NASA has strict limits on the maximum number of spores on a spacecraft's surface to be able to sustain life, or possibly to sustain life in a fundamentally evolved state, in its space missions to celestial bodies in the solar system. As cleanroom procedures become more efficient, these limits are likely to be gradually reduced. Of course, the clean room requirements of other aviation types are basically the same.

Several promising technologies can help contractors reduce the number of spores to reach acceptable levels, quickly measure microbes, and determine the detailed genome of the spacecraft's microbes. NPR 8020.12 allows for alternatives methods to 125°C dry heat sterilization as long as the program and quality control are approved by the NASA Planetary Protection Official (PPO). These methods are then listed in the approved PP (Planetary Protection) program. By quoting the specification figures, aircraft hardware drawings can adopt these unique microbial decrement methods. Microbial barriers can be used to prevent previously contaminated areas from being repeatedly contaminated; A minimum pressure of 1,244Pa (5 inches of water column) is required to prevent microbial invasion. High-efficiency air filter HEPA (0.3 μm, efficiency 99.97%) is also a recognized high-efficiency microbial barrier. NASA requires the spacecraft to be assembled in a clean room with a minimum of ISO Class 8 (Fed. Std. 209E Class 100,000).

For a Mars landing mission, the maximum number of spores allowed for the entire spacecraft is 300,000 (or <300 bacterial spores/m2); all other targets still have a probabilistic requirement for slope stability. Each spacecraft can have 300,000 spores on all surface areas, suitable for non-specific areas of Mars (most surfaces); and the total allowable amount including organisms (Such as canned capsules) inside the hardware is 500,000. Spacecraft that are in contact with “special areas” or search for life must meet the 300,000 requirements and reduce the surface bioburden to 10,000 by dry heat sterilization, which means that there will be no more than 30 visible spores on the surface of the spacecraft.

Most aerospace cleanrooms have unknown microbial deposition rates and surface microbial populations, and there are usually no microbiology laboratory available for immediate use. When constructing a suitable microbiology laboratory to implement NPR5340.1, the first thing the PP program should do is to make their clean room as sterile as possible. To this end, a temporary laboratory can be constructed using a Class 100 (ISO Class 5) clean bench, and a desktop thermostat.. Preliminary testing of clean rooms (including thermal vacuum Chambers, acoustic and vibration facilities) and related equipment can be completed using commercially available settling plates (to capture microbial fallout) and trypsin soy AGAR (TSA) based contact plates (to measuring clean room surfaces). These programs are primarily designed to detect and calculate the number of heterotrophic, mesophilic, aerobic/anaerobic microorganisms. The microorganisms most likely to survive in space and planetary environments are salt-loving organisms, certain species of Bacillus and extreme microorganisms.