Safety Case Review Process

At various stages throughout the creation process. Safety Case reviews were undertaken. Again, the benefits of GSN became clear during these reviews. At one point, the near-complete document (comprising 26 pages of GSN diagrams) was presented to representatives from the MoD at the project PDR. This took just 30 minutes. 

As implied by its title, the safety update report is not submitted with the original BLA, but is submitted in the form of updates at specific points in the application review process. Applicants must submit safety update reports 4 months after the BLA submission, after receipt of a complete response letter, and other times requested by CBER. In these reports, the sponsor must update the pending BLA with new safety information learned about the product that may reasonably affect the labeling statements in the contraindications, warnings, precautions, and adverse reactions sections. The updates must include the same types of information from clinical studies, animal studies, and other sources, and must be submitted in the same format as the BLA s integrated safety summary. They must also include case report forms for each patient who died during a clinical study or who did not complete the study because of an adverse event. 

For most food contact materials, a worst-case estimate of the upper bound lifetime cancer risk (LCR) is sufficient to demonstrate safety and allows for the most efficient and complete review process possible. Although such an approach may be overly conservative, this less precise approach allows for a reasonable prioritization of resources without reducing the certainty of safety. The recommended approach for establishing this worst-case upper bound LCR from exposure to a constituent in a food additive is described in more detail below. 

Because these drug candidates have potential biological activity, precautions should be taken to limit worker exposure during scale-up operations. Personal protective equipment requirements and adequate containment and ventilation provisions should also be defined as part of the safety review process. Often this assessment can be difficult because the material produced from the pilot plant will be used for toxicology evaluation purposes. In these cases, structure-activity relationship evaluations with regard to the relative toxicity of the compound may be appropriate to estimate the extent of risk. 

The authors would like to take this opportunity to thank Patrick Mana (EUROCONTROL) for his contribution to producing the Safety Case Development Manual (EUROCONTROL 2005), and would like to extend these thanks to those who participated in the review process, which led to current version of the Manual. 

Another area of the development process where further research would be beneficial is the role of review. If we have to make a large number of updates to the safety argument based upon review comments, there are implications about the quality of the argument (even after review). It cannot be assumed that all errors in the safety case are captured by review, and it could be said that if a large number of errors are found during review then it is more likely that there are still more uncovered errors. These issues are not always addressed within the safety case, however they can impact on our confldence. 

Although the requirements for the Procurement processes are plainly stated in ZIO and easily understood, they are brief in relation to the enormity of what will be required to implement them. As is the case for the provisions in ZIO on safety design reviews, the purpose of the Procurement processes is to avoid bringing hazards and risks into the workplace. 

As is the case with ZlO s safety design review provisions, safety professionals who are not involved in the design or purchasing processes should consider ergonomics as fertile ground in which to get started. Some of the comments made in Chapter 13, Safety Design Reviews, are repeated here because they apply equally to ZlO s design and procurement provisions. 

On a broader scale, effective PSSR supports any mature, well-designed PSM program by keeping the total program robust and vibrant in the face of change. The CCPS booklet The Business Case for Process Safety summarizes the benefits of process safety - and these same benefits are supported by performing effective pre-startup safety reviews ... 

Figure 12.7 illustrates a notional representation of typical safety-relevant data and information flows as would be reviewed in the V-shape safety case process illustrated in Figure 12.4. Note that this is just showing some of the safety information exchanges that would occur within an SMS and is not how an SMS is audited. Of course, the SMS also includes all the management systems that manage these information flows.

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