SOP for Preparation of Validation Master Plan (VMP)

Purpose

This standard work describes the rationale and methods used to draft and maintain Validation Master Plans (VMP) at PharmaInfo Limited. This Standard Work outlines the process, content, and rationale for facility and project VMP documents.

Scope

This standard work provides guidance for Master Validation Plans utilized to document the validation approach, requirements and justification for the qualification and validation of a facility or project, including but not limited to:

• VMP Purpose and Scope
• Building and Facility Layout
• Process Description and Flow
• Qualification/Validation of:

1. Facility & Utilities
2. Production Equipment
3. Manufacturing Processes
4. Cleaning & Sanitizing
5. Software Systems

• Supporting GMP quality systems to maintain a validated state.

Roles & Responsibilities

Validation activities will be administered and/or carried out based on the roles and responsibilities in the corporate standards. Cite each department’s roles & responsibilities, or reference applicable corporate departmental responsibilities documents.

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Definitions and Acronyms

Master Validation Plan: Documented plan for qualification of a facility/project, which identifies the layout of the operation, associated equipment, utilities and systems to be validated. Provides extent of qualification/validation activities via protocols, SOPs, acceptance criteria & responsibilities.

Validation: Documented evidence that processes, procedures, and equipment consistently lead to predetermined expectations, specifications, and quality attributes. Collection and evaluation of data from the process design stage through commercial production, which establishes scientific evidence that a process is capable of consistently delivering quality products.

Validation Protocol: A written plan stating how validation efforts will be conducted. Includes test parameters, equipment/product characteristics, and acceptance criteria to provide documented evidence that a system, process or equipment meets specifications or intended use.

Acceptance Criteria: Specified indicators or measures employed in assessing the ability of a component, structure, or system to perform its intended function.

Equipment Qualification: Documented evidence demonstrating that equipment is designed/selected adequately, installed properly, and operates/performs for its intended purpose. Adequate controls are confirmed, and the equipment is shown to be in a state of control.

Facility Qualification: Documented evidence demonstrating that a production facility is designed, selected, and constructed adequately to support manufacturing and not adulterate the product.

Utility Qualification: Documented evidence demonstrating that a production utility is designed/selected adequately and operates/performs for its intended purpose to support manufacturing and not adulterate the product.

Installation Qualification (IQ): Documented verification that all aspects of a system, facility, utility or equipment that can affect product quality are installed according to specifications and design criteria.

Operation Qualification (OQ): Documented verification that all aspects and functions of a system, facility, utility or equipment that can affect product quality operate properly within all anticipated operating ranges as required by the process, capability, procedures, and design specification.

Performance Qualification (PQ): Documented verification that all aspects of a system, facility, utility, or equipment that can affect product quality produce the required output over an extended period under typical operating conditions and interferences.

Process Validation (PV): Documented evidence intended to examine the chemical characteristics of the formula during the entire production process, to ensure it meets specified strength, potency, purity, and/or quality attributes. All operations that may impact product characteristics must be examined.

Cleaning Validation (CV): Documented evidence that provides a high degree of assurance that an approved cleaning procedure will remove from equipment products and cleansers below acceptable limits, such that it is suitable for processing a product.

Sanitizing Validation: Documented evidence that provides a high degree of assurance that an approved sanitization procedure will reduce microbes and provide equipment contact surface bioburden reduction below acceptable limits, such that it is suitable for processing a product.

Critical Equipment: Equipment that has direct product contact/impact or ensures proper labeling and traceability of the product. Equipment that can affect the strength, identity, purity, potency, quality, and/or quality of the product.

Software Validation: Confirmation by examination and provision of objective evidence that software specifications conform to user needs and intended uses, and that the particular requirements implemented through the software can be consistently fulfilled.

Critical Process Parameter (CPP): A process parameter that must be controlled within predefined limits to ensure the product meets its predefined quality attributes.

Critical Quality Attribute (CQA): A CQA is a physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality.

Procedure

The VMP will provide a documented plan for the qualification and validation of a facility/project, which identifies the layout of the operation, associated equipment, utilities and systems to be validated. The VMP provides an organized summary of the facility/plant validation program, including the extent of qualification/validation activities via protocols, SOPs, acceptance criteria & responsibilities.

The VMP will also provide the design philosophy for maintaining supporting and maintaining product quality, including what standards and regulations the facility is intended to meet. Within each section of the MVP, provide justification and rationale for the validation approach and requirements of each validation element.

Purpose

The purpose of this Validation Master Plan is to outline the validation and qualification requirements associated with the [project statement] or production of [Description of Products] at the PharmaInfo facility.

This document supports the Validation Policy [Validation Policy] within PharmaInfo and will address all areas of validation and qualification required for the PharmaInfo.

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Scope

Provide the product(s) description/list and validation elements within the scope of the VMP. Provide a list of the validation elements, for example:

1. Facility Qualification
2. Utility Qualification
3. Production Equipment Qualification
4. Process Validation
5. Packaging Validation
6. Cleaning Validation
7. Sanitizing/Sterilizing Validation
8. Software Validation

Definitions and Acronyms 

Provide a listing of relevant definitions and/or acronyms.

Plant Operating Description

• Provide the plant/facility design philosophy for maintaining supporting and maintaining product quality, including what standards and regulations the plant is intended to meet. Include the location of the facility/project.
• Reference applicable standards utilized to design and construct the facility, including intended capabilities and classifications to adequately support product quality.
• Specify a high-level description of intended product types/production. Note the flow of material, personnel, and waste into/within/out of the facility, utilizing diagrams where helpful (optional). Provide a brief Project/Facility history, with a description of plant zones. List supporting utilities with classifications, capabilities, and specifications, as well as facility classification.

Plant Layout

Describe the Plant Layout for each zone:

• Raw material receipt, testing, storage & release process
• Processing layout including cleaning & equipment storage
• Warehouse, storage, and staging
• Personnel, Plant Access, Production Space, Gowning, Office, Team/Locker, Restrooms, Housekeeping & Training space.

Process Flow

Provide a sufficiently detailed description of the process flow, to characterize the manufacture of the product. Describe the process flow in a methodical and organized manner. Mention all major unit operations, how they are utilized, and relevant process steps. Also include what controls are in place to control the quality, status, and release of materials and stock at relevant phases of manufacture. Include all relevant aspects of processing to define the manufacturing process, including (but not limited to):

• Incoming/Receiving
• Warehousing/Temperature-Controlled Space
• Software Systems used in the release
• Production process description
• Cleaning/Sanitizing equipment
• Quality checks, product testing & release

Master Validation Plan Elements

• Specify the extent of qualification/validation required to support the manufacture of the product safety, identity, strength, purity, potency, and quality of product via protocols, SOPs, acceptance criteria & specifications.
• Within each element, provide justification and rationale for the validation approach and requirements of each validation element. Provide a description of risk analysis or risk-based approach utilized in developing the validation approach where applicable (optional). Provide a list of validation and protocol requirements for each validation element. Reference supporting development programs, and relevant qualification/validation procedures where applicable.

Facilities, Warehousing & Storage

State the validation requirements for the facility, warehouse(s), and other product-impactful storage locations. Provide justification, and risk assessment (optional), for the validation approach. List, or reference a master list, for each element and validation protocol number (with status). Reference Facility and Storage qualification procedures that dictate and support the validation activities.

Examples can include (but are not limited to):

• Production Facility
• Incoming / Intermediate / Bulk / Finished Good Warehousing
• Controlled Temperature / Refrigeration Units
• HVAC for air quality, temperature & humidity control

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Utilities

State the validation requirements for each product supporting utility, including critical testing requirements as applicable (ie, Purified Water system testing for 30 consecutive days). Provide justification, and risk assessment (optional), for the validation approach. Provide a list, or reference a master list, for each system, equipment ID and validation protocol number (with status). Reference Facility and Storage qualification procedures that dictate and support the validation activities.

Utility examples can include (but are not limited to):

• RO Water System
• Steam
• Compressed Air
• Gases

Production Equipment

The qualification will be performed on Critical equipment to ensure it operates and performs according to its intended use. Provide the validation requirements for each critical production unit operation (ie, Mix Tank).

Provide a list, or reference a master list, for each system, equipment ID, and validation protocol number (with status). Provide justification, and risk assessment (optional), for the validation approach.

Examples can include (but are not limited to):

• Mix Vessels & Agitators
• Product Coder
• Product Transfer Pumps
• Product Filler

Product/Process Validation

• Process (PV) (template notes, packaging validation if applicable) and packaging validation (PkV) will be performed to demonstrate that the manufacturing process is reproducible and can consistently deliver a product that meets release specifications.
• State the products/product families requiring validation. Provide the Rationale and justification for Process Validation Requirements, based on demonstrated product knowledge. Reference process development work and data as applicable for support.
• If a family approach is utilized, provide Rationale and justification for the family selection. Justification can be provided for the similarity of process steps or product characteristics to group the family of products. The scientific rationale included in reasoning for why product groupings were chosen, which could be based on various factors, such as Critical Processing Parameters (CPPS), similar process steps, and similar raw materials/ingredients.

• Where a worst-case product is utilized to represent a product family, the rationale or characteristics of a worst-case will be documented. Note the basis for defining batch size, number of batches, and sampling requirements, which may require additional sample points and/or additional tests to be performed.
• State the validation requirements for each critical production unit operation (i.e., Mix Tank). Provide a list, or reference a master list for each formula/SKU and associated validation protocol number.

Cleaning Validation

• Cleaning Validation will be performed to demonstrate that the cleaning process(es) is/are reproducible and can consistently remove product and cleanser to acceptable limits.
• State the cleaning families requiring validation. Provide the Rationale and justification for the selection of the families. Reference cleaning development work as applicable for support.
• Provide Rationale and justification for the family selection. The scientific rationale included in reasoning for why cleaning families were chosen, which could be based on various factors, such as: cleanser, Maximum allowable carryover (MACO), raw material/components similarity, solubility, and coupon studies.
• Where a worst-case product is utilized to represent a cleaning family, the rationale or characteristics as a worst-case will be documented. Note the basis for defining acceptance limits, MACO, markers for cleanliness, product/raw toxicity, and cleanser toxicity.
• State the validation requirements for each cleaning family. Provide a list, or reference a master list, for each cleaning process and associated validation protocol number.

Sanitizing Validation

• Sanitizing Validation will be performed to demonstrate that the sanitizing process(es) is/are reproducible and can consistently reduce microbes/bioburden to acceptable limits.
• State the equipment groups requiring sanitizing validation. Provide the Rationale and justification for the selection of the groups. Reference development work as applicable for support.
• Provide Rationale and justification for the equipment groupings. The scientific rationale included in reasoning for why equipment groups were chosen, which could be based on various factors, such as: sanitizer, concentration, contact time, equipment geometry/size, and coupon studies. Note the basis for defining acceptance limits, and reference the environmental monitoring program.
• State the validation requirements for each sanitizing group. Provide a list, or reference a master list, for each sanitizing process and validation protocol number (with status).

Software Validation

Cite each software system, and a brief description of the purpose of the system to support the product. Provide the validation requirements for each software system. Provide a list, or reference a master list, for each system and qualification protocol number (with status). Provide justification, and risk assessment (optional), for the validation approach.

Examples can include (but are not limited to):

• Computerized Manufacturing Maintenance System (CMMS)
• Laboratory Information Management System (LIMS)
• Warehouse Management System
•  Manufacturing Execution System(s) (MES)

Additional VMP Elements

Signature List

The purpose of the signature list is to ensure that all functions involved in the execution and support of the VMP and validation program are aware of the VMP requirements. At a minimum, Manufacturing and Quality Assurance management will approve of the VMP, to ensure the application and maintenance of the facility/project validation program. Other functions may also approve of the VMP, as applicable, to ensure proper support of the validation and validated state of the plant/facility.

1. Plant Engineering
2. Research & Development
3. Project Management
4. Maintenance
5. Metrology
6. Change Control

Schedule & Resourcing (Optional)

List the project/facility or validation milestones, and requisite timing. Note the expected validation resource requirements to support the development, drafting, execution, and closure of validation activities.

Project VMP Production Lot Release Requirements

The validation release requirements for the product will be specified. Product release requirements for product families, including their representative (or worst case) products as well as the remaining products will be stated. Requirements for release could include (but may not be limited to) successful completion of:

• Equipment & Utility Qualification
• Process Validation
• Cleaning and sanitizing Validation
• Successful environmental monitoring program results

References

Cite references to qualification and validation procedures within the validation program. Also, reference other relevant procedures and programs required to maintain production in a state of control. These can include (but are not limited to):

• Master Validation Plan Form
• Validation Policy
• Qualification & Validation Procedures
• Good Documentation Practices SOP
• Facility/Project Standards
• Change Control Policy
• Training Program
• Calibration/Metrology/Preventive Maintenance Program
• Quality Manual

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