Process review

After internal and external review, the RfDgS for the chemical warfare agents were presented before the Material/Chemical Risk Assessment (MCRA) Work- 

Mustard formulations H (sulfur mustard) HD (sulfur mustard) HT (sulfur mustard) 

Organic arsenical L (lewisite) Nerve agents GA (tabun) 

Lethal blister agent (vesicant) Lethal blister agent (vesicant) Lethal blister agent (vesicant) 

5-(2-diisopropylaminoethyl)methyl phospho-nothioate, 0-ethyl ester 

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In the United States, through the NDA review process, pharmaceutical companies that seek FDA approval for new dmg products are assessed user fees by FDA to gain faster approval, by virtue of the U.S. Prescription Dmg User Fee Act of 1992. These assessments are used to increase the new dmg review staff of the FDA, which has agreed to reduce the NDA review time to 12 months by 1997 (6). 

Other offices within ODER may become involved in the review process via consults. Eor example, the Office of Epidemiology and Biostatistics analyzes statistical data, the Office of Research Resources provides bioavailabiHty reviews, and the Office of Compliance determines from the results of inspections whether the firms meet EDA s Current Good Manufacturing Practice (cGMP) regulations. Advisory committees composed of independent experts are often asked to meet and further analyze the data. Often they also advise as to what additional data and information may be needed. After PDA s review is completed, PDA issues either a Summary Basis of Approval (SBA) for the dmg or a recommendation against approval. If approved, PDA releases the SBA and a summary of the safety and effectiveness data to the general pubHc. 

The review and interpretation of toxicology studies is a professional matter, requiring experience in both the laboratory conduct of such studies and the practice of appHed toxicology. Although all studies should be reviewed on a case-by-case basis, there are some general considerations to be kept in mind during the review process, described below. 

Chemical Exposure Index (CEI) Chemical Exposure Index, 1994). The CEI provides a method of rating the relative potential of acute health hazard to people from possible chemical release incidents. It may be used for conducting the initial process hazard analysis and it establishes the degree of mrther analysis needed. The CEI also may be used as part of the site review process. 

To distinguish between a review and an audit, some definitions will be provided. A review is a critical examination or evaluation of any operation, procedure, condition, event, or equipment item. Reviews can take many forms and be identified as project reviews, design reviews, safety reviews, pre-start-up reviews, and so on. The following discussion of the review process will deal with project reviews associated with capital projects and focus on the area of process safety. 

The project review process involves multiple steps that should be definea in management gmdelines (CCPS, 1993, pp. 57-61). The steps include (1) review pohcy, (2) review scheduling, (3) reviewtech-nique, (4) review team representation, (5) review documentation, (6) review follow-up, (7) review follow-up verification, and (8) review procedures change management. These steps define how a review, whether it be a safety review, environmental review, pre-start-up review, or whatever, is conducted and how closure of review aclion items is achieved. 

Review Follow-up Verification In addition to someone tracking the follow-up through progress reports, responsibility should be assigned to verify that any process changes were ac tuaUy made in the field. This verification can be done by a review team as part of a process pre-start-up review. It could also be part of the project team management responsibihty or assigned to a particular functional (i.e., safety and loss prevention) representative. The closure of the review process is complete once implementation is verified. 

Review process steps and hazards associated with process with operators before start of campaign... 

Review process steps with each operator prior to start of infrequently run campaigns... 

The names or acronyms given to many applications are not easily recognized for the applications ability to meet a particular need. The list therefore includes several types of systems that have no direct applicability to SARA requirements (e.g., wastewater treatment plant optimization assistance with ordering chemicals). The creation of a comprehensive list of environmented applications provides a higher level of assurance that software that is relevant to Title III has not been overlooked. The list can also be used to eliminate systems from the review process and reduce the effort needed to identify a system that has the required capabilities. 

Exxon Chemical (French et al., 1996 Wixom, 1995) has developed an inherent safety review process, and its application at various points in the process life cycle. 

Reducing and eliminating hazards and their associated risks is the second major objective. Applying inherent safety principles early in the product/process development effort provides the greatest opportunity to achieve the objectives of the inherent safety review process for the project at hand. If these principles are applied late in the effort the results may have to be applied to the project after next as the schedule may not permit implementation of the results. 

Experience has shown that reactive chemistry hazards are sometimes undetected during bench scale and pilot plant development of new products and processes. Reactive chemistry hazards must be identified so they can be addressed in the inherent safety review process. Chemists should be encouraged and trained to explore reactive chemistry of "off-normal operations. Simple reactive chemicals screening tools, such as the interactions matrix described in Section 4.2, can be used by R D chemists. 

Companies may wish to develop workshops to train potential team members in the inherent safety review process. The workshop can provide background information on inherent safety concepts, the extensive systems required to manage hazardous materials, and information on the inherent safety review process. Videos, problems, examples, and team exercises can be included to enliven the education process. 

Implementing an inherent safety review process is one mechanism companies can use to institutionalize inherent safety. The review process should integrate well with company systems for process safety management, new product development, and project execution. Safety, health, and environmental considerations in the new product or process development effort can be strengthened via the introduction of the inherent safety review. Companies may also build inherently safer design concepts into their existing process safety management system and process hazard reviews. 

To be successful, a team selected from different groups within the project team should participate in the preparation and review of these plans. In addition, a schedule of the review and approval process for these plans needs to be established, accepted by all reviewers, and distributed before release of the first draft. Reviewers should meet an established schedule for review and submission of comments. A distinction between review and approval authority should be determined. The review process determines if all of the required elements are identified. This review can take considerable time, depending on the complexity of the project. The approval process is important when all comments are incorporated. The key responsible persons associated with the project should accept and approve the changes to the document. 

For a report of this magnitude, confidence in the correctness of the result can only coinc i rom a systematic and deep peer review process. The peer review process of WASH-1400 was dofccii ve in many ways and the review was inadequate. 

Some of the methods used in the standards are based on many years of research and validation, while others are relatively new and not validated to the same degree. It is therefore important to realize that a standard is not an everlasting document, but must be revised on a regular basis. These revisions rake place at least every fifth year, and experience with use and new knowledge are incorporated into the review process. 

Users should be the prime participants in the preparation process so that the resultant documents reflect their needs and are fit for the intended purpose - hence the requirement that documents be reviewed as well as approved. You will need to be able to demonstrate that your documents have in fact been reviewed prior to issue. The presence of a signature on the front cover is not sufficient evidence. To demonstrate that documents have been reviewed you will need to show that nominated personnel have been issued with drafts for comment and that they have provided comments which have been considered by the approval authorities. A simple method is to employ a standard comment sheet on which reviewers can indicate their comments or signify that they have no comment. During the review process you may undertake several revisions. You may feel it necessary to retain these in case of dispute later, but there is no compulsion for you to do so, providing you have evidence that the review took place. You also need to show that the current issue has been reviewed so your comment sheet needs to indicate document issue status. 

Another interesting aspect of this requirement is that the implementation of changes is to include updates to all appropriate documents. This means that the impact of a customer change order on your internal documents needs to be evaluated and the corresponding changes made to all affected documents. This should be performed as part of the change review process (see later in this chapter). 

Remember as you set priorities that you and your team must consider the expected benefit to the company, division, or unit as a whole, rather than simply addressing a single gap. Obviously, any specific immediate risk you identify in the course of your assessment must be dealt with quickly and responsibly however, be careful not to let anomalous findings skew your perspective on broader priorities. For example, the absence of a capital project review process is a significant gap. However, if there is only one project per year this gap may have lower priority than an existing but seriously deficient operator training program. 

You can quickly identify these plant sections by reviewing process flow diagrams and valving arrangements. Isolation points are defined by control valves or powered block valves that can be remotely activated. Process hazard analysis techniques help you identify the maximum credible accident scenarios. (Note that manual valves should not be considered reliable isolation points unless they are located to be accessible following a major accident. However, remotely-activated valves can only be considered reliable isolation points if there are adequate reliability engineering and maintenance programs in place.)... 

This book attempted to review processes for manufacturing drugs still in the developmental stage-those which had attained generic name status but not trade name status in most cases. Many of these have since fallen by the wayside. 

OSHA 1910.119 does not mandate the specific type of investigation a plant must conduct when a reportable incident occurs. However, it provides stipulations that must be met for the following investigator qualifications, time requirements, report content, review process, and corrective actions. 

The Prescription Drug User Fee Act allows the FDA to charge fees in order to hire more staff to speed up the review process and thus deliver faster approval decisions. 

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