Design rationale, documenting

The company should designate and document the rationale for the point at which production of the API begins. For synthetic processes, this is known as the point at which API starting materials are entered into the process. For other processes (e.g., fermentation, extraction, and purification), this rationale should be established on a case-by-case basis. Table 9 gives guidance on the point at which the API starting material is normally introduced into the process. 

Design processes and their results are not sufficiently well documented. This lack of documentation prevents tracing (i) of ideas which have not been pursued further for one or the other reason, (ii) of all the alternatives studied, (iii) of the decision making processes, and (iv) of the design rationale. 

The benefits of documenting design rationale are manifold. Explicit representations of design rationale support a consistent view among the stakeholders involved in a design project, they help to keep track of possible effects when requirements for an artifact change, and they can improve later design projects when similar problems are to be solved. 

Decision state The document status (green hook and red cross) displays whether an alternative was selected or rejected and provide an indicator for further handling of a document. In this way, all decisions in the course of a project can be captured. Beyond that, the rational behind the decision is documented by an application of the Issue Based Information System, IBIS [798]. The benefit of documenting design rationale is pointed out e.g. by Conklin and Yakemovic [607] (see also Sect. 2.5). 

The design constraints identified as necessary to control system hazards are passed to the implementers and assurers of the individual system components along with standards and other requirements. Success is determined through feedback provided by test reports, reviews, and various additional hazard analyses. At the end of the development process, the results of the hazard analyses as well as documentation of the safety-related design features and design rationale should be passed on to the maintenance group to be used in the system evolution and sustainment process. 

FMEA is used to assist analysts to perform hazard analyses and it is regarded as a supplement rather than a replacement for hazard analyses. Safety analysts can use FMEA to verify that all safety critical hardware has been addressed in the hazard analyses. The FMEA for hardware systems is an important technique for evaluating the design and documenting the review process. All credible failure modes and their resultant effects at the component and system levels are identified and documented. Items that meet defined criteria are identified as critical items and are placed on the Critical Item List (CEL). Each entry of the CIL is then evaluated to see if design changes can be implemented so that the item can be deleted from the CIL. Items that cannot be deleted from the CIL must be accepted by the programme/project, based on the rationale for acceptance of the risk. The analysis follows a well-deflned sequence of steps that encompass (1) failure mode, (2) failure effects, (3) causes, (4) detectability, (S) corrective or preventive actions, and (6) rationale for acceptance. 

Additional guidance on the development pharmaceutics aspects of this type of product is included in document CPMP/QWP/604/96, adopted July 1999. This emphasizes the need for information on the rationale for the design of the product—e.g., therapeutic benefit, pharmacokinetics, and physical properties of the active ingredient. 

Technical evaluation of options and consequence and risk analyses may be prepared. The analyses might include calculation of consequence severities for possible incidents. Subsequently, the basis for a mitigation system may be generated. This might involve, for example, a secondary containment structure, explosion suppression system, or scrubber. The rationale and technical design basis for such decisions should be documented and retained as part of the process knowledge. 

This document sets out how a trial is to be conducted. It contains the rationale for the clinical trial, the methodology on how the trial is designed, the number... 

Documentation should be provided in each case to outline the rationale for location and design of monitoring stations and the rationale for data validation for photochemical oxidants. 

This document describes the objectives, design, methodology, statistical considerations and organisation of a trial. Other information should be present, such as the background and rationale, for the clinical trial. It is a document key to any clinical trial. There should be a logical approach to preparing a protocol (see Box 7.2). 

There is clearly much to do to validate a biotechnology process. Obviously not all of it can be accomplished prior to entering clinical trials. As a process is designed, documentation should be sufficient so that the rationale for the devel-... 

A decision not to perform the review (e.g., evidence that code is developed under a quality system and formal reviews have already been conducted and reported) should be documented in the project validation plan, complete with the rationale. It is recognized that under its software quality assurance program the supplier may conduct similar examination of the software using only internal resource. Considering GMP implications, the pharmaceutical manufacturer would normally require that the software designer or programmer does not carry out any software review in isolation. 

The improving support of IT security development process implies more precise designs, easier rationale and documenting, lower development and evaluation costs. To achieve these, the following features were implemented ... 

Common Criteria assume to perform and document the rationale at the end of the development process, and this may be difficult to carry out. The presented tool offers some flexibility, allowing to reveal any gaps in the design earlier, after each design stage, and distinguishing two phases in each rationale stage ... 

How to Apply for Designation as an Orphan Product is an FDA guideline providing useful definitions of a rare disease, of a scientific rationale for a therapy, and of the standard of potential clinical superiority. It also provides a detailed application outline and developmental procedure. The document s final section describes the unusual situation in which a nonorphan indication may qualify if there is no reasonable expectation of recovering development costs. 

Automating the conceptual design of chemical processes offers significant benefits, such as quick evaluation of many alternative chemical production routes efficient development of economic, operable, and safe processes intelligent documentation of the design process and its rationale, as well as invaluable accumulation of past experience and easy verification and modification of past designs. 

In a subsequent study, the synthesis of urea and thiourea derivatives of types 3a and 3b were undertaken in an attempt to obtain new hosts that might yield more stable complexes with glutamic acid (of types 4a and 4b) and that might, in fact, hold together in polar solvents. The rationale for the design was based on the previously documented observation that both 1,3-dimethylurea and 1,3-dimethyl-thiourea form stable host-guest complexes with acetate in deutero-dimethyl sulfoxide the K values for the latter are 45 dm moF and 340 dm moF , respectively. 

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