The Needle Gets Another Shot

By Paul Thomas, Managing Editor

As any pediatrician or parent knows all too well, nobody loves the needle, but rumors of its demise have been greatly exaggerated. Granted, companies are working hard on alternative delivery forms, and most patients would rather inhale a powder or swallow a pill than receive — or give themselves — a shot. Nevertheless, advances in technology and market conditions are giving the needle new life. Driving this “renaissance for injectables” are:

• The rise in biologics, which require the stability found in liquid or lyophilized formulations;



• New “needleless” injection and advanced syringe technologies that minimize the pain and difficulty of taking parenterals;



• Improved means of reconstitution and delivery of lyophilized product;



• The home-healthcare trend, which has spurred interest in pre-filled syringes — a $5-billion market that could double within the next 10 years, according to the Freedonia Group (Cleveland).

For many drugs, the promise of newer and better delivery routes has failed to materialize. Most prescription products are developed as injectables with the hope that they may one day migrate to oral or another delivery route. But changing the drug delivery mechanism is extremely challenging, far more so than reformulation (see "Follow Your Nose: Taking Nasal-Delivery Drugs to Market" below), itself no easy feat.

What’s easiest for patients — oral, nasal, buccal, transdermal — is typically the hardest for drug manufacturers to provide, says John Paproski, VP of innovation for West Pharmaceutical Services (Lyonville, Pa.). By focusing on patient convenience, Becton Dickinson and other syringe providers have redefined the needle, even as “new” delivery technologies struggle for market share. One of the poster drugs of the new delivery methods, Pfizer’s inhalable diabetes treatment, Exubera, did not come to market quickly or easily, and will face intense scrutiny in its post-market period. In the meantime, more patients are relying on disposable pen injectors and a variety of syringes to get their insulin.

CMOs carry the load

Contract manufacturers, especially those who specialize in fill-and-finish operations, are increasing their capacity for liquid and lyophilized parenterals, improving their flexibility to handle small-, medium- and large-volume products, and minimizing changeover times to accommodate an increasing number of campaigns. CMOs “have to be everything to everybody,” says Joe Mase, group marketing manager of Baxter BioPharma Solutions (Bloomington, Ind.), a leading provider of fill-and-finish services for IVs, pre-filled and other syringes, injection cartridges and liquid and lyophilized vials.

Biopharmaceuticals are driving demand, Mase notes. More than 50% of Baxter’s business in Bloomington is for large-molecule drugs, many of which can now be administered in silicone-free pre-filled syringes. Baxter’s newest offering is the Clearshot, a copolymer pre-filled syringe that is molded from resins, cooled and filled on the same manufacturing line, all within a barrier isolator. Baxter operates one such line in its Cleveland, Miss., facility, and aims to have two lines operating soon, says Mase.

DSM Pharmaceuticals (Greenville, N.C.) is adding a clinical trial materials (CTM) sterile facility that will be commercially available this fall, and a suite for cytotoxics in 2007. Clear customer demand has driven both expansions, says Terry Novak, senior VP for marketing, sales and business development.

DSM is mulling a move into pre-filled syringes. “There’s plenty of capacity out there,” says Novak, but room for more CMOs to participate in the market. Ben Venue Labs (Bedford, Ohio), a division of Boehringer-Ingelheim, is also contemplating syringe filling. VP of operations Dave Henderson says he sees a definite shortage of contract syringe fill-and-finish operations.

Lyo’s share

Lyophilization capacities are also increasing. Ben Venue is currently in its fifth phase of construction since 1997, which, when completed, will add six new freeze drying machines by next year, bringing the total to 27. Eight of the dryers are in the cytotoxic and genotoxic suites, “and we still have a lack of capacity,” says Henderson. “The cyto/geno arena is increasingly being contracted out,” he adds.

A table-top filling station for BD's Uniject device. Courtesy of Luciano Packaging.

Contractors play a guessing game in judging lyo demand, since drugs that are developed in freeze-dried form are often later stabilized as liquids — Amgen’s Enbrel and Abbott’s Humira are two examples.

DSM is also adding capacity. “There seems to be a balance between supply and demand” in the lyo market, Novak claims. “What could throw that balance off is if a few major biologic products are approved over the next few years that exceed expectations.”

Patheon is expanding lyophilization capacity at several locations and has created a development center of excellence at its Ferentino, Italy site. Drug manufacturers are often "forced into lyophilization" because their products cannot be formulated as stable liquids formulations or sterile powders that can be filled, notes Paul Turner, Patheon's director of business development in Europe. “It chooses them.”

However, there appears to be room for niche manufacturers to compete. Consider the filling of highly viscous liquids. Hyaluron Contract Manufacturing (Burlington, Mass.) — whose name derives from its original product, hyaluronic acid — specializes in this application. Getting drugs as thick as honey into syringe barrels is no easy task, says Rebecca Butler, corporate and legal affairs manager. The company plans to increase its 34,000-square-foot facilities by another 60,000 square feet in the next few years, she says.