Facility Design and Cleanliness Classes
📌 Cleanliness classifications (A, B, C, D, E) are determined by the maximum allowable particle count, which acts as an indicator for microorganisms, since bacteria lack self-locomotion.
📌 Building features must prevent particle accumulation; thus, corners must be sloped (landai) instead of having sharp right angles (siku-siku).
📌 Floors and walls in sterile areas cannot use materials like ceramic or granite with visible grout lines (nat); instead, they must be smooth and coated with epoxy, which simplifies cleaning but is susceptible to acid damage.

HVAC and Environmental Control
🌬️ Temperature control requires a range of 18°C to 24°C in critical areas, necessitating the use of Air Handling Units (AHU), not standard split AC units, due to poor circulation and humidity control in the latter.
🌬️ Grade A areas utilize HEPA filters with an efficiency equivalent to 99.99% fresh air filtration, ensuring continuous air rotation to prevent particle accumulation.
🌬️ Pressure differentials must be strictly maintained between rooms (e.g., weighing room positive pressure relative to the corridor) to control contamination flow, especially for highly potent substances like hormones or cytotoxics.

Water Systems and Utilities
💧 Production areas strictly prohibit tap water; only Purified Water (PW) or Water for Injection (WFI) is permitted, with piping clearly color-coded (e.g., Red for WFI, Blue for PW) for safety.
💧 WFI pipes carry extremely hot water (near 100°C), emphasizing the need for operator awareness and adherence to safety protocols to prevent severe burns.

Area Designation and Activities
🏭 Grade E (Black Area) is typically used for secondary packaging, visual inspection, coding, labeling, leak testing, and warehousing of raw/packaging materials.
🏭 Grade D (Grey Area) handles non-sterile operations and processes immediately preceding terminal sterilization, such as autoclave loading for vials after initial filling and labeling.
🏭 Grade C is used for aseptic processes like Washing, Filling (for terminal sterilization products), Mixing, and holding tanks, operating under unidirectional airflow (UDAF) to minimize turbulence.

Cleaning, Sterilization, and Monitoring
🧼 Facility cleaning requires validation and the use of particle-free materials like wipers (not standard mops) and low-foaming detergents (e.g., Pol), as foam itself is considered a particle source.
🧼 Rooms undergo periodic sterilization via fogging (often using formaldehyde/formalin), which requires the AHU to be switched off during the process to protect the cooling coils from corrosion.
🧼 Environmental monitoring relies on particle counters (inline or portable), and regular checks (e.g., swap tests by IPC personnel) confirm the absence of microbial colonies post-sterilization.

Personnel and Hygiene Protocols
🧑‍🔬 Personnel in sterile areas must undergo rigorous training, starting as cleaners for induction and then progressing through On-the-Job Training (OJT), which can last up to 6 months for supervisors.
🧑‍🔬 Personnel entering critical zones (Grade B and above) must adhere to strict hygiene: mandatory clean showering, no deodorant, and wearing multi-layered, anti-static garments (e.g., blue, cream, white layers for transition from E $\rightarrow$ D $\rightarrow$ C $\rightarrow$ B).
🧑‍🔬 Entry into Grade B for filling operations requires passing a personnel hygiene validation via contact plates placed on critical body areas (e.g., armpits, back of knees, forehead) to confirm no microbial transfer.

Key Points & Insights
➡️ Document everything: meticulous record-keeping (batch records, deviations, maintenance logs) is crucial for traceability and investigating failed sterilization tests (TMS).
➡️ Aseptic Area Integrity: Be highly suspicious of equipment failures in autoclaves (e.g., failure to reach sterilizing temperature) as leaking gasket seals are a common cause, requiring immediate abortion of the batch for rework.
➡️ Operator Criticality: Visual inspectors' eye health must be regularly monitored (e.g., every 6 months), as their role in identifying reject vials (Grade I/Black Area) is fundamental to product quality.

📸 Video summarized with SummaryTube.com on Nov 25, 2025, 01:51 UTC