Optimizing API Production as a True Manufacturing Partner

The required attributes of a good API — namely quality, safety and effectiveness — stem from good manufacturing processes. With an ever-expanding global patient population and the increased requirement for outsourcing, carefully selecting the right facilities and, ultimately, the right contract development and manufacturing organization (CDMO), has never been more important. 

With an established track record of high-quality, reliable cost-effective performance and highly experienced employees, Avara Pharmaceutical Services is rapidly becoming recognized as a full-service CDMO with integrated capabilities designed to meet customers’ needs. Many outsource service providers are strategically acquiring sites that expand their ability to be part of the global supply chain solution. Since 2015, Avara has acquired four manufacturing sites from large pharmaceutical companies as part of its global strategy to provide high-quality manufacturing and timely delivery from a comprehensive integrated network of facilities. Two of the new facilities, Arecibo, Puerto Rico (acquired from Merck) and Norman, Oklahoma (acquired from Astellas), provide secondary manufacturing/drug product and packaging. The remaining two, Avlon in the UK (acquired from AstraZeneca) and Shannon, Ireland (acquired from UCB) specialize in APIs/primary manu­facturing.

CDMOs integrate all aspects of drug development and manufacturing, including APIs and formulations. This approach is attractive to drug makers, who generally want to simplify their supplier bases while ensuring quality and regulatory compliance within their supply networks. It is a risk-sharing strategy that to be successful requires true partnerships and complete trust in the operations and leadership of any prospective CDMO partner. 

This is fundamentally needed when we consider that the Active Pharmaceutical Ingredient (API) market is expected to reach $213.97 billion by 2021 from its current $157.95 billion in 2016, according to Research and Markets. “At Avara, we are acutely aware of the need for highly competent and reliable outsourcing partners to truly support customers by managing their supply chain,” according to Gary Butler, Vice President and Site Director at Avlon.

“At Avara, we are acutely aware of the need for highly competent and reliable outsourcing partners to truly support customers by managing their supply chain,” according to Gary Butler, Vice President and Site Director at Avlon. 

Choosing API Sites to Serve the Market

Key criteria that Avara applies in qualifying one potential API site over another are the culture of the site and its history of performance. Both Avlon and Shannon meet these standards. Avlon and Shannon each offer high hazard chemistry; Shannon’s multiproduct API facility can also handle many difficult chemistries, most prominently nitration. Shannon features a number of different milling and blending technologies to add additional value to the API. The Avlon and Shannon facilities have strong technology transfer records and cGMP manufacturing environments supported by the latest processing and fini­shing technologies. “Avlon and Shannon have a proven track record for many years delivering complex products and projects with the customer always as the center of the focus and as a true partner,” explains Werner Kunz, Vice President and Site Director at the Avara Shannon Site.

Another criterion supporting Avara’s strategic acquisition strategy is that the potential site has an excellent compliance and regulatory history, with no environmental liabilities and a strong process safety record. Each of Avara’s API sites also has excellent FDA and MHRA inspection records. Avlon is a top-tier Control of Major
Accident Hazards (COMAH) site, with extensive experience handling the materials and processes required for high hazard chemistries. Given the rising demand for API suppliers, such API manufacturing capa­bilities are increasingly critical to serving a
partner’s drug development strategies.

The personnel tie all of this together. An organization with a strong culture that combines a deep understanding of specialty API production, based on a wide range of technical competencies with a safety mind-set, represents the secure trusted partner that drug owners require to assure long-term strategic success.

API Optimization at Avlon and Shannon

Avlon supplies APIs for two of AstraZene­ca’s (AZ) best-selling drugs, Crestor® (rosuvastatin) and Seroquel® (quetiapine), which together accounted for a third of the company’s sales at one point. Despite going off patent, they are still top-five brands for AZ. The site remains a critical part of AZ’s supply chain, through its deal with Avara. AstraZeneca invested strategically in the Avlon site, installing advanced R&D, clinical trial material production, scale-up and full-scale manufacturing capabilities. Avara’s strategy for the site is similar. In fact, Avara is currently bringing existing additional chemistry labs and a kilo-scale lab with two walk-in facilities back online. 

The Avlon team’s experience managing the life cycles of Crestor and Seroquel offers continued value. Demand for Crestor and Seroquel has significantly exceeded initial volume expectations. Avlon was able to increase existing capacity and optimize the chemistry and manufacturing processes with augmented batch sizes and improved cycle times. Applying advanced problem solving, chemistry and statistical techniques, and experimental design to multistage processes has allowed the site to increase production from 100 to over 400 tons/year.

Shannon continues to produce the API for UCB’s Neupro®, a €350 million/year Parkinson’s disease therapy, which is still under patent protection. The site was also heavily involved in late-stage chemical development for three current market NCEs, with combined revenues of more than $2.0 billion/year, and in the past was also very active in developing chemical processes for the generics market. It also currently manufactures 70-80 tons/year of two particular APIs for many clients and worldwide supply. With a level of manufacturing competence matching sister-site Avlon, Shannon maintains an on-time in-full (OTIF) record of nearly 100%. 

“Avlon and Shannon have a proven track record for many years delivering complex products and projects with the customer always as the center of the focus and as a true partner,” explains Werner Kunz, Vice President and Site Director at Shannon.

Combined Capabilities

While Avlon and Shannon have unique histories, both sites share the attributes of expertise and experience that will enable them to represent an integrated, single offering. With experience in lean manufacturing and operational excellence based on Six Sigma principles, both have a strong best-in-class culture and a track record of implementing process improvements to reduce the cost of goods and avoid capital expenditures. Each site has delivered products over a long period of time, stewarding them through their life cycles. The veteran personnel at Avlon and Shannon know where the value lies within the supply chain, and have identified the work needed to deliver opportunities and mitigate risk for their customers.

Avara pursues its market strategy to operate as a tightly integrated CDMO, rather than a collection of stand-alone sites. From the moment any acquisition deal is signed, the company works to integrate its operations and people into every aspect of the corporate culture under a single brand, in which common values and standards are shared. Although Avlon and Shannon bring individual capabilities, together the sites are key elements of Avara’s strategic global manufacturing model, ready to put their capacity and experience to work for global partners.

Communities of practice covering areas such as Operational Excellence; Safety, Health & Environment (SHE); and Manufacturing have already been established across the sites, each sponsored by a site leader with an agreed common agenda that will be deployed uniformly across all sites.

To be an effective partner, Avara also recognizes the need for autonomy at a given site. This is in order to maintain total customer focus depending on the product and supply chain. With highly experienced management, staff and operators, each site can define its role for customers and align itself to meet those needs. That role is the same, ultimately, for all sites — fulfilling the company promise to the customer that Avara will deliver reliably, to the highest-quality standards, on-time and in-full, while using its skills and experience to take out costs and manage supply chain issues.


Jim Scandura

Jim Scandura has a wealth of pharmaceutical industry experience through projects with i-Solutions — a Life Sciences specialty consulting company. He has managed three major pharmaceutical manufacturing network change programs, three consent decree recovery efforts, over 30 manufacturing-site audit and operational improvement efforts, integration of a large R&D center, and the direct management and integration of several manufacturing sites. Mr. Scandura has experience working for Bristol-Myers Squibb, GSK, Roche, Valeant, Patheon, Aptuit and many other pharmaceutical companies. Previously, he was Senior Vice President at Johnson Controls Inc. and, prior to that, served in the U.S. Navy Nuclear Submarine Service.