EMA vs FDA Expectations on Process Validation

In pharmaceutical manufacturing validation of manufacturing process ensures that the manufacturing process is consistent and producing a product that meets the specification and quality parameters. European Medicines Agency and US Food and Drug Administration both accept the concept of process validation but there are some differences in their validation approaches. In this post, we will understand the difference between expectations of EMA and FDA on process validation.

What is process Validation?

FDA defines process validation as – “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 product.” — FDA Guidance (2011)

EMA defines validation as a part of good manufacturing practices with its requirements outlined in detail in Annex 15 of the EU GMP Guidelines.

Both adjacent say that validation is not a one-time activity but it is a life cycle process that starts with product development and continues throughout the product life cycle.

 

1. Lifecycle Approach

Both EMA and FDA have a lifecycle approach for process validation but they have variations in terminology and focus.
FDA has a three-stage model for process validation.

A) Stage 1: Process Design: It defines the process design on the basis of development and scale of studies.

B) Stage 2: Process Qualification: It confirms the process performance during commercial production in large equipment and facilities

C) Stage 3: Continued Process Verification (CPV): It confirms assurance during continuous production of product.

In EMA’s process validation lifecycle, it is not divided into stages but EMA covers prospective, concurrent and retrospective validation. It strongly suggests the use of validation master plan in Annex 15 section 6. It recommends the requirement of ongoing process verification.

2. Process Qualification: Equipment and Facility Focus

Both FDA and EMA require IQ, OQ and PQ to demonstrate that the process works perfectly under commercial production.

A) PQ is done in a stage 2 of the validation lifecycle in FDA guidelines while EMA requires IQ, OQ and PQ for equipment and facilities.

B) FDA requires successful qualification of equipment utilities and facilities before process performance qualification while EMA expects documented evidence with GMP Annex 15.

C) FDA requires minimum therapeutic commercial batches to demonstrate the consistency of the process while EMA does not mandate any specific number of batches but requires scientific justification for the consistency.

3. Continued Process Verification (CPV) vs Ongoing Process Verification (OPV)

Both FDA and EMA have ongoing monitoring mandatory for the process to ensure the control of process.

FDA’s continued process verification is data driven, real time monitoring that focuses on its statistical process control, control charts and trends that is a part of product lifecycle management document while EMA’s ongoing process verification is referred to in Annex 15 that is based on real time or retrospective data and incorporated in the product quality review.

4. Documentation and Validation Master Plan (VMP)

A) FDA does not mandate a validation master plan but expects an equivalent structured document while EMA instructs to use a validation master plan.

B) FDA focuses on protocols reports and scientific justifications for validation activities while EMA focuses on scope, responsibilities and timelines for all the validation activities.

Both EMA and FDA guidance on process validation share the fundamental principle that process validation is a lifetime activity but they differ in terminology and structure, documentation requirements, batch requirements and flexibility in ongoing verification. The following table summarizes these differences.

Aspect	FDA	EMA
Process Stages	Clearly defined (3 stages)	Implicit, life-cycle focused
VMP Requirement	Not mandatory	Mandatory
Use of Statistics	High emphasis	Encouraged, but flexible
Retrospective Validation	Discouraged	Permitted with justification
Number of PQ Batches	Minimum 3 recommended	Risk-based

Get ready to use editable Validation Protocols in MS-Word FormatView List

Share

Tweet

Share

Pin it

Share