Biologics’ Drug Delivery Systems

Peter Soelkner

Peter Soelkner

Managing Director, Vetter Pharma-Fertigung GmbH & Co. KG, Germany

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In this interview, Peter Soelkner of Vetter discusses drug delivery trends for biologics and, in particular, prefilled syringes. He offers insight into the advantages and challenges of this system for biologics, important issues to consider upfront, and talks about two differing manufacturing technologies for prefilled syringes.

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To begin, what trends do you see in drug delivery systems for biologic drugs?

There are several trends that we see in drug delivery systems in general, and more specifically, in the fast and continuously growing biologic drug sector:

The first trend is the need for drug delivery systems that are patient friendly. This means the development of drugs that are of a very high compatibility with the human body, and that can be made available in more convenient delivery forms, especially ones where patients can self-administer.

This trend corresponds with the expanding home healthcare market which is itself, a direct result of a rapidly aging world population including in the Asian countries.In order to control costs, healthcare authorities are putting pressure on the industry to develop medicines which enable patients to undertake more procedures in a private setting and avoid more cost-intensive therapies that would occur in either a hospital or a doctor’s office.

Another trend is the rapid increase in therapies focused on conditions with small patient populations, or Orphan Drugs, which by definition are drugs developed for treating condition affecting fewer than 200,000 persons. Finally, we are seeing one negative trend that unfortunately is costing the industry a significant amount of moneyand even more importantly, putting patient’s lives at risk. This negative trend is, of course, drug counterfeiting. A very important step the industry and the government are taking together to fight this growing problem is the clear identification of products through a process known as ‘serialisation’. This process has already been implemented in China, South Korea and other countries and within the next few years will be enacted in till more countries in Asia and worldwide.

In this context do you see an increasing demand for prefilled syringes? What are the factors driving this demand?

Let me answer that question by taking a look at the drug development sector since projects that are in early and late-stage development phases are a good indicator for determining demand.

Factors which include a higher complexity of new compounds in development, have led to a drug development model that is far more intricate than some years ago.To succeed in today’s market and well into the future means companies must make innovation central to their drug development business approach. That means looking outside traditional methods of drug delivery in the clinical phases. The reasons that support the taking of an innovative approach include:

• Several syringe market reports which indicate that the global prefilled syringe market is expected to show continued positive growth due to rapidly increasing development of biologic drugs and other suitable compounds.

• The rising demand for greater ‘friendly’ patient and caregiver administration, starting in the clinical phase and continuing in the commercialisation of a drug.

With more biologics competing in the same therapeutic space, launching directly in a syringe can help set a drug product apart from the competition and offer an advantage that other companies may not be able to beat.

In summation, we see increased interest and demand in prefilled syringes. For many indications, prefilled syringes seem to be the way of the future. Being part of this future via early-in-the-process clinical syringe development provides an innovative approach for innovative companies to gain an early market advantage.

What are the advantages of prefilled syringes for delivering biologic formulations compared to other injection technologies?

As already discussed, the key to the rapidly changing healthcare market is offering solutions for the need of patient friendly systems. Prefilled syringes are such a system. Instead of undertaking several preparation steps prior to administration, the prefilled syringe, also called an “all in one system”, provides a number of advantages in the clinical stage as well as in the day-to-day operations of a product already launched. These include:

Improved trial appeal, making it easier to recruit medical clinics for clinical trials that use prefilled syringes instead of traditional vials

Greater patient compliance and consistency resulting from the ‘user-friendly’ nature of prefilled syringes

Precision single-unit dosing which better meets the requirements of today’s more complex compounds

The avoidance of overfilling which reduces loss and thus, saves valuable API as compared to vials

The possibility of a higher drug reimbursement from payers

An increase in the value of a drug product early in its life-cycle given its competitive edge

An increased attractiveness to out-licensing partners

What are the challenges in the manufacture of this drug delivery device?

It is our experience that creating easy-to-apply systems often means a more complicated production process at the outset. After all, a syringe system is a sophisticated and complicated instrument, consisting of a number of individual components. The correct interaction between the components that comprise each module is critical to its successful operation.

To illustrate, let us look at the administration of a drug using a syringe system. The system itself requires a plunger rod that operates in concert with the other components, particularly the glass barrel itself. To achieve a smooth operation, a small coat of silicone is applied at the inner surface of the glass barrel. It is a significant challenge to determine the correct amount of silicone required to achieve the correct movement of the plunger rod while avoiding any interaction between the silicone and the drug substance coming into contact with each other.

And, because the glass barrel of a syringe is more complex than the glass of a vial, consisting of a finely shaped area within the barrel, there is a higher risk for mistakes or damage to the barrel such as glass scratches, or even glass breakage. This is why all partners involved in the supply chain are focused individually and collectively on this issue. Glass manufacturers, along with manufacturers of the prefilled syringes; which can be either the biopharmaceutical company or their assigned contract development and manufacturing organization (CDMO) and, if applicable, the processors,strive to achieve optimal results for the benefit of the patient.

If a manufacturer is considering prefilled syringes as part of its drug-delivery option for a drug, what would be the most important issues they would need to take into account before proceeding?

This is an excellent question since its answer helps to better illustrate the thinking that must be done prior to committing to prefilled syringes. The first consideration is the issue of dosing. For example, before making the decision to use prefilled syringes, a biotech company must first answer the question “what different drug concentration presentations do we want to bring to market?” The answer to this question will have different actions associated with it depending upon whether the product is to be offered in just one, or in multiple syringes.

Other critical issues that must be considered include silicon oil reactivity, the use of non-fluro tech or flurotech stoppers, glide and release forces, and the time that the drug will be held in storage. Additionally, issues such as plunger rod and finger flange design, secondary packaging issues like blistering, and other manufacturing issues must be carefully verified, discussed, and decided upon prior to making the overall decision to use prefilled syringes.

Thinking about the two prominent manufacturing technologies for prefilled syringes, presterilised or bulk process,what influences the choice of the correct technology for each individual product?

Overall, the choice of selected technology is often driven by the characteristics of the drug substance itself. This is particularly true for sensitive biologics or complex compounds that have diverse product specifications. The choice of the right syringe platform technology is a decisive factor for the successful development and commercialization process.

The two prefilled syringe platforms available in the market; presterilized and bulk syringes have their differences. Presterilized syringes are tub-based, ready-to-use systems that are well-suited for a broad range of drug products. The washing, siliconization, nesting, and sterilization takes place at the supplier for the primary packaging, while filling occurs at the filling site.

When working with sensitive biologics, the possibility for customization is often a ‘must have’ option. That is why bulk syringes are often a good choice for complex compounds such as monoclonal antibodies, peptides, interferons, vaccines or opthalmics. With bulk syringes, as opposed to presterilized syringes, the pre-treatment steps of washing, siliconization and sterilization take place at the filling site in an integrated, customizable inline-process. Also, the tighter specifications of the bulk process often help to reduce particle levels, adjust silicone levels to meet exact specific product requirements, offer different methods of sterilization, and increase dosing and fill-volume accuracy for small volumes.

A full range of readily available bulk syringe formats also allows for numerous customizable options. Obviously, the advantages of using this format are maximum possible control of the process and flexible primary packaging material combinations.

In summation, both prefilled syringes platforms offer biotechnological companies innovative delivery options and value in drug development programs for sensitive biologics. But, it is the nature of the compound itself that most often drives choice. Therefore, knowing how the two platforms differ will be essential in choosing the right syringe system for the individual drug product.

By design, a significant amount of research into areas such as patient requirements and device design are necessary when intending to market a new parenteral drug. However, profit margins are also essential. Can the two coexist?

Increasingly, healthcare authorities expect the industry to develop medicines that allow patients to take more control over their own health care. That means the potential for self-administration in the home. The primary purpose behind this request is an attempt to control costs through the avoidance of cost-intensive therapies in either a hospital setting or a doctor’s office. When we consider the ever-increasing complexity of drug products, this is a difficult, but not an impossible task to balance. Certainly, it creates challenges for all parties involved in the drug manufacturing industry that must develop new packaging and delivery formats that meet or exceed the required standards of these drugs, all while controlling costs.

At the end of the day, however, we must never forget the human element of our business, always keeping in mind the fact that patients rely on our industry to help make their lives easier and safer when managing their disease, and helping to improve their quality of life.

Is there anything further you want would like to add or any closing thoughts for our readers?

I would like to emphasize that syringes, in their role as an advanced drug delivery system, can offer significant potential for biotech companies, particularly in their use with innovative drugs. Undertaking a drug development program with a clear goal in mind from the very start can often make the difference between success and failure. That is why the involvement of an experienced service partner early in the process can help maximize the value of a complete drug package which consists of the compound itself, the drug delivery system, as well as the experience and trust the CDMO partner brings to the development and manufacturing project and process.

Therefore, when choosing a partner, customers should consider the total project including decisive aspects of quality, experience, flexibility, financial stability and a shared vision. We see these as central to a due diligence approach in the partner selection process.

Company Profile:

Vetter is a global leader in the fill and finish of aseptically prefilled syringe systems, cartridges and vials. Headquartered in Ravensburg, Germany, with production facilities in Germany and the United States, the contract development and manufacturing organisation (CDMO) is an innovative solution provider serving the top 10 (bio-) pharmaceutical companies, as well as small and midsize companies. Its portfolio spans state-of-the-art manufacturing from early clinical development through commercial filling and final packaging of parenteral drugs. Known for quality, the company of approximately 3,900 employees offers a foundation of experience spanning more than 35 years, including dozens of customer product approvals for novel (bio-) pharmaceutical compounds. More than 70% of Vetter’s active projects are biologics, and Vetter currently manufactures five of the world’ top 10. The CDMO is also committed to patient safety and compliance with user friendly solutions such as Vetter-Ject®, as well as its dual-chamber syringe Vetter Lyo-Ject® and cartridge system V-LK®. Vetter’s branch office in Singapore and its subsidiary in Tokyo, Japan, increase the presence of the company and the awareness of its service portfolio in the Asian healthcare market. Visit www.vetter-pharma.com.

AuthorBio

Peter Soelkner has been a Managing Director of Vetter Pharma-Fertigung GmbH & Co. KG since June 2008. In 2009, he was also appointed Managing Director of Vetter Pharma International GmbH, the company’s marketing and sales organization. Soelkner graduated from the University of Dortmund, Germany, in 1992 with a degree in chemical engineering and earned an MBA from Columbia University, New York, in 2001. Before joining Vetter, he held positions in Germany and North America at Sartorius AG and Sartorius North America Inc., in R&D, marketing, key account management and general management roles. At Vetter, from 2003 to 2007, Soelkner managed the company’s key account program and global end-to-end supply chain. He left the company for a year to serve as Vice President of global key account management at Sartorius Stedim Biotech (USA), before returning to Vetter in 2008.

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