Drug Delivery for Biologics

Reconciling safe, effective packaging with complex molecules

By Graham Reynolds
West

In recent years, an increasing number of biopharmaceuticals has received regulatory approval. As this industry gains momentum, the need for safe and effective packaging and delivery systems that can address the unpredictable characteristics of biological compounds is an issue of growing concern for drug manufacturers. The delivery system is often far from top of mind when biopharmaceutical companies begin to develop a drug. However, the costly and sensitive nature of biologics calls for sophisticated packaging components that must be considered early in the development process in order to design a solution that can help prevent product loss, ensure shelf life and protect each drug from the individual challenges inherent in its makeup throughout its lifecycle.

Effective packaging and delivery can help drug manufacturers meet regulatory requirements and industry standards for safety and quality in complex drugs such as biologics. It can also help manufacturers differentiate their drugs by equipping them with packaging components that maintain the effectiveness of the drug and prevent contamination. Incorporating decisions about containment materials and drug delivery systems early on in the drug development process can help ensure compliance, increase safety and enhance the patient’s experience once the product reaches the market.

Lifecycle Management

During a drug’s lifecycle, several forms of packaging and contain closure systems may be employed. In development, drugs will often be initially stored in bulk containers, then moved to a standard system of vial, stopper and seal during clinical testing. As the drug moves to market, additional containment and delivery or injection systems may be developed. For each new containment or delivery system, testing is required and can often be time consuming and costly.

In some cases, the earliest entry of a drug to the market may be facilitated by the use of a traditional container closure system such as a vial, with some form of reconstitution system if the product is lyophilized. This system is often used for convenience and may not be the final or best delivery system for the drug. Many drugs then move to prefilled syringe systems that may later be used within a device such as an auto-injector. The drug molecule is the same, but the delivery system has changed, and costly testing may be required to ensure that the new container closure system does not react with the drug.

The use of a consistent packaging material throughout a drug’s lifecycle can be helpful in transitioning from storage to a vial/stopper system to a prefilled syringe system. Fortunately, new materials such as cyclic olefin polymers are highly moldable and can be used in various forms to help facilitate the transition from one containment system to another. For example, Daikyo Crystal Zenith® (CZ) resin is a break-resistant, inert, silicone-free material. A viable alternative to glass, CZ can be molded in a variety of shapes and sizes that can be used with a drug at various stages of storage, transport and delivery. Having the same material for bulk storage, vials and prefillable syringe systems provides consistent functionality and minimizes the material contamination risk as the drug moves from research to clinical trials to commercialization. This is especially important for biologics, which may react with particulate from silicone-oil and tungsten contamination.

An essential point to consider early on in the drug development process is what form the final delivery device will take. Device requirements are driven either as a means of product lifecycle management or by companies entering an established market area where devices are commonly used (such as in the treatment of various autoimmune diseases). Because biologics are often large molecule products that do not transport well through non-injectable delivery methods, delivery devices such as auto-injectors and prefillable syringes are often ideal for administration. While different technologies, such as inhalation and transdermal patches, have been attempted, in many therapeutic areas injection has proven to be the most effective method of delivery. Drug manufacturers need to enter the market directly with a competitive delivery system to ensure product differentiation or additional patient benefits. Such distinction is critical to competing with established products.

Working closely together, drug and packaging manufacturers can look for ways to use packaging and delivery systems to set a product apart from the competition. There are several reasons the relationship should start early on in the drug development process. The primary consideration should be to ensure that packaging is right for the drug product to ensure safety and efficacy. In addition, packaging can be a significant factor in the regulatory approval process. While the focus of the regulatory bodies may be on the drug itself, the reality is that when that drug hits the market, it arrives inside a container closure system. How the drug product is going to be delivered should be determined based on the clinical application. This will help the manufacturer to understand what type of primary packaging is needed, and how that packaging will fit with the delivery system. Selecting the right system early on in the process can help manufacturers not only distinguish their product in a crowded market, but also increase their chances of a successful move to commercialization. By ensuring a good fit early in the development process, pharmaceutical companies can essentially build in increased compliance and ease of transition to delivery devices along the path to approval.

Compliance and Safety

As patient preference becomes increasingly involved in determining the best treatment option, drug manufacturers need to consider the ease of delivery for end users — patients and healthcare workers — and adapt their designs accordingly. Customized drug delivery systems can be a benefit to both patients and caregivers through ease of administration and control of proper dosing. New technologies can also help increase compliance and safety for patients with chronic conditions that require frequent treatment.

An increased incidence of chronic conditions such as diabetes, multiple sclerosis and rheumatoid arthritis has resulted in the development and launch of an increasing number of new biologics designed to treat these conditions. Most of these diseases require regular injections, often administered by the patient or caregiver. This, in turn, has created a need for drug delivery devices and systems that can be easily and safely used in either a clinical or homecare setting.

Several pharma and biotech companies have advanced devices capable of increasing patient compliance in the clinic or at home. In some cases, a range of delivery device options is available to support a single drug. For example, a single drug used to treat multiple sclerosis may be available in a ready-to-use, prefilled syringe, or in an auto-injector for patients with dexterity issues. Such devices may have both visual and audible signals to aid end users who may have trouble determining when the dose has been given fully. Electronics can also be incorporated to provide instant user instructions in cases of rarely-used emergency treatments or as a means of aiding compliance.

Another example is diabetic insulin, which is available in multiple formats including syringes, pens and pumps. As these delivery devices become more complex, many use electronic feedback to track patient compliance. Information about the medication can be downloaded from the pen or pump directly to the caregiver. A physician can then quickly and easily determine if the patient has been following his or her medication schedule. Linking diagnosis to treatment, in conditions such as diabetes, is also becoming a more active area in terms of device development.

Other areas of treatment require needle-free systems. For example, when treating hemophilia, needle-free systems and devices have been used extensively to eliminate needles during the reconstitution process. The use of vial adapters, needleless transfer devices and diluent-filled Luer lock syringes has helped to eliminate dangerous needles from the reconstitution process and create a safer environment for patients suffering from hemophilia.

Improved needle technology in self-injection devices can also help increase compliance by lessening anxiety for the patient. Auto-injectors can hide the needle before and after injection, helping to reduce needle phobia. These sterile, single-use disposable systems are ideal for homecare use because they eliminate preparation steps and automate injection, delivering drugs at the touch of a button.

Another added benefit of advanced drug delivery devices is the ability to aid in provider safety. In recent years, there has been an increased focus on preventing needlestick injuries among healthcare professionals. According to the National Institute for Occupational Safety and Health (NIOSH), approximately 600,000 to 800,000 needlestick injuries occur annually in the U.S.1 These injuries carry the risk of serious infection from diseases such as HIV and hepatitis. To combat this risk, there are several new syringe technologies available that are designed to reduce the likelihood of healthcare workers being accidentally stuck by a needle. These include passive needleguard systems which eliminate exposure of the needle before and after injection, protecting healthcare workers from accidental needlestick injuries. These systems allow for safer injection without altering the caregiver’s administration technique.

Solutions Through New Technology

As the use of biologics continues to rise in the marketplace, the link between packaging and delivery system manufacturers and biopharmaceutical manufacturers must be strong. The interdependence of the packaging and delivery system needs to be carefully considered at an early stage, and a thorough understanding of both is important to ensuring a successful drug/delivery system combination.

The key goals in designing any drug delivery system should always be the safety and effectiveness of the drug product. To accomplish these goals it is critical for biopharmaceutical companies to have a thorough knowledge of the potential interactions between a drug and its packaging. This is especially important for sensitive biologics, which require sophisticated packaging and delivery systems. As more and more drug manufacturers ramp up production of biologics, the issue of how to best package and deliver these costly and unpredictable compounds will continue to rise in importance. It is essential that packaging that does not impact the effectiveness of the drug through contamination or interaction of substances that have migrating potential.

It is important for drug manufacturers to have a clear understanding of the role packaging should play in the drug development process as well as how it fits into the regulatory and quality environment. By working with a packaging provider who has an intimate knowledge of the regulatory and quality requirements of the medical field, drug manufacturers can make more informed decisions about which container and delivery systems are most effective for a particular drug and increase their ability to create a device that establishes the drug product as a leader in the market. New technologies and innovative materials provide ideal lifecycle management solutions and can help ensure high quality solutions for drug purity and patient safety.

Partnering with a provider that has expertise in the field of drug packaging and delivery systems should be an important part of the launch plan for any biologic. By developing a thorough understanding of the drug’s intended use and the patient’s needs, packaging manufacturers can lend their expertise to drug manufacturers to develop a delivery system that differentiates the drug in the market and helps to ensure that the patient’s needs are met. Having a sophisticated drug delivery system, as well as advice from a partner with experience and understanding of the drug packaging industry and end user needs, will not only aid in product compliance, but also may help get products to market faster.

Reference

1.National Institute for Occupational Safety and Health, NIOSH Alert: Preventing Needlestick Injuries in Health Care Settings, November 1999, NIOSH Publication No. 2000-108.

Daikyo Crystal Zenith® is a registered trademark of Daikyo Seiko, Ltd. Crystal Zenith technology is licensed from Daikyo Seiko, Ltd.

The photo on page 88 is courtesy of West Pharmaceutical Services: “Delivery devices such as auto-injectors and prefillable syringes like the Daikyo Crystal Zenith® 1mL insert needle syringe system or the Luer lock syringe seen here are often ideal for biologic drug administration.”

Graham Reynolds is vice president, marketing and innovation, Delivery Systems, at West. He can be reached at graham.reynolds@westpharma.com.