Pharmaceutical cleanroom zoning: grades, airlocks and pressure steps

By ZY Cleanroom · Updated 2026-11-01 · Sources at the end of the page

The four grades

Annex 1 sets total particle limits at rest and in operation (Table 1, para 4.27). It also sets action limits for microbes in air (Table 6, para 9.30). The use column is a short summary of paras 4.4, 8.6 and 8.10.

Zoning rules that drive the layout

Entry to cleanrooms goes through change rooms that act as airlocks (para 4.1). Airlocks should be present between different grades. Separate airlocks for people and for materials where possible (para 4.12).

The last stage of an airlock should match the grade of the room it leads to, in the at-rest state (para 4.12). Airlocks to grade A and B need interlocked doors. Airlocks to grade C and D need at least a visual or audible warning (para 4.13).

Sinks and drains are not allowed in grade A and B (para 4.9). Surfaces must be smooth, impervious and unbroken, and ceilings must be sealed against the space above (paras 4.5 and 4.8).

Fit pressure indicators between rooms. Critical pressure differences need continuous monitoring, recording and an alarm (para 4.16).

Transfers, windows and airflow proof

Annex 1 calls the movement of equipment and materials one of the greatest potential sources of contamination (para 4.10). Transfer into grade A or B should be one-way, ideally through double-ended sterilisers sealed into the wall (para 4.11). Removal uses a separate one-way route, or time separation by procedure.

Grade A and B areas should allow observation from outside, through windows or remote cameras (para 4.17). Airflow patterns must be shown by visualisation studies, at rest and in operation, and the video kept (para 4.15).

FDA's 2004 guidance says the area next to the aseptic line should be at least ISO 7 in operation. The maker may class it ISO 6, or hold the whole filling room at ISO 5. ISO 8 suits less critical work such as equipment cleaning.

Pressure and air change figures

FDA's 2004 guidance says at least 10 to 15 Pa should be held between adjacent rooms of different class, with doors closed. It gives at least 12.5 Pa over an unclassified room next to the aseptic area. It says at least 20 air changes per hour is typically acceptable for ISO 8 supporting rooms and much higher for ISO 7 and ISO 5.

Annex 1 says pressure advice may change where hazardous material must be contained. Then the design may use positive or negative pressure airlocks (para 4.14).

Worked example (arithmetic, not a standard)

Take the 10 Pa minimum step from Annex 1. A chain of an unclassified corridor, grade D, grade C and grade B has three steps. The grade B room then sits at least 30 Pa above the corridor. The real set points come from the contamination control strategy, not from this sum.

This guide covers sterile products only. For non-sterile products, check the GMP rule of your market.

If you have a room list and grade plan for a pharmaceutical project, send it to ZY Cleanroom and we will review the panel, door and ceiling scope with you.

Related guides

• How long does it take to build a cleanroom?
• What a cleanroom costs to run: energy, filters and testing
• How to audit a cleanroom panel factory, on site or by video
• Cleanroom cost per m²: published ranges by ISO class
• Turnkey cleanroom contractor
• Room list builder

Sources

• EudraLex Volume 4, Annex 1: Manufacture of Sterile Medicinal Products (published 25 August 2022, applied from 25 August 2023; checked 1 November 2026)
• FDA, Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing, Current Good Manufacturing Practice (September 2004, nonbinding; checked 1 November 2026)