responsible to execution the validation activities.
3.2 Head
of Quality Assurance holds the overall responsibility.
4.0 Abbreviations and Definitions
4.1
None
5.0 Materials and Equipment
5.1 None
6.0 Precaution / Health and Safety Considerations
6.1
None
7.0 Procedure
7.1 Validation policy
7.1.1 The manufacturing plant shall be commissioned by “Month, Year”. We intend to subject our facility, environment, equipment, utilities, process and product to validation as per the guidelines laid down in this document. It is our endeavor to put in place a quality system to achieve GMP compliance as per National and International Regulatory Requirements. To meet this end a Master Validation Plan has been prepared, which serves as a guideline for the various validation activities to be carried out and as a commitment of NAME Pharmaceuticals Ltd towards the implementation of quality systems.
7.2 Validation Approach: Validation activity shall be organized in following sequence:
7.2.1 Identification of task force for validation activity
Validation
programme is coordinated by a task force comprising of different functions that
are involved in the programme. The
members of this task force are drawn from departments namely Manufacturing,
Quality Control, Quality Assurance and Maintenance. The task force approves and issues written protocols and reviews the
data obtained in order to approve or reject the programme results.
Group 1: Group
dealing with facilities / utilities / equipment
Ø Authority
in-charge for organizing :
Engineering Department
Ø Regulatory
input : Regulatory Department
Ø Design
input : Project Department
Ø Preparation
of Qualification protocols and validation exercise: Engineering Department
Ø Co-ordination
of protocols / report approval : QA & Production Department
Ø Performance
monitoring through analysis : QC Department
Ø Authorized
the protocols / report : Plant Manager
Group 2:
Group dealing with lab controls
Ø Authority
in-charge for organizing : QC
Department
Ø Regulatory
input : Regulatory Department
Ø Preparation
of Qualification protocols and validation exercise: QC & PD Department
Ø Co-ordination
of protocols / report approval : QA Department
Ø Performance
monitoring through analysis : QC Department
Ø Authorized
the protocols / report : Plant Manager
Group 3:
Group dealing with product / process controls
Ø Technology transfer : PD Department
Ø Authority
in-charge for organizing : QA
Department
Ø Regulatory
input : Regulatory Department
Ø Preparation
of Qualification protocols and validation exercise: QA Department
Ø Co-ordination
of protocols / report approval : QA Department
Ø Performance
monitoring through analysis : QC Department
Ø
Authorized the protocols / report : Plant Manager
Group 4:
Group dealing with computer system (software) validation
Ø Authority
in-charge for organizing : IT
Department
Ø Preparation
of Qualification protocols and validation exercise: IT Department
Ø Co-ordination
of protocols / report approval : QA Department
Ø Performance
monitoring through analysis : QA Department
Ø Authorized
the protocols / report : Plant Manager
7.2.2 Defining the
system to be validated
The system and extent of validation shall be defined
prior to the validation exercise. The extent of validation shall meet appropriate requirements to arrive
at desired conclusion after meeting the regulatory requirements and guidelines.
The
system shall be defined explicitly in respective validation protocols. The
experiments and acceptance criteria shall address for the same.
7.2.3 Protocol
preparation / Experimental design
A written plan serving as a guide for executing
validation activities shall be prepared prior to validation exercise. This written plan shall be termed as validation protocol. The
protocol should address
the requirements for validation. It shall contain,
Ø Objective
Ø Responsibility for each activity
Ø Operating and processing instruction for validation
exercise based on corresponding standard
operating procedures
Ø Experimental design
Ø Test parameters
Ø Test process for monitoring
Ø Acceptance criteria for test results
Ø Sample methodology and plan
Ø Identification of worst cases
Ø Material and equipment to be used
Ø Calibration and testing specifications
Ø Format for data handling
7.2.4 Protocol approval
Individual protocol shall be prepared by respective Department personnel and approved by Head of Quality Assurance.
7.2.5 Validation
execution as per protocol & data recording
The approved protocol shall stand as written guidelines
and validation activities shall be executed strictly as per validation protocol. Data generated
following observations and measurement shall be recorded which be subsequently complied as report after
evaluation.
7.2.6 Data
evaluation & conclusions
The observations recorded shall be presented in a manner
to interpret the same easily. Evaluation shall be done and based on which conclusions shall be
drawn for each experiments spelt in the protocol.
7.2.7 Validation
report approval
Based on the conclusions drawn Head of Quality Assurance shall assert his opinion to declare
the validity of the programme.
7.2.8 Process or
equipment / facility transfer for routine use
Any process, equipment or facility shall be put into
effect only after completion of the respective validation programme and
authorization of the programme from Head of Quality
Assurance.
7.2.9 Training
The task force assigned for each group of validation
shall undergo training on validation approach as stated in Validation Master
Plan.
7.2.10 Revalidation
criteria
Revalidation criteria and schedule for validation shall
be explicitly spelt out in the individual validation protocol. The revalidation criteria
and schedule shall be based on scientific standpoint.
In the event of any failure in validation, the cause of
failure should be corrected & documented and the said activity shall be revalidated.
7.3 Types of Validation: Following types of validation
have been identified:
The
facility shall be qualified to ascertain that it meets to the designed and
intended standards. A
Qualification Protocol shall be prepared by Manager Projects. This protocol shall cover the following aspects:
i.
Location of the
facility
ii.
Construction material
and quality
iii.
Painting
iv.
Prevention of entry of
Pests and rodents
v.
Layout facilitating the
linear flow of Men and Materials
vi.
Adequacy of storage
space to aid proper segregation
vii.
Heat Ventilation Air
Conditioning System (HVAC)
viii.
Water System
ix.
Lighting &
Electrical points
x.
Compressed air
distribution
xi.
Drainage system
xii.
Scrap Management
xiii.
Quality Control
xiv.
Effluent Treatment
Plant
xv.
Other Utilities
xvi.
Administrative Office
and Training facility
xvii.
Safety and Security
xviii.
Gardening
7.3.2 Equipment
Quotations shall be invited from manufacturers for each equipment. They shall be evaluated for suitability, past performance history, self-experience, if any and cost.
For each equipment, a specification sheet detailing the user requirements, prepared by Head of respective department and checked by Plant Manager, shall be issued to the chosen manufacturer.
During the fabrication of the equipment a 3-level inspection shall be carried out at the site of the manufacturer.
The
first inspection shall involve:
Stamping on material, material
testing, layout finalization, equipment drawing and drawing release for
fabrication.
The second inspection shall involve:
Inspection of bought out items (by
Vendor/fabricator), In process - fabrication quality check -
suggestion/modification and documentation, orientation with respect to room layout
and suggested and documented suitable changes.
The final inspection shall involve:
Checking of the fabricated equipment
and ensuring the compliance to Design Qualification Protocol.
The qualification of equipment shall be carried out by Engineering, Production and QA personnel. The protocol shall be checked by head of user department, approved by Head of Quality Assurance and authorized by Plant Manager.
7.3.3 Utilities
All the utilities coming in direct contact with
the product shall be validated.
7.3.3.1 Water System
The water system shall be subjected to validation for compliance to chemical & microbiological parameters as per the specification laid down for Purified water in United States / British Pharmacopoeia.
The equipment of the Water System shall be qualified for Design, Installation, Operation and Performance
A protocol shall be prepared by QA, and the validation shall be carried out by Engineering and QA personnel with analytical support from QC. The validation shall be carried out over a period of 12 months in three phases, by gradually reducing frequencies and no. of sampling points.
The protocol shall be approved by Head of Quality Assurance.
7.3.3.2 Compressed air
The compressed air shall subject to validation for moisture content and bio-load.
A protocol shall be prepared by QA, and the validation shall be carried out by Maintenance and QA personnel with analytical support from QC. Compressed air at all user points shall be validated for moisture content and bio-load initially for a period of 3 days. Revalidation shall be carried out annually.
7.3.3.3 HVAC
The HVAC systems shall be qualified for Design, Installation, and Operation & Performance. The HVAC system has been designed to achieve a standard equivalent to Class 100,000 in Production, primary packaging and dispensing (raw materials) areas.
The performance of HVAC system shall be validated for following parameters:
i) Particle count :
The area shall be assessed and validated for the particle count to establish that it confirms to the standards for which it is designed. This activity shall be carried out by an external agency.
The external agency shall be chosen based on their experience, qualification of personnel and calibration of the particle counter to national traceability.
The
particle count shall be done at a frequency of six months for one year and
subsequently it shall be done annually.
ii)
Temperature and Humidity
Mapping:
The area shall be assessed and validated for temperature and humidity mapping to establish that it confirms to the designed standards.
This shall be carried out by monitoring temperature at all the corners and center of the area at regular intervals of 15 min for 3 days.
Where the area is designed for controlled humidity, it shall be validated for humidity mapping to establish that it confirms to designed standards.
iii) Air Changes per hour:
The number of air changes in the areas under a particular HVAC system shall be validated to establish its conformance to the designed standards.
This shall be carried out by initially by the
installing agency. Subsequently it shall be carried
out annually by an external agency.
iv)
Pressure Differentials:
The HVAC system shall be validated for the pressure differentials of each area with respect to the corridor, to confirm that they meet the designed.
This shall be carried out by initially by the
installing agency. Subsequently it shall be carried
out annually by an external agency.
v) Bio-load:
All the manufacturing, primary packaging and
dispensing areas (for raw materials), shall be qualified for bio-load. This
shall be carried out by exposing settle plates in the above areas for 2 hours
in at rest conditions. The bio-load shall comply as per the standards laid out
in USP.
7.3.4 Process
Process validation shall be carried out for all the products manufactured in the facility.
Process
validation shall be carried out for a minimum of 3 consecutive batches.
A comprehensive protocol shall be laid down for validation of process for all products. The validations shall be carried out by a validation team as described in Group 3 (Comprising of PD, Production, QC & QA personnel)
The Validation protocol shall identify the critical
parameters involved in manufacturing and packing and stages to be validated.
Acceptance criteria shall be ascertained for each parameter. A conclusion shall
be drawn based on the observations.
The protocol and report shall be approved by Head of
Quality Assurance.
7.3.5 Cleaning
A comprehensive, scientifically justified and practical cleaning validation protocol shall be laid down for validation of cleaning procedures of each equipment. An acceptance criterion shall be based on the worst case identified by drawing a matrix of the products with respect to their daily dosage and batch sizes. Products with different strengths of same active shall be bracketed.
The validation shall be carried out by a team comprising of Production, QA & QC personnel.
The
protocol and report shall be approved by Head of Quality Assurance.
7.3.6 Analytical Methods
All the analytical methods followed shall be validated as per ICH guidelines.
Analytical
Method Validation shall be carried out by Product Development and Quality
Control personnel. The protocol and report shall be approved by Head of
Quality Assurance.
7.3.7 Personnel
Training shall be carried out on the basis of an SOP and this training shall be spread across the calendar year and will be module based. All the personnel shall be given on-job and periodic GMP training.
The technicians & staff shall be divided into groups. All the employees shall be trained on at least one module pertaining to GMP, each month. The topics shall cover the outline of GMP activities and documents required by the regulations.
The objective will be to impress upon the need and the importance of GMP related activity and to create awareness and understanding of the concepts.
The
performance of the technicians & staff shall be assessed by the way of a questionnaire
at the end of the training session. The answers to these shall be assessed and
re-training needs shall be identified and addressed.
7.3.8 Computer / Software
The software programme used for material management in the plant, shall be validated retrospectively as per the GMP standards and as per 21 CFR part 11 US Federal regulations.
A Validation Protocol and report shall be prepared by the Information Technology Department detailing the following aspects:
a)
Receipt, Issue &
control of Starting materials
b)
Status labeling and
controls for the same
c)
Access control governed
by passwords and restriction of authority for the above functions.
7.4 Validation Schedule
Validation
shall be conducted at regular schedules as mentioned in the individual
protocol. The individual protocol shall also lay down the guidelines for
re-validation.
7.5 Change Control
For any change from the predetermined attributes a Change control procedure shall be followed as per the SOP.
The Change shall be initiated by the concerned
department along with requisite justification and shall be approved by Head of
Quality Assurance.
7.6 Personnel and their Qualifications
The personnel engaged in carrying out validation
activities shall have adequate qualification,
experience and skills appropriate to the respective activity. Personnel shall
be trained and after evaluation only they shall be delegated for validation
activities.
7.7 Supporting Programmes
Validation shall be supported by other programmes that
may include calibration of measuring devices, training of personnel.
Certification of calibration traceable to national standards, safety programmes and documentation
control.
7.8 Annexure
To provide adequate evidence, validation documents shall
include annexure wherever applicable
and they shall include:
Ø Material Specifications
Ø Standard Operating Procedures
Ø Batch Manufacturing Records
Ø Calibration Records and certificates
Ø Pre validation data
Ø Training records
Ø Environmental records
Ø Pre-qualification records
Ø Safety data
Ø List of equipment
8.0 Reference Document
8.1 WHO GMP Guideline trs-986. Annex-2
8.2 In-house
9.0 Annexure
9.1 None
10.0 Revision History
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Version No. |
Brief Reason for the Revision |
Effective Date |
Remarks |
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01. |
New |
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11.0 Training
11.1 Training is required for Officer /Sr.
Officer of Production, Quality Control, Product Development, Quality
Assurance and Engineering Department trained by Head of Quality Assurance.
