Application: Controlled Execution
Domain 2: Application
Application tests execution: aseptic technique, parameter control, sampling, and concurrent documentation during a live bioprocess run. The Craftsman Bio Process exam focuses on repeatable craft - whether your technique and decisions keep the process inside its validated envelope.
Core rules
- Aseptic technique: gown and glove correctly, disinfect gloves, maintain a sterile field, minimize open time, avoid turbulent movement near open connections, and use isolator or RABS barriers where available.
- Inoculation: verify cell density or viability, inoculum volume, and container integrity; make sterile connections per procedure; record the inoculation time.
- Parameter control: operate within the normal operating range (NOR). A proven acceptable range (PAR) may be wider, but exceeding the NOR requires a deviation and justification, even if the value remains inside the PAR.
- Sampling: take representative samples at specified points, label them aseptically, and avoid dead legs or non-representative ports.
- Hold times: track in-process hold times such as media hold or pool hold, and record start and end times.
- Documentation: record at the time of action. Back-filling entries undermines data integrity.
Worked example
During fermentation, dissolved oxygen falls below setpoint. The operator wants to raise agitation above the NOR. Correct action: adjust within the NOR first - for example, increase airflow within its limit or add oxygen within the approved range - notify the supervisor, and document the action. Reasoning: the NOR is the validated operating envelope. Exceeding it, even toward a PAR value, changes the process and needs a deviation; making two parameter changes at once also obscures cause and effect.
Traps that cost marks
- Adjusting two parameters simultaneously and losing traceability.
- Sampling after a hold-time limit has expired.
- Signing a step before performing it.
- Ignoring foam, overflow, or filter fouling until the next scheduled check.
- Treating a PAR as routine operating space.