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Cynthia A. Challener is a contributing editor to Pharmaceutical Technology.
Advanced drug delivery technologies can increase efficacy and safety, extend patent lives, and provide competitive differentiation for biopharmaceuticals.
While clearly the active pharmaceutical ingredient is the primary component of any formulated drug, the mechanism of drug delivery plays a critical role in determining the safety and efficacy of therapeutics. Access to novel drug delivery mechanisms and devices can have a significant impact for drug manufacturers. In fact, drug delivery technologies can help drug manufacturers in differentiating new therapeutics from existing products, provide a means for extending patent protection, and enable novel treatments. While the majority of drug delivery devices are related to oral delivery, however, it is not surprising given the growth of the biopharmaceutical market that the fastest growing segments of the drug delivery market address the delivery of biologic drugs. Different models for development, including outsourcing, partnering, collaboration, and licensing have resulted.
The novel peptides, protein, nucleic acid, growth factor, cytokine, interferon, and antibody-based drugs available today provide new mechanisms for treating diseases, but also pose challenges with respect to successful drug delivery. "The large size of most biopharmaceuticals, combined with their other molecular properties, lead to poor physical and chemical stability within the body and limited membrane permeability, and severe toxicity when applied systematically. Therefore researchers are developing a range of new delivery technologies and materials to enable these new drugs to be delivered intact to their target sites," says Rajveer Singh Rathor, a senior research analyst for healthcare with MarketsandMarkets.
One of the key drivers for growth in the drug delivery market for biologic drugs is the growth of the biopharmaceutical market itself. Another major driver of the drug delivery market in general (for both large and small molecule therapies) is the expiry of patents for certain blockbuster drugs, according to Shalini Dewan, a senior research analyst with BCC Research, a publisher of technology market research reports based in Wellesley, Mass. She adds that growing demand for self-administration and home healthcare devices; the rising incidence of chronic diseases such as cardiovascular diseases, diabetes, and cancer; the growing focus on pediatric and geriatric patients; and the increasing demand for minimally invasive surgeries are other factors contributing to growth in the drug delivery market. In addition, pharmaceutical companies are increasingly adopting drug delivery technologies to differentiate their products in the highly competitive environment, according to Rathor.
At the same time, both analysts point to recent drug failures and recalls, stringent regulatory processes, various technical barriers, and the difficulty in striking the right partnership deals to the development of drug delivery platforms as negative factors affecting the growth of the drug delivery market.
Thus in 2012 BCC Research estimates the overall market for drug delivery systems including both large and small molecule drugs was $147 billion and expects it will reach $175.1 billion by 2018, growing at a compound annual growth rate (CAGR) of 3%. MarketsandMarkets has higher expectations, and believes that the market will grow at a CAGR of 9.5% from 2012 to reach $224 billion by 2017.
North America, which has a well-established healthcare infrastructure and a large number of leading pharmaceutical and biopharmaceutical companies (around 80% of the world’s research and development in biopharmaceutical is conducted by US-based firms), is the largest market for drug delivery, accounting for 45-50% followed by Europe with 25-30%, according to MarketsandMarkets. North America and Europe are expected to grow at a slower pace (8-9%/year) than emerging markets, primarily due to a certain amount of saturation in the market, but also due to increasing competition from drug delivery firms in emerging countries and unstable and uneven reimbursement policies for innovative drug delivery devices. The Asian region however, and particularly India and China, is expected to grow at a double-digit CAGR from 2012 to 2017 due to the expansion of the Asian economy, an increase in disposable income, the development of healthcare infrastructures, increasing penetration of health insurance, and the rising prevalence of chronic diseases, according to Rathor.
Advantages of advanced delivery
Advanced drug delivery systems offer several advantages over conventional delivery systems, such as improved therapy through increased efficacy and duration of drug activity, decreased dosing frequency, more convenient routes of administration, and improved targeting of a specific site in order to reduce unwanted side effects, according to Dewan. "The challenge for both drug and drug delivery companies is to deliver both existing and emerging drug technologies in a manner that will improve drug administration for patients," she observes. "Drug delivery technologies have grown phenomenally from plain drug reformulation and release technologies to innovative platforms that hold huge potential for the effective delivery of biological and novel drugs." adds Rathor.
Technologies of note
MarketsandMarkets divides the global drug delivery market into nine segments based on the route of drug administration, including oral, pulmonary, transdermal, injectable, ocular, nasal, topical, implantable, and transmucosal. While oral drug delivery technologies represent the largest share (close to 40%) of the overall market, pulmonary, transdermal, and injectable technologies are growing the fastest with estimated double-digit growth rates. "A growing number of companies are investing in technologies including orally disintegrating tablets (ODT), dry powder inhalers (DPIs), pen injectors, auto injectors, buccal films, nasal sprays, intraocular implants, and infusion pumps, many of which are designed for use with biologic drugs. The developments in these areas are a result of their proven technology, high dose efficacy, and their ability to offer enhanced patient convenience and compliance," Rathor explains.
For biopharmaceuticals, pegylation is currently the leading drug delivery technology and is used with products such as interferon. Pen injectors, which are used for insulin delivery in the treatment of diabetes mellitus, are the leading device for biopharmaceuticals. The rising incidence of diabetes will continue to drive the growth of this drug delivery technology, according to Rathor. He also notes that pen injectors offer the simplest and safest way of delivering biopharmaceuticals such as peptides, hormones, and monoclonal antibodies that cannot be taken orally. Liposomal delivery is another very popular method for the delivery of biologic drugs.
Polymers, including pegylated drugs, have played an important role in the advancement of drug delivery technology by providing opportunities for controlled release of therapeutic agents in constant doses over long periods, according to Dewan. Research is ongoing to develop controlled-release systems for biopharmaceuticals. New transdermal technologies have created opportunities for developing delivery mechanisms for existing molecules with no viable delivery systems and existing drugs that can benefit from additional delivery systems, such as compounds that previously were unable to be delivered through the skin, according to Dewan. One such example is WEDD (Wearable Electronic Disposable Drug Delivery) developed by Travanti Pharma, a Teikoku Pharma affiliate company, is a proprietary drug delivery technology platform for electronic transdermal (iontophoretic) delivery of therapeutic agents using an applied electromotive force. Targeted technologies based on loaded nano-carriers (nano-shells or nanoparticles) are also attracting increasing interest, with gold nano-carriers leading growth in revenue. "Targeted drug delivery is a more personalized approach based on an individua's unique genome and immune response.
The more scientists learn about the molecular causes for disease, the better targeted and effective nanotechnology-enabled drug delivery therapies will become,” Dewan says. Finally, she notes that increasing interest in prodrugs is due to their ability to overcome formulation, delivery, and toxicity barriers for better drug utilization.
The importance of partnering
There are several different models for the procurement of drug delivery technology in the biopharmaceuticals industry, including in-house development, co-development, and licensing, depending on the need of the biopharmaceutical manufacturer, Rathor notes. For example, Caisson Biotech signed a development and license agreement with Novo Nordisk in 2012 giving Novo Nordisk exclusive rights to use Caisson’s proprietary heparosan-based drug delivery technology for engineering and developing compounds within undisclosed therapeutic areas. On the other hand, Novo Nordisk has an in-house manufacturing facility for pen injectors.
Nectar Therapeutics has also worked with many biopharmaceutical companies, such as Roche, Astrazeneca, Amgen, Baxter, Novartis, and Pfizer, to develop biological products (i.e., Pegasys, Neulasta, Omontys, Cimzia, Mircera, PEG-Interon) based on Nectar’s patente PEGylation technology. These products have been developed by their respective companies using PEGylation technology of Nector Therapeutics, according to Rathor.
In a third representative collaboration, Radius Health and 3M Drug Delivery Systems formed a exclusive partnership for the development and commercialization of BA058-transdermal in December 2012. BA058 is a novel, synthetic proprietary peptide analog of human parathyroid hormone related protein which is used to treat patients with osteoporosis that are at high risk of fracture. This agreement updates the general development agreement announced in May 2011 by the two companies for BA058-TD.