May 29, 2018 PAP-Q2-18-CL-020
The fill-finish step in the manufacturing of drugs is a crucial one because it is the last step completed before a product is packaged and delivered to the patient. It requires specialized capacities and equipment and receives intense scrutiny from a regulatory perspective. Aseptic fill-finish processes are even more complicated.
There is a growing need for these capabilities as the increasing complexity of small-molecule APIs drives an increase in parenteral delivery and the percentage of biologic drugs (both branded and biosimilars), the vast majority of which are formulated as parenterals, continues to rise. Because with parenteral delivery the active agent enters the bloodstream directly, this method is advantageous for the delivery of medicines used to treat nausea and unconsciousness and during clinical emergency conditions. It is also beneficial for the delivery of small-molecule APIs with poor bioavailability and drugs with narrow therapeutic indications.1
The global fill-finish manufacturing market is predicted by Markets and Markets to expand at a CAGR of 8.6% from $2.96 billion in 2017 to $4.47 billion in 2022.2 Europe is expected to account for the largest share of the market, with many major players enhancing their presence in the region, while Asia Pacific will experience the most rapid growth. Stricter regulatory oversight of aseptic fill-finish operations has also led some contract manufacturers to exit the market. Lyophilization (freeze-drying) capacity has also been tightening, in part due to quality and regulatory issues at various manufacturing sites around the world, with demand for aseptic fill-finish manufacturing exceeding available capacity in some cases.3
Aseptic fill-finish operations carry more risk than non-sterile processes. Filling must be accomplished in a sterile environment (cleanroom, isolator, RABS), and greater levels of testing are required. All components used in the aseptic fill-finish process must be sterilized/sanitized before use. Sterilization with pressurized steam, irradiation or hydrogen peroxide must also be performed in a manner that does not impact the quality and stability of the drug product.4 For those products that require lyophilization, steps must be taken to ensure that risk of contamination is minimized during the loading and unloading processes. Visual inspection of packaged products is also required.
Due to the challenges associated with aseptic fill-finish operations today, many biopharmaceutical companies are relying on contract development and manufacturing organizations (CDMOs) to manage this important step in the manufacture of their drug products. In fact, the contract manufacturing segment of the fill-finish manufacturing market is growing faster than the pharma in-house segment.1
Many drugs today are being developed by small, virtual pharma companies that do not have any in-house production capabilities and thus rely completely on outsourcing partners. Larger companies that do have in-house fill-finish capabilities still outsource projects to CDMOs due to capacity constraints or for when specialized capabilities are required, such as for highly potent compounds. Some use CDMOs to establish a backup source, particularly for drug products that are medically necessary. Others may conduct fill-finish operations at early development stages then switch to an outsourcing partner for later stage development and commercial operations.5 In fact, choosing the right aseptic-fill-finish partner can add value to a project.3
One constant in the pharmaceutical industry is innovation, which leads to constant evolution of manufacturing needs. The shift away from blockbusters to specialized therapies targeting small patient populations is leading to demand for more flexible and efficient fill-finish operations.6 For instance, the use of restricted access barrier system (RABS) rather than isolators can facilitate multi-product fill-finish operations.3 In addition, because delivery systems are integral to patient-centric drug products, the choice of packaging systems used in fill-finish operations is often considered much earlier in the development process.6
Avara has eight sites: three in the United States, including corporate headquarters; one in Puerto Rico; one in the UK; one in Ireland, one in Italy; and one in France. The site in Liscate, Italy was acquired from Pfizer in early 2018 to expand our services through the addition of sterile processing capabilities, including 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 for products that require high-containment. The highly experienced staff at Liscate have a proven 15-year track record in contract manufacturing.
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. Packaging services include single vials, vials in trays/cartons and kits, which can be completed manually or using automation, including high-volume automated packaging and labeling.
Avara Pharmaceutical Services, founded in 2015, has been designed and constructed from the start to provide flexible development and manufacturing support for API formulation and manufacturing and the manufacturing and packaging of small molecule drugs, including highly potent compounds. We have secondary manufacturing technologies including granulation, coating, blending, encapsulation, compression and drying of tablets and capsules, as well as sterile processing of liquids and lyophilized fill-finish of sterile injectable products, including high-containment capabilities.
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. Each site has significant professional experience, state-of-the-art capability and a long history of delivering high-quality pharmaceuticals that meet or exceed customer expectations and regulatory requirements in every major market around the world.
Avara has an established track record of high-quality, reliable, cost-effective performance provided by highly experienced employees. We are recognized as a full-service CDMO with integrated capabilities designed to meet customers’ needs with respect to all aspects of drug development and manufacturing, including APIs and formulations. By offering end-to-end services and forming partnerships with our customers, we help them reduce risk and simplify their supplier bases while ensuring quality and regulatory compliance within their supply networks.
Although Avara was built through acquisition, we have established a tightly integrated CDMO by bringing the operations and people at each site into every aspect of the corporate culture under a single brand that is based on common values and standards. Operational Excellence; Safety, Health & Environment (SHE); and Manufacturing practices are established across the sites and deployed uniformly. Each site, however, retains the necessary autonomy to maintain total customer focus depending on the product and supply chain, with experienced managers empowered to align their site capabilities to meet the specific needs of their customers. The role of each and every Avara site is to reliably deliver product to the highest quality standards on-time and in-full while reducing costs and avoiding supply chain issues.
Our total commitment to our customers and the delivery on our promises for scope, schedule, quality/regulatory compliance and price were recognized recently with the announcement by Life Science Leader that Avara Pharmaceutical Services will receive awards in the six core categories (Capabilities, Compatibility, Expertise, Qual-
ity, Reliability and Service) of the 2018 Contract Manufacturing Organization (CMO)
Leadership Awards. This industry recognition can be credited to the members of the Avara global team, who are key to our success.
The pharmaceutical industry is at a critical juncture. Change is essential or we will lose the ability to develop and manufacture new medicines.7 Avara Pharmaceutical Services was created to help revolutionize the CDMO experience in preparation for the changes that must come. We are already simplifying the supply chain by offering end-to-end integrated services through a global network of state-of-the-art facilities. We are also focused on improving customers’ cost structures by finding new ways to drive efficiencies, providing security of supply, enhancing regulatory compliance and building long-term confidence by delivering on our commitments.
We are, in fact, committed to creating value across the entire supply chain. We focus on and care about our people, who are our greatest asset. They all recognize the need for an operational approach that maximizes efficiency, productivity and quality. We are also committed to forming long-term strategic partnerships with our customers, providing security of supply and meeting regulatory compliance requirements — all at a fair price.
Overall, at Avara we want to help our customers succeed by accelerating the delivery of drugs to the marketplace while facilitating the changes that must happen in the industry. We will continue to expand our portfolio with a focus on key regions around the world, including emerging markets, and services that can add or be complementary to our existing offerings. Emphasis will continue to be placed on the maximization of productivity and the minimization of unexpected issues, with total focus on serving our customers.
Andrea began his career with Pfizer in 1997 as a Business Control Analyst. In September 2015, he became Site Integration Leader for Liscate as part of the Hospira acquisition. In June 2016, Andrea returned to the Ascoli site as Director, Technology Services/OpEx/Business Development. In January 2017, he became the Site Leader for Liscate and worked on transitioning the company; he joined Avara in January 2018. Andrea has a degree in Business Economics and an M.B.A.