High Efficiency Particulate Air (HEPA)

An essential element in ensuring aseptic conditions is the maintenance of HEPA filter integrity. Integrity testing should be performed at installation to detect leaks around the sealing gaskets, through the frames or through various points on the filter media. Thereafter, integrity tests should be performed at suitable time intervals for HEPA filters in the aseptic processing facility. For example, such testing should be performed twice a year for the aseptic processing room. Additional testing may be needed when air quality is found to be unacceptable, or as part of an investigation into a media fill or drug product sterility failure. Among the filters that should be integrity tested are those installed in dry heat depyrogenation tunnels commonly used to depyrogenate glass vials.

Vaccine manufacturing process

Vaccines are a group of pharmaceuticals that include some of the oldest biologically-made compounds. The Smallpox vaccine was introduced by Edward Jenner as early as in 1796 and Louis Pasteur created the first live attenuated bacterial (Chicken Cholera) and viral (Rabies) vaccines at the end of the 19th century.

A vaccine contains an antigen that is capable of inducing an immune response in a living organism and as such, typically enhances the organism’s ability to fight off or minimize disease. These antigens can be live attenuated (weakened) microorganisms such as in the MMR (Measles, Mumps, Rubella) virus vaccine, inactivated microbes (bacteria, virus) or parts thereof (proteins, polysaccharides) such as the DTaP (Diphtheria, Tetanus, acellular Pertussis) vaccine.

Filtration Technique

Filtration is a common method of sterilizing drug product solutions. An appropriate sterilizing grade filter is one which reproducibly removes all microorganisms from the process stream, producing a sterile effluent. Such filters usually have a rated porosity of 0.2 micron or smaller.

Whatever filter or combination of filters is used, validation should include microbiological challenges to simulate "worst case" production conditions regarding the size of microorganisms in the material to be filtered and integrity test results of the filters used for the study. The microorganisms should be small enough to both challenge the nominal porosity of the filter and simulate the smallest microorganism that may occur in production. The microorganism Brevundimonas diminuta (ATCC 19146) when properly grown, harvested and used, can be satisfactory in this regard because it is one of the smallest bacteria (0.3 micron mean diameter).

Part IV: Qualification of Water and Air Handling Systems

3. Steps of Validation

Validation plans for water and air systems typically include the following steps:

1. Establishing standards for quality attributes of water and air to manufacture pharmaceuticals.

2. Defining systems and subsystems suitable to produce the desired water and air by considering the quality grades of water and air.

3. Designing equipment, controls, and monitoring technologies.