Table IV

Summary of Benchmarking Questions and Results

#	Question	Response
1	Do you consider a shake-down run to be non-GMP (not for potential human use)?	86%—Yes
2	Do you consider an engineering run to be GMP for potential human use?	71%—Yes
For subsequent questions, use the definition of shake-down as non-GMP, NfHU and engineering runs as GMP, fHU
2a	Do you typically perform a shake-down run prior to clinical lots in a clinical only facility?	50%—Yes
2b	Do you typically perform a shake-down run prior to clinical lots in a commercial only facility?	43%—Yes
2c	Do you typically perform shake-down runs prior to process validation/PPQ lots in a commercial facility?	57%—Yes
2d	Do you perform the shake-down run through the entire drug substance manufacturing process (cell culture & purification)?	57%—Yes
3a	Do you currently combine shake-down and engineering runs?	29%—Yes
3b	Do you consider the shake-down runs to demonstrate process performance only, i.e., not including product quality attributes?	43%—Yes
4	Do you have different quality standards for engineering (GMP) vs clinical runs?	33%—Yes
5a	Do you typically perform an engineering run prior to a campaign of clinical lots in a clinical-only facility?	20%—Yes
5b	Do you typically perform an engineering run prior to a campaign of clinical lots in a commercial facility?	40%—Yes
5c	Do you typically perform an engineering run prior to a campaign of PV lots in a commercial facility?	67%—Yes
6a	What value do you get from a shake-down run?	Enables robust transition from laboratory/pilot to manufacturing scale (i.e., it is the final stage of process development and process confirmation Minimizes subsequent non-conformances (NCs) Useful for external transfers (CMO, partner organizations) Operator training Useful for testing new equipment
6b	What value do you get from an engineering run?	Increases confidence for successful PPQ campaign–readiness to proceed to PPQ Confirms that operational parameters and product quality can be met at large scale Allows release for clinical use
7a	How do you justify the value and cost of performing a shake-down run?	Cost of shake-down batches is less than the cost of GMP batch failure (time and resources for investigation) Risk assessment is performed to justify necessity based on unit operation and facility readiness Shake-down run is performed at small scale, e.g., cell culture at full scale but downstream at laboratory or pilot scale
7b	How do you justify the value and cost of performing an engineering run?	Avoids failure during PPQ. Minimizes impact to regulatory submission and product launch May be used for clinical supply
8a	In what phase should the team start discussions on the need for shake-down or engineering runs?	Initial planning stages Gap assessment—differences between SU and RU For CMO or partner (external transfers), during initial contract negotiation discussions Prior to formal start of technology transfer or during preliminary technical evaluation of process fit
8b	When does the final decision need to be made on shake-down/engineering runs?	Initial planning stage Contract approval for CMO Summarized in technology transfer plan High level budget and timeline approval
9a	Do you consider that analytical transfer and method validation need to be completed for a shake-down run?	14%—Yes
9b	Do you consider that analytical transfer and method validation need to be completed for an engineering run?	86%—Yes
10	What tools does your company use for deciding on the need for shake-down or engineering runs?	Gap analysis between SU and RU Kepner-Trego analysis Review of customer data package for CMO transfers Risk assessment—requires assessment of the site capability (equipment, operations expertise)
11	Do you consider the duration between last campaign and PPQ campaign as a factor in deciding on the need for shake-down runs or engineering runs?	57%—Yes
12	Once a GMP engineering run is started, would you consider downgrading it to a NfHU shake-down run, i.e., continue to forward process as a non-GMP run if there are significant deviations in terms of criticality or just number of deviations associated with the lot?	57%—Yes Downgraded only after full execution of lot and then decision made for lot rejection if appropriate Case-by-case decision May stop the run mid-way if there are significant issues
13	Who recommend the shake-down or engineering runs (scope, number of runs, and timing between runs)?	Combined technology transfer team/technical team RU
14	Who approves the shake-down or engineering runs (scope, number, and timing)?	Governance or steering committee For external projects, client approves
15	How is the usefulness of shake-down and/ engineering runs messaged up to senior leadership?	Need for structured, deliberate approach to avoid failures during validation Defined escalation at technology transfer stage gates Based on risk/gap assessment, program impact and financial considerations Technology transfer steering committee informs senior leadership