August 18, 2021: Pharmaceutical Interview Questions and Answers

#HoldTimeStudiesForSterileFormulations #FiltrationHoldTime #AsepticProcessSimulation #MediFill

1. What types hold time studies required for sterile formulations?

Holing time should be done between the start of bulk product compounding and its sterilization, filtration processes, product exposure while on the processing line, and storage of sterilized equipment, containers and closures.

2. What parameters should be studied while conducting the hold time studies of sterile formulations?

Bioburden and endotoxin load should be assessed when establishing time limits for stages such as the formulation processing stage.

3. Why product filtration hold time is important for sterile formulations?

The total time for product filtration should be limited to an established maximum to prevent microorganisms from penetrating the filter. Such a time limit should also prevent a significant increase in upstream bioburden and endotoxin load. Because they can provide a substrate for microbial attachment, maximum use times for those filters used upstream for solution clarification or particle removal should also be established and justified.

4. What is the purpose of Aseptic Process Simulation?

The purpose of the Aseptic Process Simulation is to challenge the aseptic manufacturing process against potential microbiological contamination vulnerabilities. During this exercise, the ability of the process, personnel and manufacturing environment involved in the process to remove and prevent microbiological contamination of the finished drug product is being assessed.

5. What is another name of Aseptic Process Simulation?

Media fill

6. Explain the study design for Aseptic Process Simulation or Media fill.

A media fill program should incorporate the contamination risk factors that occur on a production line, and accurately assesses the state of process control.

Media fill studies should closely simulate aseptic manufacturing operations incorporating, as appropriate, worst-case activities and conditions that provide a challenge to aseptic operations.

Following factors should be considered during study design:

• Factors associated with the longest permitted run on the processing line that can pose contamination risk (e.g., operator fatigue)
• Representative number, type, and complexity of normal interventions that occur with each run, as well as nonroutine interventions and events (e.g., maintenance, stoppages, equipment adjustments)
• Lyophilization, when applicable
• Aseptic assembly of equipment (e.g., at start-up, during processing)
• Number of personnel and their activities
• Representative number of aseptic additions (e.g., charging containers and closures as well as sterile ingredients) or transfers
• Shift changes, breaks, and gown changes (when applicable)
• Type of aseptic equipment disconnections/ connections
• Aseptic sample collections
• Line speed and configuration
• Weight checks
• Container closure systems (e.g., sizes, type, compatibility with equipment)
• Specific provisions in written procedures relating to aseptic processing (e.g., conditions permitted before line clearance is mandated)

Reference: FDA Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice – September 2004

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