Organizing Technology Transfer from Research to Production

Abstract

An overview of issues to be considered when organizing the transfer of technology from the research arena to the production environment will be presented. The discussion will focus on the coordination and implementation of a transfer program for a product with emphasis being given to those factors peculiar to the pharmaceutical industry. The success of any program is highly dependent on the effectiveness of the communication preceding its implementation. Therefore, the preparation and distribution of a complete document summarizing raw material and equipment requirements, manufacturing and packaging processses, process validation parameters, quality control procedures, as well as a detailed plan of action outlining expected results and time frames, must be disseminated prior to the scale-up experience. Input from the marketing and manufacturing centers must also be integrated into the plan to ensure that the right product is developed at the right price within the desired time frame. An outline encompassing these critical aspects of a transfer program will be presented.     

Integrative process plan model and representation for intelligent distributed manufacturing planning

Process planning is one of the key functions for product design and manufacturing. Process plans have very great impact on all phases of product design and manufacture. Therefore, it is necessary to establish a high level of interaction between different product design activities and their tight integration into a coherent system. In this paper we describe a process plan model that allows for such integration. The framework for integration is briefly described and the process plan model that considers three dimensions of planning is explained. The manufacturing process plan model is defined as a three-dimensional model with the following dimensions: time/order, variability/alternatives, and aggregation. All three dimensions are defined and explained as they relate to overall manufacturing planning. The nature of these dimensions is illustrated with several examples. The implementation of the framework and the model within the distributed system IMPlanner is presented. The prototype has been implemented in the Java language and the model for data storage has been implemented in XML. The benefits of integrated consideration are described for several currently implemented applications such as feature modelling, process visualization, process network generation, cell formation, and scheduling.     

Applying GMP to Computerization in a Solid-Oral-Dosage-form-Factory

Quality Assurance and Pharmaceutical security as well must be given a particular consideration both for hardware and software when computerized pharmaceutical industrial operations are concerned

Hardware: The preparation of validation should begin with the design of a computerized system and rely upon specifications and upon defined operational limits

It is suitable to prepare documentation as from the development of the system in order to obtain a fruitful communication between all those concerned with design, implementation, maintenance, validation and auditing

A revalidation procedure should be prepared and maintained updated, in the event of a change in one or several operating conditions

Software: As with hardware, validation of software should be envisioned as early as the development phase. Preparation of test procedures and documentation should start at this very stage. Qualification and validation will be designed to find errors in the program and not to prove that no errors exist. They will be carried out at the operational boundaries of the software and will aim at testing the critical decision paths of the program. Verifications must be repeated a sufficient number of times to demonstrate that the results are repeatable

As with other pharmaceutical manufacturing systems, a formal procedure should exist to support changes made to the software. Vendor supplied software should be verified and documented with the same rigour and details that in-house developed software. Manual back-up systems must be provided for and regularly tested in the event of failure of the automated process. Computerized systems and good manufacturing practices applied to manufacturing of solid oral dosage forms: An application of the above-stated principles is given and illustrated     

Applying GMP to Computerization in a Solid-Oral-Dosage-form-Factory

Abstract

Quality Assurance and Pharmaceutical security as well must be given a particular consideration both for hardware and software when computerized pharmaceutical industrial operations are concerned

Hardware: The preparation of validation should begin with the design of a computerized system and rely upon specifications and upon defined operational limits

It is suitable to prepare documentation as from the development of the system in order to obtain a fruitful communication between all those concerned with design, implementation, maintenance, validation and auditing

A revalidation procedure should be prepared and maintained updated, in the event of a change in one or several operating conditions

Software: As with hardware, validation of software should be envisioned as early as the development phase. Preparation of test procedures and documentation should start at this very stage. Qualification and validation will be designed to find errors in the program and not to prove that no errors exist. They will be carried out at the operational boundaries of the software and will aim at testing the critical decision paths of the program. Verifications must be repeated a sufficient number of times to demonstrate that the results are repeatable

As with other pharmaceutical manufacturing systems, a formal procedure should exist to support changes made to the software. Vendor supplied software should be verified and documented with the same rigour and details that in-house developed software. Manual back-up systems must be provided for and regularly tested in the event of failure of the automated process. Computerized systems and good manufacturing practices applied to manufacturing of solid oral dosage forms: An application of the above-stated principles is given and illustrated     

Offshore manufacturing contract design based on transfer price considering green tax: a bilevel programming approach

The problem of designing offshore manufacturing contract resulting in optimal transfer price is troubling multinational companies over the past few years. This paper proposes designing offshore manufacturing contracts based on the transfer price in the form of bilevel programming problems after considering green tax. In these contract designs, a firm in a developed country sells a single product in its market. The same product is simultaneously being manufactured by another firm in a developing country with lower manufacturing cost. After anticipating the consumer demand, the seller places an order, based on which the manufacturer manufactures the ordered quantity, and offers a transfer price which in turn maximises its net profit after paying green tax to its government. While setting the transfer price, the manufacturer considers the manufacturing cost, the export duty payable to its government and the cost of shipping the product to the developed country. After buying the product from the manufacturer at the transfer price, the seller then sets the retail price which maximises its net profit after paying the import duty to its government; the retail price, however, must not be more than the maximum retail price applicable to the market. Thus, offshore manufacturing contract results in optimal after-tax profits for both the firms. An experimental study has been carried out to discuss the practical aspects of the results developed, where a US firm is offshoring its manufacturing activity to a Chinese firm in order to draw maximum profit.     

Minimum expected cost-oriented optimal maintenance planning for deteriorating structures: application to concrete bridge decks

Civil engineering structures are designed to serve the public and often must perform safely for decades. No matter how well they are designed, all civil engineering structures will deteriorate over time and lifetime maintenance expenses represent a substantial portion of the total lifetime cost of most structures. It is difficult to make a reliable prediction of this cost when the future is unknown and structural deterioration and behavior are assumed from a mathematical model or previous experience. An optimal maintenance program is the key to making appropriate decisions at the right time to minimize cost and maintain an appropriate level of safety. This study proposes a probabilistic framework for optimizing the timing and the type of maintenance over the expected useful life of a deteriorating structure. A decision tree analysis is used to develop an optimum lifetime maintenance plan which is updated as inspections occur and more data is available. An estimate which predicts cost and behavior over many years must be refined and reoptimized as new information becomes available. This methodology is illustrated using a half-cell potential test to evaluate a deteriorating concrete bridge deck. The study includes the expected life of the structure, the expected damage level of the structure, costs of inspection and specific repairs, interest rates, the capability of the test equipment to detect a flaw, and the management approach of the owner towards making repairs.     

Grouping and selecting products: the design key of Reconfigurable Manufacturing Systems (RMSs)

A Reconfigurable Manufacturing System (RMS) is a new paradigm that focuses on manufacturing a high variety of products at the same system. Having specified a design strategy for an RMS as the first design step at the tactical level, products must be grouped to identify and allocate corresponding manufacturing facilities. An interface between market and manufacturing called reconfiguration link is presented to specify and arrange products for manufacturing. The reconfiguration link incorporates the tasks of determining the products in the production range, grouping them into families and selecting the appropriate family at each configuration stage. The proposed approach of (re)configuring products before manufacturing facilitates assigning product families to the required manufacturing facilities in terms of (re)configuring manufacturing systems. This paper contributes an overall approach of grouping products into families based on operational similarities, when machines are still not identified. Since the problem of product family selection consists of quantitative and qualitative objectives, the Analytical Hierarchical Process (AHP) is then used while considering both market and manufacturing requirements. The AHP model is verified in an industrial case study through using Expert Choice software. The solutions take advantage of monitoring sensitivity analysis while changing the priorities of manufacturing and/or market criteria. The concept of the proposed model is generic in structure and applicable to many firms. However, the model must be adapted according to the specific nature of the company under study. For instance, product family choices may differ from one company to another because of the available technology and the volume and type of existing products in the production range.     

Design for manufacturing: use of a spreadsheet model of manufacturability to optimize product design and development

Product design typically precedes factory implementation and requires an understanding of factory logistics to achieve optimized design for manufacturing. We developed a spreadsheet-based model of a future factory at the very earliest stages of design of an advanced range of medical products. The algorithms have since been applied to a wide range of product designs and manufacturing operations. The model was used to optimize product design for manufacturability, develop cost-effective manufacturing processes, and design and optimize the new factory. The model incorporates cost, inventory, and factory responsiveness, and can be applied to find the optimum solution between cost and cycle time reduction. Design changes initiated as a result of analysis using the model reduced subsequent manufacturing costs significantly and reduced the launch program by two years, because confidence in the model justified the commissioning of full-scale manufacturing equipment when the product was still only at the concept stage. Electronic Publication     

Intelligent layout planning for rapid prototyping

Significant savings in cost and time can be achieved in rapid prototyping (RP) by manufacturing multiple parts in a single setup to achieve efficient machine volume utilization. This paper reports the design and implementation of a system for the optimal layout planning of 3D parts for a RP process. A genetic algorithm (GA) based search strategy has been used to arrive at a good packing layout for a chosen set of parts and RP process. A two stage approach has been proposed to initially short-list acceptable orientations for each part followed by the search for a layout plan which optimizes in terms of final product quality and build time. The GA uses a hybrid objective function comprising of the weighted measures like part build height, staircase effect, volume and area-of-contact of support structures. In essence it captures the key metrics of efficiency and goodness of packing for RP. The final layout plan is produced in the form of a composite part CAD model which can be directly exported to a RP machine for manufacturing. Design methodology of the system has been presented with some representative case studies.     

An improved compromise ranking method for evaluation of environmentally conscious manufacturing programs

An environmentally responsible or environmentally conscious manufacturing (ECM) program addresses the environmental impact of the interrelated decisions that are made at various stages of product life, from conception to design, raw ECM programs consumption, processing, delivery, use, recycling and/or disposal. The evaluation of alternative ECM programs for producing a given product is similar to many strategic initiatives and their justification methodologies. This similarity arises from the fact that there are multiple attributes that need to be considered, many of which have long term and broad implications for an organisation. Only a few decision making methods were proposed in the past for ECM program evaluation for producing a given product. There is a need for a systematic and logical scientific method or mathematical tool to guide organisations in taking a proper decision about ECM program evaluation. This paper presents a multiple attribute decision making methodology for evaluation of environmentally conscious manufacturing programs for producing a given product. The methodology is based on an improved compromise ranking method considering the ECM program selection attributes and their relative importance. The proposed ‘ECM program selection index’ helps to evaluate and rank the ECM programs for producing a given product. An example is included to illustrate the approach.     

Theory and practice of manufacturing strategy

This paper first proposes a methodology for manufacturing strategy development based on a critical review of the theory of manufacturing strategy. The methodology captures the essential factors that must be considered, and the steps that must be taken, by a firm attempting to design a viable manufacturing strategy. An exploratory study of the process of formulating and implementing manufacturing strategy practised by three firms is conducted. Their experiences in the manufacturing strategy process are reported and analysed. While the practice of each firm is different, the process of manufacturing strategy formulation seems to be in line with the conceptual models discussed in the literature. Our findings offer some evidence that manufacturing is slowly shedding its image as the ‘missing link’ in corporate strategy. While managers of the studied firms are fully aware of the competitive advantages that manufacturing can provide, they are not totally committed to articulating a manufacturing strategy because of concerns about its successful implementation. It is proposed that further research on manufacturing strategy focus on such implementation issues as the infrastructure, corporate culture, performance measurements, decision-making and managerial styles.     

Automatic process plan generation in an operative process planning system

The architecture and design of process planning systems should follow the architecture and design of the manufacturing systems they are intended to serve. This article describes a process planning system specifically intended for a workshop orientated factory, a factory which is specialized for the production of a limited number of group technological product lines. The goal of the system is to generate automatically and rapidly reliable part programs from order information. With the system, a process plan can be generated by workshop personnel on the basis of process plan specifications stored in part family models. A part program generation algorithm can then create a part program automatically by pasting together segments of program code stored in the process models of the system. The part program generator can be tailored by new parametric part program definitions related to features. The tool paths of the generated code can be visualised. The system described forms the operative process planner part of the MCOES (BE-3528) process planning system.     

Material and design considerations for rapid manufacturing

An investigation into how the advent of Rapid Manufacturing will influence an individual designer's approach to product design and materials selection is detailed. The assumption is made that Rapid Prototyping machines have evolved into viable manufacturing systems and all associated problems with accuracy, surface finish and repeatability have been resolved. Without the restriction of removing a product from a tool, designers will be free to design any complexity of geometry that they either desire or require. This tool-less approach to manufacturing will have profound implications on the way designers are accustomed to working and will eliminate most Design for Manufacture considerations. Design investigations are presented to highlight the potential importance and scope of Rapid Manufacturing. With advances in a new range of materials, some Rapid Manufacturing is happening today—albeit with existing Rapid Prototyping equipment. However, to enable designers to use existing Rapid Prototyping equipment for manufacturing purposes, there is a need for comprehensive information relating to the mechanical properties of the available materials. This is required to enable ‘Design for Rapid Manufacture’. The most comprehensive analysis to date of three new materials aimed for end-use part manufacture at differing ages, humidities and temperatures is presented.     

Metallographic Approach to Hirbine Blade Life Time Prediction

An economically optimized and safe utilization of turbine components is of vital importance to both manufacturers and operators of aero and industrial engines. Calculations of design life must take into consideration variations in several factors, such as material properties, manufacturing processes and operational conditions. Adding safety margins into the calculation results, with necessity, in a conservative figure.

The calculated life can be confirmed, or unconfirmed, by examination and testing of randomly selected components during maintenance and overhaul. Techniques for these examinations and for evaluation of the results, in terms of life predictions are not yet fully developed.

Methodology and practical results are presented, with comments on prospects and limitations. Medium strength, wrought superalloys to modern, highly alloyed cast blades are covered. Thelife limiting mechanism of the blades in the program is normally creep. Life time extension by rejuvenation has proven successful, both technically and economically. This paper will describe the practical application of this proven metallographic approach to life time prediction and extension.     

Product flexibility in selecting manufacturing planning and control strategy

The manufacturing systems capable of producing several products simultaneously are frequently subject to changes in product types due to demand fluctuations. In such systems a product flexible manufacturing planning and control (MPC) strategy is needed to change from one product type to another with minimum deterioration to system performance levels. The objective of this research is to develop a systematic analysis and evaluation approach in order to compare the MRP-push and JIT-pull strategies quantitatively based on a product flexibility measure. A new product flexibility measure is developed based on the sensitivity to change concept and presented together with the implementation in a real manufacturing system. Simulation is used to compare the performance of a JIT-pull with an MRP-push strategy based on performance measures, e.g. manufacturing lead time, work-in-process inventory, backorders, machine utilization and throughput. The performances of the two strategies are evaluated in two scenarios: (i) a single product; (ii) a second product is added (the first product being simple and the second being complex in terms of processing). The impacts of adding the second product on the performance measures for the push and pull strategies are then assessed. A multi-attribute evaluation scheme is used to compare the two strategies where the attribute values are the change in performance measures as the second product is added. The proposed product flexibility measure is utilized in the interpretation of the results.     

The pilot dimensions method: reconciling steering and conformity in workshops

In machining workshops, workpieces are produced according to dimensions known as manufacturing dimensions. For the same workpiece and the same manufacturing plan, several sets of manufacturing dimensions can be used but none satisfies simultaneously the two main missions workshops need to fulfil: (a) ensuring conformity of products to their design dimension tolerances (also called blueprint tolerances); and (b) steering machines in order to compensate for tool wear. The set of manufacturing dimensions obtained from the design dimensions using the minimal chain of dimensions method is optimal for a conformity check of workpieces but is practically unusable for steering machines because of the complexity of its relationships toward the tool correctors and tools dimensions. The pilot dimensions method consists of, on the one hand, identifying and representing these tool correctors and these tool/program dimensions on the production drawings (besides the manufacturing dimensions) and, on the other hand, determining their correction values through a mathematical set of relations after having measured the manufacturing dimensions on a workpiece. Doing so will strongly reduce adjustment time, reduce the number of workpieces used for adjustments and greatly enhance the quality of workpiece batches.     

Cost-tolerance analysis model based on a neural networks method

The purpose of tolerance design in product components is to produce a product with the least manufacturing cost possible, while meeting all functional requirements of the product. The product designer and process planner must fully understand the process accuracy and manufacturing cost of all kinds of manufacturing process to perform a good process plan job. Usually, the cost-tolerance model is constructed by a linear or non-linear regression analysis based on the data of the cost-tolerance experiment and to derive the correlation curve between the two. Though these correlation curves can show the relationship between manufacturing cost and tolerance, a fitting error is inevitable. In particular, there is considerable discrepancy in terms of the non-experimental data. A cost-tolerance analysis model based on a neural networks method is proposed. The cost-tolerance experimental data are used to set the training sets to establish a cost-tolerance network. Three representation modes of the cost-tolerance relationship are presented. First, the cost-tolerance relationship is derived from the grid points setting by the required tolerance accuracy. Second, a reasonable manufacturing cost of an unknown cost-tolerance experimental pair can be derived by the simulation of a cost-tolerance network. Third, an inference model based on a network's output is proposed to express the scope of the cost variation of various tolerances by means of a cost band. Comparison is also made with the high-order polynomial power function and exponential function cost-tolerance curves adopted by Yeo et al . Analytical results prove that the application of the cost-tolerance analysis model based on neural networks yields better performance in controlling the average fitting error than all conventional fitting models. The representation model using a cost band can identify precisely the possible cost variation range and reduce the chances of error in the tolerance design and cost estimation. It can thus provide important references for tolerance designers and process planners.     

Water global recourse management through the use of microalgae addressed to sustainable development

Cost advantages are the primary drivers for water resource management friendly investments. Therefore, acceleration of sustainable development requires the implementation of new innovation approach. At present, preventative measures of algal bloom development are not achieving sustainable results and spread of the blue-green infection can reach catastrophic dimension. Our vision of water recourse management includes the use of bloom and wastewater cleanup microalgae biomass aimed at supplying biofuel manufacturing profitably and boosting feed, biopharmaceuticals, etc., manufacturing in cost effective manner. Microalgae must be the key tool for the new design and building sustainable development of life and water resource management. Offered sustainable development business model, convenient for policymakers and companies, will make global goal of bioculture fully achievable as well as makes it imperative for the world to devise an international response and a plan of action.     

Revisiting the cell formation problem: assigning parts to production systems

Before manufacturing cells can be identified from a population of parts and machines, the parts must be carefully analysed to determine the small subset of parts that are appropriate for cellular manufacturing. When this is not done it becomes very difficult to identify the cells because the algorithms that are used have high computational requirements and high space requirements. The computational requirements and space requirements for the rank order clustering algorithm and the similarity coefficient algorithm are determined. Other algorithms that have been proposed for solving the ‘cell formation problem’ are more elaborate than these and are therefore likely have higher computational and space requirements. A procedure for assigning parts to production systems is presented in this paper. An illustrative example, taken from an actual implementation, is described to show how the procedure can be used.