Fermenter in the laboratory – is this already a production area?!?

During the AGCT project management courses, we often receive questions about the demarcation of laboratory and production areas in genetic engineering facilities. Does this have any practical implications? Is a facility with a fermenter automatically a production area? Does this depend on the size of the fermenter or its technical equipment? What safety measures apply to laboratories with only a small fermenter?

Time for us to check the specifications:

Legal basis: The Genetic Engineering Act (GenTG) initially only defines “genetic engineering facilities” (Section 3 No. 4 GenTG); a differentiated analysis of facility types is not carried out. However, according to Section 7 Paragraph 2 Sentence 2 GenTG, it is the responsibility of the Federal Government to “[…] establish the safety measures required for the Laboratory and production areas, animal husbandry rooms and greenhouses […]“ to be regulated.

This differentiation has been made in Annexes 2 – 4 of the Genetic Engineering Safety Ordinance (GenTSV).

The following definitions apply:

• Laboratory area: “Area in which genetically modified organisms (GMOs) are usually produced or in which GMOs are handled experimentally in typical laboratory equipment” (Section 3 No. 9 GenTSV).

• Production area: “Area in which a) GMOs are generally propagated in standardised processes or substances are obtained with their help or b) GMOs are produced in exceptional cases” (Section 3 No. 10 GenTSV).

The distinction is thus made activity-related and looks at the regular Work.

If GMOs are (newly) produced or are used experimentally, this is a laboratory area.

If GMOs are propagated (industrially/standardized) or used to obtain substances, this is considered a production area. The term "production" is not defined by the term "product," meaning it is irrelevant whether something is produced for later sale or distribution to the market. Nor is the distinction based on fermenter size.

Section 14 (2) GenTSV also applies:

“The safety measures according to Annex 2 Part A for the laboratory area can also be applied to typical laboratory work in the production area, and the safety measures according to Annex 2 Part B for the production area can also be applied to typical production work in the laboratory area.”

Laboratory and production activities do not have to be carried out in separate areas, provided that the respective safety measures are observed in relation to the activity.

Impact on application: You can obtain the initial approval of your genetic engineering facility using the following forms:

• AZ-S1 (display of an S1 system)
• A (Registration of an S2 facility/approval of an S3/S4 facility):

Neither form requires you to define your facility as a laboratory, production facility, animal husbandry, or greenhouse; each facility is a "genetic engineering facility." Depending on the activity, however, Forms A and AZ-S1 must be supplemented with specific forms describing the safety measures in each area:

• AL for safety measures in the laboratory area
• AP for safety measures in the production area
• Working Group for Safety Measures in Greenhouses and Climate Chambers
• AT for safety measures in animal husbandry

Both forms AL and AP require information for fermenters. Therefore, Form AP does not necessarily have to be used if a fermenter is available. This depends on the activity being performed. If the fermenter is used as a typical laboratory device for experimental handling of GMOs, the information must be provided in Form AL, paragraph 6. If the fermenter is part of a standardized process for propagation or substance extraction, the information is provided in Form AP, paragraph 6. In both forms, the fermenter room can be listed as such in the room list.

Impact on security measures: The reference in Section 14, Paragraph 2 of the GenTSV (see above) also answers the question of the applicable safety measures. If a fermenter is operated in a laboratory setting, this is typical production work in a laboratory setting. Consequently, in addition to the safety measures for laboratory areas (Annex 2, Part A, GenTSV), those for production areas (Annex 2, Part B, GenTSV) must also be met. These include, among other things, sufficient inactivation capacity for GMOs (cf. Annex 2, Part B, I. a. 5, GenTSV) and the presence of sufficient containment devices for the uncontrolled release of GMOs (cf. Annex 2, Part B, I. a. 9, GenTSV). In practice, the provisions of the GenTSV should therefore be reviewed during the planning phase of the construction of production facilities.