The Combination Factor

Combination products and copackaged medical products are evolving. Growth in drug self-administration is being fueled by changing patient populations, efforts by managed-care providers to control healthcare costs, and a focus on safety and compliance. According to Code of Federal Regulations Title 21, a combination product comprises any combination of a drug and a device; a biological product and a device; a drug and a biological product; or a drug, device, and a biological product.

In the United States, the big pharmaceutical focus for these devices has been about ensuring combination product quality, complying with needlestick prevention laws in healthcare facilities, and easing self-administration of prefilled medication by patients at home. In Europe, the prefilled market is more mature, but according to Stephen Allan, vice president, marketing and communications, Unilife Corp. (unilife.com), a strong conversion to prefilled safety during the coming years is expected as the EU member states introduce legislation mandating the use of needlestick prevention devices in healthcare facilities.

According to Greystone Research Associates (greystoneassociates.org), more than 2.4 billion prefilled syringes are used annually, with the market growing at about 12% per year. As the use of prefilled syringes continues to grow, the issue of their safety is receiving increased attention.

These analysts also believe that advances in drug formulation and inhalation device design are creating new opportunities for inhaled drug delivery as an alternative to oral and parenteral delivery methods. While nebulizers have evolved relatively independently of the drug formulations they deliver, the existing generation of metered-dose inhalers and dry-powder inhalers have been developed or tailored for the specific pharmaceutical being delivered, resulting in improved performance.

According to Allan, pharmaceutical companies are increasingly seeking to collaborate with total-solution providers in the drug-delivery device field. Unilife has found that pharmaceutical partners desire a specialist partner that can design, develop, and manufacture innovative high-quality device solutions addressing both the specific therapeutic characteristics of the drug product and its safe, simple delivery to the patient.

Parenteral delivery
To comply with legislation across international markets that mandate the use of products that can protect healthcare workers from needlestick injuries, pharmaceutical companies are attaching ancillary safety products onto standard prefilled syringes. These ancillary safety products have the potential to increase pharmaceutical packaging, transport, and disposal volumes by up to 70%.

In March, Unilife Corp. commenced initial production of the Unifill ready-to-fill (prefilled) syringe at its FDA-registered manufacturing facility in York, PA. The Unifill syringe is the world’s first prefilled syringe with safety features fully integrated within the glass barrel, the company reports, which will enable Unilife to accelerate discussions with more than 20 pharmaceutical companies.

“Devices that carry some level of market exclusivity and can thus deliver powerful brand differentiation and enhance patient care are highly desired,” Allan says. “Having a me-too prefilled syringe or an auto-injector is no longer enough. The more superior the prefilled syringe in terms of safety, convenience, and ease-of-use, the greater your chances of beating the competition in a particular therapeutic drug class.”

The market is expected to progressively shift from the use of ancillary safety products that are attached onto standard prefilled syringes to prefilled syringes, such as Unilife’s Unifill range, that have fully integrated safety features fully integrated within the glass barrel. “Given the unique characteristics of the Unifill syringe as a primary drug container and its competitive strength against ancillary safety

products, it is strongly positioned to help pharmaceutical customers optimize, or even extend, product lifecycles,” Allan explains.
In March, West Pharmaceutical Services Inc. (westpharma.com and CareFusion (carefusion.com) announced they would jointly develop and market a new, needle-free vial access device. The new product, which will be available in late 2011, is intended to help prevent leaks and reduce surface contamination and risk of exposure during a drug product’s reconstitution process.
“It is significantly smaller than other systems on the market, and the two components are individually packaged and could be combined with the customer’s drug product,” says Graham Reynolds, vice president, marketing and innovation, pharmaceutical delivery systems, West.

(See related chart at right for branded combination products delivered via pre-filled syringes, pens, and autoinjectors approved during the last year.)

InhaleR delivery systems
Greystone analysts believe that for inhaled drug developers and their device suppliers, understanding the concerns, preferences, and limitations of consumers to self-medicate via inhalation will be the driving force for future-generation inhaler designs. These factors will mean the difference between successful ventures in this market and entities that will fail to prosper in spite of highly favorable market dynamics.

Boehringer Ingelheim Pharmaceuticals Inc.’s (boehringer-ingelheim.com) Spiriva Handihaler is one example of a device used to control symptoms of chronic obstructive pulmonary disease. Approved in 2009, the Spiriva Handihaler is packaged with step-by-step patient instructions on how to use the device. (See related chart above for branded combination products delivered via inhalers during the last year.)

Transdermal delivery
Generic companies like Alvogen Inc. (alvogen.com) and Covidien (covidien.com) have launched transdermal products in 2011. The products include Alvogen’s AB-1 rated Nitroglycerin Transdermal Delivery System and Covidien’s Fentanyl Transdermal System patch. (See related chart for branded combination products delivered transdermally during the last year on page 32).
Alvogen’s AB-1 rated Nitroglycerin Transdermal Delivery System, which is available in patient-ready, 30-count cartons, includes several key packaging features designed to improve care. Some of these features are GS1 Databar (formerly called RSS) bar coding on each individual unit; the smallest available patch sizes of any generic nitroglycerin system; and hypoallergenic, transparent patches.

Covidien’s Fentanyl Transdermal System patch, an opioid analgesic indicated in opioid-tolerant patients for management of persistent, moderate-to-severe chronic pain, is a generic alternative to the branded Duragesic patch. Covidien expects to launch the Fentanyl Transdermal System in the United States in 25 mcg/hr, 50 mcg/hr, 75 mcg/hr, and 100 mcg/hr strengths.

Pumps and Sprays
In the area of spray pumps, MeadWestvaco Corp. (meadwestvaco.com) announced the availability of its Preservative Free Pump Topical for sampling in February. The five-fold mechanical protection system ensures germ-free pump dosing to the patient.
Insulet Corp. (myomnipod.com) and GlaxoSmithKline Inc. (gsk.com) announced an exclusive distribution agreement for the OmniPod Insulin Management System in Canada in March. The OmniPod Insulin Management System is the world’s first tubing-free insulin pump. Omni-Pod offers people living with insulin-requiring diabetes all the benefits of insulin pump therapy, with freedom, comfort and ease. OmniPod has just two components: the small, discreet, waterproof Pod that can be worn on many parts of the body to hold and deliver insulin; and the Personal Diabetes Manager, a hand-held device that communicates wirelessly to program the Pod, calculates suggested doses, and has a built-in FreeStyle blood glucose meter.