Regulatory Aspects of Aseptic Processing c GMP Aseptic

Regulatory Aspects of Aseptic Processing c. GMP

�Aseptic processing is used for critical processing steps �Therefore, regulators are very concerned that aseptic processing can be done properly �Aseptic processing must be done in a GMP manner REGULATORS

�The QA unit is independent of manufacturing �QA is responsible for reviewing everything related to drug production �QA MUST APPROVE EACH LOT BEFORE IT CAN BE SOLD QUALITY ASSURANCE

�Things QA must review and approve: ◦ Raw materials before they are used ◦ All production documentation ◦ All test results ◦ All equipment and process validations ◦ All deviations and investigations ◦ All production activities ◦ The condition of the facility QUALITY ASSURANCE (continued)

�QA has the responsibility of reviewing production activities �This means that a QA person can be in the room watching you work �QA cannot be part of the manufacturing activities, just observers ◦ Participating could cause a conflict of interest issue to arise QA-ON-THE-FLOOR

�There must be enough people present to properly complete manufacturing activities �There must be proper supervision of manufacturing personnel �Each person involved in manufacturing shall be qualified for their role through a combination of experience and education �Each person shall also be trained on the manufacturing process they are performing PERSONNEL

�All documents relating to manufacturing must be: �Reviewed and approved after the batch is completed and the record filled out �Clear, complete, accurate �Retained at least 1 year after the expiration date of the lot �GDP compliant DOCUMENTATION

�Materials cannot be used in a drug-making process unless they are known to be good �Incoming materials are tested for identity, purity, and or any other parameter that is relevant �The test are carried out against an internal specification that defines acceptable results MATERIALS

�Incoming materials are Quarantined until testing is complete �Materials that pass testing are Released �Materials that fail testing are Rejected �Only Released Materials may be used in production MATERIALS (continued)

�Each action is signed for the person who did it �Each critical action must be witnessed and the witness (“checker”) must also sign �Sampling is defined and controlled, and testing is compared to a specification PRODUCTION CONTROLS

�Filled products must be sealed to protect them until use �The closure of the drug contianer must be tested to last for the entire shelf-life of the drug �The container closure must be able to withstand the conditions of storage CONTAINTER CLOSURE

�Labeling is every bit as important as manufacturing �If a drug is made properly, but labeled improperly, the drug is “Misbranded” �Labeling and label reconciliation is controlled by a record, just like production LABELING

�Most labels are explicitly approved by the FDA �Changes to labels must be approved as well LABELING (continued)

�Validation is the testing of a machine to ensure that it works properly every time �For filling processs, the operators are part of the process- therefore, they must be part of validation ◦ This is called “Qualifying” the operator- you are demonstrating that they perform the critical process properly �Media fills are one ways that filling process is validated. VALIDATION

�Every single vial must be examined �Whomever examines them must be trained on identifying contamination �Whomever examines them should be independent of manufacturing to avoid conflict of interest. READING THE RESULTS