New technologies raise the stakes
Changing times call for new strategies to streamline supply chain management. To speed products to market, pharma companies are relying on automation and innovation as lifelines to stay afloat. We offer a look at the latest technologies in clinical packaging and how they improve time and cost efficiencies.
Photo courtesy of Catalent Pharma Solutions
Unprecedented changes in today’s industry environment, coupled with a volatile global economy, pose significant challenges to pharmaceutical and biotechnology companies. Pressured to ramp up shrinking development pipelines while reducing costs and time to market, companies are increasingly turning to automation and innovation to improve efficiencies. State-of-the art technologies have come to the rescue, helping supply chain managers speed supplies to clinical trials and products to market.
What’s Driving Automation?
Competition in the global healthcare industry has never been greater. Considering it takes 10 to 15 years to develop a new prescription drug, with the average cost of $1.3 billion, and a biologic at $1.2 billion,1 accelerating development and streamlining the supply chain are critical to the industry’s success. Each additional day a drug spends in clinical development can cost a company as much as $600,000 in lost revenue for a niche drug and $8 million for a blockbuster.2
Faced with looming patent expirations, generic competition and shrinking pipelines, large pharma is consolidating through mega-mergers and acquisitions of biotech and specialty firms. The recent Pfizer/Wyeth and Merck/Schering-Plough mergers significantly broaden their pipelines, leveraging the combined product offerings for additional growth. The merged companies will have expanded opportunities through the introduction of potential new combinations and formulations of existing products.
To build pipelines and spur future growth, pharmaceutical companies of all sizes are conducting more clinical trials than ever before. Growing numbers of smaller companies, particularly biotech and specialty firms, are also conducting clinical trials. An estimated 1,600 smaller companies are currently running at least one active clinical trial, a 60% increase against the figure from five years ago.3
And the nature of trials has changed, posing new demands on clinical packaging managers. Increased regulatory requirements, cost pressures, and a growing demand for comparative effectiveness research and additional data are driving larger, longer, more complex clinical trials, as well as more global and comparative trials. The size of Phase III studies have multiplied over the past five years, from around 2,000-3,000 subjects to more than 10,000 subjects. Between 2000 and 2005, the burden on investigative site personnel to execute study protocols increased 10.5% as the number and frequency of procedures per protocol increased.4 With adaptive trial designs on the rise, managers must be prepared for rapid fluctuations in demand for supplies. Drug labeling for clinical supplies is also a more complex, time-consuming process today, as labels must contain a more diverse range of information.
To address these trends, companies are leveraging automation and innovation to achieve a more effective, efficient supply chain. Clinical packaging, traditionally a largely manual function, has been slowly progressing to increased levels of automation and convergence with information technology. These advances not only increase production speed, but also provide competitive and cost benefits in reduced labor and earlier market entry. They also improve product safety, and eliminate worker safety issues, training and potential errors of equipment operators.
Advances in Clinical Packaging Automation and Innovation
Below are several examples of the latest technologies in clinical packaging:
Pre-filled Syringe Labeling and Plunger Rod Insertion
For the growing pipelines of biotech products, such as sterile vaccines, and the increasing size of clinical trial populations, an innovative device is available that can label pre-filled syringes with different filling volumes and insert plunger rods in a single machine run, considerably slashing time. The machine performs both functions at a great speed, processing 3,500 pre-filled syringes per hour and significantly increasing productivity. The device also automatically applies variable text labels for blinded trials. Another advantage is safety; instead of manual insertion of the plunger rod, the machine applies a constant pressure to insert the rods, whether they are screwed or pressed, minimizing the risk of contamination from movement of the stopper.
Blister Card/Wallet/Tray Sealing and Trimming
Highly automated inline card sealing equipment is an efficient approach for small- to large-scale processing, and is particularly beneficial for large- or small-format, high-volume clinical trial packaging. Compared with standard-machine package assembly, automated assembly with an inline sealer produces approximately five to ten times the amount of units per shift, depending on the card size. Cards can as large as 36-by-20 inches.
The equipment has automated blister-card feeders, integrated automated blister-strip feeders, a semi-automated reject station, and dual inline heat sealing stations. After an electronic arm removes rejects, the machine’s pick-and-place station conveys all good products to a pack-out area. A major advantage is the machine’s dual sealing stations, which speed throughput, cutting blister package sealing time nearly in half. The second station can also be used as an ambient cooling system to reduce curling of blister cards.
The inline sealer also provides online printing of text or lot codes on blister cards. Not only can ultraviolet invisible codes be printed on blister cards, but other equipment is available that can also print UV codes onto blister strips and bottles. Black lights are installed in all of these operations to read the UV-printed codes. The online printing on the card sealer also allows for basic directions to be printed on the card if necessary.
The hydraulic press can seal and cut preformed blister units, blister cards and trays. The machine can be used to support adaptive clinical trials, and to cut blister strips or hospital units into various formats so that they can be reconfigured in a blister card to support different dosing regimens.
Blistering and Slitting/Chopping Into Units
Highly or fully automated form, fill, and seal machines are available to speed blistering processes. A nitrogen flush capability reduces oxygen and moisture in blister packs, which is particularly important for products with high sensitivity to these elements. A fully automated product feeding system can fill several products into blisters simultaneously. The same equipment can score forming material used in child-resistant blister units and 3D breakaway blisters, and create blister units with unformed indexes to allow a header for labels. It has deep draw cavity depth of up to 20 mm. Dual printers can print one color on the front and back of blister lidding material or two colors (including UV invisible) on the same side. With the add-on slit/chop machine, a blister web can be slit and cut into any strip length, increasing output and reducing rejects from having to manually tear blisters.
For companies requiring blinded clinical supplies, fully automated machines can fill and overencapsulate drugs with high dosing accuracy at great speed, allowing clinical trial sponsors to reach the next milestone considerably faster.
The equipment is capable of overencapsulating hard gelatin capsules in all common sizes with powders, tablets, capsules, pellets and other solid dosage forms in various combinations, as well as multi-product overencapsulation. An automated feeding tool enables rapid feeding of various tablet shapes and sizes. The machine also provides fully automatic check-weighing of all filled capsules.
Each capsule size or tablet shape requires a different feeding part. Depending on the company’s technical expertise, custom-built, automated feeding parts can be manufactured in-house within a few days, considerably shortening the lead time before production, compared to external ordering of machine parts.
Drug labeling, particularly for clinical trials, has become a more complex, time-consuming process, due to increased regulatory requirements. Labels for global trials must comply with the regulatory requirements of each participating country. For randomized labels used in clinical trial packaging, traditionally a very manual process, an innovative device generates and prints a randomization code and applies the label at the same time. The device slashes randomized labeling time approximately in half. The required data are sent from a PC to two built-in thermotransfer printers simultaneously. After printing, both labels are automatically applied to the blister pack. The device is used for single- or double-sided labeling of blister packs with pre-printed or inline printed labels.
A fully validated, global clinical labeling system with a central server makes labeling available from all global packaging company sites. This efficient, flexible system is particularly advantageous for global clinical trials. Labels can be designed at one site and both accessed and printed at another site. The system also manages and controls the creation and approval of label design, print orders, randomizations and phrase library details, and incorporates standard approved label texts.
Although almost all clinical companies monitor their production rooms for temperature, humidity, and pressurization, and all have an assortment of humidification and de-humidification rooms, recently there has been increased demand for ultra-low de-humidification in the primary production environment. The increased frequency of which these requests occur are a direct result of more and more products becoming increasingly unstable in ambient conditions. Innovative companies have primary rooms that can hold a relative humidity (RH) as low as 14% (+/- 1%) RH and maintain ranges of 5% RH anywhere from 14-30% RH to support this need.
Invest or Outsource?
Companies must weigh the cost-benefits of these higher levels of automation, and if pursued, whether capital investment or outsourcing to a clinical packaging firm is preferable. Contracting non-core functions such as packaging is becoming an important industry strategy for managing rapid change and creating a more cost-efficient, flexible infrastructure. Contract Pharma’s 2008 Outsourcing Survey reported that 62% of pharma/biotech companies planned to spend up to 10% more in 2009 on outsourcing, and nearly a quarter planned to spend more than 20%.5
Progressive clinical supply service organizations provide immediate access to a broad range of state-of-the-art equipment and innovations, new capabilities and world-class expertise. They enable companies to avoid capital outlays and respond quickly and efficiently to new industry needs and requirements.
Building an efficient and effective supply chain is critical to the success of drug development and bringing new products to market. Keeping up to date on the latest advances in automation and innovation and assessing their value for your company are important steps toward this goal. Looking forward, new technologies will become increasingly important tools to help companies remain competitive.
- Pharmaceutical Research and Manufacturers of America, Profile 2008 Industry Outlook. Study from Tufts University Center for the Study of Drug Development, November 2006.
- From Cutting Edge Information report cited by SDI. http://www.sdi.com/en/solutions/industry/life-sciences/.
- Getz, Ken and Wenger, Julia, “High times for the CRO heavyweights.” Scrip supplement, March 2007.
- Outlook 2008, Tufts Center for the Study of Drug Development (CSDD), p.6.
- 4th Annual Outsourcing Survey. Contract Pharma, May 2008.
William Zeigler is manager of Project Planning at Catalent Pharma Solutions. He can be reached at firstname.lastname@example.org. Peter Brun is Director, Clinical Supply Services at Catalent. He can be reached at email@example.com.