Process Validation Approach Selection Worksheet

Document type	Form
Topic area	Process Validation
Level	Intermediate
Updated	September 2026

This is a ready-to-use worksheet for deciding whether a process should be validated using the traditional, continuous, or hybrid approach described in EU GMP Annex 15 and FDA’s 2011 process validation guidance. Replace every <<FILL: ...>> placeholder. Apply the same criteria, in the same order, to every process the Validation Master Plan governs, and record which criterion drove the outcome so the decision is defensible and repeatable across validation leads. A filled specimen covering all three outcomes follows.

Document control header

Field	Entry
Process or unit operation assessed	`<<FILL>>`
Program / product	`<<FILL>>`
Assessed by	`<<FILL>>`
Date	`<<FILL>>`
Parent VMP document number	`<<FILL>>`

Selection criteria

#	Criterion	Question	Answer
1	Manufacturing history	How many commercial-representative batches or runs exist for this process today?	`<<FILL>>`
2	QbD characterization depth	Was this process developed with Quality by Design characterization deep enough to define a design space and support continuous or near-continuous monitoring?	`<<FILL: yes/no, with basis>>`
3	Monitoring infrastructure	Does real-time or near-real-time monitoring exist, or is it planned, for the critical process parameters that would need to be tracked continuously?	`<<FILL: yes/no>>`
4	Prior validation status	Was this process already qualified using a traditional, batch-based approach?	`<<FILL: yes/no>>`
5	Regulatory filing basis	Does the filed or planned regulatory submission describe a specific validation approach for this process that constrains the choice?	`<<FILL>>`

Decision logic

If	Then the approach is	Rationale
Little manufacturing history, no QbD-depth characterization	Traditional	A defined batch count culminating in a PPQ campaign is the only approach the process’s current knowledge base supports
Developed from the start with real-time/near-real-time monitoring and a mature design space	Continuous process verification	The process has the monitoring infrastructure and characterization depth to demonstrate control without relying on a fixed batch count
Substantial manufacturing history, including prior traditional qualification, now adding continuous monitoring going forward	Hybrid	Annex 15 names this case explicitly; prior qualification work is not repeated, monitoring is added prospectively

Outcome

Field	Entry
Approach selected	`<<FILL: traditional / continuous / hybrid>>`
Criterion that drove the decision	`<<FILL>>`
Approved by	`<<FILL>>`
Date	`<<FILL>>`

Filled specimen

Three processes from Acme Therapeutics’ clinical-stage AAV gene therapy program, assessed the same day using the same worksheet, reaching all three outcomes.

Process 1: Viral vector purification, first commercial-scale campaign

#	Criterion	Answer
1	Manufacturing history	Two engineering runs, zero commercial-representative batches
2	QbD characterization depth	No, process characterization is limited to a small-scale DOE, not yet extended to full-scale design-space work
3	Monitoring infrastructure	No continuous monitoring installed on this skid
4	Prior validation status	Not previously validated
5	Regulatory filing basis	BLA module describes a traditional PPQ campaign with a batch-count justification

Outcome: Traditional. Driven by criteria 1 and 2, no manufacturing history and no QbD-depth characterization to support any alternative.

Process 2: Fill-finish, high-throughput commercial line

#	Criterion	Answer
1	Manufacturing history	Six years of commercial batches across two prior products on the same line
2	QbD characterization depth	Yes, extensive design-space work completed during the line’s original qualification for a different product
3	Monitoring infrastructure	Yes, in-line fill-weight and headspace monitoring already installed and generating continuous data
4	Prior validation status	Yes, this specific line was validated traditionally for its first product
5	Regulatory filing basis	No prior filing constrains the approach for this new product on this line

Outcome: Hybrid. Driven by criterion 4, substantial history and prior traditional qualification of the line itself, combined with criterion 3, monitoring infrastructure already in place to add ongoing verification going forward without repeating the original qualification.

Process 3: Lyophilization cycle, new cell therapy program

#	Criterion	Answer
1	Manufacturing history	None, first program using this lyophilizer
2	QbD characterization depth	Yes, a full design-space study was run at development scale specifically to support real-time cycle monitoring
3	Monitoring infrastructure	Yes, the lyophilizer was purchased with integrated product-temperature and chamber-pressure continuous monitoring as a program requirement
4	Prior validation status	Not previously validated
5	Regulatory filing basis	Planned filing describes continuous process verification for this step

Outcome: Continuous process verification. Driven by criteria 2 and 3, deep QbD characterization and monitoring infrastructure built in from the start, despite no manufacturing history, which criterion 1 alone would have pointed toward traditional.

Common inspection findings this worksheet prevents

Two comparable processes validated under different philosophies with no recorded reason, because the choice was made informally by whichever validation lead happened to own the protocol.
A continuous process verification claim with no design-space or monitoring-infrastructure evidence behind it, asserted because the term sounded more current than “traditional.”
A hybrid approach used to justify skipping qualification work a process’s actual history does not support, rather than the case Annex 15 defines, adding monitoring to an already-qualified process.