The global pharmaceutical market is evolving, driven by greater international regulatory requirements for improved quality as well as local healthcare policy such as the expansion of universal health coverage for China’s nearly 1.4 billion citizens launched in 2011-its annual spending projected to grow about 12 per cent in both 2017 and 2018, according to Deloitte research.
To meet the growing demand for medications and to deliver them in safe, patient-centric ways that meet the needs of the various populations they serve, pharmaceutical companies need packaging partners that offer a variety of systems to serve the healthcare systems of different Asia-Pacific locales.
For instance, diabetes treatment is on the rise in China thanks to universal health insurance, along with more widespread occurrence and timely diagnosis of the disease. That is driving the need for insulin in syringes, as care providers treat what the International Diabetes Federation terms “the world’s largest diabetes epidemic [that] continues to grow at a fearsome pace.”
As China works to curb diabetes-one in three of the world’s diabetics lives in China, with an astounding half a billion potentially with pre-diabetes elevated glucose levels-there may be acall for auto-injectors and other more costly treatment medications and delivery systems in the future. But for the near term, the industry will continue to meet demand through traditional means.
Another example: In India, two spheres of drug development are emerging, each with their own set of standards. Domestically, the emphasis is on generics and other cost-controlled medications to create affordable care for the highest number of people. For export, Indian manufacturers must adhere to quality standards that the destination countries mandate. As of today, roughly two-thirds of drugs manufactured in India are for export, and the industry as a whole continues to grow in capacity, year after year.
Traditionally, drug development may have started with the packaging system; however, it is increasingly important that companies ‘start with the end in mind.’ As an example, consideration of the final method of delivery and the patient population should drive container development. A drug designed for self-injection by an impaired patient, which requires a dosage of 2mL per month to provide optimum outcomes, may require a wearable injector incorporating a drug container capable of containing 2mL of liquid and delivering in a comfortable way over an extended period of time.
This drives the selection of a delivery technology, which in turn drives the selection of a drug container. Medications to be delivered in hospitals often require consideration of other factors. For example, if the drug will be delivered by injection, how would the pharmaceutical company address increasing requirements for needle safety systems? If reconstitution or transfer is necessary, how can this be done effectively and quickly, while protecting the healthcare worker and patient alike?
Overall, the trends to watch in 2017 and beyond that will inform regional drug manufacture and the delivery systems that contain them are as follows:
QbD Processes Help Meet Regulatory Mandates: Using Quality by Design (QbD) provides a methodology for generating a deeper product and process understanding in the injectables market. Interest in QbD principles originated in the past decade out of regulatory pressures and the industry’s ongoing focus on quality and efficiency in drug manufacturing. Recently, QbD advanced through the entire supply chain with the understanding and requirement that all companies involved in the development, manufacturing, containment and delivery of drugs adopt QbD principles when bringing new products to market.
QbD principles can require a significant up-front investment, which can understandably lead some in the industry to initially shy away. That said, the investment delivers an improved, data-driven output that can lead to a superior product. Additionally, QbD initiatives also lead to a process that allow stakeholders to better understand risk and how to minimise it. APAC drug producers who export to Western countries will implement QbD techniques more frequently than for domestic drugs– but that will change as China has begun to change its approval system and other countries begin to examine new quality mandates.
More Stringent Local Regulations: In China, with the formal introduction and implementation of ‘quality management regulation of medical manufacture (revised in 2010)’, a series of standards related to sterile medicinal products has been put into practice. The annex of ‘Sterile Medicinal Products’, introduced as supportive document of ‘quality management regulation of medical manufacture (revised in 2010)’, has also been carried into effect from the 1st March 2011. It is emphasized in the annex that materials preparation, manufacture and distribution of product, filling and packing must be done separately in the clean area.
The level of clean area for manufacturing sterile medical products should be defined in accordance with elements as product characteristics, technology, equipment, etc. Environment for every step of the manufacturing process should reach the dynamic cleanness standard, and the risk of particulate or microbial contamination for products or materials under the process should be controlled as much as possible. Five years later, the pharmaceutical industry continues to innovate around meeting these standards.
Increased Demand for Combination Products: Self-administration and biologics have only increased the popularity of combination products, such as wearable auto-injector systems used for the management of chronic diseases. Biologics, which are primarily being administered through injections, have played a large part in the demand for combination products. Auto-injectors, wearables and other new systems will only increase the already budding demand in the coming years as APAC companies create them for export to Europe and the Americas; in the longerterm there is no doubt that other global regions will embrace them as their own health systems evolve.
Flexible Manufacturing Enables Personalised Medicine: Many pharmaceutical companies are looking for ways to institute adaptive filling techniques. Flexible manufacturing allows systems to be adjusted for a variety of dosage forms which, in turn, potentially reduces costs and space requirements. A primary driver of flexible manufacturing is the healthcare system’s ongoing shift to personalised medicine, leading to smaller quantities of drug products and more sophisticated therapies, such as biologics.
Flexible manufacturing enables drug companies to quickly transition fill lines from vial format to cartridge to pre-filled syringes, depending on the needs of the injectable medicine. Injectable drug delivery system manufacturers will be tasked with creating innovative methods to allow adaptive filling to occur. Although commercial utilisation of flexible manufacturing is likely further down the road, some pharmaceutical companies have started to examine its utility around clinical trials, where smaller quantities are needed.
The Rise of Continuous Manufacturing Methodologies: To date, the pharmaceutical industry has been largely focused on manufacturing in batch quantities. The process is quite straight forward: make a certain number of batches, validate and submit the data. However, this method is somewhat behind the curve when compared to other manufacturing operations, such as oil refining, steel casting, paper production and natural gas processing. Expect pharma to continue to explore continuous manufacturing, where product testing occurs during the production process using real-time analytics to identify and react to irregular trends. The result is an increase in quality and a higher level of confidence throughout the process.
Continuous manufacturing also offers greater cost reduction because production doesn’t have to stop between each batch and it drastically reduces the amount of unusable end products. Although historically, this has been a bit of a challenge for pharma, the introduction of different techniques and process analytical technologies part of which is driven by QbD approaches – is pushing the industry in this new, data-driven direction.
Orphan Disease Treatments Drive Smaller Batches: On the other side of the ‘batch vs. continuous manufacturing coin, orphan diseases’-rare conditions that decades ago would not have been sustainable to create traditional drugs can be treated with new biologics under development. Small pharmaceutical companies with agile research teams will bring smaller-batch drugs to market. But they will have special considerations such as short shelf life, creating just-in-time manufacturing challenges to meet.
These ompanies will rely on packaging partners to help select and design the most appropriate, patient-centric delivery systems so they can concentrate on creating the most effective molecules to treat patients in need. The packaging partners will have to also create agile methods that may revolve around the ability to ship a single crate of product with flexible manufacturing methods instead of pallets and truckloads at a time.
Supply Chain Risk Mitigation: Typically, when examining supply chain risk, factors such as transportation, political climate and global economics are considered. For obvious reasons, supply chain disruption can have a very adverse impact in delivering needed pharmaceutical products, including packaging/delivery systems, to the end user.
Because of this, we are now seeing increased discussion in the injectable sector around the origin of materials and the ability to quickly shift to another region should one be compromised by natural disasters or other natural irregularities that compromise safety. As risk management technologies continue to improve, pharmaceutical companies have greater insights into the probability that supply chain risks may occur and, in turn, allow the industry to react more quickly to avoid disruption.
Biosimilars Control Costs, Need Delivery Differentiation: 2015 saw the first FDA-approved biosimilar, and this was just the tip of the proverbial iceberg in the US market. Biosimilars cost a fraction to bring to market compared to biologics. With several companies competing for the same biosimilar, the mechanism of administration can be a key differentiator. For injectable biosimilars currently in the pipeline, it will be important to examine drug delivery options that can improve the patient experience while ensuring, when possible, a delivery format that patients are currently familiar and comfortable with.
In the broader sense, there will be continuing growth in emerging markets -especially in India-driven by increasing access to healthcare. The advent of biosimilars may open opportunities for increased access to biologics. This is a significant area of opportunity for many companies planning to enter the market with biosimilars versions of key drugs like Enbrel®, Humira® and Remicade®, while innovators continue to explore new indications and options for lifecycle management.
Looking beyond 2017
It has often been stated that “drugs don’t work in patientsthat don’t take them,” and it is clear that pharmaceutical and biotech companies are spending a huge amount of effort on ways to improve patient adherence. Such a venture can be enhanced by newer capabilities in terms of connected health systems, as well as a more thorough understanding of patient psychology. In many cases, rewards are seen as a greater motivator than reminders.
In addition, increasing emphasis is being placed on patient on-boarding and training. Compliance rates for chronic medicines are low, and it has been shown that many patients do not use devices correctly. Connected health systems offer access to huge amounts of data that can help understand patient behaviour. We have already seen increased awareness by patients, which is supported by access to information on specific medicines, social-media-based communication and increased advertising. The advent of connected health devices will further increase patients’ ability to monitor and control their healthcare.
In summary, there is a need for an increased focus on patient outcomes, while ensuring a continued focus on integrated drug delivery systems. Early collaboration between pharmaceutical and biotech companies and a range of key partners will be critical to ensure optimum speed to market, effective drug delivery, and enhanced outcomes for patients around the world.