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

Manufacturing Process Validation

1. Service Description

We provide complete robust process validation service to avoid GMP-related recalls associated with post-production problems.  The primary reasons for those problems include poorly characterized product design and manufacturing processes, inadequate or poorly planned and executed design and process validations, and lack of adequate production controls. As a result, customers are exposed to unnecessary hazards, product quality is inconsistent, and businesses are adversely affected.

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.

Process Requirements are defined by the processes’ ability to produce product meeting predetermined specifications. This service covers the elements of process validation and present industry “best practices”. Service includes design verification and validation, process validation planning, and installation, operation and performance qualification, and process validation.

Validation requires that you first establish a process that can consistently conform to requirements and then that you run studies demonstrating that this is the case.

Manufacturing Process Validation Lifecycle

Figure 1 - Manufacturing Process Validation Lifecycle


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 > 40 % > 60 % > 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 process validation approach is based on Proven Acceptable Range (PAR) so that expected performance of the process relative to the end- product’s ability meets pre-determined specifications.

  1. Document Schedule for Process Validation Activities
  2. Document Validation Resources and Responsibilities
  3. Specification Documentation and Review
  4. Quality Plan Documentation
  5. Risk Identification, Analysis and Management
  6. Validation Plan Documentation
  7. Internal User Testing
  8. Validation Protocol Planning Table Creation
  9. Criteria for Validation Entry
  10. Tools, Techniques and Methods
  11. Challenge the process to the full range of operating parameters - (parameters established during process development)
  • Define all critical characteristics of the process

  • Define process capability/reliability into consideration

  • Systems operate consistently and reliably at the normal operating limits

  • Appropriate challenges are employed

  • Use Actual Product and Process Parameters and Procedures

  • Process Capability is Verified Based on PQ Runs

  • Include Start-Up and Shut-Down Between Runs

  • At Least Three Successive and Successful Runs

  • One of the outputs of OQ and PQ will be to development of attributes for continuous monitoring and maintenance

  • Establish Standard Operating Procedures and Work Instructions

             There are many tools we use as part of validation

  • Control charts
  • Capability studies
  • Designed experiments
  • Tolerance analysis
  • Robust design methods
  • Failure modes and effects analysis
  • Sampling plans, and
  • Mistake proofing are a few
  1. Validation Environment
  2. Validation Protocol Execution
  3. Pass / Fail Criteria
  4. Validation Deviation Management
  5. Validation Protocol / Report List and Status
  6. Validation Summary Report

Manufacturing Process Validation Workflow

Figure 2 - Manufacturing Process Validation Workflow


4. Definitions

Installation Qualification: Establishing by objective evidence that all key aspects of the process equipment and ancillary system installation adhere to the approved design criteria and that the recommendations of the manufacturer of the equipment are suitably considered.

Operational Qualification: Establishing by objective evidence parameters which result in production that meets all predetermination requirements.

Performance Qualification: Establishing by objective evidence that the process, under anticipated conditions, including worst case conditions, consistently produces a product which meets all predetermined requirements.

Process Validation: Establishing by objective evidence that a process consistently produces a result or product meeting its predetermination specifications.

Process Validation Protocol: a document stating how validation will be conducted, including test parameters, product characteristics, manufacturing equipment, and decision points on what constitutes acceptable test results


5. Applicable Laws, Regulations and Standards

  1. The FDA’s Medical Device Quality System’s Manual
  2. Title 21 CFR 211.100 - Sampling and testing of in-process materials and drug products
  3. FDA - Guide to Inspections Validation Of Cleaning Processes
    Guide to Good Manufacturing Practice (GMP) requirements by WHO
  4. FDA - Guideline On General Principles Of Process Validation
  5. FDA - PAT - A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance