Interested in linking to "Facing the Pharmaceutical Future "?
You may use the Headline, Deck, Byline and URL of this article on your Web site. To link to this article, select and copy the HTML code below and paste it on your own Web site.
By Dr. Jérôme Freissmuth
In 2013, the pharmaceutical industry will continue to witness major changes and challenges. Considering global economic uncertainties, increasing healthcare costs and expiring patents, the industry appears to be in a state of turmoil. At the same time, markets are diversifying and new fields of growth are opening up. Rapid development of the emerging markets, progress in drug research, the rise in generics production, the availability of high-potency drugs and innovations in manufacturing processes will sustainably modify the global pharmaceutical landscape.
According to a recent survey, global annual spending on pharmaceuticals is set to reach almost $1.2 trillion U.S. dollars in 2016. The so-called “pharmerging” markets account for more than two-thirds of the world population. Doubling their spending on pharmaceuticals over the next five years, these markets will reach 30% of global expenses by 2016, as population growth and rising incomes contribute to the dramatically higher use of medicines. Improved access to drugs is supported by a broad range of governmental healthcare policies and programs. Due to increasing cost pressure and increased local demand, production is being relocated to the emerging markets. In many cases, this also applies to the production of generics. While the share of the industrialized nations in global pharmaceutical expenditure will continue to decline, spending on generics will increase due to expiring patents accompanied by higher generic use for off-patent molecules.
Biologics will also contribute to higher spending, as research brings clinical advances for the treatment of patients all over the world. Cutting-edge developments in personalized medicine have led to sophisticated solutions tailored to stratified groups. We observe a global trend towards combining pharmaceuticals with medical technology applications. The development of new drug delivery devices increasingly focuses on patients’ individual needs. Some of the devices such as inhalers are necessary applications to transport the active substance to where it is needed. Tools such as insulin pens have been optimized, in particular with respect to convenience and ease of use, while the equipment generally tends to be smaller and much safer to handle. In this sense, medical technology applications improve the quality of patients’ lives. At the same time, drug delivery devices are used as a targeted measure for product differentiation. The availability of high-potency treatments has also exploded in the past decade. High-potency active pharmaceutical ingredients (HPAPIs), for example, is a fast growing segment, and is projected to grow at a compound annual growth rate (CAGR) of 9.9% through 2018 .
To keep pace with these advances, engineering expertise is required to design equipment that can handle, package and secure such substances. Pharmaceuticals, biopharmaceuticals, vaccines and anti-virals must be manufactured and packaged with the utmost caution and attention to detail. It is with these requirements in mind that we see five particular trends emerging in the field of pharmaceutical processing and packaging equipment, namely: a rising demand for pharmaceutical quality and safety through inspection technology; the ability to handle potent substances; adapting lines for small batch sizes and research purposes; an increasing use of single-use components; and the need to improve productivity by optimizing manufacturing processes with respect to Overall Equipment Effectiveness (OEE).
Ensuring Pharma Quality and Safety
Strict pharmaceutical quality and safety standards such as the FDA’s Process Analytical Technology (PAT) guidance, as well as Good Manufacturing Practice (GMP) set the framework for pharmaceutical manufacturing processes. They aim at reducing the risk of product recalls and, most importantly, are designed to safeguard consumers’ welfare. In order to comply with these regulations, the industry requires reliable and high-end inspection technology equipment to be integrated in their production lines. Since 100% control has become obligatory, manufacturers are continuously challenged to increase output and improve efficiency, as well as inspection accuracy; the main focus will be on fully automated solutions. Manual and semi-automated devices remain in use for research purposes, customized smaller batch applications and the re-inspection of rejects from fully automated machines. Physical inspection via spectroscopic methods, pressure decay or high-voltage can be used to detect leakages and fissures of containers.
Quality control is essential for liquid and solid pharmaceuticals such as syringes, ampoules, vials, as well as tablets and capsules. One of the most common and reliable methods for particle inspection is the “static division” (SD) technology. It derives its name from the ability to differentiate static from moving objects, using light transmission to detect moving particles by measuring dynamic light fluctuation. Projecting light through the liquid onto an optical SD sensor enables the differentiation between particles contained in the liquid and immobile objects. The SD technology is also suited for inspecting filling levels. In turn, sophisticated high-speed cameras allow for the reliable detection of particles and cosmetic container defects. The combination of these two inspection methods provide for best inspection results.
Machines based on x-ray technology provide the means for comprehensive quality and weight control of capsules. These technologies are advancing rapidly due to software development and new imaging capabilities. More recently developed inspection platforms are able to check simultaneously all quality features like weight, foreign particles, deformation of capsule top and bottom, as well as length in real-time and at high throughput rates. The exact process control adopts several functions of visual systems for error identification and provides significant benefits such as reduced reject rates and the prevention of packaging errors.
Managing High-potency Substances
The use of high-potency pharmaceuticals has grown extensively, causing manufacturers to pay more heed to protecting all elements of the supply chain from their potentially harmful effects. Particularly in the past 10 years, containment has steadily moved up the agenda for drug manufacturers and will continue to do so. Advances in oncology and immunology have led to increased use of highly potent and cytotoxic substances in the treatment of cancer, and hence new challenges in the containment of these substances. In the supply chain, both workers and the drugs themselves are at risk if containment technologies are not applied effectively. Also, for high potency drugs such as hormones, Good Manufacturing Practice guidelines require dedicated facilities to minimize the risk of cross contamination.
The handling of highly potent drugs is therefore built around the principle of protecting drugs and employees from contact with each other, with as little manual intervention as possible. The latest equipment solutions favor the use of automation and robotics technology to reduce human contact with any substances that are being manufactured. As a result of the increasingly strict guidelines from regulators, manufacturers increasingly rely on the use of barrier technology such as isolators.
Barrier Technology allows fully enclosed, sealed and pressurized units completely separated from operators. They offer far greater sterility assurance than conventional cleanrooms, and can significantly lower costs associated with more traditional filling and finishing methods. The most advanced, closed restricted access barrier systems (cRABS) contain toxic compounds, usually in their use of positive pressure and air filtration systems within the chamber. Technological advances in air suits, gloves and sleeves further diminish the risk of cross-contamination. Automated cleaning features allow for machine parts to be cleaned without manual disassembly, and give employees greater protection from potentially harmful substances.
Producing Small Batch Sizes
Although personalized medicine still is at an early stage of development, targeted drugs that take account of genetic variations will allow large numbers of patients to receive highly individualized treatment in the near future. Personalized medicine will continue to demand ever more flexible and versatile processing and packaging solutions. Smaller batch sizes shift the emphasis from speed and mass production of standard dosage products to more individualized products packaged in high-quality materials. Short start-up times, easy changeovers and a high degree of automation are key considerations.
Before being introduced to the market, personalized medicine requires a great research and development effort. Devised on very small laboratory equipment, the recipes need to finally be transferred to production-scale machinery. However, manufacturing lab equipment is highly complex and costly. New machinery developments demonstrate the possibility of covering almost the entire manufacturing process in one single machine, thereby dramatically reducing investment costs. From research and development via scale-up to industrial production scale, manufacturers strive to reduce time to market. Laboratory processes can be optimized by implementing small and flexible machinery. Key production parameters are clearly defined and allow for an easier transfer from lab to production scale. Recently developed software is now able to calculate the required process conditions and, hence, to considerably save time. Numerous trials provide scientists with the required information to transfer small batch trial results to large production machinery.
In the fast-paced pharmaceutical market, it is difficult for manufacturers to anticipate which products will be required next. Therefore, new machinery must be future-proof, have scalable and flexible platforms, and be adaptable to new products, characteristics and formulations. These solutions are supported by the enhanced use of pre-sterilized packaging styles like syringes, vials and cartridges. With their flexible platforms, “state-of-the-future” machinery is capable of processing many different containers. Moreover, equipment providers will be well-advised to increase their services in terms of formulation and development support. This service can range from operator training sessions for a trouble-free deployment to the rental of entire laboratories, including personnel and equipment, for the development of galenic formulations. The data generated in these test runs must be suited for an easy scale-up to the customer’s own production equipment.
Utilizing Single-use Components
The demand for greater flexibility and the elimination of possible contaminants will find another effective ally in the form of single-use components. This trend is a consequence of industry safety regulations, growing use of highly potent substances, and a shift towards smaller batch sizes. The time-consuming process of cleaning, sterilization and validation of product contact parts, particularly during changeovers, has long been a hindrance in achieving operational efficiency. Single-use, pre-validated, pre-assembled and pre-sterilized components including hoses, product bags, filling needles and tubing mitigate inefficiencies and can eliminate the capacity losses resulting from lengthy cleaning validation as well as the risk of contamination between batch runs.
Published in the February issue of Pharmaceutical Manufacturing magazine
1. IMS Institute for Healthcare Informatics (2012): “The Global Use of Medicines: Outlook Through 2016.”
PharmaManufacturing.com is the site for knowledge, news and analysis for manufacturing and other professionals working in the pharmaceutical, biopharmaceutical and biotech industries.