AS PUBLISHED IN Q4 2018 PHARMA'S ALMANAC
As APIs and drug formulations become more sophisticated, pharma companies are relying heavily on contract service providers with specialized capabilities. Two such specialized service areas of growing importance in the industry are aseptic processing and high containment. In order to create value for our customers and accelerate drug development, Avara Pharmaceutical Services has strategically applied our extensive experience and expertise in these fields.
Why Niche Capabilities are Important
The pharmaceutical industry is a mature sector facing significant challenges. If drug manufacturers are to continue providing novel life-improving and life-saving medicines — at a fair price that still allows for profitable operation of the entire supply chain — productivity and efficiency must be increased, and collaboration across the supply chain expanded and improved.
These changes are needed at a time when drug substances and formulated drug products are rapidly becoming more complex. Continued investment in innovation and the development of proprietary solutions that address the needs of current and next-generation therapies is essential. Specialized technologies that support the processing, formulation and packaging of highly potent compounds, controlled substances, poorly soluble drugs and sterile products are particularly important.
Investing in all the resources necessary to maintain expertise and capabilities in niche technologies is not economically practical, even for large pharmaceutical companies. As a result, drug makers are outsourcing to contract development and manufacturing organizations (CDMOs) with a breadth of advanced, specialized and often proprietary technologies that enable the development of optimal synthetic routes and final formulations. CDMOs with specialized capabilities that fully evaluate and characterize the solid-state chemistry of molecules and facilitate more efficient manufacturing, formulation development, clinical trial supply, process scale-up and technology transfer while enhancing safety and quality are essential to the pharmaceutical industry's future.
Spotlight on Sterile Manufacturing
Sterile manufacturing operations carry more risk than non-sterile processes and are typically more complicated. They require a sterile environment (cleanroom, isolator, RABS) and greater levels of testing. All equipment components used in aseptic processes that might come in contact with the ingredients and/or product must be sterilized/sanitized before and after use.
Injectable products must be sterilized via sterile filtration or terminal sterilization without impacting the quality and stability of the drug product. Products requirizing lyophilization must be processed with minimal risk of contamination. Visual inspection of packaged products is generally required. Aseptic spray-drying of poorly soluble APIs for parenteral applications eliminates the need for terminal sterilization but requires specialized capabilities.1
Finding the right CDMO partner for sterile manufacturing is crucial as innovators are being pushed to accelerate the development of novel drugs, which are increasingly difficult to sterilize.2 Personalized medicines are more sophisticated and sensitive — and are also produced in smaller quantities. This has increased demand for small-volume aseptic processing and requires more flexible and efficient aseptic processing operations.3Forward-thinking CDMOs are implementing risk-based approaches to sterile manufacturing and packaging to ensure the use of processes that provide the highest quality and most reliable outcomes.3
Not surprisingly, there is growing need for specialized capabilities in sterile manufacturing. The fill-finish manufacturing market is predicted to expand at a CAGR of 8.6% from $2.96 billion in 2017 to $4.47 billion in 2022.4 The strong interest in parenteral formulations is attributable to the poorly soluble small-molecule APIs and the increasing percentage of biologic drugs, most of which require injectable delivery.
Highlighting Containment Needs
Aseptic processing requires containment to ensure prevention of contamination. Higher levels of containment are required for hazardous reactions, including those involving energetic chemistry. The manufacture and handling of highly potent compounds requires specialized containment capabilities with respect to personnel, equipment and facilities, in order to protect the drug product, the operators and the environment. Most manufacturing processes for oral solid dosage (OSD) drugs require some level of containment.5
However, containment does not only refer to closed systems and can be achieved in a number of ways.6 For potent compounds, the occupational exposure limit (OEL) is typically used to determine the necessary level of containment. For hazardous reactions, the potential energetic release is considered. Selecting the most appropriate containment solution for a specific process can be challenging. It is therefore essential that pharmaceutical companies work with CDMOs with extensive experience managing many different processes that require different levels of containment, including API synthesis, granulation, tableting, product transfer and fill-finish.
An Expanding Sterile Manufacturing Portfolio
Avara Pharmaceutical Services provides flexible development and manufacturing for small-molecule API production and final product formulation, manufacturing and packaging. Our initially acquired facilities support API and OSD manufacturing, and, in response to the growing market demand, Avara has made acquisitions to expand capabilities in sterile processing.
At our site in Liscate, Italy, which was acquired from Pfizer, we offer liquid and lyophilized fill-finish of sterile injectable products. The facility has development labs and small-scale equipment, along with the capability to manufacture at commercial scale, including products that require high containment. Specific capabilities include aseptic filling of ampoules and liquid vials, lyophilization, terminal sterilization of ampoules and aseptic spray-drying. Aseptic powder filling in RABS will be offered pending validation of recently installed equipment, as will a range of packaging services.
Avara recently acquired the largest sterile manufacturing facility for injectable medicines in Canada from Novartis, along with the adjacent Sandoz Development in Boucherville, Quebec. This further expands our sterile processing capability.
The site provides drugs to the Canadian healthcare system (mostly hospitals) and to the U.S. market. The injectable and ophthalmic products produced at the site are manufactured using unique processes that require specialized expertise. The site has become an internationally recognized Center of Excellence for injectable products.
Avara signed a long-term supply agreement to maintain the same supply, quality and service formerly provided by the facility and to provide development services. Sandoz selected Avara to “continue to focus on helping patients in Canada to get access to the same high quality and affordable medicines.”7
Through the targeted acquisition of world-class manufacturing facilities from branded pharmaceutical companies, Avara is building a pharmaceutical services company with complementary offerings in key regions.
Complements Existing High-Containment Capabilities
The high-containment capabilities in sterile manufacturing are a strong addition to Avara’s containment capabilities installed at our Shannon, Ireland and Avlon, UK API sites for hazardous process chemistry — and at our Norman, Oklahoma and Arecibo, Puerto Rico facilities for highly potent OSD products. In addition, we have the capability and systems in place at the Norman, Arecibo and Boucherville sites for the production and handling of controlled substances.
At these sites, Avara has systems that allow for quick changeover capability and flexible yet effective cleaning procedures. We also have similar equipment for small- and large-scale manufacturing and the ability to readily combine and connect additional systems/components for new processes. All of the facilities have proven track records and experience in developing optimized routes for complex molecules and formulated products.
For API production, Shannon offers different milling and blending technologies, while Avlon is a top-tier Control of Major Accident Hazards (COMAH) site. For kilogram-scale manufacturing, the capabilities of the two sites are complementary and support pre-clinical through phase III projects. Both sites also have significant commercial scale capabilities. In addition to traditional chemistries, Avara has specialized capabilities at the lab to kilogram scales in hazardous chemistry, cryogenic chemistry, milling and crystallization, as well as expertise in chiral chemistry and chemo- and biocatalysis.
The Arecibo facility in Puerto Rico offers manufacturing and packaging capabilities for OSD products, including high containment. The facility has been operating for over 35 years and has a track record as a compliant and reliable source of supply for multiple blockbuster products.
The Oklahoma facility has provided contract services for OSD forms for over 25 years, including development, commercial manufacturing, formulation, analytical support and warehousing. The site has the capability to produce over two billion tablets per year.
Bringing It All Together
Through the targeted acquisition of world-class manufacturing facilities from branded pharmaceutical companies, Avara has built a pharmaceutical services company with complementary offerings in key regions. We are committed to expanding our global network to ensure ever-improved efficiency, productivity and reliability for our customers. We strive to maximize production while minimizing associated issues, serving customers at various stages of development and production and meeting rigorous quality expectations and regulatory requirements.
Avara is a full-service CDMO with integrated capabilities designed to meet
customers’ needs in many aspects of drug development and manufacturing.
By offering end-to-end services and forming partnerships with our customers, we help them reduce risk and simplify their supply chains.
Avara has developed a robust process for the transition and integration of each new facility into our global network. We have a standard IT system and a transition process that facilitates adoption of the Avara culture and our cooperative collaboration. In addition, all of our customer-facing processes are standardized at all locations.
Avara’s leadership team consists of industry veterans who understand the outsourcing market from both the customer and service-provider perspectives. We apply that understanding to every customer interaction, and are committed to creating value across the supply chain. We are committed to helping our customers succeed by accelerating the delivery of drugs to the marketplace while meeting or exceeding the strict regulatory requirements of the industry.
- Tiene, Guy. “Spray Drying Enhances Solubility and Bioavailability: Regulatory approval of the first aseptically spray-dried drug validates this newer technology.” Pharmaceutical Manufacturing. 31 May 2017. Web.
- Langhauser, Karen. “Contorting Convention: Modern aseptic performance demands new flexibility in both mindset and technology.” Pharmaceutical Manufacturing. 31 May 2017. Web.
- Siew, Adeline. “Elucidating Parenteral Packaging Requirements for Future Drugs.” Pharmaceutical Technology Europe. 30: 14–17 (2018).
- Fill-Finish Manufacturing Market Worth 4.47 Billion USD by 2022. Rep. Markets and Markets. 19 Jan. 2018. Web.
- “Understanding Containment.” GEA Pharma Systems. 22 Jul. 2016. Web.
- Gottlieb, Oliver. “High containment becomes high priority in the pharma industry.” Tech Talk. 2018. Web.
- “Important Announcement.” Sandoz Canada. 25 May 2018. Web.
About The Author
Chairman and CEO of Avara Pharmaceutical Services
Tim Tyson, Chairman and CEO of Avara Pharmaceutical Services and previously the CEO of Aptuit has been instrumental in bringing more than 50 life-saving and life-improving medicines to market. Prior to that he was President and CEO of Valeant Pharmaceuticals and served as President of GlaxoSmithKline Global Manufacturing & Supply, where he had responsibility for over 100 manufacturing sites and outsourced manufacturing worldwide. Mr. Tyson holds a bachelors degree in engineering from the United States Military Academy at West Point and MBA and MPA degrees from Jacksonville State University (USA).