The business environment of the pharmaceutical industry is becoming increasingly demanding, here only those companies committed to excellence will thrive. The integration of the control and enterprise systems will allow companies to see and analyze much more information from the manufacturing operations and will allow them to optimize manufacturing.
GROWTH OF AUTOMATION
While automation started and progressed slowly in Pharmaceutical Industry, it has come to play an increasingly important role in keeping the industry moving ahead. Pharma lagged while other industries, such as general chemical and specialty chemical, were regularly moving to new technology applications and improving manufacturing performance. But in the past few years, the pace of innovation has accelerated greatly and shows no sign of slowing down. Predictive Intelligence and the field device alerts are gaining importance, aiming at increased availability. Asset Management has become an important part of Automation and is leveraging the best the technology can offer. This article looks at major automation trends in the field from 1977 to the present and gives some ideas on possible future trends.
THE OLD DAYS (PRE, 1977)
The first programmable logic controller (PLC) debuted in 1969, but its wide-spread use in the pharmaceutical industry was still years, if not decades, away. Channel-based analog equipment was the standard. Single controls — either pneumatic or electronic — were mounted on walls in big racks. There was little if any recording of data other than manual data record keeping by operators, and that was done on paper. Circular chart recorders and strip chart recorders were the main way of recording process parameters.
THE LATE 70S AND EARLY 80
The first distributed control systems (DCSs) came out in 1975. At first used mostly in the chemical industry, DCS began to gain popularity in the Pharmaceutical industries by the latter part of the decade and in the early 80s. The Food and Drug Administration (FDA) was ramping up its regulatory requirements and automation was seen as a good tool to facilitate compliance. Use of this tool accelerated as batch control automation and batch unit operations control became available in 1983. The ability to use “configurable off the shelf” software to write sequences, take automatic actions based on failure, create recipes, and synchronize parallel unit operations delivered significant improvements to manufacturing. Implementing commercial off the shelf (COTS) was a large, challenging task as control rooms and wiring were centralized with everything coming back to a combination of a main control room and a massive main wiring hub. Thinking about batch software logic and failure handling was new to many people.
THE LATE 80S TO EARLY 90S
Once people gained experience automating batches, batch standards began to be developed. The goal was to have everyone talking the same language, using well defined terms and having a common architecture. The first batch automation standard, S88 (on which work began in 1988), was approved by ISA in 1995. This standard was initially implemented in two applications: PID’s Open Batch and Consilium’s Director. These applications became the basis for many of the batch automation solutions that developed around the S88 standard. In addition to developing standards, the World Batch Forum was started in 1994. This forum for the batch process industries focused on best practices in automating and applying technology to batch manufacturing.
By the mid 90s a number of product platforms built on these new standards began to appear. The concept of class-based configuration software was introduced. Class-based software facilitated common libraries of building-block modules linked to unique instances of the modules as they are applied. The library modules are then quickly replicated but change control can also easily be applied as the various instances can maintain the characteristics of the class, making it easy to change them and document the change. While not initially applied to their full extent, these concepts became an enabler for the modular construction approach utilized by most Pharmaceutical companies in the early 00s.
In addition to automation standards, regulatory concerns for managing all the systems automating production and the data being created were being developed. In response to the uncertainty of validating computer systems, end users, automation vendors, and consultants came together to define and standardize practices. In 1994, the Parenteral Drug Association (PDA) issued Technical Report No. 18: Validation of Computer-Related Systems. In 1995 the Good Automated Manufacturing Practice (GAMP) Forum issued the GAMP Guide for Validation of Automated Systems. GAMP became the user community’s voice for comments and response to the various governmental regulations. Also, PDA issued Technical Report No. 32 to define good practices for auditing suppliers. Although 21 CFR Part 11 was not formally issued until 1997, work started on it in the early 90s. Part 11 focused on how to design, implement, test, and manage change with automation systems and the electronic data created. By the late 90s, the focus had clearly begun to shift from applying technology to managing records and proving regulatory compliance.
THE LATE 90S TO EARLY 00S
The standardization movement gained momentum as the new century approached and began. Users in the Pharmaceutical industry began to ask for standardized, configurable, off-the-shelf equipment.
Through the second half of the 90s some disruptive technology began to appear, with an aggressive move away from customized hardware development to standard common off the shelf products using Ethernet communications.
Pharmaceutical companies started using distributed hardware and putting Ethernet-enabled I/O in the field. This was followed by the movement of controllers and their cabinets into the field and the centralized control rooms began to be superseded. Yet pharmaceutical companies were quite conservative when it came to adopting the digital field buses that were becoming common in other industries and are only now moving in this direction.
The regulatory burden peaked at the turn of the century with both industry specific regulations like Part 11 and the Y2K computer system concerns. With the enforcement of Part 11, the industry invested in more current technology that better addressed electronic data and records. Many companies scrambled (some without complete success) to achieve compliance. On the one hand, Part 11 helped drive modernization of automation systems, but on the other hand, it contributed to a sense of confusion and panic. Yet because Part 11 spurred the industry to improve user security, data security, and record security, Pharmaceutical companies are generally ahead of chemical and other industries in these areas as well as lot tracking and batch management. For many companies, Y2K and Part 11 were the drivers for modernizing their automation systems.
Then, the regulatory burden began to lighten. In response to the industry, the FDA in 2004 announced their initiative “cGMPs for the 21st Century”. They began to encourage Pharmaceutical companies to apply risk-based approaches and to use more current technology without the fear of validation backlash. As a result we are already seeing among other things, more wide-spread adoption of digital buses and more use of advanced control technologies. Emphasis on systems with built in compliance to S88 and CFR Part 11 is increasing.
OTHER RECENT CHANGES
In the last four or five years, there has been an acceleration in the aggressive use of skid-mounted equipment. Companies are trying to buy skids that do water deionization, for example, with all equipment in place and ready to be bolted together. Close on the heels of this has been the adoption of a modular construction format for plants. While this helped to make the overall build process faster, in combination with the spread of standards and class-based approaches, it also had a significant impact on automation and technology.
Another major change in the last three or four years is the integration of companies from top to bottom. Increasingly, the control system and the enterprise system are connected, although it is important to establish appropriate safeguards to keep intruders from gaining access to vital production data or, worse, hacking into and sabotaging production. Much of this integration is being driven by the conversion from paper to paperless, and will drive the next transformation in how Pharmaceutical companies operate. This integration of the control and enterprise systems will allow companies to see and analyze much more information from the manufacturing operations and will allow them to optimize manufacturing.
Latest automation systems have in-built compliance for S88 and CFR Part 11 to address the industry standards. The current advancements include increasing the ease of integration and leveraging the predictive intelligence of the field devices to increase the availability.
Recently, more companies are taking advantage of Operational Excellence programs. In 1977 or the early 80s, a pharmaceutical company was a research and development, marketing and sales organization with a little black box called manufacturing in the middle. Margins were high and as long as the products went out the door in good order there was little need to look at manufacturing efficiency. This, in fact, was one of the major reasons that pharmaceutical manufacturing has been more conservative than other industries. That has clearly changed. The business is more competitive, customers are increasingly price conscious and manufacturing and supply chain efficiency is increasingly urgent. The plant floor and production are now tied to how the labs work, to timely releases of new products, and to overall profitability. Putting the right kind of automation platform in place can facilitate making this happen.
Another recent trend is flexibility. The industry is moving from products that historically have been produced through organic-based synthesis to biologic products. Biologics are inherently more complex. They may also be targeted to specific groups, even to individuals. The breadth of products requires a great increase in flexibility on the part of the manufacturer.
The business environment of the pharmaceutical industry is becoming increasingly demanding, where only those companies committed to excellence will thrive; those that don’t may well find their survival in danger. The challenges are clear to all: decreasing levels of reimbursement, lawsuits, fewer blockbuster discoveries, unexpected competitors, and the list goes on. The solution for most companies today can be summed up as the pursuit of excellence — superiority in operations and execution of business processes — and has come to be called Operational Excellence.
EYE ON THE PRIZE
Simply making improvements in a few areas is not enough to achieve Operational Excellence. It requires a level of corporate performance that will garner praise from the investment analysts who advise the actual owners of the company. It requires using the right tools, methods, and advice and combining them with dedication to achieving true world-class status.
It requires constant work, attention to detail, and the honesty to examine one’s own shortcomings and correct them, and to never settle for what once worked, or works in some places, but constantly striving for the elusive goal of being the best of the best. Many factors contribute to world-class performance, but the best opportunity for achieving operational excellence is where the money is spent and made: production.