Automation for the Pharmaceutical Industry

Automation is the result of industrialization, driven by the need to increase productivity, to achieve consistent quality products, and to remove mundane, repetitive, strenuous, hazardous and heavy work from workers. Early attempts at automation took the form of mere mechanical machines, to electro-mechanical devices such as motors. Innovations in technology now comprise the essential building blocks of automation.

Technological advancements have revolutionized automation to the current level of complexity and flexibility.

Today, with information technology, automation has extended its scope to include the management of data, connectivity and portability. Automation in its broadest sense has expanded from its original industrial manufacturing base to laboratories and businesses.

Automation applications continue to grow with enabling technologies such as wireless, nanotechnology, advance storage and memory, advance software algorithms, artificial intelligence, sensors and analyzers.

Industrial and laboratory automation can be further classified into process and discrete automation. Process automation deals mainly with handling raw materials in forms such as liquids or powders. We see this in oil refinery, oil and gas, and chemical industries. Discrete automation essentially deals with assembly of parts requiring high levels of mechanical motion to produce consumer electronics products and products for the automotive industries.

Automation in Pharmaceutical Manufacturing

The manufacturing industry is the first to have adopted automation. It is in manufacturers' interests to increase productivity, improve quality of products and reduce waste for obvious reasons, the primary of which is to reduce costs. Pharmaceutical manufacturing is no different. As an addition requirement, the pharmaceutical industry is highly regulated as public health safety is of primary importance.

Regulation is thus a major consideration for automation as it ensures compliance with safety considerations and guidelines. GAMP (Good Automated Manufacturing Practice) guidelines from ISPE (International Society for Pharmaceutical Engineering) and FDA's 21 CFR part 11 regulations are fundamental to automation advocates and developers in the pharmaceutical industry.

Pharmaceutical manufacturing is a hybrid industry with almost a 50/50 split on process and discrete manufacturing processes. Process automation system applies in the primary manufacturing of API (Active Pharmaceutical Ingredients). In the secondary manufacturing of formulation and packaging, both process and discrete automation technologies apply (ie. compounding, filling, washing, labelling machine, and packing).

The production of APIs is a typically batchoriented process. Automation systems that are designed with inherent batch features will be well suited here. Systems designed specifically with built-in compliance to ISA S88 concepts of batch automation, recipe management and complaint enabled 21 CFR part 11 features will ensure a structured approach to a successful implementation. It also provides operational efficiency and flexibility in production and compliancy. When the time comes to introduce new API formulations, the system is inherently ready to easily add a new recipe. Other features include the ability to integrate safety systems particularly in chemical API facilities where hazardous materials are present and the process system has to be handled safely and automatically.

Automation in secondary manufacturing is characterized by the physical properties of drugs, its packaging and its final form. Physical properties can be classified as solids or liquids. With solids, powders have to be formulated to its final dosage through process steps such as weighing, blending, granulating, tableting, capsuling, and filling into bottles. Liquids have to be formulated in a stirring vessel, filled into vials, ampoules, or containers.

These process steps are done with automatic machines requiring reliable, repetitive, coordinated and precise motion controls. These machines are equipped with human machine interfaces to aid in the operations and production lines. As part of production quality control, automated inspection machines are also deployed to ensure quality of the formulation and final packaging by weight, level, vision, etc. These products will end up in final packaging for shipment. Besides conveyor systems and electro-mechanical machines used at this stage, robotics technology is sometimes employed as well.

Additionally, there is automation for production management that spans deep into IT (information technology). There are electronics batch records, historic references for the long term collection and storage of production information, and MES (manufacturing execution system) for the management of manufacturing resources such as inventory records, product specifications, workflow management, and laboratory information. MES is the link from plant management to business processes such as logistics, finance, and sales.

Automation in Laboratories

Compared with automation in manufacturing, automation in R&D laboratories is a more recent phenomenon. Though lab automation systems have been around since the '90s, it is only in recent years that it has taken off driven largely by laboratories devoted to activities such as high-throughput screening, combinatorial chemistry, automated clinical and analytical testing, diagnostics, and large scale biorepositories - all of which are required to remain competitive.

Increasing demands for R&D, testing requirements, and precision in laboratories by pharmaceutical companies' appetite for new drug discoveries also proliferated the adoption of automation in laboratories. Advancements in robotics and other technologies have made a fully automated laboratory a reality. The sheer throughput of measurements and data from the high speed and large quantity handling of samples demands a good automated information system. Examples of such systems include LIMS (Laboratory Information Management System) and the workflow manager.

Automated laboratories can be found in the UK, the US, Japan and Korea. The latter two countries seem to be the forerunners with Japan having about 50, and Korea nine. The situation in the rest of Asia is, however, very different. In Singapore, the first fully automated laboratory is at the National University Hospital.

Trends

The foundation for automation in the pharmaceutical industry is clearly established. The functions that have already embraced automation will continue to prevail with incremental improvements from the normal cycle of technology innovation. Areas that are likely to witness quantum leaps will be in the integration between development work and manufacturing, efficiency and utilization, and preventive counterfeiting solutions.

Adopting a common platform from lab to large-scale manufacturing is a long-term trend that makes sense. One of the issues that is apparent is the current disconnection between drug discovery, pilot scale plant and large scale manufacturing. A trend that will benefit research-based pharmaceutical companies would be their ability to integrate, and provide users with an automation platform that will transcend from laboratory developments to large-scale manufacturing.

This provides a common look and feel to the operation plus application portability, thus saving time and money for engineering departments when they scale up. This approach will also offer opportunities of improving the automation strategy during this developmental process and accelerate the engineering time at each stage contributing to fast track engineering effort, and reduce operator training requirements.

Another ground-breaking trend is in Process Analytical Technology (PAT). This plays an increasingly important role in helping pharmaceutical companies focus on continuous improvement and be more innovative in terms of technology adoption to improve their manufacturing processes. This leads to improvement in product yields, better utilization, and less waste, translating into cost savings for patients. The implementation of PAT at the development stage of R&D and/or pilot scale plants will enable better understanding of the process and support the transfer of technology from development to large scale manufacturing.

PAT is more than just instrumentation. It must be able to interface and collect data from various instruments and analyzers, and has to perform complex multivariable calculations and modeling to understand the critical process factors. In addition, it has to provide connections to various automation components and functions to become an integral part of the manufacturing process. This provides manufacturers a way to achieve real-time release of products.

Counterfeiting is an increasing problem for drug manufacturers. Up to 10% of drugs in the market today are counterfeited, amounting to about $32 billion loss in revenue for manufacturers. Technologies such as data matrix code and RFID, among other systems, are finding its way to become part of the anti-counterfeiting infrastructure. These technologies also serve as its logistic tracking systems over ID barcodes. These technologies are already available as part of the automation solution in the packaging process. With an IT infrastructure built around it, one will have a track-and-trace or what is known as the e-Pedigree solution.

Conclusion

Companies are exploring new drugs, especially in the new biotech space. Many will outsource their clinical and commercial manufacturing. Some will need to move into their own pilot facilities for clinical scale production and eventually commercial scale manufacturing facilities. This is the time to understand more about different automation solutions and options available, to understand the benefits versus cost to reap the full benefits in the future. An opportunity to leap frog against competition is to become efficient and profitable by adopting new concepts and technologies.

At the other end, established pharmaceutical manufacturers are in general very reluctant to modernize their existing facilities due mainly to the perceived cost of regulatory compliance. This observation is even more pronounced in the Asia- Pacific region as manufacturers are mainly generics producers. Validated state of their plant prevents them from moving forward. This risk prevents them from adopting a continuous improvement philosophy, leaving the pharmaceutical industry lagging behind industries such as food and beverage and automotive.

Leading regulators such as the US FDA recognize this and are putting guidelines in place to offer the pharmaceutical industry the flexibility to adopt technology that would help improve quality, yield and bring costs down. Initiatives such as risk-based approach and quality by design are helping pharmaceutical manufacturers move towards this direction. This general observation can also be said about new plant investments to adopting new concepts and technologies.

With the possibility of risk-based approach to validation, PAT initiatives and quality by design, manufacturers can better understand their design space, validate it and improve the processes within the design space without affecting the validated state.