Antrix, Inc ANTRIX, Inc
Regulatory Affairs & Quality Assurance Consulting Services for
Medical Device and Medicinal Drugs
O 408 733 1199
F 408 730 5959

Site Quality, Site Regulatory Plan, Validation Master Plan and ISO 13485 certification

1. Service Description

Site Quality Plan will describe the procedures, process and tools to be followed to manufacture quality products meeting specification requirements.

Site Regulatory Plan will describe the regulations, certifications, site certifications that need to be in place before the products can be manufactured and shipped.

Validation Master Plan for your new or existing site will describe the general corporate philosophy and expectations that are to be followed in the validation efforts. 

There will be productivity increase and cost savings of more than 80% using our service. Your company will save money from several thousand to millions of dollars adding to your bottom line profit.

The Validation Master Plan service will:

  1. It will define in general terms the nature of tests to be performed. 
  2. It will identify the systems, equipment, controls, computer systems, processes to be validated.

Timing of Master Validation Plan - The Validation Master Plan is a document that is developed during:

  1. The initial stages of design for a construction project.
  2. The development stages for a new product.
  3. The planning stages for a modified plant or product.

Validation plans are written in advance of beginning the actual validation work. The Plan provides a road map detailing

  1. what is to be done,
  2. when it will be done, and
  3. who will do it.

2. Cost Savings - Return on Investments (ROI)

Amount of money saved by your company on using our service based on the company size is provided in the Table 1.0.

Projected savings is based on

  1. Process efficiency gains (people)
  2. Less personnel requirements (people)
  3. Infrastructure efficiency gains (systems)
  4. Infrastructure validation and maintenance (systems)
  5. Delivering quality products
  6. Avoid regulatory noncompliance cost
  7. Avoid regulatory fines cost

Compared to cost associated with company's inefficient internal manual methods, , systems, tools, software’s, and personnel etc. Detailed Return on Investment (ROI) information is available on request.

Company Size Small Medium Large
$Savings > 30 % > 50 % > 80 %
Annual Sales < $100 million $100 million < Sales < $500 million > $500 million
Number of Submissions <= 2 per year 2 < Sub <= 4 per year > 4 per year

Table 1.0 - Amount of money saved by your company on using our service. Company size is based on annual sales as per FDA classification.

3. Solution Approach

Our site quality plan will cover

  1. Organization's quality policy
  2. Allocation of responsibilities
  3. Consultation Procedures
  4. Communication procedures and requirements
  5. Monitoring procedures and requirements
  6. Review procedures and requirements
  7. Record keeping procedures and requirements
  8. Reporting procedures and requirements
  9. Training procedures and requirements
  10. Procedures for dealing with non-compliance
  11. Standard operating procedures
  12. Safe operating procedures
  13. Work instructions
  14. Emergency procedures
  15. Permit requirements
  16. Sampling and testing procedures and requirements
  17. Product specifications
  18. Delivery standards

Our site regulatory plan will cover

  1. Current medical device regulations to be followed including regulatory agencies site registration, ISO 13485 certifications etc.
  2. Applying ongoing changes to regulations

Following are the list of critical elements that will be included in the Master Validation Plan.

  1. Purpose
    The purpose section defines the important activities to successfully validate the items like facilities, utilities, equipment, process used to manufacture of given product by the company. It contains generic description of the items to be validated. References to the manufacturing of the product under the regulatory practices like cGMPs etc.
  2. Scope
    The scope section covers the products and the facility geographic locations. It includes the exclusionary statement for the items to be validated by third party or contracted out. Statements to the effect about compliance regulations followed like for Drugs - 21 CFR Part 210 and 211, Medical Devices – 21 CFR 820 and Biologics – 21 CFR Part 600 are made here. Section also covers intended use, description of critical utilities, process, equipment etc and overall approach to validation.
  3. Definition
    Definition section covers the definitions of Validation, Concurrent, Prospective, Retrospective, Computerized System Validation, IQ, PQ, OQ, Revalidation, QA, QC, Standard Operating Procedures and other definitions relevant to the Master Validation Plan.
  4. References
    This section contains the References to Compliance Regulations, Guidelines from various agencies like FDA, ISO, and State etc.
  5. Validation Project Organization and Responsibility
    Project Organization section contains list of departments from which the resources will be utilized like Facilities, Manufacturing, R&D, QA, or outside third party vendor that will be used. The responsibility section drills down on who is responsible for each of the validation activities. For example R&D to be responsible for development of prototype product and establishing specifications, QA to be responsible for providing oversight to ensure integrity and consistency of validated process etc.
  6. Approval of Validation Documents
    This section list validation document approval team for IQ, OQ, PQ, Protocols, certifications, test reports and final reports etc. generated either by company or by outside contractors.
  7. Validation Standard Operating Procedures
    Contains list of SOP’s that describe or support the validation procedure. SOP’s Like Validation Study Numbering, Study Report, IQ, OQ, PQ Preparation and Execution, Computer System Validation, Change Control, Revalidation Policy, Final Report etc. are covered. This is followed by synopsis of the SOP’s that will be either written or updated.
  8. Validation Scheduling and Control
    Section lays down sequential and some of the concurrent approach to be adopted for validation to achieve a validated state. This is accomplished by successful execution of a series of qualifications (IQ, OQ, PQ) and protocols.  The section essentially focuses on when these qualifications and single validations are taken in sum that overall system validation is demonstrated.  Lists on based on the complexity and functional requirements of a given system, one or more qualification activities that need to be performed. Example workflow may look like
    Equipment Installation --> Documentation --> Establish Change Control --> SOP --> Calibration --> OQ --> CSV --> PQ --> Sampling, Cleaning, Environmental Monitoring etc.
  9. Validation/Qualification Protocol Matrix
    This section contains purpose of the validation like entire system performs consistently and reliably to manufacture high quality product at lower cost. Also defines Summary Matrix containing the list of Equipments, Utilities etc. IQ/OP/PQ/VP to be performed, Responsible Department, Revalidation Review Time, SOP, Acceptance Criteria etc.
  10. Product Validation
    Outlines the validation activities that occur including development of a protocol to demonstrate that the manufacturing process will consistently produce product meeting final product specifications. The study of process manipulations as per the manufacturing batch record including sampling product at appropriate steps that will be covered are described here. Lists parameters such as manufacturing time, product temperature, room temperature, weights, equipment setting etc. that will be recorded as in process data.
  11. Process Description
    This section covers the process validation which could cover aseptic process and product processing etc.  The product processing portion covers the study that will consists of performing all process functions and manipulations according to the manufacturing batch record, and sampling. Scientific rationale on number of batches (usually 3 is used as magic number) that will be manufactured and placed on stability to ensure that all pre-determined in-process and final product specifications are met and measure variability among successive run is covered in this section.
  12. Facility Validation
    Contains information about place where the facility is located, area of the facility, manufacturing, laboratory and office spaces.  Flow diagrams for material flow and product flow are provided with indicated markups in the diagram. Warehousing incoming/outgoing materials information. Facility cleaning validation program is described to limit microbial or particulate contamination etc. Environmental Monitoring section containing description about the particle counts, bioburden etc.
  13. Utilities Validation
    This section contains description about the HVAC, Heating, Ventilation, Air Conditioning System, Water System, Vacuum System, Compressed Air, Plant Steam Chilled water system as applicable and associated validation activities that need to be performed.
  14. Equipment Validation
    Equipments that are used for manufacturing the product as part of process are listed including validations that need to be performed. Details of the equipment are usually deferred to in the equipment validation file. Also if application temperature chambers, equipment cleaning are described including guidelines to validate them.
  15. Personnel
    Lists group that support product manufacturing and associated personnel training to perform their job functions related description. This could also include Personnel Flow Diagrams.
  16. Additional Programs
    This section defines Training, Calibration, Change Control, SOP, Batch Record Information & Review, PM, log books and revalidation programs

4. Definitions

A Validation Master Plan is an approved document that summarizes a firm's intentions and methods to be used validate the equipment, systems, controls or processes. May apply to a whole facility, a specific product line, or a manufacturing process.

5. Applicable Laws, Regulations and Standards

  1. FDA - Title 21 CFR Part 820, 820.70, 820.72, 820.75, 820.90, 820.100, 820.120, 820.130, 820.140, 820.150, 820.160, 820.181, 820.184, 820.186, 820.198
  2. FDA - Title 21 CFR Part 211, Subpart C - Buildings and Facilities, Subpart D - Equipment, Subpart E - Control of Components and Drug Product Containers and Closures, Subpart F - Production and Process Controls, Subpart G - Packaging and Labeling Control, Subpart H - Holding and Distribution
  3. FDA - Guide to Inspections Validation Of Cleaning Processes
  4. Guide to Good Manufacturing Practice (GMP) requirements by WHO
  5. FDA - Guideline On General Principles Of Process Validation
  6. FDA - PAT - A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance