Sterile drug products differ from other products in that they are required to be free of viable microorganisms and are manufactured to meet allowable endotoxin limits.
The result of the loss of sterility assurance or endotoxin levels exceeding allowable limits in product have a high likelihood of causing harm to the patient, while the likelihood of detecting a sterility or endotoxin failure is low.
Therefore, risk in sterile product manufacturing, specifically aseptic processing, is relatively high when compared to other pharmaceutical processes, making risk management particularly important.
Process failures that can result in elevated endotoxin levels and lack of sterility assurance pose a significant risk to patient safety. The ability to detect a process failure is low given the current methods for sterility testing.
The probability of a process failure that could adversely affect the sterility of the product in aseptic processing is higher and less predictable than in terminal sterilization, given the inherent exposure to environmental contaminants.
Quality risk management can be an effective method of identifying and reducing aseptic processing risk, thus improving the assurance of sterility, endotoxin control and subsequent patient safety.
Quality risk management should be linked to the Critical Quality Attributes (CQAs) of the product that can affect patient safety or harm the patient. Product CQAs include identity, purity, safety and strength.
Steps involved in Risk Management
The below diagram are Examples for FMEA Risk assessment tool for Risk Assessment for Lyophilized Vial Capping.
1. Personnel should adhere to SOPs for the prevention of microbiological contamination of the aseptic processing area (APA).
2. Personnel should check to see if the gowns and other stuff fit properly and are not torn or defective. If a gown or gloves are found to be defective, necessary counteractions such as changing or layering of new garments over the defective ones should be immediately taken.
3. Personnel should refrain from speaking after gowning and should avoid direct contact with the Guidance on the Manufacture of Sterile Pharmaceutical Products by Aseptic Processing wall, floor, or sanitized surfaces unless necessary.
4. Applicable SOPs should include a provision that restricts unnecessary personnel movement, such as touching of materials and walls, while staying in the APA.
5. Personnel operating in indirect support areas should not be permitted to enter critical or direct support areas or rooms if they do not change gown and other stuff or are not adequately trained on proper gowning procedures.
6. The number of personnel operating in the APA should be set at a minimum for each shift of manufacturing operations, including the preparatory stage. Personnel handling sterile pharmaceutical products, containers, or closures and those engaging in operations in an environment where sterile pharmaceutical products, containers, or closures are exposed should be identified and recorded.
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