|Publication number||USRE43527 E1|
|Application number||US 12/313,804|
|Publication date||Jul 17, 2012|
|Filing date||Nov 25, 2008|
|Priority date||May 6, 2004|
|Also published as||US7392107, US7428442, US7444197, US7471991, US7509185, US8660680, US9008815, US9195228, US20050251278, US20060271227, US20060276923, US20070198116, US20070288114, US20090143892, US20100324716, US20110046770, US20160041551|
|Publication number||12313804, 313804, US RE43527 E1, US RE43527E1, US-E1-RE43527, USRE43527 E1, USRE43527E1|
|Inventors||Shane M. Popp|
|Original Assignee||Smp Logic Systems Llc|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (364), Non-Patent Citations (71), Classifications (12), Legal Events (1)|
|External Links: USPTO, USPTO Assignment, Espacenet|
The invention described herein relates to methods, systems, and software program that are modified for use in software and hardware validation of pharmaceutical manufacturing processes. The invention further relates to the enhancement of quality assurance implementation protocols in current good manufacturing practice in manufacturing, processing, packing, and/or holding of drugs.
Over the last two decades, significant changes in the environment of pharmaceutical regulation have occurred and have resulted in incremental adjustments in regulatory approaches to product quality. These changes included an increased number of pharmaceutical products and a greater role of medicines in health care, decreased frequency of manufacturing inspections as a result of fewer resources available for pharmaceutical manufacturing inspections, accumulation of experience with, “and lessons learned from”, various approaches to the regulation of product quality, advances in the pharmaceutical sciences and manufacturing technologies, application of biotechnology in drug discovery and manufacturing, advances in the science and management of quality and, globalization of the pharmaceutical industry. The cumulative impact of these changes has been greater than the sum of the parts and there is an industry wide need to develop integrated approaches to monitor and assess the validation of processes and overall quality of products provided to end users and patients.
Looking ahead the most up-to-date concepts of risk management and quality systems approaches should be incorporated while continuing to ensure product quality. The latest scientific advances in pharmaceutical manufacturing and technology are encouraged. Additionally, the submission review program and the inspection program should operate in a coordinated and synergistic manner and regulation and manufacturing standards should be applied consistently. The management of validation and quality assurance programs should encourage innovation in the pharmaceutical manufacturing sector in order to provide the most effective public health protection. Resource limitations prevent uniformly intensive coverage of all pharmaceutical products and production. Significant advances in the pharmaceutical sciences and in manufacturing technologies have occurred over the last two decades. While this knowledge has been incorporated in an ongoing manner into product quality regulation, the fundamental nature of the changes dictates a thorough evaluation of the science base to ensure that product quality assurance and validation not only incorporates up-to-date science, but also encourages further advances in technology. Integrated quality systems orientation principles from various innovative approaches to manufacturing quality that have been developed in the past decade should be evaluated for applicability and current Good Manufacturing Practices requirements and related pre-approval requirements should be evaluated according to applicable principles. In addition, interaction of the pre-market Chemistry, Manufacturing, and Controls review process and the application of current Good Manufacturing Practices requirements should be evaluated as an integrated system.
With the globalization of pharmaceutical manufacturing requires a global approach to integration keeping in mind the overall objective of strong public health protection. To accomplish these needed goals there is a need to carry out the following actions. The artisan should use emerging science and data analysis to enhance validation and quality assurance programs to target the highest risk areas. From the aforementioned, the evaluation of the feasibility of establishing dedicated and integrated cadres of pharmaceutical validation and quality assurance experts should become readily apparent to one of ordinary skill in the art. Also apparent to one of ordinary skill in the art is the ability to provide a cost-efficient network of validation and quality assurance protocols. By providing an integrated and user friendly approach to validation and quality assurance the overall benefit to the public at-large is pharmaceutical end products available at lower costs. This is turn will allow more persons or animals to benefit from innovations that occur in the treatment of disease. Additionally, there is also a need to use these modalities as research tools to monitor, assess, and further the state of the art in all areas of life science treatment and studies, specifically biotechnology and pharmaceuticals.
The invention provides for a software program that validates devices used in the manufacture, processing, and storing of drugs. As used herein, the term “drug” is synonymous with “pharmaceutical”. In certain embodiments, the program can be modified to conform to the programming language and operating system requirements of an individual system. In a further embodiment, the program is used to validate hardware use in drug manufacture. In another embodiment, the program is used to validate software used in drug manufacture. In another embodiment, the program is used to monitor quality assurance protocols put in place by the quality control unit.
The invention further provides methods for validating drug manufacture using the application software. In one embodiment, the method comprises installation during the concept phase of manufacturing. In another embodiment, the method comprises installation at which time the manufacture process is on-line. In another embodiment the method comprises installation during the course of quality assurance. In another embodiment, the method comprises monitoring the validation and quality assurance based on a routine maintenance schedule.
The invention further comprises a system which integrates application software and methods disclosed herein to provide a comprehensive validation and quality assurance protocol that is used by a plurality of end users whereby the data compiled from the system is analyzed and used to determine is quality assurance protocols and validation protocols are being achieved.
Outline of Sections
II.) Software Program
IV.) KITS/Articles of Manufacture
Unless otherwise defined, all terms of art, notations and other scientific terms or terminology used herein are intended to have the meanings commonly understood by those of skill in the art to which this invention pertains unless the context clearly indicates otherwise. In some cases, terms with commonly understood meanings are defined herein for clarity and/or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a substantial difference over what is generally understood in the art. Many of the techniques and procedures described or referenced herein are well understood and commonly employed using conventional methodology by those skilled in the art, such as, for example, the widely utilized current Good Manufacturing Practice guidelines.
As used herein the terms “drug” and “pharmaceutical” include veterinary drugs and human drugs, including human biological drug products.
“abstraction” means the separation of the logical properties of data or function from its implementation in a computer program.
“access time” means the time interval between the instant at which a call for data is initiated and the instant at which the delivery of the data is completed.
“accuracy study processor” means a software tool used to perform calculations or determine accuracy of computer manipulated program variables.
“adaptive maintenance” means software maintenance performed to make a computer program usable in a changed environment.
“address” means a number, character, or group of characters which identifies a given device or a storage location which may contain a piece of data or a program step.
“algorithm” means any sequence of operations for performing a specific task.
“algorithm analysis” means a software verification and validation (“V&V”) task to ensure that the algorithms selected are correct, appropriate, and stable, and meet all accuracy, timing, and sizing requirements.
“alphanumeric” means pertaining to a character set that contains letters, digits, and usually other characters such as punctuation marks, etc.
“analog” means pertaining to data [signals] in the form of continuously variable [wave form] physical quantities; e.g., pressure, resistance, rotation, temperature, voltage.
“analog device” means a device that operates with variables represented by continuously measured quantities such as pressures, resistances, rotations, temperatures, and voltages.
“analog-to-digital converter” means input related devices which translate an input device's [sensor] analog signals to the corresponding digital signals needed by the computer.
“analysis” means a course of reasoning showing that a certain result is a consequence of assumed premises.
“application software” means software designed to fill specific needs of a user.
“bar code” means a code representing characters by sets of parallel bars of varying thickness and separation that are read optically by transverse scanning.
“BASIC” means an acronym for Beginners All-purpose Symbolic Instruction Code, a high-level programming language intended to facilitate learning to program in an interactive environment.
“basic input/output system” means firmware that activates peripheral devices in a PC. Includes routines for the keyboard, screen, disk, parallel port and serial port, and for internal services such as time and date. It accepts requests from the device drivers in the operating system as well from application programs. It also contains autostart functions that test the system on startup and prepare the computer for operation. It loads the operating system and passes control to it.
“batch processing” means execution of programs serially with no interactive processing.
“benchmark” means a standard against which measurements or comparisons can be made.
“bias” means a measure of how closely the mean value in a series of replicate measurements approaches the true value.
“block” means a string of records, words, or characters that for technical or logical purposes are treated as a unity.
“block check” means the part of the error control procedure that is used for determining that a block of data is structured according to given rules.
“block diagram” means a diagram of a system, instrument or computer, in which the principal parts are represented by suitably annotated geometrical figures to show both the basic functions of the parts and the functional relationships between them.
“blueprint” means an detailed plan or outline.
“boot” means to initialize a computer system by clearing memory and reloading the operating system. A distinction can be made between a warm boot and a cold boot. A cold boot means starting the system from a powered-down state. A warm boot means restarting the computer while it is powered-up. Important differences between the two procedures are; 1) a power-up self-test, in which various portions of the hardware [such as memory] are tested for proper operation, is performed during a cold boot while a warm boot does not normally perform such self-tests, and 2) a warm boot does not clear all memory.
“bootstrap” means a short computer program that is permanently resident or easily loaded into a computer and whose execution brings a larger program, such an operating system or its loader, into memory.
“boundary value” means a data value that corresponds to a minimum or maximum input, internal, or output value specified for a system or component.
“boundary value analysis” means a selection technique in which test data are chosen to lie along “boundaries” of the input domain [or output range] classes, data structures, procedure parameters, etc.
“branch analysis” means a test case identification technique which produces enough test cases such that each decision has a true and a false outcome at least once.
“calibration” means ensuring continuous adequate performance of sensing, measurement, and actuating equipment with regard to specified accuracy and precision requirements.
“certification” means technical evaluation, made as part of and in support of the accreditation process, that establishes the extent to which a particular computer system or network design and implementation meet a pre-specified set of requirements.
“change control” means the processes, authorities for, and procedures to be used for all changes that are made to the computerized system and/or the system's data. Change control is a vital subset of the Quality Assurance [QA] program within an establishment and should be clearly described in the establishment's SOPs.
“check summation” means a technique for error detection to ensure that data or program files have been accurately copied or transferred.
“compiler” means computer program that translates programs expressed in a high-level language into their machine language equivalents.
“computer system audit” means an examination of the procedures used in a computer system to evaluate their effectiveness and correctness and to recommend improvements.
“computer system security” means the protection of computer hardware and software from accidental or malicious access, use, modification, destruction, or disclosure.
“concept phase” means the initial phase of a software development project, in which user needs are described and evaluated through documentation.
“configurable, off-the-shelf software” means application software, sometimes general purpose, written for a variety of industries or users in a manner that permits users to modify the program to meet their individual needs.
“control flow analysis” means a software V&V task to ensure that the proposed control flow is free of problems, such as design or code elements that are unreachable or incorrect.
“controller” means hardware that controls peripheral devices such as a disk or display screen. It performs the physical data transfers between main memory and the peripheral device.
“conversational” means pertaining to a interactive system or mode of operation in which the interaction between the user and the system resembles a human dialog.
“coroutine” means a routine that begins execution at the point at which operation was last suspended, and that is not required to return control to the program or subprogram that called it.
“corrective maintenance” means maintenance performed to correct faults in hardware or software.
“critical control point” means a function or an area in a manufacturing process or procedure, the failure of which, or loss of control over, may have an adverse affect on the quality of the finished product and may result in an unacceptable health risk.
“data analysis” means evaluation of the description and intended use of each data item in the software design to ensure the structure and intended use will not result in a hazard. Data structures are assessed for data dependencies that circumvent isolation, partitioning, data aliasing, and fault containment issues affecting safety, and the control or mitigation of hazards.
“data integrity” means the degree to which a collection of data is complete, consistent, and accurate.
“data validation” means a process used to determine if data are inaccurate, incomplete, or unreasonable. The process may include format checks, completeness checks, check key tests, reasonableness checks and limit checks.
“design level” means the design decomposition of the software item; e.g., system, subsystem, program or module.
“design phase” means the period of time in the software life cycle during which the designs for architecture, software components, interfaces, and data are created, documented, and verified to satisfy requirements.
“diagnostic” means pertaining to the detection and isolation of faults or failures.
“different software system analysis” means Analysis of the allocation of software requirements to separate computer systems to reduce integration and interface errors related to safety. Performed when more than one software system is being integrated.
“dynamic analysis” means analysis that is performed by executing the program code.
“encapsulation” means a software development technique that consists of isolating a system function or a set of data and the operations on those data within a module and providing precise specifications for the module.
“end user” means a person, device, program, or computer system that uses an information system for the purpose of data processing in information exchange.
“error detection” means techniques used to identify errors in data transfers.
“error guessing” means the selection criterion is to pick values that seem likely to cause errors.
“error seeding” means the process of intentionally adding known faults to those already in a computer program for the purpose of monitoring the rate of detection and removal, and estimating the number of faults remaining in the program.
“failure analysis” means determining the exact nature and location of a program error in order to fix the error, to identify and fix other similar errors, and to initiate corrective action to prevent future occurrences of this type of error.
“Failure Modes and Effects Analysis” means a method of reliability analysis intended to identify failures, at the basic component level, which have significant consequences affecting the system performance in the application considered.
“FORTRAN” means an acronym for FORmula TRANslator, the first widely used high-level programming language. Intended primarily for use in solving technical problems in mathematics, engineering, and science.
“life cycle methodology” means the use of any one of several structured methods to plan, design, implement, test and operate a system from its conception to the termination of its use.
“logic analysis” means evaluates the safety-critical equations, algorithms, and control logic of the software design.
“low-level language” means the advantage of assembly language is that it provides bit-level control of the processor allowing tuning of the program for optimal speed and performance. For time critical operations, assembly language may be necessary in order to generate code which executes fast enough for the required operations.
“maintenance” means activities such as adjusting, cleaning, modifying, overhauling equipment to assure performance in accordance with requirements.
“modulate” means varying the characteristics of a wave in accordance with another wave or signal, usually to make user equipment signals compatible with communication facilities.
“Pascal” means a high-level programming language designed to encourage structured programming practices.
“path analysis” means analysis of a computer program to identify all possible paths through the program, to detect incomplete paths, or to discover portions of the program that are not on any path.
“quality assurance” means the planned systematic activities necessary to ensure that a component, module, or system conforms to established technical requirements.
“quality control” means the operational techniques and procedures used to achieve quality requirements.
“software engineering” means the application of a systematic, disciplined, quantifiable approach to the development, operation, and maintenance of software.
“software engineering environment” means the hardware, software, and firmware used to perform a software engineering effort.
“software hazard analysis” means the identification of safety-critical software, the classification and estimation of potential hazards, and identification of program path analysis to identify hazardous combinations of internal and environmental program conditions.
“software reliability” means the probability that software will not cause the failure of a system for a specified time under specified conditions.
“software review” means an evaluation of software elements to ascertain discrepancies from planned results and to recommend improvement.
“software safety change analysis” means analysis of the safety-critical design elements affected directly or indirectly by the change to show the change does not create a new hazard, does not impact on a previously resolved hazard, does not make a currently existing hazard more severe, and does not adversely affect any safety-critical software design element.
“software safety code analysis” means verification that the safety-critical portions of the design are correctly implemented in the code.
“software safety design analysis” means verification that the safety-critical portion of the software design correctly implements the safety-critical requirements and introduces no new hazards.
“software safety requirements analysis” means analysis evaluating software and interface requirements to identify errors and deficiencies that could contribute to a hazard.
“software safety test analysis” means analysis demonstrating that safety requirements have been correctly implemented and that the software functions safely within its specified environment.
“system administrator” means the person that is charged with the overall administration, and operation of a computer system. The System Administrator is normally an employee or a member of the establishment.
“system analysis” means a systematic investigation of a real or planned system to determine the functions of the system and how they relate to each other and to any other system.
“system design” means a process of defining the hardware and software architecture, components, modules, interfaces, and data for a system to satisfy specified requirements.
“top-down design” means pertaining to design methodology that starts with the highest level of abstraction and proceeds through progressively lower levels.
“traceability analysis” means the tracing of Software Requirements Specifications requirements to system requirements in concept documentation.
“validation” means establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes.
“validation, process” means establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality characteristics.
“validation, prospective” means validation conducted prior to the distribution of either a new product, or product made under a revised manufacturing process, where the revisions may affect the product's characteristics.
“validation protocol” means a written plan stating how validation will be conducted, including test parameters, product characteristics, production equipment, and decision points on what constitutes acceptable test results.
“validation, retrospective” means validation of a process for a product already in distribution based upon accumulated production, testing and control data. Retrospective validation can also be useful to augment initial premarket prospective validation for new products or changed processes. Test data is useful only if the methods and results are adequately specific. Whenever test data are used to demonstrate conformance to specifications, it is important that the test methodology be qualified to assure that the test results are objective and accurate.
“validation, software” means, determination of the correctness of the final program or software produced from a development project with respect to the user needs and requirements. Validation is usually accomplished by verifying each stage of the software development life cycle.
“structured query language” means a language used to interrogate and process data in a relational database. Originally developed for IBM mainframes, there have been many implementations created for mini and micro computer database applications. SQL commands can be used to interactively work with a data base or can be embedded with a programming language to interface with a database.
“Batch” means a specific quantity of a drug or other material that is intended to have uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacture.
“Component” means any ingredient intended for use in the manufacture of a drug product, including those that may not appear in such drug product.
“Drug product” means a finished dosage form, for example, tablet, capsule, solution, etc., that contains an active drug ingredient generally, but not necessarily, in association with inactive ingredients. The term also includes a finished dosage form that does not contain an active ingredient but is intended to be used as a placebo.
“Active ingredient” means any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or other animals. The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in the drug product in a modified form intended to furnish the specified activity or effect.
“Inactive ingredient” means any component other than an active ingredient.
“In-process material” means any material fabricated, compounded, blended, or derived by chemical reaction that is produced for, and used in, the preparation of the drug product.
“Lot number, control number, or batch number” means any distinctive combination of letters, numbers, or symbols, or any combination thereof, from which the complete history of the manufacture, processing, packing, holding, and distribution of a batch or lot of drug product or other material can be determined.
“Quality control unit” means any person or organizational element designated by the firm to be responsible for the duties relating to quality control.
“Acceptance criteria” means the product specifications and acceptance/rejection criteria, such as acceptable quality level and unacceptable quality level, with an associated sampling plan, that are necessary for making a decision to accept or reject a lot or batch.
II.) Software Program (Computer Product)
The invention provides for a software program that is programmed in a high-level or low-level programming language, preferably a relational language such as structured query language which allows the program to interface with an already existing program or a database. Preferably, however, the program will be initiated in parallel with the manufacturing process or quality assurance (“QA”) protocol. This will allow the ability to monitor the manufacturing and QA process from its inception. However, in some instances the program can be bootstrapped into an already existing program that will allow monitoring from the time of execution (i.e. bootstrapped to configurable off-the-shelf software).
It will be readily apparent to one of skill in the art that the preferred embodiment will be a software program that can be easily modified to conform to numerous software-engineering environments. One of ordinary skill in the art will understand and will be enabled to utilize the advantages of the invention by designing the system with top-down design. The level of abstraction necessary to achieve the desired result will be a direct function of the level of complexity of the process that is being monitored. For example, the critical control point for monitoring an active ingredient versus an inactive ingredient may not be equivalent. Similarly, the critical control point for monitoring an in-process material may vary from component to component and often from batch to batch.
One of ordinary skill will appreciate that to maximize results the ability to amend the algorithm needed to conform to the validation and QA standards set forth by the quality control unit on each step during manufacture will be preferred. This differential approach to programming will provide the greatest level of data analysis leading to the highest standard of data integrity.
The preferred embodiments may be implemented as a method, system, or program using standard software programming and/or engineering techniques to produce software, firmware, hardware, or any combination thereof. The term “computer product” as used herein is intended to encompass one or more computer programs and data files accessible from one or more computer-readable devices, firmware, programmable logic, memory devices (e.g. EEPROM's, ROM's, PROM's, RAM's, SRAM's, etc.) hardware, electronic devices, a readable storage diskette, CD-ROM, a file server providing access to programs via a network transmission line, wireless transmission media, signals propagating through space, radio waves, infrared signals, etc. Those of skill in the art will recognize that many modifications may be made without departing from the scope of the present invention.
The invention provides for a method of analyzing data that is compiled as a result of the manufacturing of pharmaceuticals. Further the invention provides for the analysis of data that is compiled as a result of a QA program used to monitor the manufacture of drugs in order to maintain the highest level of data integrity. In one embodiment, the parameters of the data will be defined by the quality control unit. Generally, the quality control unit will provide endpoints that need to be achieved to conform to current Good Manufacturing Practices regulations or in some instances an internal endpoint-that is more restrictive to the minimum levels that need to be achieved.
In a preferred embodiment, the invention provides for data analysis using boundary value analysis. The boundary value will be set forth by the quality control unit. Using the boundary values set forth for a particular phase of manufacture the algorithm is defined. Once the algorithm is defined, an algorithm analysis (i.e. logic analysis) takes place. One of skill in the art will appreciate that a wide variety of tools are used to confirm algorithm analysis such as an accuracy study processor.
One of ordinary skill will appreciate that different types of data will require different types of analysis. In a further embodiment, the program provides a method of analyzing block data via a block check. If the block check renders an affirmative analysis, the benchmark has been met and the analysis continues to the next component. If the block check renders a negative the data is flagged via standard recognition files known in the art and a hazard analysis and hazard mitigation occurs.
In a further embodiment, the invention provides for data analysis using branch analysis. The test cases will be set forth by the quality control unit.
In a further embodiment, the invention provides for data analysis using control flow analysis. The control flow analysis will calibrate the design level set forth by the quality control unit which is generated in the design phase.
In a further embodiment, the invention provides for data analysis using failure analysis. The failure analysis is initiated using the failure benchmark set forth by the quality control unit and then using standard techniques to come to error detection. The preferred technique will be top-down. For example, error guessing based on quality control group parameters which are confirmed by error seeding.
In a further embodiment, the invention provides for data analysis using path analysis. The path analysis will be initiated after the design phase and will be used to confirm the design level. On of ordinary skill in the art will appreciate that the path analysis will be a dynamic analysis depending on the complexity of the program modification. For example, the path analysis on the output of an end product will be inherently more complex that the path analysis for the validation of an in-process material. However, one of ordinary skill will understand that the analysis is the same, but the parameters set forth by the quality control unit will differ.
The invention provides for a top-down design to software analysis. This preferred embodiment is advantageous because the parameters of analysis will be fixed for any given process and will be set forth by the quality control unit. Thus, performing software safety code analysis then software safety design analysis, then software safety requirements analysis, and then software safety test analysis will be preferred.
The aforementioned analysis methods are used for several non-limiting embodiments, including but not limited to, validating QA software, validating pharmaceutical manufacturing, and validating process designs wherein the integration of the system design will allow for more efficient determination of acceptance criteria in a batch, in-process material, batch number, control number, and lot number and allow for increased access time thus achieving a more efficient cost-saving manufacturing process.
IV.) Kits/Articles of Manufacture
For use in basic input/output systems, hardware calibrations, software calibrations, computer systems audits, computer system security certification, data validation, different software system analysis, quality control, and the manufacturing of drug products described herein, kits are within the scope of the invention. Such kits can comprise a carrier, package, or container that is compartmentalized to receive one or more containers such as boxes, shrink wrap, and the like, each of the container(s) comprising one of the separate elements to be used in the method, along with a program or insert comprising instructions for use, such as a use described herein.
The kit of the invention will typically comprise the container described above and one or more other containers associated therewith that comprise materials desirable from a commercial and user standpoint, programs listing contents and/or instructions for use, and package inserts with instructions for use.
A program can be present on or with the container. Directions and or other information can also be included on an insert(s) or program(s) which is included with or on the kit. The program can be on or associated with the container.
The terms “kit” and “article of manufacture” can be used as synonyms.
The article of manufacture typically comprises at least one container and at least one program. The containers can be formed from a variety of materials such as glass, metal or plastic.
Various aspects of the invention are further described and illustrated by way of the several examples that follow, none of which is intended to limit the scope of the invention.
In one embodiment, the invention comprises the validation and quality control of drug products manufactured during the clinical phase of development. Generally, A phase I human clinical trial is initiated to assess the safety of doses of a drug product candidate in connection with the treatment of a disease. In the study, the safety of single doses when utilized as therapy is assessed. The trial design includes delivery of single doses of a drug product candidate escalating from approximately about 25 mg/m2 to about 275 mg/m2 over the course of the treatment in accordance with a pre-defined schedule (i.e. parameters defined by quality control unit).
Patients are closely followed for one-week following each administration of the drug product candidate. In particular, patients are assessed for safety concerns (i.e. toxicity, fever, shaking, chills, the development of an immunogenic response to the material.) Standard tests and follow-up are utilized to monitor each of these safety concerns. Patients are also assessed for clinical outcome and particularly treatment of the disease being evaluated.
The drug product candidate is demonstrated to be safe and efficacious, Phase II trials confirm the efficacy and refine optimum dosing.
The drug product candidate is safe in connection with the above-discussed trial, a Phase II human clinical trial confirms the efficacy and optimum dosing for monotherapy. Such trial is accomplished, and entails the same safety and outcome analyses, to the above-described trial with the exception being that patients do not receive other forms of treatment concurrently with the receipt of doses of the drug product candidate.
Once again, as the therapy discussed above is safe within the safety criteria discussed above, a Phase III human clinical trial is initiated.
As previously set forth, the acceptance criteria of all components used in the drug product manufacture for the purposes of the clinical trial are determined by the quality control unit. The analysis of the software and hardware occurs using any of the methods disclosed herein. (See for example
Provided the drug product candidate has been awarded regulatory approval and is manufactured for commercial use. The invention comprises a method for monitoring the acceptance criteria of all components used in the drug product manufacture. The analysis of the software and hardware occurs using any of the methods disclosed herein. (See for example
The invention comprises the integration of the computer product into a manufacturing hardware system. In this context, the term “hardware” means any physical device used in the pharmaceutical manufacturing process including, but not limited to, blenders, bio-reactors, capping machines, chromatography/separation systems, chilled water/circulating, glycol, coldrooms, clean steam, clean-in-place (CIP), compressed air, D.I./R.O. watersystems, dry heat sterilizers/ovens, fermentation equipment/bio reactors, freezers, filling equipment, filtration/purification, HVAC: environmental controls, incubators/environmentally controlled chambers, labelers, lyophilizers/freeze, dryers, mixing tanks, modular cleanrooms, neutralization systems, plant steam and condensate, process tanks/pressure, vessels, refrigerators, separation/purification equipment, specialty gas, systems, steam generators/pure steam systems, steam sterilizers, stopper washers, solvent recovery systems, tower water systems, waste inactivation systems/“kill” systems, vial inspection systems, vial washers, water for injection (WFI) systems, pure water systems, washers (glass, tank, carboys, etc.).
It will be understood by one of skill in the art that the computer product integrates the hardware via generally understood devices in the art (i.e. attached to the analog device via an analog to digital converter).
The computer product is integrated into the manufacturing system on a device by device basis. As previously set forth, the acceptance criteria of all devices used in the drug product manufacture for the purposes of the manufacturing process are determined by the quality control unit. The analysis of the software and hardware occurs using any of the methods disclosed herein. (See for example
The invention comprises the integration of the computer product into a manufacturing software system. In this context, the term “software” means any device used in the pharmaceutical manufacturing process including, but not limited to user-independent audit trails, time-stamped audit trails, data security, confidentiality systems, limited authorized system access, electronic signatures, bar codes, dedicated systems, add-on systems, control files, Internet, LAN's, etc.
The computer product is integrated into the manufacturing system on a device-by-device basis. As previously set forth, the acceptance criteria of all devices used in the drug product manufacture for the purposes of the manufacturing process to are determined by the quality control unit. The analysis of the software and hardware occurs using any of the methods disclosed herein. (See for example
The invention comprises the integration of the computer product into a quality assurance system. In this context, the term “quality assurance” means the planned systematic activities necessary to ensure that a component, module, or system conforms to established technical requirements. A quality assurance system will compliment either of the systems set for in the examples entitled “Integration of program into manufacturing hardware system” or “Integration of program into manufacturing software system” to ensure data integrity and reliability from the data that is generated set forth in either of the examples entitled “Implementation in Clinical Manufacturing Process” or “Implementation in Post-Clinical Commercial Manufacturing Process”.
The computer product is integrated into the manufacturing system on a device-by-device basis. As previously set forth, the acceptance criteria of all devices used in the drug product manufacture for the purposes of the manufacturing process are determined by the quality control unit. The analysis of the software and hardware occurs using any of the methods disclosed herein. (See for example
The invention comprises a program and method integrated into a comprehensive cost-saving pharmaceutical manufacturing system. A user, preferably a system administrator, logs onto the system via secure means (i.e. password or other security measures known in the art) and inputs the boundary values for a particular component of the drug manufacturing process. The input is at the initial stage, the end product state, or any predetermined interval in between that has been established for routine maintenance by the quality control unit. The data is generated using any one of the various analysis methods described herein (as previously stated the type of analysis used is functional to the device or protocol being monitored or evaluated). Subsequent to the data analysis, any modifications or corrective action to the manufacturing process is implemented. The data is then stored by standard methods known in the art. Scheduled analysis of the stored data is maintained to provide a preventative maintenance of the manufacturing process. Over time, costs are reduced due to the tracking of data and analysis of troubled areas and frequency of hazards that occur on any given device in the manufacturing process. The system is implemented on every device which plays a role in drug manufacturing. The data compiled from every device is analyzed using the methods described herein.
The present invention is not to be limited in scope by the embodiments disclosed herein, which are intended as single illustrations of individual aspects of the invention, and any that are functionally equivalent are within the scope of the invention. Various modifications to the models and methods of the invention, in addition to those described herein, will become apparent to those skilled in the art from the foregoing description and teachings, and are similarly intended to fall within the scope of the invention. Such modifications or other embodiments can be practiced without departing from the true scope and spirit of the invention.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US4443861||Apr 13, 1981||Apr 17, 1984||Forney Engineering Company||Combined mode supervisory program-panel controller method and apparatus for a process control system|
|US4558413||Nov 21, 1983||Dec 10, 1985||Xerox Corporation||Software version management system|
|US4646229||Nov 15, 1982||Feb 24, 1987||At&T Bell Laboratories||Time-ordered data base|
|US4687662||Jan 15, 1986||Aug 18, 1987||Warner-Lambert Company||Therapeutic effervescent composition|
|US4813013||Dec 22, 1986||Mar 14, 1989||The Cadware Group, Ltd.||Schematic diagram generating system using library of general purpose interactively selectable graphic primitives to create special applications icons|
|US4852047||Apr 14, 1987||Jul 25, 1989||Universal Automation Inc.||Continuous flow chart, improved data format and debugging system for programming and operation of machines|
|US4860204||Feb 5, 1987||Aug 22, 1989||Softron, Inc.||Computer based workstation for development of graphic representation of computer programs|
|US4894511||Aug 26, 1986||Jan 16, 1990||Physical Sciences, Inc.||Source of high flux energetic atoms|
|US5006992||Sep 30, 1987||Apr 9, 1991||Du Pont De Nemours And Company||Process control system with reconfigurable expert rules and control modules|
|US5029179||Apr 10, 1990||Jul 2, 1991||Schwartz Electro-Optic, Inc.||Laser apparatus and method for simple conversion between standing-wave and ring resonator configurations|
|US5038138||Apr 17, 1989||Aug 6, 1991||International Business Machines Corporation||Display with enhanced scrolling capabilities|
|US5041195||Nov 13, 1989||Aug 20, 1991||Physical Sciences Inc.||Gold electrocatalyst, methods for preparing it, electrodes prepared therefrom and methods of using them|
|US5041197||Jan 25, 1989||Aug 20, 1991||Physical Sciences, Inc.||H2 /C12 fuel cells for power and HCl production - chemical cogeneration|
|US5084144||Jul 31, 1990||Jan 28, 1992||Physical Sciences Inc.||High utilization supported catalytic metal-containing gas-diffusion electrode, process for making it, and cells utilizing it|
|US5122717||Oct 24, 1990||Jun 16, 1992||Toshiba Kikai Kabushiki Kaisha||Apparatus for producing NC programs using menu icons to define operations and producing method thereof|
|US5132193||Mar 7, 1991||Jul 21, 1992||Physical Sciences, Inc.||Generation of electricity with fuel cell using alcohol fuel|
|US5133842||Mar 15, 1991||Jul 28, 1992||Physical Sciences, Inc.||Electrochemical cell having electrode comprising gold containing electrocatalyst|
|US5134560||Oct 23, 1989||Jul 28, 1992||International Business Machines Corporation||Method and system for generation of manufacturing process plans|
|US5191534||Aug 21, 1990||Mar 2, 1993||International Business Machines Corporation||Engineering and manufacturing change control mechanism|
|US5235605||Nov 18, 1992||Aug 10, 1993||Schwartz Electro-Optics, Inc.||Solid state laser|
|US5235610||Sep 16, 1991||Aug 10, 1993||Schwartz Electro Optics, Inc.||Prism gain module and method|
|US5247693||Nov 17, 1992||Sep 21, 1993||The Foxboro Company||Computer language structure for process control applications and method of translating same into program code to operate the computer|
|US5278979||Dec 20, 1990||Jan 11, 1994||International Business Machines Corp.||Version management system using pointers shared by a plurality of versions for indicating active lines of a version|
|US5301336||Jul 12, 1989||Apr 5, 1994||National Instruments, Inc.||Graphical method for programming a virtual instrument|
|US5315530||Aug 14, 1992||May 24, 1994||Rockwell International Corporation||Real-time control of complex fluid systems using generic fluid transfer model|
|US5325481||Apr 12, 1991||Jun 28, 1994||Hewlett-Packard Company||Method for creating dynamic user panels in an iconic programming system|
|US5333265||Oct 22, 1991||Jul 26, 1994||Hitachi, Ltd.||Replicated data processing method in distributed processing system|
|US5345457||Oct 15, 1993||Sep 6, 1994||Schwartz Electro-Optics, Inc.||Dual wavelength laser system with intracavity sum frequency mixing|
|US5358695||Jan 21, 1993||Oct 25, 1994||Physical Sciences, Inc.||Process for producing nanoscale ceramic powders|
|US5367624||Jun 11, 1993||Nov 22, 1994||Consilium, Inc.||Interface for controlling transactions in a manufacturing execution system|
|US5377003||Apr 29, 1994||Dec 27, 1994||The United States Of America As Represented By The Department Of Health And Human Services||Spectroscopic imaging device employing imaging quality spectral filters|
|US5392207||Aug 20, 1993||Feb 21, 1995||Allen-Bradley Company, Inc.||Programmable motion controller with graphical programming aid|
|US5447708||May 10, 1993||Sep 5, 1995||Physical Sciences, Inc.||Apparatus for producing nanoscale ceramic powders|
|US5461477||Mar 10, 1995||Oct 24, 1995||Physical Sciences, Inc.||Method and apparatus for imaging|
|US5528368||Dec 23, 1994||Jun 18, 1996||The United States Of America As Represented By The Department Of Health And Human Services||Spectroscopic imaging device employing imaging quality spectral filters|
|US5532928||Feb 15, 1995||Jul 2, 1996||Recra Environmental, Inc.||Computer system and method for waste accounting, reduction, and evaluation|
|US5548535||Nov 8, 1994||Aug 20, 1996||Advanced Micro Devices, Inc.||Monitor utility for use in manufacturing environment|
|US5552412||Jan 9, 1995||Sep 3, 1996||Pfizer Inc||5-substitued-6-cyclic-5,6,7,8-tetrahydronaphthalen2-ol compounds which are useful for treating osteoporosis|
|US5556447||Jan 23, 1995||Sep 17, 1996||Physical Sciences, Inc.||Process for treating metal-contaminated materials|
|US5565073||Jun 5, 1995||Oct 15, 1996||Fraser; Mark E.||Electrochemical peroxide generator|
|US5576946||Nov 7, 1995||Nov 19, 1996||Fluid Air, Inc.||Icon based process design and control system|
|US5586313||Feb 12, 1993||Dec 17, 1996||L.I.D.P. Consulting Services, Inc.||Method for updating a file|
|US5603894 *||Oct 31, 1994||Feb 18, 1997||Abbott Laboratories||Method of sterilizing a pharmaceutical composition|
|US5647968||Apr 17, 1996||Jul 15, 1997||Psi Technology Co.||Process for making peroxide|
|US5652911||Feb 10, 1995||Jul 29, 1997||U.S. Philips Corporation||Multinode distributed data processing system for use in a surface vehicle|
|US5664112||Mar 2, 1992||Sep 2, 1997||Alternative Systems, Inc.||Integrated hazardous substances management unit|
|US5712990||Oct 3, 1991||Jan 27, 1998||International Technology Corporation Of California||Economical automated process for averting physical dangers to people, wildlife or environment due to hazardous waste|
|US5726984||Oct 5, 1995||Mar 10, 1998||Norand Corporation||Hierarchical data collection network supporting packetized voice communications among wireless terminals and telephones|
|US5732397||Mar 16, 1992||Mar 24, 1998||Lincoln National Risk Management, Inc.||Automated decision-making arrangement|
|US5734026||Oct 27, 1993||Mar 31, 1998||Pharmacia & Upjohn Aktiebolag||Process for manufacturing crystals of growth hormone and crystals thereby obtained|
|US5734380||Sep 27, 1996||Mar 31, 1998||Adams; James S.||Method for controlling the presentation of displays in a multi-window computer environment|
|US5740190||May 23, 1996||Apr 14, 1998||Schwartz Electro-Optics, Inc.||Three-color coherent light system|
|US5767941||Apr 23, 1996||Jun 16, 1998||Physical Sciences, Inc.||Servo tracking system utilizing phase-sensitive detection of reflectance variations|
|US5774489||Mar 28, 1996||Jun 30, 1998||Schwartz Electro-Optics, Inc.||Transversely pumped solid state laser|
|US5774875||Nov 12, 1996||Jun 30, 1998||Base Ten Systems, Inc.||Pharmaceutical recordkeeping system|
|US5787000||May 27, 1994||Jul 28, 1998||Lilly Software Associates, Inc.||Method and apparatus for scheduling work orders in a manufacturing process|
|US5793013||Jun 7, 1995||Aug 11, 1998||Physical Sciences, Inc.||Microwave-driven plasma spraying apparatus and method for spraying|
|US5796403||Sep 27, 1996||Aug 18, 1998||Adams; James S.||Method of display categorization in a multi-window display|
|US5831859||May 25, 1995||Nov 3, 1998||Base Ten Systems, Inc.||Pharmaceutical recordkeeping system with labelling for manufacturing raw materials|
|US5832449||Nov 13, 1995||Nov 3, 1998||Cunningham; David W.||Method and system for dispensing, tracking and managing pharmaceutical trial products|
|US5835922||Sep 29, 1997||Nov 10, 1998||Hitachi, Ltd.||Document processing apparatus and method for inputting the requirements of a reader or writer and for processing documents according to the requirements|
|US5847957||Jun 16, 1997||Dec 8, 1998||Base Ten Systems, Inc.||Web access for a manufacturing execution system|
|US5860020||Mar 25, 1996||Jan 12, 1999||Mannesmann Vdo Ag||Operating system for real-time hybrid environment|
|US5864483||Aug 1, 1996||Jan 26, 1999||Electronic Data Systems Corporation||Monitoring of service delivery or product manufacturing|
|US5892947||Jul 1, 1996||Apr 6, 1999||Sun Microsystems, Inc.||Test support tool system and method|
|US5901879 *||Oct 17, 1997||May 11, 1999||Duhaime; Richard||Precision liquid dispenser device|
|US5953688||May 7, 1997||Sep 14, 1999||Institute For Information Industry||Multi-port data collection system|
|US5956938||Oct 25, 1996||Sep 28, 1999||Research Support Instruments, Inc.||Microwave electro-thermal thruster and fuel therefor|
|US5970503||Jun 12, 1996||Oct 19, 1999||Base Ten Systems, Inc.||Method for online revision control|
|US5997155||Mar 31, 1997||Dec 7, 1999||Physical Sciences, Inc.||Integrating projection optic|
|US5997361||Jun 30, 1997||Dec 7, 1999||Litton Systems, Inc.||Electronic cable connector|
|US6025769||Oct 7, 1996||Feb 15, 2000||University Of Houston||Strong high-temperature superconductor trapped field magnets|
|US6034768||Jul 13, 1998||Mar 7, 2000||Physical Sciences Inc.||Induced breakdown spectroscopy detector system with controllable delay time|
|US6049742||Sep 26, 1997||Apr 11, 2000||International Business Machines Corporation||Projected supply planning matching assets with demand in microelectronics manufacturing|
|US6055507||Aug 20, 1998||Apr 25, 2000||Cunningham; David W.||Method and system for dispensing, tracking and managing pharmaceutical trial products|
|US6067549||Dec 11, 1998||May 23, 2000||American Management Systems, Inc.||System for managing regulated entities|
|US6083281||Nov 14, 1997||Jul 4, 2000||Nortel Networks Corporation||Process and apparatus for tracing software entities in a distributed system|
|US6106274||Mar 11, 1998||Aug 22, 2000||The Budd Company||Molding apparatus with charge overflow|
|US6112130||Oct 1, 1997||Aug 29, 2000||Kabushiki Kaisha Toshiba||Semiconductor product manufacturing execution system and semiconductor product manufacturing method|
|US6122622||Feb 18, 1998||Sep 19, 2000||H. B. Fuller||Computer aided system for compliance with chemical control laws|
|US6123964||Oct 23, 1996||Sep 26, 2000||Merck & Co., Inc.||Wet granulation formulation of a growth hormone secretagogue|
|US6141647||Apr 15, 1996||Oct 31, 2000||The Dow Chemical Company||System and method for integrating a business environment, a process control environment, and a laboratory environment|
|US6169928||Jun 30, 1998||Jan 2, 2001||Ge Fanuc Automation North America, Inc.||Apparatus and method for sharing data among a plurality of control devices on a communications network|
|US6215898||Apr 15, 1997||Apr 10, 2001||Interval Research Corporation||Data processing system and method|
|US6223343||Apr 3, 1998||Apr 24, 2001||State Farm Mutual Automobile Insurance Co.||Computer system and method to track and control element changes throughout application development|
|US6226369||Feb 23, 2000||May 1, 2001||Cybiotronics Limited||Telephone with novel FSK decoding means, simultaneous off-hook caller ID reception means, and set of configurable function key means|
|US6235938||Jun 10, 1999||May 22, 2001||Yale University||Transition metal-catalyzed process for preparing N-aryl amine compounds|
|US6243615||Sep 9, 1999||Jun 5, 2001||Aegis Analytical Corporation||System for analyzing and improving pharmaceutical and other capital-intensive manufacturing processes|
|US6256640||Mar 20, 2000||Jul 3, 2001||American Management Systems, Inc.||System for managing regulated entities|
|US6263438||Sep 8, 1998||Jul 17, 2001||Walker Digital, Llc||Method and apparatus for secure document timestamping|
|US6272506||Sep 12, 1997||Aug 7, 2001||Doxis, Llc||Computerized verification form processing system and method|
|US6279026||Dec 4, 1998||Aug 21, 2001||Honeywell International Inc||Timeout object for object-oriented, real-time process control system and method of operation thereof|
|US6324522||Sep 15, 1998||Nov 27, 2001||Mro Software, Inc.||Electronic information network for inventory control and transfer|
|US6347533||Mar 4, 2000||Feb 19, 2002||Peter Tung||Hydraulically balanced fully thermally coupled system|
|US6370422||Mar 19, 1999||Apr 9, 2002||Board Of Regents, The University Of Texas System||Fiber-optic confocal imaging apparatus and methods of use|
|US6385768||Sep 30, 1999||May 7, 2002||Unisys Corp.||System and method for incorporating changes as a part of a software release|
|US6393458||Apr 9, 1999||May 21, 2002||Genrad, Inc.||Method and apparatus for load balancing in a distributed object architecture|
|US6397115||Oct 8, 1999||May 28, 2002||Smithkline Beecham||Hazardous material classification system|
|US6419953||Dec 18, 1998||Jul 16, 2002||Abbott Laboratories||Controlled release formulation of divalproex sodium|
|US6441552||Apr 29, 1999||Aug 27, 2002||Physical Sciences Inc.||Apparatus and methods for generating persistent ionization plasmas|
|US6446136||Dec 31, 1998||Sep 3, 2002||Computer Associates Think, Inc.||System and method for dynamic correlation of events|
|US6456737||Aug 17, 2000||Sep 24, 2002||Interval Research Corporation||Data processing system and method|
|US6470227||Dec 2, 1998||Oct 22, 2002||Murali D. Rangachari||Method and apparatus for automating a microelectric manufacturing process|
|US6483112||Jul 14, 1999||Nov 19, 2002||E. Neil Lewis||High-throughput infrared spectroscopy|
|US6501869||Mar 14, 2001||Dec 31, 2002||George Mason University||Optical switching system|
|US6505085||Mar 4, 1999||Jan 7, 2003||Massachusetts Institute Of Technology||Method and apparatus for creating time-optimal commands for linear systems|
|US6509145||Sep 30, 1999||Jan 21, 2003||Medtronic, Inc.||Process for reducing mineralization of tissue used in transplantation|
|US6567788||Aug 5, 1998||May 20, 2003||The United States Of America As Represented By The Secretary Of The Navy||Programmed logistic system and method for transportation and reception of commodities|
|US6581020||Oct 10, 2000||Jun 17, 2003||Velquest Corporation||Process-linked data management system|
|US6606524||Feb 11, 2000||Aug 12, 2003||Samsung Electronics Co., Ltd.||System and method for controlling an in-line apparatus|
|US6631630||Sep 22, 2000||Oct 14, 2003||Board Of Trustees Of Michigan State University||Hydroforming of composite materials|
|US6645529||Jan 8, 2001||Nov 11, 2003||Dr. Gergely & Co.||Instant granules and process for their formulation|
|US6687558||Feb 4, 2003||Feb 3, 2004||Steve W. Tuszynski||Manufacturing design and process analysis system|
|US6687887||Jan 31, 2002||Feb 3, 2004||Cadence Design Systems, Inc.||Method and apparatus for performing extraction using a model trained with Bayesian inference using a hybrid monte carlo method|
|US6690464||Feb 18, 2000||Feb 10, 2004||Spectral Dimensions, Inc.||High-volume on-line spectroscopic composition testing of manufactured pharmaceutical dosage units|
|US6691070||Nov 3, 2000||Feb 10, 2004||Mack Information Systems||System and method for monitoring a controlled environment|
|US6692764||Sep 23, 2002||Feb 17, 2004||Merck & Co., Inc.||Wet granulation formulation for bisphosphonic acids|
|US6697783||Sep 29, 1998||Feb 24, 2004||Medco Health Solutions, Inc.||Computer implemented medical integrated decision support system|
|US6707122||Oct 26, 2000||Mar 16, 2004||Nec Laboratories America, Inc.||Extraordinary magnetoresistance at room temperature in inhomogeneous narrow-gap semiconductors|
|US6718291||Jun 22, 2000||Apr 6, 2004||Vadim Shapiro||Mesh-free method and system for modeling and analysis|
|US6732019||May 10, 2002||May 4, 2004||Siemens Westinghouse Power Corporation||Business management system and method for a deregulated electric power market using online diagnostic services|
|US6735748||Jan 31, 2002||May 11, 2004||Cadence Design Systems, Inc.||Method and apparatus for performing extraction using a model trained with bayesian inference|
|US6738450||Dec 10, 2002||May 18, 2004||Agilent Technologies, Inc.||System and method for cost-effective classification of an object under inspection|
|US6776486||Aug 9, 2002||Aug 17, 2004||Crossbows Optical Limited||Progressive addition power lens|
|US6778882||May 10, 2002||Aug 17, 2004||Siemens Westinghouse Power Corporation||Business management system and method for a deregulated electric power market with sharing of supply chain data|
|US6816793||Jun 29, 2001||Nov 9, 2004||Smithkline Beecham Corportion||Method for predicting flow properties of powders|
|US6850809||May 26, 2000||Feb 1, 2005||Oracle International Corporation||Methods, devices and systems for splitting an integrated manufacturing and distribution plan for use by separate manufacturing and distribution execution systems|
|US6852219||Mar 3, 2003||Feb 8, 2005||John M. Hammond||Fluid separation and delivery apparatus and method|
|US6857112||Jan 31, 2002||Feb 15, 2005||Cadence Design Systems, Inc.||Method and apparatus for performing extraction using machine learning|
|US6862488||Jul 5, 2002||Mar 1, 2005||Validation Commerce, Llc||Automated validation processing and workflow management|
|US6865508||Dec 27, 2002||Mar 8, 2005||Kabushiki Kaisha Toshiba||Log analysis method and recording medium storing log analysis program|
|US6883148||Jan 31, 2002||Apr 19, 2005||Cadence Design Systems, Inc.||Method and apparatus for creating an extraction model using Bayesian inference|
|US6892366||Jan 31, 2002||May 10, 2005||Cadence Design Systems, Inc.||Method and apparatus for performing extraction using a model trained with Bayesian inference via a Monte Carlo method|
|US6904370||Dec 30, 2003||Jun 7, 2005||Compliance Software Solutions Corp.||System, method, and computer-readable medium for collection of environmental data and generation of user report for compliance with FDA requirements|
|US6907591||Jan 31, 2002||Jun 14, 2005||Cadence Design Systems, Inc.||Method and apparatus for performing extraction using a neural network|
|US6944512||Apr 9, 2003||Sep 13, 2005||Seimens Aktiengesellschaft||Device and method for carrying out the decentralized production of desired products from different starting materials, and an automated process system|
|US6944662||May 4, 2001||Sep 13, 2005||Vinestone Corporation||System and methods providing automatic distributed data retrieval, analysis and reporting services|
|US6965895||Jul 12, 2002||Nov 15, 2005||Applied Materials, Inc.||Method and apparatus for analyzing manufacturing data|
|US6966235||Oct 6, 2000||Nov 22, 2005||Paton Eric N||Remote monitoring of critical parameters for calibration of manufacturing equipment and facilities|
|US6968292||Mar 2, 2004||Nov 22, 2005||Paragon Technical Services, Inc.||Industrial controller event logging|
|US6977385||Feb 19, 2003||Dec 20, 2005||Agfa-Gevaert||Storage phosphor screen having binderless colored layers|
|US6979578||Mar 27, 2003||Dec 27, 2005||Lam Research Corporation||Process endpoint detection method using broadband reflectometry|
|US6980852||Aug 23, 2002||Dec 27, 2005||Subqiview Inc.||Film barrier dressing for intravascular tissue monitoring system|
|US7006882||Jan 9, 2004||Feb 28, 2006||Macronix International Co., Ltd.||Machine control system|
|US7020876||Jun 30, 2000||Mar 28, 2006||Fisher-Rosemount Systems, Inc.||Campaign management for batch processes|
|US7027883||Oct 8, 2003||Apr 11, 2006||Taiwan Semiconductor Manufacturing Co., Ltd.||Tool reserve for single fabrication and homogenous MES|
|US7031784||Dec 23, 2004||Apr 18, 2006||Taiwan Semiconductor Manufacturing Co., Ltd.||Systems and methods for manufacturing execution system integration|
|US7033023||Aug 17, 2004||Apr 25, 2006||Signet Armorlite, Inc.||Progressive addition power lens|
|US7050875||Jul 1, 2003||May 23, 2006||General Electric Company||System and method for detecting an anomalous condition|
|US7051293||Jan 31, 2002||May 23, 2006||Cadence Design Systems, Inc.||Method and apparatus for creating an extraction model|
|US7069101||Jul 29, 1999||Jun 27, 2006||Applied Materials, Inc.||Computer integrated manufacturing techniques|
|US7079912||Nov 25, 2002||Jul 18, 2006||Philip Morris Usa Inc.||System and method for high speed control and rejection|
|US7089072||May 26, 2004||Aug 8, 2006||Taiwan Semiconductor Manufacturing Company, Ltd.||Semiconductor manufacturing fault detection and management system and method|
|US7103524||Jan 31, 2002||Sep 5, 2006||Cadence Design Systems, Inc.||Method and apparatus for creating an extraction model using Bayesian inference implemented with the Hybrid Monte Carlo method|
|US7112351||Feb 25, 2003||Sep 26, 2006||Sion Power Corporation||Methods and apparatus for vacuum thin film deposition|
|US7113845||Aug 9, 2005||Sep 26, 2006||International Business Machines Corporation||Integration of factory level and tool level advanced process control systems|
|US7123974||Nov 19, 2002||Oct 17, 2006||Rockwell Software Inc.||System and methodology providing audit recording and tracking in real time industrial controller environment|
|US7127330||May 10, 2002||Oct 24, 2006||Siemens Power Generation, Inc.||Business management system and method for a deregulated electric power market using consumer site anomaly detection|
|US7133727||Oct 10, 2003||Nov 7, 2006||Invensys Systems, Inc.||System and method for continuous online safety and reliability monitoring|
|US7162534||Jul 10, 2001||Jan 9, 2007||Fisher-Rosemount Systems, Inc.||Transactional data communications for process control systems|
|US7169107||Aug 23, 2002||Jan 30, 2007||Karen Jersey-Willuhn||Conductivity reconstruction based on inverse finite element measurements in a tissue monitoring system|
|US7174230||Feb 28, 2002||Feb 6, 2007||Applied Materials, Inc.||Computer integrated manufacturing techniques|
|US7174353||Oct 24, 2003||Feb 6, 2007||International Business Machines Corporation||Method and system for preserving an original table schema|
|US7184820||Aug 23, 2002||Feb 27, 2007||Subqiview, Inc.||Tissue monitoring system for intravascular infusion|
|US7184964||Jul 18, 2001||Feb 27, 2007||Wu-Chieh Wang||Application of supply chain unit cell or cell group or boundary conservation of value and quantity to computer management system|
|US7187992||Jan 7, 2004||Mar 6, 2007||Tuszynski Steve W||Manufacturing design and process analysis system|
|US7197405||Feb 4, 2005||Mar 27, 2007||Medpro Holdings, Llc||Interactive method of providing analysis of potency and purity of pharmaceutical compounds|
|US7207505||Jun 4, 2004||Apr 24, 2007||Bender Martin P||Method for producing small granules|
|US7216007||Jul 6, 2005||May 8, 2007||Honeywell International Inc.||System and method for providing direct web access to controllers in a process control environment|
|US7216084||Feb 24, 2004||May 8, 2007||Medco Health Solutions, Inc.||Computer implemented medical integrated decision support system|
|US7231398||Oct 21, 2002||Jun 12, 2007||Siemens Aktiengesellschaft||Provision of information in an automation system|
|US7233830||May 31, 2005||Jun 19, 2007||Rockwell Automation Technologies, Inc.||Application and service management for industrial control devices|
|US7240119||Nov 4, 2002||Jul 3, 2007||Ge Fanuc Automation North America, Inc.||Method for configuring a programmable logic controller using an extensible markup language schema|
|US7249356||Apr 29, 1999||Jul 24, 2007||Fisher-Rosemount Systems, Inc.||Methods and structure for batch processing event history processing and viewing|
|US7257501||Nov 17, 2005||Aug 14, 2007||Honeywell International Inc.||Apparatus and method for identifying informative data in a process control environment|
|US7269640||Jan 23, 2002||Sep 11, 2007||Ge Fanuc Automation North America, Inc.||Methods and systems for management and control of an automation control module|
|US7280893||May 10, 2002||Oct 9, 2007||Siemens Power Generation, Inc.||Business management system and method for a deregulated electric power market|
|US7299102||Dec 2, 2004||Nov 20, 2007||Norman Ken Ouchi||Method and system for engineering change implementation|
|US7302307||Sep 20, 2006||Nov 27, 2007||International Business Machines Corporation||Micrologistics tracking system and method for an automated manufacturing facility|
|US7305278||Nov 15, 2004||Dec 4, 2007||International Business Machines Corporation||Enterprise factory control method and system|
|US7317959||Nov 28, 2002||Jan 8, 2008||Siemens Aktiengesellschaft||System and method for modeling and/or executing software applications, especially MES applications|
|US7322048||Oct 22, 2002||Jan 22, 2008||Remedan Aps||Control device for a computer and a computer comprising such a control device|
|US7343605||Nov 28, 2002||Mar 11, 2008||Siemens Aktiengesellschaft||System and method for communicating between software applications, particularly MES (manufacturing execution system) applications|
|US7347613||Apr 25, 2005||Mar 25, 2008||Harsco Technologies Corporation||Apparatus for continuous blending|
|US7359760||Jan 25, 2006||Apr 15, 2008||Brother Kogyo Kabushiki Kaisha||Data processing device and data processing method|
|US7367242||Feb 27, 2006||May 6, 2008||Board Of Trustees Operating Michigan State University||Active sensor for micro force measurement|
|US20010042068||Jan 12, 2001||Nov 15, 2001||Nikon Corporation||Methods and apparatus for data classification, signal processing, position detection, image processing, and exposure|
|US20010054032||Dec 8, 2000||Dec 20, 2001||Insyst Ltd.||Method and tool for data mining in automatic decision making systems|
|US20020011852||Mar 21, 2001||Jan 31, 2002||Andreas Mandelis||Non-contact photothermal radiometric metrologies and instrumentation for characterization of semiconductor wafers, devices and non electronic materials|
|US20020015176||Jan 26, 2001||Feb 7, 2002||Toshiyuki Takao||Product production system, apparatus for managing productions, and method for producing designated products|
|US20020042762||Aug 30, 2001||Apr 11, 2002||Mcquade Richard||Tracking the distribution of prescription drugs and other controlled articles|
|US20020044128||Apr 30, 2001||Apr 18, 2002||Masakazu Hayashi||Method and apparatus for displaying information and program and medium used therefor|
|US20020046290||Sep 26, 2001||Apr 18, 2002||Johann Andersson||Computer system|
|US20020113151||Jun 18, 2001||Aug 22, 2002||Forber Jones Robin M.||Methods and apparatus for spray forming, atomization and heat transfer|
|US20020116083||Oct 16, 2001||Aug 22, 2002||Schulze Bradley D.||System and method for automated monitoring and assessment of fabrication facility|
|US20020128886||Jul 18, 2001||Sep 12, 2002||Wu-Chieh Wang||Application of supply chain unit cell or cell group or boundary conservation of value and quantity to computer management system|
|US20020138510||Jan 24, 2001||Sep 26, 2002||Sun Microsystems, Inc.||Method, system, and program for tracking quality assurance processes|
|US20020147569||Apr 9, 2001||Oct 10, 2002||Lay Samuel C.||Automatic testing of redundant switching element and automatic switchover|
|US20020156548||Feb 28, 2002||Oct 24, 2002||Applied Materials, Inc.||Computer integrated manufacturing techniques|
|US20020165806||Jan 23, 2002||Nov 7, 2002||Kataria Anjali Rani||System and method for managing a regulated industry|
|US20020187137||Jun 12, 2001||Dec 12, 2002||Bates James N.||S-methylcysteine, S-ethylcysteine, and related S-alkylthiols as antagonists to the effects of S-nitrosothiols and nitric oxide|
|US20020198964||Jun 26, 2001||Dec 26, 2002||International Business Machines Corporation||Method and system for wireless remote monitoring and control of a manufacturing execution system|
|US20030018400||May 21, 2002||Jan 23, 2003||Tuttle Timothy D.||Method and apparatus for creating time-optimal commands for linear systems|
|US20030040844||May 10, 2002||Feb 27, 2003||Spool Peter R.||Business management system and method for a deregulated electric power market using online diagnostic services|
|US20030040845||May 10, 2002||Feb 27, 2003||Spool Peter R.||Business management system and method for a deregulated electric power market using customer circles aggregation|
|US20030041016||May 10, 2002||Feb 27, 2003||Spool Peter R.||Business management system and method for a deregulated electric power market using cooperatively produced estimates|
|US20030041017||May 10, 2002||Feb 27, 2003||Spool Peter R.||Business management system and method for a deregulated electric power market using consumer selected special offers|
|US20030041037||May 10, 2002||Feb 27, 2003||Spool Peter R.||Business management system and method for a deregulated electric power market with sharing of supply chain data|
|US20030041038||May 10, 2002||Feb 27, 2003||Spool Peter R.||Business management system and method for a deregulated electric power market in a shortage situation|
|US20030041039||May 10, 2002||Feb 27, 2003||Spool Peter R.||Business management system and method for a deregulated electric power market using workspace portals.|
|US20030046252||May 10, 2002||Mar 6, 2003||Spool Peter R.||Business management system and method for a deregulated electric power market using suppliers' special offers|
|US20030069795||Sep 23, 2002||Apr 10, 2003||Boyd Amy Hancock||Supplier data management system|
|US20030069894||Sep 17, 2001||Apr 10, 2003||Darlene Cotter||Computer-based system for assessing compliance with governmental regulations|
|US20030074223||Sep 24, 2002||Apr 17, 2003||Scott Laboratories, Inc.||Methods and apparatuses for assuring quality and safety of drug administration and medical products and kits|
|US20030125904||Dec 27, 2002||Jul 3, 2003||Kabushiki Kaisha Toshiba||Log analysis method and recording medium storing log analysis program|
|US20030139939||May 10, 2002||Jul 24, 2003||Spool Peter R.||Business management system and method for a deregulated electric power market using consumer site anomaly detection|
|US20030149501||Feb 4, 2003||Aug 7, 2003||Tuszynski Steve W.||Manufacturing design and process analysis system|
|US20030149608||Feb 5, 2003||Aug 7, 2003||Kall Jonathan J.||Suite of configurable supply chain infrastructure modules for deploying collaborative e-manufacturing solutions|
|US20030149717||Jan 31, 2003||Aug 7, 2003||William Heinzman||Batch processing job streams using and/or precedence logic|
|US20030150909||Nov 27, 2002||Aug 14, 2003||Kimberly-Clark Worldwide, Inc.||Quality management by validating a bill of materials in event-based product manufacturing|
|US20030154144||Nov 27, 2002||Aug 14, 2003||Kimberly-Clark Worldwide, Inc.||Integrating event-based production information with financial and purchasing systems in product manufacturing|
|US20030172371||Mar 28, 2003||Sep 11, 2003||Werner Offenmuller||System and method for managing software applications, particularly manufacturing execution system (MES) applications|
|US20030176981||Jun 29, 2001||Sep 18, 2003||Chow Kwok Yui||Method for predicting flow properties of powders|
|US20030180957||Dec 20, 2002||Sep 25, 2003||Sense Proteomic Limited||Target and method|
|US20030183777||Feb 19, 2003||Oct 2, 2003||Luc Struye||Storage phosphor screen having binderless colored layers|
|US20030200130||Apr 29, 2003||Oct 23, 2003||Kall Jonathan J.||Suite of configurable supply chain infrastructure modules for deploying collaborative e-manufacturing solutions|
|US20030207795||Jul 2, 2002||Nov 6, 2003||Pilon Aprile L.||Methods for the production of purified recombinant human uteroglobin for the treatment of inflammatory and fibrotic conditions|
|US20030216630||Aug 23, 2002||Nov 20, 2003||Inotech Medical Systems, Inc.||Conductivity reconstruction based on inverse finite element measurements in a tissue monitoring system|
|US20030216662||Aug 23, 2002||Nov 20, 2003||Inotech Medical Systems, Inc.||Film barrier dressing for intravascular tissue monitoring system|
|US20030216663||Aug 23, 2002||Nov 20, 2003||Inotech Medical Systems, Inc.||Tissue monitoring system for intravascular infusion|
|US20030223033||Aug 9, 2002||Dec 4, 2003||Crossbows Optical Limited||Progressive addition power lens|
|US20030225124||Feb 12, 2003||Dec 4, 2003||Spiridon Spireas||Stable formulations of ACE inhibitors, and methods for preparation thereof|
|US20040006486 *||May 29, 2002||Jan 8, 2004||Schmidt Dieter H.||Paperless recorder for tamper-proof recording of product process information|
|US20040011288||Feb 25, 2003||Jan 22, 2004||Affinito John D.||Methods and apparatus for vacuum thin film deposition|
|US20040015521||May 14, 2003||Jan 22, 2004||Hudicka Joseph R.||Non-intrusive, automated upgrading of electronic records|
|US20040032592||Nov 1, 2002||Feb 19, 2004||Venugopal Vijayakumar C.||Method for in-situ monitoring of patterned substrate processing using reflectometry|
|US20040032593||Mar 27, 2003||Feb 19, 2004||Lam Research Corporation||Process endpoint detection method using broadband reflectometry|
|US20040034543||Jan 15, 2003||Feb 19, 2004||Koninklijke Ahold Nv||Methodology to design, construct, and implement human resources business procedures and processes|
|US20040068454||Oct 3, 2002||Apr 8, 2004||Jacobus Greg C.||Managing procurement risk|
|US20040068455||Oct 3, 2002||Apr 8, 2004||Jacobus Greg C.||Graphical user interface for procurement risk management system|
|US20040077075||May 1, 2003||Apr 22, 2004||Massachusetts Institute Of Technology||Microfermentors for rapid screening and analysis of biochemical processes|
|US20040078732||Oct 21, 2002||Apr 22, 2004||International Business Machines Corporation||SMP computer system having a distributed error reporting structure|
|US20040107415||Nov 25, 2003||Jun 3, 2004||Konstantin Melamed||Web-interactive software testing management method and computer system including an integrated test case authoring tool|
|US20040117126||Nov 25, 2003||Jun 17, 2004||Fetterman Jeffrey E.||Method of assessing and managing risks associated with a pharmaceutical product|
|US20040123864 *||Jan 24, 2001||Jul 1, 2004||Hickey Anthony J.||Dry powder inhaler devices, multi-dose dry powder drug packages, control systems, and associated methods|
|US20040153171||Sep 12, 2003||Aug 5, 2004||Brandt David D.||System and methodology providing automation security architecture in an industrial controller environment|
|US20040158475||Feb 6, 2003||Aug 12, 2004||Harry Juzeszyn||System and method for data handling in pharmaceutical manufacture|
|US20040167648||Jan 7, 2004||Aug 26, 2004||Tuszynski Steve W.||Manufacturing design and process analysis system|
|US20040177055||Jun 21, 2002||Sep 9, 2004||Luder Heidemann||Method and data processing device for activating manufacturing execution system (mes) components|
|US20040186648||Mar 18, 2004||Sep 23, 2004||Yuhong Zheng||Boundary auto-calibration scheme for proportional poppet valve pressure control|
|US20040204972||Apr 14, 2003||Oct 14, 2004||Animesh Anant||Software tool for evaluating the efficacy of investments in software verification and validation activities and risk assessment|
|US20040205406||May 10, 2001||Oct 14, 2004||Marappa Kaliappan||Automatic test system for testing remote target applications on a communication network|
|US20040243260||Sep 19, 2003||Dec 2, 2004||Fisher-Rosemount Systems, Inc.||Integrated electronic signatures for approval of process control and safety system software objects|
|US20050012895||Aug 17, 2004||Jan 20, 2005||Crossbows Optical Limited||Progressive addition power lens|
|US20050015166||Aug 9, 2004||Jan 20, 2005||Kataria Anjali Rani||System and method for managing a regulated industry|
|US20050015741||Nov 28, 2002||Jan 20, 2005||Dirk Langkafel||System and method for tracing and/or evaluating the exchange of information|
|US20050033468||Aug 4, 2003||Feb 10, 2005||James Pate||Method and apparatus for integrating Six Sigma methodology into inspection receiving process of outsourced subassemblies, parts, and materials: acceptance, rejection, trending, tracking and closed loop corrective action|
|US20050033977||Aug 6, 2003||Feb 10, 2005||Victor Zurita||Method for validating a system|
|US20050038565||Apr 26, 2004||Feb 17, 2005||Power Michael A.||Process control method with integrated database for electronically documenting the configuration, modification and operation of a controlled process|
|US20050055110||Jul 27, 2004||Mar 10, 2005||Tuszynski Steve W.||Manufacturing design and process analysis and simulation system|
|US20050065818||Feb 24, 2004||Mar 24, 2005||Medco Health Solutions, Inc.||Computer implemented medical integrated decision support system|
|US20050106355||Jan 12, 2004||May 19, 2005||Kohlman Randolph S.||Patterned textile product|
|US20050107895||May 27, 2002||May 19, 2005||Efstratios Pistikopoulos||Process control|
|US20050137735||Dec 23, 2003||Jun 23, 2005||Song Steve Loy Wee||Virtual platform to facilitate automated production|
|US20050197786||Dec 23, 2004||Sep 8, 2005||Conformia Software, Inc.||System and method for managing the development and manufacturing of a pharmaceutical drug|
|US20050251276||Apr 23, 2004||Nov 10, 2005||Taiwan Semiconductor Manufacturing Co., Ltd.||System and method for real-time fault detection, classification, and correction in a semiconductor manufacturing environment|
|US20050267611||May 31, 2005||Dec 1, 2005||Internation Business Machines Corporation||System, method and program for tracing manufacturing processes|
|US20050278052||Jun 15, 2004||Dec 15, 2005||Kimberly-Clark Worldwide, Inc.||Generating a reliability analysis by identifying causal relationships between events in an event-based manufacturing system|
|US20050288979||Jun 15, 2004||Dec 29, 2005||Lucent Technologies Inc.||System and method for mitigating inventory risk in an electronic manufacturing services-based supply chain management and manufacturing execution system|
|US20060000470||Jun 9, 2005||Jan 5, 2006||Clarke Allan J||Apparatus and method for producing a pharmaceutical product|
|US20060002986||Jun 9, 2005||Jan 5, 2006||Smithkline Beecham Corporation||Pharmaceutical product|
|US20060010426||Jul 9, 2004||Jan 12, 2006||Smartware Technologies, Inc.||System and method for generating optimized test cases using constraints based upon system requirements|
|US20060013473||Jul 21, 2005||Jan 19, 2006||Vulcan Patents Llc||Data processing system and method|
|US20060015536||Feb 10, 2004||Jan 19, 2006||Buchanan Bruce R||Database and method of use for authenticity verification of pharmaceuticals|
|US20060016830||Jun 9, 2005||Jan 26, 2006||Smithkline Beecham Corporation||Apparatus and method for pharmaceutical production|
|US20060017916||Jun 9, 2005||Jan 26, 2006||Clarke Allan J||Apparatus for producing a pharmaceutical product|
|US20060020578||Jul 21, 2004||Jan 26, 2006||Rockwell Software, Inc.||Time stamp methods for unified plant model|
|US20060026193||Aug 2, 2004||Feb 2, 2006||Rockwell Software, Inc.||Dynamic schema for unified plant model|
|US20060035395||Aug 12, 2005||Feb 16, 2006||Venugopal Vijayakumar C||Process endpoint detection method using broadband reflectometry|
|US20060047453||Aug 9, 2005||Mar 2, 2006||Michael Reeve||Quality analysis including cumulative deviation determination|
|US20060047705||Oct 28, 2005||Mar 2, 2006||Kimberly-Clarke Worldwide, Inc.||Intelligent agent system and method for evaluating data integrity in process information databases|
|US20060056732||Aug 26, 2005||Mar 16, 2006||David Holmes||Method and apparatus for determining offsets of a part from a digital image|
|US20060064182||Sep 17, 2004||Mar 23, 2006||Fisher-Rosemount Systems, Inc.||System and method for detecting an abnormal situation associated with a reactor|
|US20060070014||Sep 27, 2004||Mar 30, 2006||Taiwan Semiconductor Manufacturing Company, Ltd.||Real time monitoring system of semiconductor manufacturing information|
|US20060074522||Sep 30, 2004||Apr 6, 2006||Liang Po H||Method and system of automatic dispatch|
|US20060074917||Sep 30, 2004||Apr 6, 2006||Rockwell Automation Technologies, Inc.||Scalable and flexible information security for industrial automation|
|US20060089739||Oct 22, 2004||Apr 27, 2006||Fisher-Rosemount Systems, Inc.||Method and system for batch process arbitration in a process control system|
|US20060095545||Oct 4, 2004||May 4, 2006||Siemens Aktiengesellschaft||Interface unit for automation systems and method of providing and installing such an interface|
|US20060100786||Nov 5, 2004||May 11, 2006||Particle Coating Technology Solutions, Inc.||Pan coating simulation for determining tablet coating uniformity|
|US20060124443||Oct 18, 2005||Jun 15, 2006||David Tuschel||Control and monitoring of non-resonant radiation-induced nucleation, crystallization, and polymorph formation|
|US20060129259||Oct 4, 2005||Jun 15, 2006||Clay Tornquist||Automatic calculation of minimum and maximum tolerance stack|
|US20060129265||Dec 11, 2004||Jun 15, 2006||Ouchi Norman K||Directed defective item repair system and methods|
|US20060149407||Feb 27, 2006||Jul 6, 2006||Kimberly-Clark Worlwide, Inc.||Quality management and intelligent manufacturing with labels and smart tags in event-based product manufacturing|
|US20060155410||Jan 10, 2005||Jul 13, 2006||Applied Materials Inc.||Spilt-phase chamber modeling for chamber matching and fault detection|
|US20060167579||Dec 20, 2005||Jul 27, 2006||Omron Corporation||Quality variation display device, quality variation display method, quality variation display program, and storage medium storing such program|
|US20060184264||Feb 16, 2005||Aug 17, 2006||Tokyo Electron Limited||Fault detection and classification (FDC) using a run-to-run controller|
|US20060199260||Sep 26, 2005||Sep 7, 2006||Zhiyu Zhang||Microbioreactor for continuous cell culture|
|US20060206368||Mar 1, 2006||Sep 14, 2006||Stefan Bamberger||Integration of MES and controls engineering|
|US20060208191||Jan 9, 2006||Sep 21, 2006||Kessler William J||System for monitoring a drying process|
|US20060214948||Mar 23, 2006||Sep 28, 2006||Murthy P V R||Path coverage criterion in specification-based testing based on an extended context-free grammar-based test specification model and a new test generation algorithm|
|US20060239116||Apr 25, 2005||Oct 26, 2006||Harsco Technologies Corporation||Apparatus for continuous blending|
|US20060259500||Sep 29, 2005||Nov 16, 2006||Rockwell Automation Technologies, Inc.||Library that includes modifiable industrial automation objects|
|US20060267852||Nov 28, 2005||Nov 30, 2006||Jiho Ahn||Antenna-feeder device and antenna|
|US20060282223||Oct 17, 2005||Dec 14, 2006||Lewis E N||Pharmaceutical mixture evaluation|
|US20070005307||Apr 24, 2006||Jan 4, 2007||Hiroshi Sato||Design support method and design support system|
|US20070011227||Jul 6, 2005||Jan 11, 2007||Honeywell International Inc.||System and method for providing direct web access to controllers in a process control environment|
|US20070011415||Jul 6, 2005||Jan 11, 2007||Honeywell International Inc.||Apparatus and method for deterministic garbage collection of a heap memory|
|US20070011660||Jul 6, 2005||Jan 11, 2007||Honeywell International Inc.||Deterministic runtime execution environment and method|
|US20070016542||Jul 1, 2006||Jan 18, 2007||Matt Rosauer||Risk modeling system|
|US20070037570||Aug 15, 2005||Feb 15, 2007||Incode Telecom Group, Inc.||Embedded wireless benchmarking systems and methods|
|US20070049267||Aug 15, 2006||Mar 1, 2007||Incode Telecom Group, Inc.||Embedded wireless location validation benchmarking systems and methods|
|US20070050070||Aug 3, 2006||Mar 1, 2007||Pfizer Inc||Automated batch manufactuirng|
|US20070061166||Aug 28, 2006||Mar 15, 2007||Narayanan Ramasubramanian||Techniques for improving loss ratios|
|US20070067458||Sep 20, 2005||Mar 22, 2007||Rockwell Software, Inc.||Proxy server for integration of industrial automation data over multiple networks|
|US20070088534||Oct 18, 2006||Apr 19, 2007||Honeywell International Inc.||System, method, and computer program for early event detection|
|US20070100471||Oct 28, 2005||May 3, 2007||Honeywell International Inc.||System and method for dynamically creating and editting function block types in a process control environment|
|US20070100472||Oct 31, 2005||May 3, 2007||Honeywell International Inc.||System and method for creating serial interface protocols in a process control environment|
|US20070100894||Oct 31, 2005||May 3, 2007||Honeywell International Inc.||Apparatus and method for encoding data change rates in textual programs|
|US20070101091||Oct 31, 2005||May 3, 2007||Honeywell International Inc.||System and method for managing a short-term heap memory|
|US20070104949||Jun 21, 2004||May 10, 2007||Misapor Ag||Granulate made of sintered or cellular broken glass|
|US20070112442||Nov 17, 2005||May 17, 2007||Honeywell International Inc.||Apparatus and method for analyzing model quality in a process control environment|
|US20070112531||Nov 17, 2005||May 17, 2007||Honeywell International Inc.||Apparatus and method for identifying informative data in a process control environment|
|US20070113051||Oct 17, 2005||May 17, 2007||Honeywell International Inc.||Apparatus and method for live loading of control applications in a process control environment|
|US20070136667||Dec 14, 2005||Jun 14, 2007||Honeywell International Inc.||System and method for providing context sensitive help information|
|US20070142941||Nov 10, 2006||Jun 21, 2007||Rockwell Automation Technologies, Inc.||Historian module for use in an industrial automation controller|
|US20070144240||Apr 22, 2004||Jun 28, 2007||Biode Inc.||Measurement of density and viscoelasticity with a single acoustic wave sensor|
|US20070149586||Feb 23, 2007||Jun 28, 2007||Rottapharm S.P.A.||New crystalline and stable form of andolast|
|US20070200781||Nov 14, 2006||Aug 30, 2007||Jiho Ahn||Antenna-feeder device and antenna|
|US20070214520||Jan 17, 2007||Sep 13, 2007||Thomas Scheibel||Recombinant spider silk proteins|
|US20070239367||Mar 22, 2007||Oct 11, 2007||Medpro Holdings, Llc||On-site method of providing analysis of potency and purity of pharmaceutical compounds|
|US20080009959||Aug 6, 2007||Jan 10, 2008||Enright Kerry J||Enterprise factory control method and system|
|US20080066019||Sep 13, 2006||Mar 13, 2008||Fisher-Rosemount Systems, Inc.||Compact Batch Viewing Techniques for use in Batch Processes|
|US20080077617||Sep 27, 2006||Mar 27, 2008||Rockwell Automation Technologies, Inc.||Universal, hierarchical layout of assets in a facility|
|EP0503521B2||Mar 9, 1992||Nov 9, 2005||Akzo Nobel N.V.||Low dose dry pharmaceutical preparations|
|EP0593114B1||Oct 1, 1993||Feb 13, 2002||OcÚ-Technologies B.V.||Method of assigning a colour indication to picture elements in a colour reproduction system|
|EP0696001B1||Jul 21, 1995||Dec 5, 2001||Mitsubishi Denki Kabushiki Kaisha||Information processing system and method of computation performed by using an information processing system|
|EP0700680B1||Aug 28, 1995||Nov 10, 1999||Bristol-Myers Squibb Company||Gepirone dosage form|
|EP0999506A1||Nov 3, 1998||May 10, 2000||David W. Cunningham||Method and system for dispensing, tracking and managing pharmaceutical trial products|
|EP1117007A2||Dec 7, 2000||Jul 18, 2001||Fuji Photo Film Co., Ltd.||Development processing apparatus and developing method for photosensitive material|
|EP1136951A2||Mar 22, 2001||Sep 26, 2001||Optimod Software Systems, Ltd.||Method for accelerating mesh generation|
|EP1349177A2||Feb 13, 2003||Oct 1, 2003||Agfa-Gevaert||Layer arrangement having a binderless coloured layer|
|EP1481294B1||Feb 4, 2003||Oct 11, 2006||TUSZYNSKI, Steve W.||Manufacturing design and process analysis system|
|EP1714695A1||Apr 18, 2006||Oct 25, 2006||TechniKrom, Inc.||Automated industrial biosynthesizer and method|
|EP1798814A2||Nov 14, 2006||Jun 20, 2007||Ahn, Ji-Ho||Antenna and antenna-feeder device|
|EP1830386A2||Feb 22, 2007||Sep 5, 2007||Microsaic Systems Limited||Personalised mass spectrometer|
|WO1997016434A1||Oct 4, 1996||May 9, 1997||Pfizer Inc.||(-) cis-6(s)-phenyl-5(r)[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol d-tartrate|
|WO2001015705A1||Aug 30, 1999||Mar 8, 2001||Cypros Pharmaceutical Corporation||Use of fructose-1,6-diphosphate as an inotrope drug for cardiopulmonary bypass surgery|
|WO2002016924A1||Aug 22, 2001||Feb 28, 2002||Wenman Richard A||Acoustic interferometry method and device|
|WO2002087546A2||Mar 13, 2002||Nov 7, 2002||Pfizer Products Inc.||Method for manufacturing a low dose pharmaceutical composition|
|WO2003058533A1||Dec 27, 2002||Jul 17, 2003||Kimberly-Clark Worldwide, Inc.||Integrating event-based production information with financial and purchasing systems in product manufacturing|
|WO2003063680A2||Jan 21, 2003||Aug 7, 2003||Inotech Medical Systems, Inc.||Tissue monitoring system for intravascular infusion|
|WO2004059531A1||Dec 17, 2003||Jul 15, 2004||International Business Machines Corporation||Optimization of temporal and spatial data processing in an object relational database system|
|WO2004072868A1||Feb 10, 2004||Aug 26, 2004||Verication, L.L.C.||Database and method of use for authenticity verification of pharmaceuticals|
|WO2004107087A2||May 28, 2004||Dec 9, 2004||Flextronics Design Limited||Generating test cases|
|WO2005038821A2||Oct 16, 2004||Apr 28, 2005||Fei Company||Charged particle extraction device and method of design there for|
|WO2005114138A2||Apr 22, 2004||Dec 1, 2005||Biode, Inc.||Measurements of density and viscoelasticity with a single acoustic wave sensor|
|WO2006017808A2||Aug 4, 2005||Feb 16, 2006||Fujifilm Dimatix, Inc.||Print head nozzle formation|
|WO2006069797A1||Dec 30, 2005||Jul 6, 2006||Pall Corporation||Methods and apparatus for observing vessel contents|
|WO2006071808A2||Dec 21, 2005||Jul 6, 2006||Conformia Software, Inc.||Systems and methods for managing the development and manufacturing of a drug|
|WO2006113450A1||Apr 13, 2006||Oct 26, 2006||Honeywell International Inc.||Decision support method and system|
|WO2007017552A1||Jul 31, 2006||Feb 15, 2007||Mika Tapio Reijonen||Method and apparatus using of the electric field for controlling of the crystallizing of material or materials|
|WO2007017738A2||Aug 3, 2006||Feb 15, 2007||Pfizer Products Inc.||Automated batch manufacturing|
|WO2007050013A1||Oct 18, 2006||May 3, 2007||Alfa Laval Corporate Ab||Multipurpose flow module|
|WO2007064624A1||Nov 28, 2006||Jun 7, 2007||Honeywell International Inc.||System and method for providing a software installation or removal status display|
|1||A Model for Integrating Material Management in a Production Environment, Ham, et. al., Paper No. AUTOW-P109, pp. 1-9, May 3, 2004.|
|2||Acoustic-Resonance Spectrometry as a Process Analytical Technology for Rapid and Accurate Tablet Identification, Medendorp, et. al. AAPS Pharm. Sci. Tech 2006; 7(1) Art 25.|
|3||Analyzing Software Errors in Safety-Critical Embedded Systems, Lutz, pp. 1-22 (Feb. 24, 1994).|
|4||Challenges and Issues in Veterinary Pharmacology and Animal Health 2004-Preface, Martinez, et. al. AAPS Journal 2005; 7(2) Art. 26, pp. 266-271.|
|5||Challenges and Issues in Veterinary Pharmacology and Animal Health 2004—Preface, Martinez, et. al. AAPS Journal 2005; 7(2) Art. 26, pp. 266-271.|
|6||Compliance Information on 21 C.F.R Part 11; Rockwell Automation Whitepaper, Jan. 2001, pp. 1-29.|
|7||Compliant Manufacturing with SAP in the Pharmaceutical Industry, Sabogal, et. al., Pharm. Ind. 66, Nr. 11a 1405-1412 (2004).|
|8||Council for Education in Pharmaceutical Medicine, IFAPP, pp. 1-9, Oct. 8, 2003.|
|9||Effects of Average Signed Area Between Two Item Characteristic Curves and Test Purification Procedures on the DIF Detection via the Mantel-Haenszel Method, Wang, et. al., 2004.|
|10||Efficiency of the Mantel . . . and Logistic Discriminant Function Analysis Methods in Detecting Differential Item Functioning for Polytomous Items, Su, et. al., 18(4) 313-350 2005.|
|11||Elastic-Plastic Behavior and Limit Load Analysis of Pipe Bends Under Out-Of-Plane Moment Loading and Internal Pressure, Mourad, Univ. of Cairo, Dec. 1999, pp. 1-188.|
|12||Experimental Designs at the Crossroads of Drug Discovery, Olsen, Umea university (2006), pp. 1-80.|
|13||Fit Indices Versus Test Statistics, Yuan, Multivariate Behavioral Research, 40 (1), 115-148 (2005).|
|14||Fundamental Modeling and Simulation of Pharmaceutical Powder Blending, Ngai, May 27, 2003, pp. 1-21.|
|15||General Principles of Software Validation; Final Guidance for Industry and FDA Staff, pp. i-iv, pp. 1-47, Jan. 11, 2002.|
|16||General Principles of Software Validation; Final Guidance for Industry and FDA Staff; pp. i-iv, 1-43, Jan. 11, 2002.|
|17||Global Manufacturing: MES and Beyond Benchmark Report, Aberdeen Group, pp. 1-27 (May 2006).|
|18||Glossary of Computerized System and Software Development Terminology, pp. 1-39, Aug. 1995.|
|19||Guidance for Industry 21 CFR Part 11 Electronic Records, Electronic Signatures Validation Draft Guidance, US Department of Health and Human Services, Aug. 2001, pp. 1-24.|
|20||*||Guidance For Industry 21 CFR Part 11: Electronic Records; Electronic Signatures Validations Draft Guidance U.S. Department of Health andn Human Services, Aug. 2001 pp. 1-21.|
|21||Guidance for Industry, FDA Reviewers and Compliance Guide on: Off-the-Shelf Software Use in Medical Devices, U.S. DHHS, Sep. 9, 1999, pp. 1-26.|
|22||Guidance for Industry; PAT-A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance, Sep. 2004 pp. 1-19.|
|23||Guidance for Industry; PAT—A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance, Sep. 2004 pp. 1-19.|
|24||Guidance for Management of Computers and Software in Laboratories with Reference to ISO/IEC 17025/2005, EuroLab Technical Report, pp. 1-31, Oct. 2006.|
|25||Guide to Inspection of Computerized Systems in Drug Processing, National Center for Drugs and Biologics, et. al. pp. 1-27, Feb. 1983.|
|26||Identification, Integration and Tracking Software System Safety Requirements, Russo, et. al., pp. 1-14, Aug. 1994.|
|27||*||IEEE Standard for Software Safety Plans IEEE Std 1228-1994 pp. i-v and 1-17 (1994).|
|28||In-Line Process Analysis of Residual Moisture in a Fluid Bed Granulator-Dryer using NIR Spectroscopy, Mattes, et. al. Spectroscopy, Jan. 2005.|
|29||In-Line Process Analysis of Residual Moisture in a Fluid Bed Granulator—Dryer using NIR Spectroscopy, Mattes, et. al. Spectroscopy, Jan. 2005.|
|30||In-Situ Studies of Sulfamerazine and Carbamazepine Crystallization, Rivera, Univ. of Puerto Rico Thesis (2005) pp. 1-82.|
|31||International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use; Q8: Pharmaceutical Development, pp. 1-4, Oct. 8, 2003.|
|32||International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use; Q9: Quality Risk Management, Nov. 11, 2003, pp. 1-3.|
|33||Near-Infrared Spectroscopy and Imaging: Basic Principles and Pharmaceutical Applications, Reich, Adv. Drug Delivery Rev. 57 (2005) pp. 1109-1143.|
|34||NIST-Software Error Analysis; NIST Special Publication 500-209, Peng, et. al., Mar. 1993, pp. 1-103.|
|35||NIST—Software Error Analysis; NIST Special Publication 500-209, Peng, et. al., Mar. 1993, pp. 1-103.|
|36||Nondestructive and On-Line Monitoring of Tablets Using Light-Induced Flourescence Technology, Lai, et. al., AAPS PharmaSciTech 2004; 5(1) Article 3.|
|37||Opening the PAT Toolbox, Folestad, et. al., Eur. Pharma. Rev. (2003) vol. 8; Part 4, pp. 36-42.|
|38||Optical, Tunable Filter-Based micro-Instrumentation for Indusrial Applications, Kotidis, et. al. Oct. 20, 2003, pp. 1-14.|
|39||Process Analytical Technology (PAT) and Scable Automation for Bioprocess Control and Monitoring-A Case Study, Ganguly, et. al., Pharm. Eng. Jan./Feb. 2006 pp. 1-9.|
|40||Process Analytical Technology (PAT) and Scable Automation for Bioprocess Control and Monitoring—A Case Study, Ganguly, et. al., Pharm. Eng. Jan./Feb. 2006 pp. 1-9.|
|41||Process Analytical Technology Case Study, Part I: Feasibility Studies for Quantitative NIR Method Development, Cogdill, et. al., AAPS Pharm. Sci. Tech. Feb. 2, 2004.|
|42||Process Analytical Technology Case Study, Part II: Development and Validation of Quantitative Near Infrared Calibrations . . . Cogdill, et. al., AAPS PharsSciTech. Apr. 19, 2005.|
|43||Process Analytical Technology Outsourcing-Impacts on Manufacturing and Process Knowledge, Radspinner, et. al. GOR vol. 7, No. 4 pp. 55-58 Winter 2005.|
|44||Process Analytical Technology Outsourcing—Impacts on Manufacturing and Process Knowledge, Radspinner, et. al. GOR vol. 7, No. 4 pp. 55-58 Winter 2005.|
|45||Process Analytical Technology; Concepts and Principles, Balboni, Pharma. Tech. Oct. 2003, pp. 1-6.|
|46||Process Control System Just the Right Prescription: Application Profile, Rockwell Automation, Mar. 2001, pp. 1-4.|
|47||Quality Management System (QMS) for Active Pharmaceutical Ingredient (API) Manufacturers, Inegrating GPM (ICH Q7a) into ISO (9001:2000), pp. 1-73, Sep. 2005.|
|48||Quantitative Analysis of Film Coating in a Pan Coater Based on In-Line Sensor Measurements, Perez-Ramos, et. al.. AAPS Pharma. Sci. Tech. Feb. 2, 2005, pp. 1-40.|
|49||Real-Time On-Line Monitoring of Fluid Bed Dryers Using NIR Spectroscopy, Das, et. al. May 16, 2005.|
|50||Safety Software Quality Assurance Functional Area Qualification Standard, Department of Energy, pp. 1-23, Dec. 2003.|
|51||Safety-Critical Software: Status Report and Annotated Biography; Technical Report, Place, et. al., pp. 1-90, Jun. 1993.|
|52||SAX: Solution Atomization and SonoXrystallization; Technology for Manufacture of Micro and Nanocrystalline Drug Particles, Ruecroft, et. al., pp. 1-27 (2006).|
|53||Small Changes, Big Effects in Biological Manufacturing, Bush, Pharma. Sci. & Tech. News, Nov. 2004, pp. 16-18.|
|54||Software System Safety Guide, Russo, pp. 1-41, May 1992.|
|55||Software Testing: Advanced Level Syllabus, ISTQB, Sep. 2003, pp. 1-42.|
|56||Stable Isotopes Provide a New PAT Tool, Jasper, et. al., Pharm. Mfg. 4(5): 28-33 (May 2005).|
|57||Standard for Software Component Testing, BCS SIGIST, Draft Apr. 27, 2001, pp. 1-67.|
|58||Streamlined Recipe Rollout: Application Profile, Rockwell Automation, Mar. 2001, pp. 1-4.|
|59||System Validation with Experion PKS, Whitepaper Honeywell, Sep. 13, 2002, pp. 1-19.|
|60||Terahertz Sources and Detectors and Thier Application to Biological Sensing, Crowe, et. al., Phil. Trans. R. Soc. Lond. A (2004) 362, 365-377 (online Dec. 16, 2003).|
|61||The Effect of Shear Mixing on the Blending of Cohesive Lubricants and Drugs, Llusa, et. al., Pharma. Tech., pp. 1-7, Dec. 1, 2005.|
|62||The Effects of Physical Parameters on LIBS Analysis of Intact Tablets, Archambault, et. al., AAPS Pharma. Sci. Tech., pp. 1-39, Apr. 19, 2005.|
|63||The Interoduction of Process Analytical Technology, Using Near Infrared Analysis, to a Pharmaceutical Blending Process, Naicker, et. al., Mar. 6, 2007.|
|64||The Role of PAT in Developing New Products, Kraunsoe, APACT Presentation, Apr. 20, 2005, pp. 1-28.|
|65||There is no Execution without Integration, MES Adoption drives performance, pp. 1-21, The Aberdeen Group, Mar. 2007.|
|66||Trends in Integrated Manufacturing, Supplement of BioProcess Internation, Sep. 2004, pp. 1-39.|
|67||U.S. Department of Health and Human Services, Off-the-shelf software use in Medical devices, Sep. 9, 1999.|
|68||Use of Impedence Methods in Pharmaceutical Methods, Moldenhauer, Rapid Micro. Newsletter, Jul./Aug. 2003 vol. 2 Issue 3 pp. 1-6.|
|69||Using Cycle Time Analysis to Enhance Operations and Improve Yield, Dream, Pharm. Eng. Sep./Oct. 2006, pp. 1-6.|
|70||Validation and Compliance; Software Systems Prepare Manufacturers for Com(PAT)ibility, Rios, Pharma. Tech., May 2004, pp. 1-8.|
|71||Whitepaper, Emerson Process Management Manufacturing Execution Systems Capabilities, Mar. 2007, pp. 1-27.|
|U.S. Classification||700/110, 700/207, 700/109|
|International Classification||G06F19/00, G06Q10/00|
|Cooperative Classification||G05B23/0224, G05B23/0235, G05B2219/11, G05B2219/1112, G06Q10/06|
|European Classification||G06Q10/06, G05B23/02S4H|