Process Validation

Process Validation is generally accepted as a regulatory requirement for most life science industries / products below we have extracted a few regulatory expectations.

If we may discuss Medical Device process validation for example, the US FDA expectations for Medical Device Process Validation is outlined in CRF 820 QUALITY SYSTEM REGULATION - Production and Process Controls Sec. 820.75 Process Validation, similar regulations are contained in ISO 13485 in section 7. This is complemented by the GHTF document - Titled "Quality Management Systems - Process Validation Guidance".

In the EU and PIC/S countries the regulations are contained in the Annex 15 as well as the following practical guidances

"PI 006-3 25 September 2007 RECOMMENDATIONS ON VALIDATION MASTER PLAN INSTALLATION AND OPERATIONAL QUALIFICATION NON-STERILE PROCESS VALIDATION CLEANING VALIDATION" and "PI 007-5 1 July 2009 RECOMMENDATION ON THE VALIDATION OF ASEPTIC PROCESSES"

In the US, the Process Validation regulations for human and veterinary drugs, blood and biologicals are contained in the FDA CFR 211, 600 etc as well as a number of guidance and compliance policy guide, issued by the FDA. The US FDA "Guidance for Industry Process Validation: General Principles and Practices" published in November 2008. This document is the most insightful in the latest regulatory thinking and the trend into the future, maybe.

All too hard? We think that there are a few core principles and a central process which we have extracted below.

Know Your Process

Aligned with the thinking in ICH Q8, Q9 and Q10, the is an increased importance on credibly product development and product transfer. All process validation should start with a through understanding of the tolerances of critical control points, critical to quality parameters, i.e.how the process works, BEFORE starting validation.

Risk assessment

Step 1- risk/criticality identification

So first step in process validation in manufacturing is to identify the risks and critical control points of the process. Which aspects of the process will impact product quality i.e. GMP risk, if they fail, or if they fall outside the control parameters?

Step 2 - risk detection and impact

The second step is to assess the likelihood of detection and the impact of failure for each identified risk. This is then documented in a matrix which indicates the level of qualification or validation recommended.

Development of a Validation Master Plan

Developing a Validation Master Plan (VMP) early in the validation activities will communicate the planned validation activities to the organisation. Process validation is probably the most critical element of any validation effort.

The VMP should:

• detail the validation approach,
• define the systems and equipment to be validated,
• set out the number and format of the protocols, and
• establish the standards for acceptance criteria.

The validation process

The PIC/S approach to process validation includes:

• Installation Qualification (IQ) - have the correct items have been delivered, have the site requirements for the system been met and is the system functioning according to specifications? Usually verification at this stage is with the power off, typically material contact surfaces, volumes etc are verified. Accurate records of equipment installed is important, as this facilitated easy like for like changes during operation and maintenance.
• Operational Qualification (OQ) - is the system meeting specification both in terms of functional tests performed on individual components of the system and as well operational tests of the whole system? At this stage the power is on, flows can be verified, RPM and other operational requirements.
• Performance Qualification (PQ) - does the system meet the requirements for which it was specified?

Protocols for Qualification/Testing

The boring bit that everyone dreads.... writing the protocols that will be used to test the process.

If you need help with writing the protocols, PharmOut can provide templates and guidance.

Alternatively, we can do all the testing for you - either on a fixed price or a time and materials basis. You can also choose to have our validation contractors work under your supervision or we can supply very experienced validation professionals to take on the project completely.

More information

If you would like a quote or to ask questions, please contact us.