FDA Finalizes Guidance on Biologics Manufacturing Using Spore-Formers Microogranisms

Rockville, MD (Sept. 7)-The US Food and Drug Administration issued a final guidance, Manufacturing Biological Intermediates and Biological Drug Substances Using Spore-Forming Microorganisms, which provides recommendations that allow for greater flexibility when manufacturing biological products with spore-formers. The guidance finalizes a draft guidance issued Feb. 24, 2005, and addresses revised regulations that went into effect June 1, 2004.

Under the revised regulation, FDA no longer requires the use of permanently dedicated buildings and equipment for spore-formers, if certain controls and precautions are applied. “We recognize that advances in facility, system, equipment design, testing, and sterilization technologies have increased the ability of manufacturers to control and analyze the manufacture of biological products,” FDA specified in the guidance. “As industry has gained experience with these new technologies, we found that manufacturers could evaluate aspects of a biological product’s safety and purity with testing. The use of appropriate procedural controls, validated processes, and enhanced testing capability provides the manufacturer with a degree of confidence that their biological product achieves the expected levels of safety and purity. Areas of special concern, such as process containment, contamination with pathogenic and/or toxic agents, sterilization, and disinfection can be addressed using currently available procedures and processes.”

FDA also said although it recognizes that spore-formers are currently used in manufacturing processes and will likely be used in the immediate future, it encourages alternatives to spore-forming microorganisms for producing future biological products. These alternatives include using sporulation-deficient strains or recombinant proteins expressed in nonspore-forming microorganisms.

For the purposes of the guidance, the term spore-forming microorganism or spore-former includes both the spore and vegetative forms of the organism. The guidance applies to the manufacturing of biological intermediates and biological drug substances.