Bioblog: What is an ISO 7 Cleanroom?

A cleanroom is a room where the number of airborne particles is controlled. It is constructed and used in a way that minimizes the introduction, generation, and retention of particles inside it and were the control of relevant parameters such as temperature and pressure is necessary [1].

There exist standards that define how clean rooms must be constructed and the requirements of each class:

  •   FED-STD-209 E Airborne Particulate Cleanliness Classes in Cleanrooms and Clean zones was a federal standard concerning the classification of air cleanliness, intended for use in environments like cleanrooms. The standard-based its classifications on the measurement of airborne particles [2]. The standard was canceled in 2001 by the United States General Services Administration (GSA). The document was superseded by standards written for the International Organization for Standardization (ISO) [3] but is still used as a reference.
  •   ISO 14644-1: replaced federal standard 209E in 2001. The standard-based its classifications on the number of particles (≥0,5µm to ≥5µm or greater) per cubic meter (m3) of air [1].

Cleanrooms can be built and operated to meet different cleanliness classifications, depending on the environmental conditions required for their use [4]. ISO 14644-1 uses a classification based on the size and number of airborne particles/m3, as can be seen in Table 1 .

Table 1. Equivalence between ISO 14644-1 and FED-STD-209 E (Adapted from [5]).

Table 1. Equivalence between ISO 14644-1 and FED-STD-209 E (Adapted from [5]).

An ISO 7 clean room (also known as a Class 10,000 cleanroom) is the most used in medical device manufacturing and pharmaceutical compounding.

WHICH ARE THE ISO 7 CLEANROOM DESIGN AND SPECIFICATIONS?

At Table 2 is shown a little summary about the specifications and the design requirements for an ISO 7 cleanroom according to ISO 14644-1 [6].

Filtration and particle control

HEPA efficiency: 99,99% at 0,3µm final filtration is performed at the air point of the cleanroom by fan filter modules, depending on the application.

Airflow and air change rates per hour

The most common airflow is a vertical flow from the ceiling to the floor, returning for conditioning and filtration through low wall returns.

Architectural finishes

  • Wall systems: Biotech applications require non-shedding systems, with monolithic seams and coving to remove 90° angles, allowing to achieve sterile requirements.
  • Ceiling systems: Biotech and pharma applications require panelized ceiling systems to promote washable surfaces and access to maintain lights and filter media without breaching the certified space.
  • Flooring systems: the most used is a resinous floor system or a heat-sealed vinyl flooring.

Gowning and housekeeping [7]

The access to the cleanroom facility is restricted to the people who have the authorization for access or have a certain training. In other cases, untrained staff must always be escorted by a professional. Inside the cleanroom, one must have the right attire, which includes cleanroom coveralls, cleanroom gloves, shoe covers and a head gear.

Special Airlock System (SAS) [8]

Material SAS guarantees the safe transfer of objects and materials, preventing any type of contamination in both directions, without having an air filtration system.

Personnel SAS share the characteristics of material SAS except they include a HEPA air scavenging system.

The difference between this type of SAS and the previous one lies in the decontamination method.

Pressure

Pharmaceutical cleanrooms are maintained at a higher pressure than the adjacent spaces, and therefore the net airflow is out of the room. Its objective is removing more air than is introduced over a set period. There is an exception in cleanrooms that require a certain biosafety level.

WHICH IS THE DIFFERENCE BETWEEN ISO 14644-1 AND EU GMP CLASSIFICATION?

The European Commission focuses on the rules governing medicinal products in the European Union. They contain guidance for the interpretation of the principles and guidelines of good manufacturing practices (GMP) [9].

In Table 3 can be seen important requirements of these types of cleanrooms.

Table 2. EU GMP Cleanroom requirements (adapted from [10]).

The goal of these requirements is to minimize risk of microbiological contamination during preparation and sterilization processes. With these purpose, they have established a classification based on cleanroom grades: A, B,C and D [11].

Table 3. Cleanroom Grade classification chart (adapted from [11]).

Following the chart below, an ISO 7 cleanroom (ISO 14644-1) is equivalent to a Grade C at rest (GMP EU). ISO 14644-1 allows measurements to be made in a cleanroom in any of the three designated occupancy states: as-built, at-rest, or operational [5].

Today the company uses three cleanrooms ISO 7 Class C at rest to produce Venair Biotech products: extruded silicone and thermoplastic tubing as well as assembled single-use kits according to our customer needs. The cleanrooms are in Barcelona and Ho Chi Minh.

REFERENCES

[1]         “ISO 7 Clean Room Requirements | ISO 7 Cleanroom Standards.” https://www.cleanroomsbyunited.com/modular-cleanrooms/class-10000-cleanrooms/ (accessed May 24, 2021).

[2]         “FED-STD-209 E AIRBORNE PARTICULATE CLEANLINESS CLASSES.” .

[3]         “Federal Standard 209E Cancellation.” .

[4]         “ISO 14644-1 Cleanroom Standards,” p. 14644, 2012.

[5]         AENOR, “Cleanrooms and associated controlled environments - Part 1: Classification of air cleanliness by particle concentration (ISO 14644-1:2015),” 2016.

[6]         “ISO Class 7 Cleanroom Design and Build.” .

[7]         “Recommended cleanroom clothing per cleanroom classes | Berner Safety.” .

[8]         “¿Qué son los equipos SAS Salas Blancas?” https://ingelyt.com/wiki/que-son-los-equipos-sas-sala-blanca/ (accessed May 24, 2021).

[9]         “EudraLex - Volume 4 - Good Manufacturing Practice (GMP) guidelines | Public Health.” https://ec.europa.eu/health/documents/eudralex/vol-4_en (accessed May 24, 2021).

[10]      “FDA and EU GMP Annex 1 Differences in Cleanroom Specifications | RAPS.” https://www.raps.org/news-and-articles/news-articles/2019/7/fda-and-eu-gmp-annex-1-differences-in-cleanroom-sp (accessed May 24, 2021).

[11]      “GMP EU Cleanroom Classifications A B C D | High-Tech Conversions.” https://high-techconversions.com/gmp-eu-cleanroom-classifications-a-b-c-d/ (accessed May 24, 2021).