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Pharmaceutical manufacturers are under increasing pressure to shorten time-to-market, produce treatments with unpredictable product lifetimes, provide greater flexibility and, at the same time, comply with ever more stringent quality, validation, stability and traceability constraints. While this is encouraging for the contract manufacturing sector, it creates the need for even greater manufacturing flexibility.
The diversity of the pharmaceutical industry, ongoing globalization trends and the growing importance of product differentiation have presented new demands for efficiency and flexibility in the packaging process. Packaging must now be regarded as integral to the rest of the manufacturing process as it plays a vital role, not only in maintaining the competitiveness of over-the-counter (OTC) treatments, but also for the stability and, increasingly, the traceability of all pharmaceutical products.
Packaging must now guarantee product stability within specified time frames as well as ensure safe and secure storage of the product until final use. Furthermore, in many countries there are requirements for child resistance, tamper evidence, protection against counterfeiting and, simultaneously, maximum patient convenience.
This changing role for pharmaceutical packaging has created the requirement for innovative yet economical design concepts for integrated lines. The real challenge is to combine product and system flexibility with maximum efficiency of the packaging lines. The era of blockbuster products being manufactured in huge quantities during many years with massive stocks held in warehouses to guarantee product supply at short notice has passed. This scenario put no requirement on packing equipment to be flexible as the packages rarely, if ever, changed.
Now, products must be shipped from manufacturers without delay, often in several pack variants. Data, such as region-specific leaflets, country codes and languages must be implemented in the packaging process as late as possible. Technological innovations in on-line printing, labelling and even re-engineering of the process itself have had to support these needs.
With the increased importance of safe and secure supply chains in the global pharma market, PAT has been implemented under various regulations to ensure product and process quality. New technologies to aid traceability and fight counterfeiting, such as RFID tagging, are being driven by the likes of FDA as well as global commercial enterprises such as Wal-Mart.
All of this has placed a greater imperative on contract packers and co-packers, for the simple reason that increasing numbers of manufacturers are driven towards outsourcing packaging. Apart from relieving themselves of the issues relating to coding, validation and so forth, principals can introduce greater controls over timing, delivery, volume and call-off. Of course, the contractor has to equip itself to cope with these demands — including fluctuations in call-off of product.
One of the problems faced by contract packaging companies and co-packers is the complexity of modern flexible packaging systems. The prospect of linking conveyor, in-feeds, feed placement systems, wrappers, cartoners, labellers along with quality control measures such as vision systems, check weighers and barcoders, is daunting. The option is to source individual machines and equipment, and then orchestrate mechanical linkages, electronic communications and software. Specialist integrators — especially in the UK and Northern Europe — frequently handle the line set-up and implementation.
The sourcing of packaging solutions from single vendors has grown in appeal as the need for sophistication and flexibility has increased. The concept of taking equipment from a variety of disparate manufacturers poses problems of integration, but also of subsequent validation. For this reason there has been a marked rise in the using of specialist packaging system integrators. While integrators may do a professional job, they are often largely confined to dealing with software issues relating to the integration of control systems and data capture. Single vendor packaging machine companies can also address hardware compatibility, overall system efficiency and aid the validation process of the entire system.
Packing powder forms
Taking the central responsibility for the system engineering, project management and line installation enables the time-to-market to be reduced and the risk of system failure to be minimized. Moreover, the time for line qualification and validation at the end-user's side can be shortened significantly.
The validation and qualification issue is a thorny one for contract manufacturers and anything that aids rapid qualification is important. With the validation process usually taking anything up to 18 months, it has the potential to cause costly delays in the installation of new packaging equipment. This is a considerably more daunting prospect where several equipment vendors are concerned with the same line.
Such turnkey supply of packaging systems also provides the sometimes underestimated benefit of common control and quality assurance concepts. Apart from again simplifying the validation process, this factor also:
For the operators, there are long-term benefits in sustainable system reliability and simplified life cycle management, including after sales services for spare parts, service level agreements, modernization upgrades and field services.
These changes have made a big impact on the packaging industry and there is an increasing need to provide tailored, individual packaging solutions that guarantee the effectiveness of medicines. Because of degradation from environmental factors, such as light and humidity, there is often a direct link between packaging and a remedy's effectiveness.
Today, 51% of medicine is taken orally, in tablets, capsules, powders, pastilles and liquids. The introduction of new laws concerning the supply of medicines has had a serious impact on packaging for these oral medicines; for example, Regulation (EC) No. 726/2004 (replacing Regulation 2309/93) and Directive 2004/27/EC (amending Directive 2001/83/EC on human medicines). Both of these are governed under Regulation (EC) No. 658/2007, which covers failure to comply. Legislation ensures that packages are:
The standard packaging forms of oral medicines generally conform to these requirements, but some innovations that provide added benefits in one area may not conform to the expected standards governing another. For instance, in taking account of our fast-paced lifestyles and the need to take medication on the go, there has been an increase in blister packs, which provide convenience and ensure the hygiene of the tablets. Indeed, blister packaging provides the best worldwide growth prospects among all pharmaceutical packaging products, with demand increasing 6.2% annually to US$4 billion by 2007. In the US, clear flexible packaging is expected to reach $6.2 billion by 2010, of which blister packs are expected to contribute $2.7 billion. However, alongside increased hygiene and convenience, the medicine still must be child resistant and identifiable.
Not many blister packs are child resistant and this goes against proposals to ensure that medicines containing aspirin, paracetamol and iron are supplied in child resistant packaging to cut the number of accidental poisonings.
Identifiable packaging is also now being given more attention than in the past. The advantages of being able to trace a tablet, pill or capsule back to the time, day and factory where it was produced have obvious implications such as being able to verify whether products have been tampered with or have substandard ingredients, recipes or processes in their manufacture. Many health and safety organizations propose that the packaging of all medicines should carry information in a standard format, or "number plate", to allow patients and health care professionals to check drug and dosage details quickly.
Another requirement is that the packaging and labelling of medicines should be redesigned so that products are more clearly identifiable. For this reason pharmaceutical companies must undertake consumer testing of labelling to ensure it is comprehensible.
Advances in the packaging machines themselves has seen the incorporation of precise filling mechanisms, as the wrong dosage of a medicine could be life threatening. Gentle handling is also essential, and packs have to be hermetically sealed. Linked to this is the increasing trend to substitute OTC medicine for prescription-only medications. As retail medicines do not carry the benefit of a doctor's advice at the point of prescribing, the labelling, patient information and safety precautions take on an even greater imperative".
To ensure product quality and consistency, it is crucial that all the machinery uses proven technologies and control standards. This includes a standardized operating interface and control system for all components. Such units now incorporate sophisticated monitoring systems for maximum production safety. With standardization and modularity, profitability is increased as the packaging lines now allow rapid changeover times to provide different dosages of the same medicine in different pack types. There is also a growing trend for companies to supply not only the packaging hardware, but also the software to accompany the machines. Some packaging companies offer on-going training to ensure that strict packaging regulations are met.
It is rare that contract packers can afford the luxury of simply closing down operations while a new line is installed. One of the serious considerations, therefore, is how new equipment can be phased into the existing plant. Apart from the frequently encountered real estate issues of inadequate space, there are also other logistical considerations such as provision of power and so forth.
Sometimes lines can be upgraded with the incorporation of new equipment — for example, where an existing line that had fixed automation for wrapping is being upgraded to incorporate new, more flexible wrapping systems. In these cases, the expertise and experience of the machine supplier or integrator is at its most essential.
Another example of packaging line integration comes from the emerging requirement for packing prefilled syringes. As well as providing enhanced safety and accuracy, further benefits lie in prefilled syringes' ease-of-use and timesaving. Indeed, surveys within the industry have predicted increasing demand for this type of product during the next few years. The North American Medical Device Packaging Market (analyst of the study: Urmila Kishore) — a survey conducted by Frost & Sullivan, shows that the market earned revenues of $569 million in 2006, with that number predicted to rise to $918.8 million by 2013. Another survey conducted by David S. Enterline MD in the US found that the majority of medical workers favour prefilled syringes. There have also been numerous surveys conducted by pharmaceuticals companies and the internet is peppered with positive findings for this relatively new gallenic delivery solution. The most common pack styles for prefilled syringes are carton trays or thermoformed packages. However, manufacturers under pressure to increase productivity have sought packing systems with higher efficiencies. One solution is to use horizontal form-fill-seal (HFFS) technology, which is well-established in fast-moving consumer goods markets such as foods, confectionery and snacks. Such equipment offers a significant reduction in production costs by the fully automatic flow wrapping of the prefilled syringes.
A major Japanese manufacturer of prefilled syringes has installed a fully automatic flow wrapping system. The interface within the manufacturer's production process was the discharge unit from a buffering system. This had to be integrated with the flow wrapping process, as well as with an oxygen absorber supply. A new product handling solution was also needed.
After testing different handling techniques, a rotary disk feeder, in combination with a linear screw-feeding unit, was selected. This produced excellent results in relation to both reliability and product security. As a special packaging option, the sealing of customized Tyvec material was also implemented to enable sterilization procedures to be completed directly after the flow wrapping process.
The resultant integrated flow wrapping system for prefilled syringes outputs over 200 packages/min, while retaining compliance with the strict quality standards demanded within the Japanese market. The HFFS technology has allowed the customer to benefit from higher productivity, shorter changeover times for existing formats and a significant reduction in material costs.
The integration of complicated packaging lines from a single vendor source can be clearly identified from design to installation. However, there are further benefits during the lifetime of the equipment, including maximizing its uptime and efficiency. Commonly, the planned maintenance and support for plant and equipment is referred to as asset efficiency optimization. For contract manufacturers, downtime is anathema and hence, being able to rely on continuously running packaging lines is vital.
Single-sourced complete integrated packaging systems means that the equipment vendor can share the responsibility for the plant in a true partnership. Training and support is simplified and its cost is, therefore, minimized. Provided a reliable packaging machine manufacturer is selected, there is also the assurance of ongoing supplies of identical spare parts and software compatibility — a further critical factor if validation certification is to be retained following breakdowns or upgrades.
Contract packagers must invest in technology to remain competitive as the likes of food, drugs and cosmetics companies look to continually remove costs. How the required automation is assessed, specified and implemented poses the dichotomy of whether to source discrete equipment and configure the lines themselves (or employ the services of a systems integrator), or whether to single-source the entire line directly from a manufacturer. Clearly, single-sourcing is favourable for most, but the choice of partner then becomes critical.
Andreas Graf is head of System Integration business at Bosch Sigpack Systems AG (Beringen, Switzerland). Originally trained as an engineer, Andreas has worked within the pharmaceutical industry in a variety of roles for more than 10 years. He is currently studying at Zurich's Graduate School of Business Administration on a global MBA programme in partnership with the Robert H. Smith School of Business in Maryland (USA).