Request Expert

Expert served for several years as a major pharmaceutical company's chief Quality Assurance GMP/GLP computer validation auditor. He chaired the team that developed the company's first policy and guidelines regarding computer validation,- and served for several years as the company's representative to the Pharmaceutical Manufacturers Association's Computer Validation Committee, during which time he was principle author of one publication and contributed to many others. He subsequently was invited by the FDA to write a chapter on Automatic Control Systems (including system validation) in their book "Drug Biotechnology Regulation: Scientific Basis and Practices". He co-authored an invited book by ISA, published in 2008, on Automation Applications in Bio-pharmaceutals which includes extensive coverage of process and computer validation concepts. Expert is knowledgeable on what is required for those plants that must formally comply with cGMPs, and also has a good sense of risk management and pragmatism in applying validation principles to various regulated and non-regulated situations.

The leadership, auditing, and consulting activities noted above were largely driven by Expert's firsthand experience in helping develop and support one of the company's most successful internally developed computer systems, that being the custom process control and historian system that was replicated into all of the company's major research, development, and manufacturing fermentation facilities, with some in use for 25 years. He also led the team that specified, implemented and operated his company's first use of commercial process control systems for fermentation processes. He was also a key member of the team that developed the company's successful internal technical information search engine, a major IT project. Expert is a valued computer validation auditor, in part, due to the large percent of audit time he spends in the field, talking to system users, reviewing HMIs (incl. trend plots, alarm displays and logs, etc.), checking for proper wiring installation (incl. grounding and susceptibility to RFI, EMI), etc. He certainly reviews system documentation, but believes the best indicators of the state of a system are often obtained by going out on the production floor and into control rooms.

Expert is known internationally regarding chemical process control in general, and bioprocess control in particular. His work in this field was the basis of his being invited to give the feature presentation on the state-of-the-art of bioprocess control at CPC-7 in January, 2006. This paper was subsequently published in 2006 in the peer reviewed journal Computers and Chemical Engineering.

Expert's reputation in this field has been the culmination of having served as a leading pharmaceutical company's lead engineer in automating fermentation processes for over 25 years. At the beginning of this time frame (i.e. in 1972), industrial fermentations had very little automation. He subsequently helped lead his company through the evolution of bioprocess control from pneumatic controllers to electronic controllers on panel boards, to highly sophisticated DCS/historian systems and central control rooms. He implemented conventional single-loop feedback control when appropriate. He also developed several cascade control loops, some with adaptive tuning constants, and also developed applications of multivariable control. In addition, given the lack of many commercial rugged, stable, and reliable bioprocess sensors that can withstand the rigors of sterilization, he developed several "virtual" or "soft" sensors using a combination of deterministic "first principle" equations and neural nets. Some of the virtual sensors proved so accurate and reliable that they have been used as feedback (i.e. "current value" inputs) to continuous control loops. He has also used virtual sensors and other mathematical representations of a process in developing successful applications of "model reference" control in bioprocesses.

Most of the virtual sensors that Expert has developed build upon his pioneering work in applying process mass spectrometry "on-line" to bioprocesses, including its use for control purposes. Some of this work was published in the Journal of Process Analytical Technology. It was also the basis of his being awarded the Douglas Annin Award by ISA in 2001 for advancing the "state-of-the-art" of bioprocess control. His work in this field was also much of the basis of his receiving AIChE's national "Computing in Practice" Award in 2003. Use of process mass spectrometry in bioprocess control is also the topic of his invited presentation to the Society of Industrial Microbiology in Denver in June, 2007.

Due, in part, to the process control applications that Expert developed and the significant bioprocess productivity improvements that resulted, a high level of automation is now an expectation for all pilot plant and production bioprocesses in the company in which he spent his career. Additionally, his contributions to conferences and the literature have influenced a corresponding increase in the use of bioprocess automation throughout the pharmaceutical industry.

From 2000 until his retirement from his employer in 2006, Expert served as a corporate automation/engineering advisor for his employer, during which time he helped review and troubleshoot several chemical process control strategies, including non-bioprocess applications. He was also invited to serve as a contributor and reviewer of two books that were published in 2006. He also presented 2-3 invited guest lectures per year at several universities, on subjects including process control. This led to his appointment as a Visiting Professor at Purdue in 2010 where he currently teaches part time.

In 2010, Expert was inducted into the Process Automation Hall of Fame, a distinction held by less than 50 people worldwide.

Expert is knowledgeable about the various instruments / sensors used for chemical processes in general and bioprocesses in particular. These include on-line probes/sensors such as for temperature, pressure, agitation rate, gas and liquid flows, pH, redox, conductivity, high foam, dissolved oxygen and dissolved carbon dioxide. They also include at-line analyzers, such as mass spectrometers, HPLCs, gas chromatography, infrared, paramagnetic, and blood gas analyzers, etc. used to analyze gas and liquid samples for various compounds. In some cases, he has helped evolve the state-of-the-art of certain sensors, such as in improvements to dissolved oxygen measurements (commonly used in many bioreactors), paramagnetic oxygen analyzers and process mass spectrometers.

Expert also has significant experience in successfully developing virtual sensors (i.e. soft sensors) when commercially available instruments are unavailable or unsatisfactory. These have often combined first principles knowledge of a process with neural nets, with data from process mass spectrometry usually serving as key inputs. Published examples include estimation of cell mass and substrate (e.g. glucose) concentrations in bioreactor broth.

The specific process instrument that Expert is best known for in the pharmaceutical industry is process mass spectrometers. He was responsible for evaluating and implementing the first such instrument for his employer in the late 1970s. The success of this technology resulted in most of the company's research, development, and production fermentors being interfaced to mass spectrometers by the late 1980s. Expert worked closely with the leading commercial mass spectrometer vendors to advise them on needed product improvements- and also conducted formal technical evaluations of several of them when new models were developed.

His work included interfacing these systems to process control computers and in validating the systems. He also developed the majority of his company's applications that use process mass spectrometry technology. These applications, in-part, have led to the near real-time availability of many bioprocess parameters, not previously available to plant personnel, that capture the current "state" of the biological culture as well as the bioreactor. Parameter examples common to nearly all aerobic fermentations include culture oxygen uptake, culture carbon dioxide evolution, respiratory quotient, and oxygen mass transfer coefficient. These parameters are often used for process control decisions in manufacturing a "lot" of drug product. The mass spectrometer instrument systems have also been used to discover, monitor, and characterize several other volatile compounds of interest in fermentation exhaust- which, for some bioprocesses, include hydrogen sulfide, alcohols, etc. In some cases, this has led to the need to add scrubbers to the bioreactors in order to comply with environmental regulations. Some of Expert's work with process mass spectrometry has been presented at technical conferences and was also published by the Journal of Process Analytical Technology in 2006.

Expert is a recognized industry leader in the application of both conventional and advanced process monitoring technologies including, e.g., 1) alarm management, 2) artificial intelligence, and 3) data analysis/process modeling.

Most industrial processes do not follow alarm management best practices and suffer from a large number of nuisance alarms. Computer vendor limitations are sometimes also part of the problem. Expert has widespread experience in auditing, designing, and configuring alarm systems and served from 2002-2006 as his employer's corporate leader in driving alarm management improvements throughout the company. Towards this end, he led the teams that developed both corporate standards and best practices on this topic. Implementation of these requirements and best practices led to major reductions in total alarms (in some cases over 80%) in several plants. Expert has authored several journal articles on alarm management in recent years, and was the lead author of a CEP article on regulatory aspects of alarm management. He is currently serving as a pharmaceutical industry and batch process expert on ISA's SP 18 committee which developed and published an international standard on alarm management in 2009 (ANSI/ISA 18.02). He is currently co-chairing an ISA committee developing a technical report on alarm management for batch and discrete processes.

In trying to improve the state of the art of alarm management, Expert has networked with several of the leading process control computer, historian, and alarm logger vendors- and has also helped lead the development of a 3rd party solution, for use within his company, involving real-time expert systems (a branch of artificial intelligence). These systems were directly interfaced to plant process control computers and historians and took advantage of their access to all available information about the on-going process in creating "intelligent alarms" regarding the process (i.e., doing much more than comparing a single current value to a setpoint). The system also created the time-varying alarm limit bands (included on trend displays) associated with controlled parameters, provided on-line help screens to advise operators on probable root causes and expected operator responses, and also sent alarm messages to appropriate remotely located personnel via a paging system. This system was also used for many other labor saving monitoring functions. E.g. each fermentation is normally associated with up to 30 trend displays, and it takes a lot of time for technical service personnel to daily review these plots manually to determine if the production runs are proceeding normally or not. Since people analyze trend plots with "mental rules of thumb", such logic can be captured in "rules" and coded into a rule based expert system. In this way, the expert system continuously (24x7) monitors the trend plots using the same "rules of thumb" that process experts previously used, and only alerts operators or tech service personnel when it detects something abnormal or questionable. This application proved to be a major labor saving system and also resulted in plant productivity increases due to the earlier detection of poor performing bioprocesses. ROIs were consistently less than 1 year. Expert's employer's use and standardization of this technology in fermentation plants became the subject of several conference presentations, publications (including two in Intech in 1999), several technology exchange visits with other industrial companies, and two awards.

Expert led several creative alarm management solutions during the first 30 years of his career in automating life science processes in the pharmaceutical industry. He was also the corporate QA computer validation auditor for his employer for several years, with all audits including a major focus on alarm management. This led to him having corporate responsibility for alarm management during the last 5 years of his industrial career (2001-2006).

In 2004, he was invited to represent the pharmaceutical industry and batch processes on ISA's committee
developing what became the ISA 18.2 Standard on Alarm Management, published in 2009. Expert was a co-author of this standard. This subsequently was adopted as an ANSI standard and, in 2014, as an international IEC standard. Seven ISA teams were subsequently formed to develop alarm management technical reports in support of this standard, with Expert participating in all of them, and co-chairing two of them. Expert remains active to this day in updating the ISA 18.2 standard and in further development of supporting technical reports.

Some of his recent consulting projects have included helping pharmaceutical companies with alarm management (incl. developing an Alarm Philosophy document). He is knowledgeable of the additional requirements for alarm management associated with cGMPs.

Expert has been a member of many FMEA teams during his industrial career and is a formally trained facilitator in the use of this technique. Some of his consulting projects since retirement have included use of FMEA. He has applied this technique to process designs (its most frequent use), but also to manufacturing operations, packaging, and maintenance activities. He has been an invited lecturer on several occasions to present this technique to university research groups and to senior students taking their Sr. Design course as part of their Capstone Design project. He has also mentored student groups on their use of this technique in process design.

Expert spent most of the last 6 years of his career (2000-2006) in a consulting role. He was one of only 3 Engineering Advisors at Lilly, at the time of his retirement - which is the top occupied engineering level at Eli Lilly and Co. (which employs over 1200 engineers).
Topics for which Expert has consulted include compliance to cGMPS (particularly with respect to computer systems), use of Failure Mode and Effects Analysis (for which he is a trained Facilitator), Alarm Management and Modeling.He is a member of the AIChE Publications Committee and is a member of and/or consultant to several Technical Journal Editorial Boards, including those at ISA and AIChE. He formally reviews about 40 technical papers per year, submitted for publication. Journals include ISA's Intech, Computers and Chemical Engineering, Biotechnology and Bioengineering, Chemical Engineering Progress, Journal of Process Control, etc.
He has consulted by virtue of his having served as a member of 4 different PhD student thesis committees (one at MIT and three at Purdue). Subjects of these PhDs have included bioprocess data analysis advanced techniques, pharmaceutical drug development capacity modeling, and simulated moving bed chromatography failure mode analysis (FMEA).
He also consults as a result of his service as an ABET Program Evaluator in accrediting university engineering programs. In 2008, he completed a 5 month consulting contract with a leading Health company in completing development and preparing a new medical device for FDA review. The focus of the work was in validating the hardware and software of the medical device. Extensive use of FMEA (Failure Modes and Effects Analysis) was involved. He has consulted with the Dept. of Chemical Engineering at Purdue on several topics, the most recent of which was the content of their Senior Design Course. He was responsible for modifications to the Capstone Design Project - involving significant addition of safety, environmental, scale-up, process control, and failure mode perspectives.
He has also consulted with the Rose-Hulman Institute of Technology as a result of his membership on their Chemical Engineering Industrial Advisory BoardHe is consulting by virtue of his membership on ISA's SP18 Committee (which developed the new international standard on alarm management, ISA-18.02). This committee is currently developed six technical reports (one of which he chairs) in support of this standard. He is representing both the pharmaceutical industry and batch processes in advising and contributing to this committee.