Approved processes - deviating from

The system should assure all changes are reviewed and approved by a designated authority. All personnel need to understand their role in this updating process and whether they have authority to deviate from procedures. Formal review and update should be part of this system. 

Pre-start-up Safety Review (PSSR) approval of the SIS establishes the point where the SIS design and construction is considered complete. All documentation should be formally updated to as-built status, incorporating any modifications made since the last formal drawing or document revision. Once the PSSR has approved the SIS for process unit start-up, formal management of change procedures should be followed to address proposed modification to the SIS or its associated documentation. Any deviation from the approved design basis should be reviewed and approved by appropriate parties prior to change implementation. 

The roles and responsibilities of the transfer lab and the receiving lab as well as an outline describing deliverables and timelines should be defined clearly at the initiation of the assay transfer process. Once a transfer protocol is defined, any deviation from the protocol during execution should be discussed in the transfer report. Explanations as to why the deviation is acceptable should be included in the report. The transfer report should also be approved by relevant functional departments. Due to the complexity of multi-site involvement, having a good change control system in place is important for making SOP modifications or updates. 

Process owners must be capable to evaluate and interpret the effect of nonconformances and planned deviations on their systems. Process owners can evaluate the need and lead efforts for corrective or preventive action, ensuring adequate corrections and improvements are implemented. An effective QMS ensures deviations from approved processes are owned and adequately investigated by the process owner s and ultimately approved by their quality assurance counterpart. The knowledge of these events is the basis and foundation for the process owners to make a risk-based evaluation on whether or not process changes are required, documentation or training require modification, or continuous improvement efforts are warranted. 

As with any process, there will be situations that require a departure from a predetermined step. A deviation from the process must be documented exactly as it occurred, along with what caused the need for the deviation and how the deviation will impact the quality of the product. The deviation investigation and justification must be approved by both QA and production management, and the root cause of the deviation should be identified if possible. Of critical importance is a statement regarding the possible impact the deviation has on the product. 

Batch documentation is an important factor. Preparation of master batch records in accordance with plant standard operating procedures (SOPs) should be followed by an approval of the document by the sponsoring division, usually the formulator or process development staff of the R D unit. On completion of a batch, review of the batch records by the quality assurance group ensures compliance to GMP and that all necessary deviations from and modifications to the manufacturing records are properly explained and documented. 

Any deviation from instructions in the Lot Production Record must be recorded and approved by Quality Assurance. In the case of a significant deviation from the intermediate and final yield, further processing and approval must be stopped until a decision has been made on the basis of the results of tests. 

The regulations require EPA to review requests for determinations of equivalency within forty five days, and mail determinations back to the submitter. The submitter can only begin to manufacture, import or process for a use involving the alternative control measures if the EPA determines that the alternative control measures provide substantially the same degree of protection as the SNUR controls. Any deviation from the terms of the EPA s approval will be a significant new use. 

Process assurance activities are performed throughout the lifecycle, including product conception, design, implementation, operation, and maintenance. It aims to detect, record, evaluate, approve, track and resolve deviations from approved plans and procedures. For each lifecycle phase, process assurance makes sure that planning is performed, that the plan is followed, and that the products of each phase are correct and complete. 

There are of course many types of plant which process materials that are toxic, such as poisonous or radioactive substances, and corrosive fluids. Such types of plant invariably have a technology of their own, developed and proven to be adequate for the hazards involved, and any deviation from established plant designs or standard operating practices requires careful consideration, and possibly third-party or regulatory examination and approval. 

Development work utilizing reactor fanllltles which can be accomplished without deviation from Process Standards or Equipment Maintenance Standards Is permitted under a Development Test Authorization with the approval of the technical and operating conqponents. 

All personnel involved in GMP production of drugs have to take ownership of quality. It is a requirement that processes and equipment for drug manufacturing must be approved and operated by trained, qualified personnel. Quality-related activities have to be recorded to enable traceability of data and information. Deviations and excursions of processes and results from specified conditions or criteria have to be reported, investigated, and resolved. Drug products have to be tested and must meet specifications before being... 

Quality assurance wasn t satisfied with just having the data meet all the specifications or have a relative standard deviation below 6%. It was not confident that tablets in the batch with lower potency would be adequate to allow the normal expiration date for the product. Quality assurance thus did not agree that the process in the new area should be approved (i.e., validate, especially when data from the earlier blending process indicated a more uniform product. 

Signed and dated approval by the responsible person that, apart from any deviations noted as above, processing has proceeded in accordance with the Master Processing Procedure, and that process or yield variations are adequately explained ... 

Retrospective validation is very rare and must be used judiciously. This approach involves reviewing a large number of batches already produced at the plant to affirm the robustness and repeatability of a process. There are very specific assumptions that must be met before retrospective validation can even be considered. There must not have been any changes made to the process during the review time period. The process must be a well-understood and -characterized process with defined in-process tests and controls. There must not be any significant process failures or deviations during the time period. The impurity profile for the product must be well established. Even when all these conditions are met, the decision to use retrospective validation must be a last resort and the justification well documented with approval from the quality unit. 

---