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DOCUMENT NO.:

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TITLE:

Validation Master Plan (VMP) for the Pharma Co., Inc. Springfield, NY Facility

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Glossary

2.0

PURPOSE AND INTRODUCTION

3

2.1 INTRODUCTION

3

2.2 PURPOSE

3

3.0

SCOPE

4

4.0

RESPONSIBILITIES

4

4.1 SITE QUALITY ASSURANCE VALIDATION

5

4.2 SITE ENGINEERING VALIDATION

6

4.3 SITE MANUFACTURING TECHNICAL SUPPORT

6

4.4 MANUFACTURING

SITE

7

4.5 ENGINEERING

SITE

8

4.6 QUALITY CONTROL

8

4.7 REGULATORY AFFAIRS

9

5.0

DEFINITIONS, ABREVIATIONS AND REFERENCES

9

5.1 DEFINITIONS LIST

9

5.2 ABBREVIATION LIST

12

5.3 REFERENCES

12

6.0

MATERIALS

12

7.0

PROCEDURE

13

7.1 SPRINGFIELD, NY FACILITY OVERVIEW

13

7.2 VALIDATION MASTER PLAN GOVERNANCE

13

7.3 VALIDATION APPROACH

15

7.4 VALIDATION

PROCEDURES

17

7.5 VALIDATION SUPPORT SYSTEMS

18

7.6 KEY SOPs GOVERNING AND SUPPORTING THE ALLSTON LANDING VALIDATION

PROGRAM

21

7.7 IDENTIFICATION AND DESCRIPTION OF MANUFACTURING SYSTEMS AND

EQUIPMENT PRESENTLY IN USE AT THE SPRINGFIELD, NY FACILITY AND

ASSOCIATED COMPLETED VALIDATION

21

7.8 VALIDATION MASTER PLAN REVIEW

21

8.0

ATTACHMENTS

21

8.1 Attachment A: Process Flow Diagrams

21

8.2 Attachment B: Key SOPs Governing and Supporting the Springfield, NY Facility

Validation Program

21

8.3 Attachment C: Process Equipment List and Associated Validation Protocol Numbers

 

21

9.0

REVISION HISTORY

27

9.1

Revision History Table

27

 

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Validation Master Plan (VMP) for the Pharma Co., Inc. Springfield, NY Facility

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2.0 PURPOSE AND INTRODUCTION

2.1 INTRODUCTION

The validation program at the Springfield, NY Facility is intended to satisfy current domestic and international regulations, guidelines and policies for drugs, biologics and APIs to verify the equipment, systems, utilities, software and processes are properly designed, installed, and function as intended in a consistent and controlled manner. The validation program complies with Corporate Quality Standards and Polices (Ref. SOP-XXXX – Validation Program).

The revision of the Site Validation Master Plan (SVMP) comes from the validation philosophy changes resulting from the implementation of the “validation lifecycle” approach at Springfield, NY Facility. The changes made in this revision of the Springfield, NY Facility SVMP bring the plan into alignment with the new lifecycle approach. The Springfield, NY Facility has developed the site validation governance document SOP-XXXX, “Validation Project Life Cycle Approach at the Springfield, NY Facility”, which defines the validation philosophy to be used for validation at Springfield, NY Facility. SOP-XXXX uses a risk-based approach with emphasis on verification and qualification that is focused on the high risk attributes of facilities, utilities, equipment, and processes. This SVMP introduces use of subordinate VMPs (sub-VMPs) that are categorized into eight areas and address the full scope of Validation requirements applicable to the Springfield, NY Facility site in support of SVMP.

2.2 PURPOSE

The purpose of validation is to assure that the facility, manufacturing process, and supporting services are capable of supporting the manufacture of pharmaceutical product that consistently meets its predetermined quality attributes. For this reason, each facet of the Springfield, NY Facility site related to CGMP manufacture, monitoring, storage, and testing will be validated. The Validation program is integral to design, construction / fabrication, and CGMP Operation of the facility. Validation testing is intended to proactively establish CGMP compliance prior to initiating manufacture of commercial product for distribution. In addition, the sustenance operations at Springfield, NY Facility, such as quality change control, calibration program, preventive maintenance, and periodic requalification of critical equipment and processes ensure that manufacturing equipment and processes stay under the validated state.

The purpose of this SVMP is to:

Define the requirements and validation approach for validation of systems, equipment, and processes at Pharma Co., Inc. Corporation’s Springfield, NY Facility.

To list or reference the documentation supporting the current validated state of the Springfield, NY Facility.

 

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Validation Master Plan (VMP) for the Pharma Co., Inc. Springfield, NY Facility

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This SVMP explains the governance structure in place that will achieve, demonstrate and maintain acceptable standards of validation for systems, equipment, and processes used in the manufacture of drug product at the Springfield, NY Facility. If the methodologies and rationale presented herein are not followed, the rationale behind the alternate approach must be documented appropriately.

This document is designed to accomplish the following objectives:

Identify the key Standard Operating Procedures governing and supporting the validation program presented in SOP-XXXX.

Describe the manufacturing systems, equipment, and processes presently in use at the Springfield, NY Facility.

Itemize the equipment and utilities used in the Springfield, NY Facility manufacturing systems and link them to completed validation studies as evidence of a validated state.

3.0

SCOPE

This Site Validation Master Plan applies to all verification, qualification, and validation activities that support commercial manufacturing at Pharma Co., Inc. Corporation’s Springfield, NY Facility. This VMP is a high-level document that refers to various supporting documents. Validation program elements include:

Validation/qualification of facilities/utilities/equipment and corresponding automation/controls

Validation of manufacturing processes

Cleaning validation

Sterilization and depyrogenation

Enterprise Computer systems

QC Laboratory equipment and methods

Interval based requalification

The commercial products that are currently manufactured, packaged, or stored at the Springfield, NY Facility are listed in Table 7.1-1. The equipment within the scope of this Validation Master Plan are listed in Attachment D, Process Equipment List and Associated Validation.

4.0

RESPONSIBILITIES

This SVMP will be approved by the heads of the departments (or their designees) listed in this section.

 

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The validation activities in Springfield, NY Facility are the responsibility of the Validation, Engineering, Manufacturing, MTS, and Quality Assurance groups as shown in Figure 1.

MTS, and Quality Assurance groups as shown in Figure 1 . The responsibilities outlined below align

The responsibilities outlined below align with the Validation Lifecycle Approach that is presented in SOP-XXXX.

4.1 SITE QUALITY ASSURANCE VALIDATION

Generate, review, and maintain approve SVMP

Review and approve the sub-VMPs and Project VPs

Assist with the generation of User Requirements (URs) document

Review and approve the URS document

Assist with the performance of risk assessments

Review and approve Risk Assessments documents

Review and approve Critical Aspects (CAs) list and acceptance criteria, as applicable

Review and approve the Process Control Strategy

Review and approve the Operational Control Strategy

Review and approve Commissioning and Qualification and Validation Plans

Review and approve Qualification Protocols and Reports for facilities, utilities, equipment, and processes that have CAs

Review and approve Computerized Systems’ Protocols and Reports

Review and approve Performance Qualification (PQ) Protocols and Reports

 

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Review and approve Process Validation (PV) and Continued Verification Protocols and Reports

Review and approve Qualification and Validation Protocol Deviations

Approve the use of vendor documentation to verify functionality of facility, utility, and equipment

Reviewing

related

and

approving

the

Site’s

Equipment

Requalification

documents

4.2 SITE ENGINEERING VALIDATION

Review and approve SVMP

Generate, review, approve, and maintain sub-VMP for Facilities, Equipment (including QC Lab storage and process equipment, such as refrigerators, autoclaves and incubators) and Utilities, Cleaning Process, Sterilization and Depyrogenation Process, and Computerized Systems

Lead/generate, review and approve Site Project VP for new products or projects

Maintain Validation Schedule per the Project Execution Plan (PEP) and Project VP and CCR timelines

Assist with the generation of URS document

Review and approve URS document

Lead/perform risk assessments using CA list

Review and approve the Operational Control Strategy

Review and approve Risk Assessment document

Generate, review, and approve IQ, OQ, PQ Protocols and Reports for facilities, utilities, equipment, and processes

Generate, review, and approve PQ Protocols and Reports

Generate, review, and approve Protocol Deviations

Review and approve Computer Systems’ Protocols and Reports

4.3 SITE MANUFACTURING TECHNICAL SUPPORT

Review and approve the SVMP, sub-VMPs, and Project VPs, as appropriate

Generate, review, approve, and maintain sub-VMP or PV

Assist with the generation of URS document

Review and approve URS of document

Review and approve Risk Assessment document, as applicable

Review and approve Validation Plans, as applicable

 

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Review approve and assist in updating the Process Control Strategy

Generate, review, and approve the Operational Control Strategy

Lead /perform Technical Transfer activities for product transfer

Lead/perform process development / engineering runs

Lead. generate, review, and approve PV and Continued Verification Protocols and Reports

Execute PV Protocols

Generate, review, and approve PV Protocol Deviations

Create and update Manufacturing Process Descriptions and associated Manufacturing Flow Diagrams (MFDs)

Generate process related sections of the Project VPs

Review and approve Project VPs that include PV

Lead/perform risk assessments for PV

Create and update Manufacturing History File (MHF)

4.4 SITE MANUFACTURING

Assist with the performance of risk assessments

Assist with the generation of URS document

Review and approve URS document

Assist with the generation of the SVMP, sub-VMPs, and Project VPs, as applicable

Review and approve the SVMP, sub-VMPs, and Project VPs, as applicable

Review and approve the Process Control Strategy

Review and approve the Operational Control Strategy

Assist Site Engineering with generation of project schedule

Generate manufacturing SOPs for use during validation

Review and approve IQ, OQ, PQ, PV, and Continued Verification Protocols and Reports for facilities, utilities, equipment, and processes as applicable

Prepare schedule in support of IQ, OQ, PQ, PV, and Continued Verification Protocols execution

Ensure equipment/facilities/materials/personnel availability and technical support on the operation of the equipment during execution of qualification and validation activities

 

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Ensure manufacturing procedures are developed for maintaining the validated equipment in its validated state throughout its lifecycle

Review and approve Protocol Deviations affecting process equipment

Manage and execute the Site’s Equipment Requalification program

4.5 SITE ENGINEERING

Assist with the performance of risk assessments

Lead the generation of URS document

Review and approve URS document

Generate Functional Specifications based on URS

Assist with the generation of the SVMP, sub-VMPs, and Project VPs, as applicable

Review and approve the SVMP, sub-VMPs, and Project VPs, as applicable

Generate, review, approve, and maintain sub-VMP for Computer Systems

Review and approve the Operational Control Strategy

Generate, review, and approve Computer Systems Protocols and Reports

Review and approve Verification (including IQ and OQ) and PQ Protocols and Reports for facilities, utilities, equipment, and processes as applicable

Participate in execution of Verification Protocols, as necessary

Review

and

and

approve

Protocol

Deviations

affecting

facilities,

utilities,

Computer Systems

Review and approve the Site’s Equipment Requalification documents related to facilities and utilities

4.6 QUALITY CONTROL

Assist with the generation of the SVMP, sub-VMPs, and Project VPs, as applicable

Review and approve the SVMP and sub-VMPs, as applicable

manage execution of, and maintain sub-VMPs for

Generate, review, approve, QC Laboratories

Review and approve Site Project VP for new products when QC testing is required

Receive and use transferred validated methods

Review and approve method validation protocols and reports

 

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Generate, review and approve validation protocols and reports for laboratory test instrumentation

Review and approve laboratory equipment validation protocols and reports storage and process equipment, such as refrigerators, autoclaves and incubators

Review the PQ and PV protocols for analytical and microbiological testing requirements, as applicable

Perform testing required for validation samples, as applicable

Review the PQ and PV Final Reports and verify the accuracy of testing data, as applicable

Review and approve Protocol Deviations affecting QC test results and equipment

4.7 REGULATORY AFFAIRS

Assist with the review of SVMP, sub-VMPs, and validation requirements to ensure compliance with regulatory filings

Update regulatory filings as necessary based on approved validation data

Assess the impact of validation activities on current approved product filings

Provide filing dates as part of validation activity scheduling

Incorporate pertinent validation data into annual reports

5.0 DEFINITIONS, ABREVIATIONS AND REFERENCES

5.1 DEFINITIONS LIST

Cleaning

Documented evidence that a cleaning process is consistently and effectively reducing potential product and/or cleaning agent residues to pre-determined acceptable limits.

Validation (CV)

Cleaning

Documented evidence that equipment is cleaned to pre-determined specifications and may be released for use.

Verification

 

Clean in Place (CIP)

Introduction of cleaning solution and/or water rinses into equipment that

is

fixed in place, for purposes of removing potential product and/or

 

cleaning agent residues.

Clean

out

of

Cleaning of portable or disassembled equipment/parts involving the use

Place (COP)

of a cleaning station in a remote designated location.

Commissioning

A well-planned, documented, and managed engineering approach to

the startup and turnover of facilities, systems, and equipment to the

System Owner that results in a safe and functional environment that meets established design requirements and stakeholder expectations.

Concurrent

 

Validation of equipment, systems or processes while the equipment, system or process is in current use for clinical or commercial production.

Validation

NOTICE THIS DOCUMENT IS PROPRIETARY AND ITS CONTENTS ARE THE EXCLUSIVE PROPERTY OF PHARMA CO., INC.

 

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Critical

Elements of the systems or equipment, which are critical to the product quality.

Aspects (CA)

Critical Process Parameter (CPP)

A

process parameter whose variability has an impact on a critical quality

attribute and therefore should be monitored or controlled to ensure the process produces the desired quality (ICH Q8 (R2)).

Critical

Quality

A

physical, chemical, biological or microbiological property or

Attribute (CQA)

characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality (ICH Q8 (R2)).

Design Review

A

formal, documented, comprehensive and systematic examination of

the technical aspects of a product design or process. (21CFR Part

 

820.30)

Direct

Impact

Utility that is used for manufacturing of the product or critical processes (CIP, SIP) such as Water for Injection, Clean Steam, and Process

Utility

 

Gases

Family

A

Performance Qualification approach that allows for a reduced number

Approach

of

validation studies when using equipment of equivalent design,

manufacture and operational functionality. This approach is typically used for PQ for Bioreactors and Vessels

Functional

A

prospective document that builds on the User Requirement

Requirement

Specification (URS) and provides a basic narrative on what functions

Specification

the

process and its control system are expected to perform.

Installation

Establishing documented evidence that the equipment, system or software received is correct, is installed properly, in accordance with Pharma Co., Inc.’s and the manufacturer’s requirements, and has the proper documentation and support information.

Qualification

(IQ)

Matrix approach

A

validation approach that uses a philosophy which allows for the

testing of a subset of product batches or “model / placebo products to validate the entire range of a product /batch, in lieu of testing each product / batch in the matrix. Typical examples of appropriate applications of this approach include mixing validation and pooling validation. The bracketing selection is based upon product / batch attributes such as concentration, solubility, ingredient types, and batch size.

Operational

Establishing documented evidence that the equipment, system or

Qualification

software installed, functions in accordance with Pharma Co., Inc.’s and

(OQ)

the

manufacturer’s requirements over the intended range of use, or for

the

intended applications.

Performance

Establishing documented evidence that equipment or systems perform

Qualification

in

a controlled and reproducible manner in accordance with Pharma

(PQ)

Co., Inc.’s requirements under specific operational parameters, either at

the allowable upper and lower limits of the operation or using worse case conditions compared to intended operating ranges.

Process

The 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 (PV)

 

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(Guidance for Industry – Process Validation: General Principles and Practices, FDA, January 2011, Rev 1).

Project

A

prospective document that defines the scope, requirements, rationale

Validation Plan

and protocols necessary for the validation of a new project or process in

an

existing site, which is under validated state.

Prospective

Validation of equipment, systems or processes prior to the release/approval of the equipment, system or process for commercial production or commercial distribution of product.

Validation

Protocol

A

prospective or concurrent test plan with pre-established acceptance

criteria that when executed is intended to produce documented evidence that a system or system component has been properly tested.

Quality Attribute

A

physical, chemical, or microbiological property of characteristic of a

material that directly or indirectly impacts quality.

Re-Qualification

Establishing documented evidence that existing equipment and processes continue to operate in a validated state, demonstrating continued compliance, effective and reproducibility. This protocol type is utilized for time based re-qualification activities, such as autoclaves, SIP, ovens, SIP ovens, lyophilizers, environmental rooms, and cleaning and is not applicable to Change Control Request driven validation.

(Periodic

Qualification)

Re-Validation

The validation of a previously validated process typically necessitated

by

a change modification to the process.

Risk Based

An

approach that allows basing the project related activities on risk

Approach

analysis and placing extra effort on activities that are assessed as

posing a higher risk to the processes and product quality.

User

A

prospective document that describes what the equipment or system is

Requirement

supposed to do, thus containing at least a set of criteria or conditions

Specification

that have to be met. This can include regulatory, corporate, and process requirements.

(URS)

Validation

Documented evidence, which provides a high degree of assurance that

specific process will consistently meet its pre-determined specifications and quality attributes.

a

Validation

A

prospective document that defines the scope, requirements, rationale,

Master Plan

and protocols necessary for the validation of a new project or process.

Validation

A

prospective document that provides a detailed test plan used to

Protocol

qualify/validate equipment, systems, utilities, software or processes.

Validation

A

document that provides a detailed summary of the results from the

Protocol Final

execution of a Validation Protocol.

Report

 

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5.2 ABBREVIATION LIST

API

Active Pharmaceutical Ingredient

ASME

American Society of Mechanical Engineers

CFR

Code of Federal Regulations

cGMP

current Good Manufacturing Practices

CIP

Clean-In-Place

CPP

Critical Process Parameters

CQA

Critical Quality Attributes

CA

Critical Aspects

EMA

European Medicines Agency

FDA

Food and Drug Administration

GAMP

Good Automated Manufacturing Practices

ICH

International Conference on Harmonization

IQ

Installation Qualification

ISO

International Standards Organization

ISPE

International Society of Pharmaceutical Engineers

KPP

Key Process Parameter

MFD

Manufacturing Flow Diagram

OQ

Operational Qualification

PEP

Project Execution Plan

PQ

Performance Qualification

PV

Process Validation

QA

Quality Assurance

QC

Quality Control

RQ

Re-Qualification

SIP

Steam-In-Place

SME

Subject Matter Expert

SOP

Standard Operating Procedure

SVMP

Site Validation Master Plan

UR

User Requirement

VMP

Validation Master Plan

5.3 REFERENCES

See Attachment B for Key regulatory references and Corporate and site SOPs Governing and Supporting the Springfield, NY Facility Validation Program.

6.0

MATERIALS

All materials needed to perform the functions referenced in this document will be found in the individual referenced documents.

 

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7.0

PROCEDURE

7.1 SPRINGFIELD, NY FACILITY OVERVIEW

The Pharma Co., Inc., and is located at: 1 Main Street, Springfield, NY.

Pharma Co., Inc.’s Springfield, NY facility is a multi-product manufacturing facility for xxxx products. Manufacturing operations performed at the Springfield, NY facility include bulk drug substance activities, testing, labeling, and packaging.

Drug substance manufacture for Product A is performed at this facility (see Attachment A for Process Flow Diagram.)

Packaging and labeling operations are performed at this facility for Product A.

Quality Control (QC) testing for Product A may be performed in qualified laboratories at Springfield, NY Facility, and approved vendor sites.

Table 7.1-1 outlines the manufacturing activities performed at the Springfield, NY Facility for each product.

Table 7.1-1: Manufacturing Activities Performed at Springfield by Product

Product

Activities Performed at Springfield, NY Facility

Product A

Manufacturing, formulation, testing, labeling, and packaging

7.2 VALIDATION MASTER PLAN GOVERNANCE

The Validation Program incorporates evaluation and testing to establish:

Manufacturing & Laboratory Facility Installation

Direct Impact Utility Installation, Operation, & Performance

Manufacturing Equipment Installation, Operation, & Performance

Validation of Computer Systems & Software

Validation of Manufacturing Equipment Cleaning Processes and Cycles

Qualification of Laboratory Equipment and Instruments

Validation of Analytical, Physical, & Microbiological Test Methods

Transfer / Development of Manufacturing Processes

Qualification of Environmental Controls and Clean Rooms

Validation of Manufacturing Processes

Assessment and pre-determination of the longevity of CGMP equipment

It is not intended that the SVMP will describe the requirements in detail for execution of the various Validation Program elements. The detailed requirement description may be found in sub-VMPs, Standard Operating Procedures, Corporate Level Standards or Practices, or relevant protocols.

 

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This SVMP will be revised at a minimum once per year to reflect the changes made to the validated facilities, utilities, equipment, and processes at Springfield, NY Facility. In addition, a periodic SVMP Summary Report (issued annually, at minimum) will document the summary of changes to the validated systems and corresponding validation documents. The Process Equipment List and associated document numbers will be updated with the new document numbers and titles.

In order to address the full scope of Validation requirements applicable to the Springfield, NY Facility site, validation activities have been categorized into eight areas, which will be executed by corresponding sub-VMPs, to be created, and as listed below:

Sterilization and Depyrogenation Master Plan for Springfield, NY Facility

Cleaning Validation Master Plan for Springfield, NY Facility

Process Validation Master Plan for Springfield, NY Facility

Facility, Equipment, and Utility Validation Master Plan for Springfield, NY Facility

Computer System Validation Master Plan for Springfield, NY Facility

Requalification Validation Master Plan for Springfield, NY Facility

QC Laboratory Equipment and Instrumentation Qualification Master Plan for Springfield, NY Facility

Test Method Validation Master Plan for Springfield, NY Facility

The eight sub-VMPs will supplement the overarching SVMP, and will be governed by corresponding Corporate Quality Operations Standards. The Sub-VMPs will present the specific validation requirements and projects within each of these validation groupings, along with the necessary details on the scope, validation approach, roles and responsibilities, required deliverables (equipment, systems, processes to be validated and corresponding protocols and documentation, URS, SOPs, test methods, etc.), and acceptance criteria. The projected schedule and required resources will be covered by the Project Execution Plan (PEP) and Project VP.

Standard content of the Sub-VMPs will include:

Policy statement and description of Validation Methodology to be followed.

Listing

describing

of

applicable

governance

policy

and

procedures

requirements.

program

Listing of current approved documentation supporting the validated state for the program addressed.

Execution plan for the specific validation program addressed (based on calendar year)

Upon approval of the Sub-VMP, annual updates will be issued to describe the current year’s project plan status. Record of the annual review will be attached to the Sub-VMP.

 

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7.3 VALIDATION APPROACH

Validation of facilities, equipment, computer systems, and processes is performed at the Springfield, NY Facility for production, monitoring, control, evaluation, and storage of CGMP products. As indicated in the INTRODUCTION section, this site VMP is based on the Validation Life Cycle approaches presented at the site level through governing document SOP-XXXX. SOP-XXXX focuses extensively on the early phases of a project (risk assessment, requirement specification, design, construction, and engineering). The Validation Lifecycle Process Key Activities shown in Figure 2 depicts the use of risk based approach that drives the verification and qualification activities, which are within the scope of this VMP.

The Life Cycle Approach may be summarized as follows:

Facility Qualification will entail verifying that construction and utility installation is according to design, and that the process requirements are met. Equipment & Instrument Verification will verify and document that installation is according to design (Installation Qualification), meets functional requirements (Operational Qualification), and user requirements (Performance Qualification). All computer and automated control systems employed in the facility will also be validated.

Process demonstration, or engineering runs, for new processes/products will be executed utilizing the proposed manufacturing processes. The process demonstration phase will be based on documented process descriptions developed for the product to be transferred to the Springfield, NY Facility site. To support process demonstration, the test instruments will be qualified, and test methods will be validated and / or formally transferred to the site Quality Control / Microbiology Laboratories. During the demonstration phase, raw material supply, equipment settings, process parameters, batch record, product storage, standard operating procedures, and testing will be evaluated to assure satisfactory function. During the demonstration phase, evaluations specific to processing and product quality may also be undertaken.

After successful demonstration, confirmatory production performance qualification and continued verification protocols will be executed to verify and document that the manufacturing processes are capable of consistently yielding product that meets predetermined quality attributes when run at prescribed operating settings and within acceptable operating ranges. Stability testing will also be conducted to support product expiration dating intervals.

Cleaning validation will be performed for process contact surfaces to assure that the cleaning operation reduces product and cleaning agent to acceptable levels.

Subsequent to initial validation activities, the facilities, equipment, systems, and processes are to be maintained in the validated state through implementation of site procedures, including calibration, preventive maintenance, requalification, work

NOTICE THIS DOCUMENT IS PROPRIETARY AND ITS CONTENTS ARE THE EXCLUSIVE PROPERTY OF PHARMA CO., INC.

 

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order review, and change control. The validated manufacturing processes will be assessed regularly to assure that it operates within specified critical parameter ranges and the product produced continues to meet critical quality attribute specifications. As necessary validation activities can and will be repeated for facilities, equipment, instruments or processes that have been modified, replaced, or otherwise altered to a state outside of the originally validated operating parameters. The validated state of the critical processes, such as cleaning, sterilization, and storage rooms, will be requalified periodically.

NOTES about the Validation Life Cycle Process:

The activities in this process are executed by a cross functional team, which include Subject Matter Experts (SMEs) from the impacted stakeholder departments. The responsibilities of SMEs from various functional areas are listed in Section 4.0 of this VMP.

The order of activities in the Life Cycle Process follows the sequence shown in Figure 2.

The requirement documents (user, functional, regulatory, etc) are generated by contributions from stakeholder groups.

Risk assessment is conducted to identify Critical Aspects (CA) of the equipment and processes.

Relevant documents are generated and executed per the Verification Plan, such as FAT, SAT, commissioning, IQ, OQ, and approved prior to starting the next activity.

Content of the verification protocols will depend upon the risk assessment as delineated in the Verification Plan.

 

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DATE: SUPERSEDES DATE: PAGE NO.:   17 of 50 The procedures that follow are part of
DATE: SUPERSEDES DATE: PAGE NO.:   17 of 50 The procedures that follow are part of
DATE: SUPERSEDES DATE: PAGE NO.:   17 of 50 The procedures that follow are part of
DATE: SUPERSEDES DATE: PAGE NO.:   17 of 50 The procedures that follow are part of
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The procedures that follow are part of the infrastructure for the validation process and are a harmonization of these approaches supplemented by direction to specific Standards and SOPs, when appropriate.

7.4 VALIDATION PROCEDURES

Validation activities occur for new or modified equipment, systems, utilities, software, processes or routinely for the re-qualification of equipment, systems or processes per VP-XXXX, Validation Program for Springfield Manufacturing Operations.

 

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Prospective validation is required for all new facilities, equipment, systems, utilities, software, or processes that are necessary for the manufacture, testing, and storage/distribution of commercial product and for clinical material. The steps followed for a validation project are referred to as the Validation Life Cycle. Concurrent validation can be used for PV if the manufactured product must be used for commercial needs in which case, the PV test results must meet all of acceptance criteria defined in the protocol as well as any other QA, corporate, and regulatory requirements. For concurrent validation, the details of the conditions that have to be met prior to the release of the batch for commercial use must be included in the PV protocol.

The verification (commissioning, IQ, OQ, etc), PQ, and PV protocols are generated and executed per the SOPs XXXX. The verification / qualification / validation results are summarized in corresponding final reports.

The final reports are written in accordance with procedure SOP-XXXX and are reviewed and approved by the same departments that reviewed and approved the initial protocol.

7.5 VALIDATION SUPPORT SYSTEMS

7.5.1 Re-Qualification Program

The Re-Qualification (RQ) process is governed by SOP-XXXX. The purpose of this standard is to provide the mandatory compliance requirements for the routine requalification practices to be utilized for equipment and processes used in the manufacture of commercial and clinical material. The intent of requalification is to ensure critical equipment and processes continue to perform within defined limits and operate in a similar manner as originally validated. This document is intended to provide direction to all applicable Pharma Co., Inc. sites to ensure validation requalification programs comply with current regulations and guidance documents authored by regulatory agencies and industry organizations worldwide.

Detailed re-qualification requirements for equipment, systems and processes at Pharma Co., Inc. facilities, which include the Springfield, NY Facility, are governed by SOP-XXXX. This procedure is intended to define the time-based re-qualification program for equipment, systems, and processes at Pharma Co., Inc. facilities. Specifically, the procedure will identify the equipment, systems and processes requiring routine re-qualification, the required frequency and the type of testing and documentation required.

In addition, the Steam-in-Place requalification schedule at Pharma Co., Inc.’s Springfield, NY Facility is governed by SOP-XXXX. This requalification plan identifies the equipment / systems group into families requiring Steam-in-Place

NOTICE THIS DOCUMENT IS PROPRIETARY AND ITS CONTENTS ARE THE EXCLUSIVE PROPERTY OF PHARMA CO., INC.

 

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sterilization procedures as part of a validated process. This requalification plan also specifies and justifies the requalification frequency of the family group and the family group members. The validated family groups then require requalification according to SOP-XXXX.

The re-qualification program assures that critical equipment, systems, and processes continue to perform within prescribed limits and are operating in a similar manner as originally validated, thereby demonstrating a continued state of control.

The re-qualification approach is to perform similar testing utilized during the initial validation, however at an attenuated level deemed sufficient to evaluate the performance of the equipment, system or process, and detect potential adverse changes.

7.5.2 Metrology Program

Calibration policies and procedures are governed by SOP-XXXX, Metrology Program. The Metrology Program covers the services provided by the Pharma Co., Inc. Metrology Department to Pharma Co., Inc. Corporation. This includes, but is not limited to, all Manufacturing and Quality Control operations at Pharma Co., Inc.’s Springfield, NY Facility. Services by the Pharma Co., Inc. Metrology Department may also be provided to Pharma Co., Inc.’s subsidiaries and to joint projects involving other companies having partnerships with Pharma Co., Inc. and its subsidiaries.

In order for equipment to be included in this program, it must be used to measure, gauge, test, inspect or otherwise examine a quantitative value to a known degree of accuracy. If such equipment is used, it must be identified as a Critical, Non-Critical, or Reference Use Only instrument.

Instrumentation requiring calibration must be current prior to and remain current during protocol execution and throughout the Validation Program.

7.5.3 Change Control Program

The Corporate Quality Operations Standard for Change Control is documented as SOP-XXXX. The Change Control Program to ensure that equipment within the Springfield, NY Facility maintains its validated state is governed by SOP- XXXX.

These program requirements apply to all Pharma Co., Inc. functional groups involved in the manufacture and testing of products (both commercial and clinical including material/ assays used to demonstrate product comparability) at the Springfield, NY Facility.

 

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New equipment, both within Quality Control and Manufacturing intended to be validated, is covered under this Change Control System.

7.5.4 Maintenance Program

The process used for developing and optimizing an effective asset maintenance program is governed by SOP-XXXX, Springfield, NY Facility Maintenance Management Program / Work Order System Procedure. The procedure applies to new and in-service assets based on risks and operational reliability while assuring employee safety. The process calls for utilizing operational and maintenance experience relative to 21 CFR Part 210/211 and quality management systems that must be compliant with CGMP regulations. The process to determine / evaluate Part 11 compliance and security risks is included.

The maintenance program targets critical production equipment, QC Laboratory equipment and test instrumentation, plant utilities and environmental areas with significant risk to product quality. Process steps for developing / optimizing the maintenance program are described in the program. Additionally, instructions for work order management and integration with the Computerized Maintenance Management System (CMMS) are also described.

7.5.5 Training Program The general definitions, responsibilities, methodologies for assignments, assessments, documentation of training, and integration with the LMS is governed by SOP-XXXX Learning Management System. This document outlines the activities required to document training in compliance with CGMPs and other applicable regulatory requirements and ensures personnel performing work affecting product quality will be competent on the basis of appropriate education, training, and experience.

This document applies to the recording of training for full-time, part-time and non-employees (temporary/contractors) and either concurrent or subsequent entry of records into the LMS database, where applicable. If a Business Unit has its own local training procedures, that procedure may take precedence.

Training is further defined in SOP-XXXX, to establish a set of initial, minimal regulatory training requirements for personnel having the ability to impact medical device or therapeutic product quality. This document applies to all full-time, part-time, and temporary employees at all levels whose tasks affect the design, production, testing, handling and distribution of products, or affect the environment, process or systems in which products or data are produced, controlled or managed.

 

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7.6 KEY

SOPs

GOVERNING

AND

VALIDATION PROGRAM

SUPPORTING

THE

ALLSTON

LANDING

See Attachment B for a full list of key SOPs and standards used to support the Springfield, NY Facility Validation Program. The site SOPs are written, revised, and controlled per SOP-XXXX, Documentation System and Control.

7.7 IDENTIFICATION AND DESCRIPTION OF MANUFACTURING SYSTEMS AND EQUIPMENT PRESENTLY IN USE AT THE SPRINGFIELD, NY FACILITY AND ASSOCIATED COMPLETED VALIDATION

See Attachment C for a Process Equipment List and Associated Validation Protocol Numbers.

7.8 VALIDATION MASTER PLAN REVIEW

This document must be reviewed, updated and approved on an annual basis to reflect current philosophy, standards and Good Manufacturing Practices. A “VMP Review Schedule” must be generated for the time of the year, when the Site VMP and sub-VMPs will be reviewed and a VMP Review Summary Report generated.

8.0

ATTACHMENTS

8.1 Attachment A: Process Flow Diagrams

8.2 Attachment B: Key SOPs Governing and Supporting the Springfield, NY Facility Validation Program

8.3 Attachment C: Process Equipment List and Associated Validation Protocol Numbers

 

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8.1 Attachment A: Product Process Flow Diagrams

 

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8.2 Attachment B: Key Documents Governing and Supporting the Springfield, NY Facility Validation Program

Reference Documents

Food and Drug Administration (FDA) – 21 CFR Parts 11, 210 & 211

European Medicines Agency (EMA) – EudraLex Vol 4

International Committee on Harmonization (ICH) – Q7, Q8, Q9 & Q10

International Standards Organization (ISO) - ISO 9001

FDA Guidance for Industry – Quality Systems Approach to Pharmaceutical cGMP Regulations

FDA Guidance for Industry – Process Validation: General Principles and Practices – January 2011

ASTM International – Designation E2500-07, Standard Guide for the Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment

Corporate Standards:

SOP-XXXX: Change Control

SOP-XXXX: Quality Manual for the Pharma Co., Inc. Quality System

SOP-XXXX: Corporate Quality Operations Standard: Risk Management

SOP-XXXX: Corporate Quality Operations Standard for Equipment and Process Requalification

SOP-XXXX: Method Development and Validation

SOP-XXXX: Validation Program

SOP-XXXX: Laboratory Equipment Qualification

SOP-XXXX: Cleaning Validation

SOP-XXXX: Process Validation

SOP-XXXX: Sterilization and Depyrogenation Validation

 

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General and Administrative SOPs:

SOP-XXXX: Documentation System and Control

SOP-XXXX: Generation of Protocols and Final Reports for Validation

SOP-XXXX: Change Control Procedure

SOP-XXXX: Metrology Program

SOP-XXXX: Records Retention

SOP-XXXX: Springfield, NY Facility Maintenance Management Program / Work Order System Procedure

SOP-XXXX: Technology Transfer into TMD Manufacturing and Quality

SOP-XXXX: Guidance for 21 CFR Part 11 Compliance for TMD Computer Systems

SOP-XXXX: Pharma Co., Inc. Corporate Quality Manual Note: This manual also lists pertinent SOPs for validation related topics

SOP-XXXX: Documentation of Employee Training

SOP-XXXX: Installation Qualification of Laboratory Instruments

SOP-XXXX: Learning Management System (LMS)– Governance and Documentation

SOP-XXXX: cGMP & Regulatory Training Requirements for Personnel

Engineering SOPs:

SOP-XXXX: Technical Project Management Process for Springfield, NY Facility Manufacturing Facility

SOP-XXXX:

Project Lifecycle Management Process - Springfield, NY

Facility

SOP-XXXX: Commissioning Procedure for Start-Up of Systems and Equipment at Springfield, NY Facility

SOP-XXXX: Engineering Document Management Procedure at the Springfield, NY Facility

SOP-XXXX: Administration of Drawings at Pharma Co., Inc. Springfield, NY Facility

SOP-XXXX: Project Change Management Procedure at the Springfield, NY Facility

 

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Technical SOPs:

SOP-XXXX: Validation of Autoclaves

SOP-XXXX: Validation of Dry Heat Ovens used in Sterilization or Depyrogenation Processes

SOP-XXXX: Validation of Filter Integrity Test Instruments

SOP-XXXX: Validation of Temperature/Relative Humidity Controlled Warm Rooms/Chambers

Key Validation Department Operational SOPs:

SOP-XXXX: Master Validation Plan for the Pharma Co., Inc. Laboratory Information Management System

SOP-XXXX: Standard Operating Procedure Guidelines for Determination of Validation Requirements for Change Control Requests

SOP-XXXX: Guidelines for Computer Validation Protocols

SOP-XXXX: Guidelines for Generating, Approving, Amending and Closing- out a Validation Plan at Pharma Co., Inc.

SOP-XXXX: Guidelines for the Performance of Airflow Pattern Testing for Clean Rooms and Laminar Flow Hoods

SOP-XXXX: Protocol Execution Procedure at Springfield, NY Facility

SOP-XXXX: Routine Re-Qualification of Equipment, Systems and Processes

SOP-XXXX: Cleaning Validation and Changeover Verification

SOP-XXXX: Process Validation for Springfield, NY Facility

SOP-XXXX: Process Equipment Steam-in-Place (SIP) Requalification Matrices and Scheduling Plan at Springfield, NY Facility

SOP-XXXX: Cleaning Master Plan for the Springfield, NY Facility Manufacturing Facility

SOP-XXXX: Validation Project Execution Life Cycle Approach at the Springfield, NY Facility

 

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8.3 Attachment C: Process Equipment List and Associated Validation Protocol Numbers

EQ #

Description

Size

Location

IQ

OQ

CIP

SIP

CQ

PQ/PV

 

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9.0 REVISION HISTORY

9.1 Revision History Table

Revision

Description of Changes

DCR

Related

Date

Number

document

1

Initial Release

xxxx

xxxx

mm/dd/yyyy