What FDA is saying is that drug manufacturers need to have SOPs in place to prevent microorganisms from the environment and humans from contaminating the product. Production rooms in which non sterile drugs, such as tablets and pills are made have lower microbiological control standard than clean rooms in which sterile injectable drugs are made. I believe that non sterile manufacturing facilities have
Since non sterile drugs are usually consumed orally, bacteria that maybe present on the tablets would be destroyed by stomach acid in humans. Sterile injectable drugs however, are injected directly into human body. Therefore, any bacterial contamination in sterile injectable drugs is much more harmful. According to Dr. Radhakrishna S. Tirumalai, a Microbiology and Sterility Assurance Expert for US Pharmacopeia, sterile products "present the highest risk to patients".
Manufacturing facilities must be routinely sanitized by appropriate disinfectants and equipment need to be sanitized and/or sterilized by processes such as sonicating, steaming, autoclaving, and depyrogenation.
Environmental monitoring programs are put in place to collect data to determine if the manufacturing environment (the rooms, the equipment, & the personnel) are under microbial control during drug manufacturing or static activities. Next blog I will takl about the type of EM, the EM equipment used, alert/action levels.
Keith
I too love environmental monitoring and appreciate the comments you have provided. It does seem that environmental monitoring is a risk based science that does have some standards for certain products such as aseptic or "sterile" products.
ReplyDeleteI noticed you state that solid dosage products are non-sterile and therefore having micro contamination would not be of much concern due to stomach acids. I would rather say the process environment for manufacturing solid dosage is low-risk and can handle a level of organisms per cubic meter or surface area. The fact is that people taking products are sometimes immune compromised and you can not depend upon the human body to minimize those risks. As a manufacturer you have an obligation to make a minimal risk product. Also, some organisms can make it through the stomach and could also get into other oral surfaces (nasal, etc) and cause problems. SO to me the type of organisms and the level are important regardless of the product. Of course I would wonder why a Salmonella or other organism is in the solid dosage considering the water activity level is very low and tends to not support growth. Thank goodness we don't have to worry about endotoxins in solid dosage.
So I agree, the importance of environmental monitoring type of testing and levels allowed must first be determined through risk assessments and this would help if an investigation is brought up. I have had experiences where soft gels have been contaminated and the process did not remove the organisms. Even after explaining to management to not use the product because it was not one of the four organisms in the spec listed should not mean it is okay. Especially since the levels were outrageous and part of the coliform family.
These are very thoughtful comments and the risk based approach is appropriate.
ReplyDeleteThe point about the type of bacteria is a good one. Certainly Clostridium botulinum or Anthrax are organisms that should not be present in any drug,
I expect as we become more familiar with manufacturing steps in biopharmaceuticals, we'll identify a number of process steps where risk is high and therefore limits are typically more stringent.
Thanks for sharing this post.
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