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The market need for reconstitution systems: manufacturers and consumers can benefit from these advanced systems.

As the number of lyophilized, or freeze-dried, drug products on the market and in development increases, so, too, does the need for systems and devices to administer these drugs.

Many new drugs, especially those developed by biopharmaceutical companies, are initially marketed in lyophilized form. A lyophilized drug maintains its potency over time, extending its shelf-life for prolonged storage. Some drugs marketed in lyophilized form may eventually be available as liquid, but lyophilization provides the fastest route to market for many drugs, and the only option for those not stable in a liquid form.

Lyophilized products require an additional preparation step prior to administration. This process, known as reconstitution, entails mixing the dry drug with a liquid to create an injectable solution.

Many of these drugs are used to treat chronic conditions. As a result, the number of patients who have to administer the drug themselves or rely on a non-healthcare professional is increasing. The reconstitution process can be complex and may put the patient or caregiver at risk for accidental needle sticks, inadvertent exposure to the drug caused by spray-back, inaccurate dosing and non-compliance with a dosing regimen.

Traditional reconstitution requires two vials--one of the lyophilized drug and one of a diluent--a disposable syringe and two needles, it also requires training and experience and has the potential to put the person administering the drug at risk of an accidental needle stick. Further, the patient may be at risk of an under- or over-dose because the diluent may not be measured precisely. What's more, pharmaceutical manufacturers usually overfill the vial by as much as 35 percent to ensure that there is a sufficient quantity of the reconstituted drug to administer the correct dose. The overfill compensates for the inherent variability of the manual process, as well as the difficulty of removing the liquid completely from the vial.

Options for Drug Reconstitution

A number of products on the market can provide both professionals and non-professionals with safe, convenient and easy-to-use systems for reconstituting and administering injectable drugs. These systems can be provided either as a total packaged solution or as components for specialized use.

Many of the new reconstitution systems can be adapted to currently marketed drugs without the need for changing manufacturing processes or packaging components such as vials, stoppers and seals. They are offered as a total system that can be packaged with the filled drug vial and the reconstitution components. Such systems usually consist of a plastic device that joins the drug vial to the diluent container, which can be either a prefilled syringe, vial, or infusion bag. Reconstitution devices can be sterile and fully supported by appropriate regulatory filings. To enhance convenience further, all required items to perform the reconstitution can be packaged together in a kit form.

Dual-chamber syringes provide a lyophilized drug and diluent in a single unit. Reconstitution is achieved by pushing down on the syringe plunger, forcing the diluent through a channel and into the second chamber where it mixes with the drug to create a solution. The drug can then be injected using an attached needle or can be transferred through a luer connection. These systems provide a high level of end-user benefits; the pharmaceutical company, however, has additional challenges in terms of manufacturing and regulatory requirements because of the change in primary container.

One example of a simple system is the vial adapter. These systems connect a syringe of a diluent (either prefilled or filled from another container such as a vial or ampoule) to a vial with a lyophilized or dry powder drug and provide for quick and safe transfer from vials, allowing convenient, optimal quantity aspiration. The adapter is snapped to the neck of the vial after the plastic button has been flipped off. A plastic spike pierces the stopper; needles are not used. The reconstituted drug is transferred to a syringe by a luer connection. Vial adapters come in a variety of sizes and with venting and inline filter options, as well as the option of an incorporated valve system to allow for the maintenance of stability for multi-dose applications.

Adaptations of the vial adapter include systems to connect to other containers such as IV bags and cartridges (for subsequent insertion into a pen system) as well as other administration routes such as nasal or oral.

Advantages of Advanced Reconstitution Systems

* They are easy to use for a non-health care person

* They help protect against drug spray-back and accidental needle sticks

* Many provide needleless reconstitution and transfer

* Because they are convenient, they encourage patients to comply with a dosing regimen, helping to ensure a positive outcome

* They may help the pharmaceutical company reduce the amount of overfill in the drug vial because the system promotes the use of all of the drug

Marketed Products Using Advanced Reconstitution Systems

Many marketed products incorporate reconstitution systems, including drugs for the treatment of hemophilia, multiple sclerosis, rheumatoid arthritis, cancer and hormone treatments. Many devices are sold in conjunction with the drug product; devices are also sold directly to hospitals and clinics.

The Case for Advanced Reconstitution Systems

Reconstitution systems are especially beneficial for products that are used to treat chronic conditions that are administered in a home setting. Many systems are approved as medical devices by the United States Food and Drug Administration and carry CE certification for European markets.

For the person administering the drug, whether a health care professional or not, advanced reconstitution systems can help promote safe and effective drug delivery and compliance with a dosing regimen.

For pharmaceutical companies, advanced systems can differentiate products in the market. Because the dosing is accurate, manufacturers may be able to reduce the need for drug overfills. The ideal time to evaluate systems for developmental drugs is during Phase 11 and Phase III clinical trials when the effectiveness of the delivery system can be evaluated. For currently marketed lyophilized drugs, systems are available that can be used without the need to change processing and filling lines or packaging components.

Among the criteria used to select an advanced reconstitution system are the type of drug; the diluent volume type; the administration method (subcutaneous, IV, IM); requirements for linking to secondary administration (bag, auto-injector); the competitive environment; speed-to-market requirements; and overfill requirements.

The use of an advanced reconstitution system can add value to currently marketed and pipeline drug products. They provide benefits for pharmaceutical companies, people who administer drugs to patients, and can help differentiate products and promote compliance and safety.

Graham Reynolds is Vice President, Reconstitution and Transfer Systems, West Pharmaceutical Services, Inc.
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Title Annotation:Applications
Author:Reynolds, Graham
Publication:Pharmaceutical Processing
Date:Nov 1, 2006
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