With markets and opportunities constantly changing, growing, and shifting around the globe, pharmaceutical companies are now, more than ever, eager to tout their global capabilities. In the world of pharmaceutical contract manufacturing this desire is no different. While many pharmaceutical outsourcing providers may claim to have global reach, it is the rare company that can back up this statement with physical operations and personnel in many of the world’s hottest marketplaces. AMRI, which maintains its corporate headquarters in Albany, N.Y., is one of those companies that has the facilities and technical expertise to operate anywhere in the world.
The company boasts operations in Albany, Rensselaer and Syracuse, N.Y.; Burlington, Mass.; Hyderabad and Aurangabad, India; and Holywell (Wales), United Kingdom. According to Steven Hagen, Ph.D., the company’s Vice-President of Pharmaceutical Development and Manufacturing at AMRI, the company’s goal is to “carry out services in an integrated fashion. We try to utilize our assets around the world to provide timeliness, service and quality to provide value to our customers.”
The company accomplishes this by leveraging its global facilities and the specific expertise each site has to offer. As Hagen explains, “In general if you have a commodity type of product you might look toward India; if in Europe you could use our UK site; if you need high capacities or tonnage of API the Rensselaer facility is ideal for that. We have aligned our operations to provide our customers with a complete supply chain no matter where they are in the world, and the quality and capability of our staff is comparable regardless of location.”
The World Tour
The capabilities of AMRI’s worldwide facilities are loosely categorized as either providing pharmaceutical services or chemical development services. The pharmaceutical services sites mainly provide drug product development and manufacturing, as well as the associated regulatory capabilities, while the chemical development sites provide chemical process development and small and large scale API manufacturing capabilities. But within this network there is much crossover and complementary overlap.
For example, the company’s Albany site provides formulation development and preformulation studies in support of non-sterile GMP drug product manufacturing in Rensselaer, NY, and aseptic fill and finish GMP manufacturing in Burlington, MA. The Holywell, UK operation offers kilo lab, pilot plant (GMP) and large scale manufacturing capabilities. And, as Hagen points out, it also offers a number of benefits to the company and its customers, “The UK site can perform chemical process development and small scale manufacturing. We often see Holywell as an entry point into the rest of AMRI for our European customers. What we have found is that for development scale work most of our customers want someone relatively close by to get the work started and then once the project gets some legs and starts to expand you can bring it into a larger network. But at the beginning it’s very complicated; there are a lot of people involved and you need to move quickly – it’s good to have a local point of contact.”
AMRI’s Hyderabad Research Centre offers custom synthesis services from lab scale-up to kilo lab amounts. The Centre’s cGMP analytical chemistry services include: chromatographic (HPLC, GC) method development and validations; stress degradation studies to develop and validate stability indicating methods; impurity identification by LCMS, GCMS and NMR; reference standard certifications; and wet chemistry tests as per USP.
The Hyderabad research facility works in conjunction with and complementary to AMRI’s Aurangabad facility which offers facilities for generic API production and has a capacity of approximately 70,000 liters. The facility also manufactures GMP intermediates and boasts two 500 liter, two 1,000 liter glass-lined reactors, and a 750 liter cryogenic reactor.
Closer to home and falling more under the chemical development umbrella are the facilities in Albany, NY which provide services such as process development, design of experiments (DOE), critical processing parameter (CPP) studies and tech transfer along with biocatalysis and fermentation capabilities. The Syracuse, NY site offers small scale pre-clinical batch production of APIs and intermediates, rapid response services and route selection and early scale-up activities.
“All of our sites can handle API development,” notes David Lathbury, Ph.D., AMRI’s Vice President of Chemical Development, “but each have their strengths. Underneath everything is the need for process understanding and analytical capabilities. You have to put all of this together. For example you need to know – this is how it works, why it works, this is why we get these impurities, this is how we identify and control impurities and it all comes together. Process understanding ultimately leads to process validation which then enables you to file for approval. However, even in early phase API development, process understanding is vital in terms of future optimization and basic risk management.”
An AMRI-Rensselaer technician monitors the production of an API in the
GMP manufacturing facility.
“The integration of manufacturing with analytical and chemical development is our strength. Some companies do bits of it well – but our approach to eventual commercial manufacturing sets us apart from many other CMOs,” he concludes.
Commenting on the company’s wide breadth of pharmaceutical services and chemical development capabilities, Hagen sums it up succinctly, “What we’ve tried to create is a pharmaceutical services organization that can handle just about any lead compound, get it to where it can be applied to animal or human studies, work that through development and commercialization so that our customers can efficiently get it out on the market.”
The Scientific-Based Quality Driver
Underpinning all of AMRI’s development and manufacturing work is the company’s pharmaceutical and quality services (PQS) group. PQS provides an essential foundation for the company’s product development processes as it is within this group that critical support is provided as the manufacturing process is being developed, optimized and set in place.
PQS supports the company’s efforts with a wide range of pharmaceutical development, quality assurance and regulatory affairs services including:
• Analytical Development and Separation Sciences
• Spectroscopy Services
• Preformulation & Materials Science
• Formulation Development
• Quality Assurance and Regulatory Affairs Services
This department within the company is also somewhat unique as it operates differently when compared to similar groups in other companies. At AMRI a developmental scientist is assigned to the product and helps shepherd it through testing, pilot plant and into manufacturing. This elimination of “silos” ensures a smooth transition from one phase to the next.
“At AMRI our scientists don’t work in isolation,” says Junan Guo, Ph.D., Vice President, Pharmaceutical and Quality Services, “they work integrally with other groups within the company to offer an integrated approach. They offer continuous support through the drug’s development lifecycle.”
A Closer Look at AMRI's Small Scale cGMP Kilo Labs and API Operations
One of the linchpins in AMRI’s global network of facilities is its combination of small scale cGMP kilo labs along with its large-scale API manufacturing site. The small scale cGMP kilo labs are co-located with Chemical Development at the Albany headquarters campus. These kilo labs provide the first scale up of processes that come out of the Chemical Development group and serve as the conduit for further process scale up at AMRI’s large-scale manufacturing API site in Rensselaer.
Small Scale cGMP Manufacturing
• Eight separate and fully dedicated cGMP kilo suites with a total production area of ~6000 sq. ft.
• Suitable for API production at clinical Phase I, II and III.
• Small gram to 10 kg batch scale.
• A flexible mixture of 22–200 L hastelloy and glass jacketed reactor systems.
The large-scale API manufacturing Rensselaer site has been the home to various companies over the years and was initially founded by Bayer over 100 years ago and was the first US site to manufacture aspirin. In the last 15 or more years, AMRI as well as the site’s previous owners have invested tens of millions of dollars to upgrade, modernize and add capacity.
“We have everything needed to produce quality APIs safely at this 23 acre site,” says Richard Saffee, General Manager, Operations at the Rensselaer site, “but on top of that we are able to draw upon the experience of our colleagues from anywhere in the world.”
Classified by type and production capacity the Rensselaer site offers the following capabilities and equipment:
Pilot Plant Facility
• Utilizes four production suites using an open plan, multi-purpose reaction train system.
• 50 to 300 gallon glass-lined and hastelloy reactor trains.
• Multi-functional filtration/dryer technology capabilities.
• Typical production scale is 5 to 100 kg.
“The pilot plant facility is an open concept facility,” says Saffee. “We can mix and match equipment and run chemistry across all of them.”
A technician tracks the progress of a chemical transformation in the
GMP Pilot Plant in Rensselaer.
AMRI boasts three high potency (HP) compound production suites all in a state-of-the art facility. “This is one of the outstanding capabilities that this site has,” says Saffee. “The ability to start at grams and move up to higher quantities – our customers tell us that rarely can they find a CMO that has this capacity and capability.”
AMRI boasts three high potency (HP) compound production suites all in a state-of-the art facility. “This is one of the outstanding capabilities that this site has,” says Saffee. “The ability to start at grams and move up to higher quantities – our customers tell us that rarely can they find a CMO that has this capacity and capability.”AMRI boasts three high potency (HP) compound production suites all in a state-of-the art facility. “This is one of the outstanding capabilities that this site has,” says Saffee. “The ability to start at grams and move up to higher quantities – our customers tell us that rarely can they find a CMO that has this capacity and capability.”
HP Production Suites include:
Small Scale Suite
• Howorth Technologies 3.8 m3 Isolator
• Capable of total containment for glass reactors up to 25-L.
• Typical production scale is 25 g to 2 kg.
Mid Scale Suite
• Flanders 1.74 m3 Isolator.
• Walk-in laminar fume hoods with 50-L to 400-L glass and Hastelloy reactors.
• Typical production scale is 1 kg to 40 kg
Large Scale Suite
• Howorth Technologies isolators.
• Reactors up to two Hastelloy 1200-L reactors.
• Typical production scale is 3 kg to 120 kg.
• Services and overhead connectivity are “plug and play” for rapid re-configuration of equipment trains.
Moving on to the larger production capabilities at the site, AMRI Rensselaer offers:
• Four large production buildings.
• 42 discrete chemical reactors, comprising a mixture of glass-lined steel, hastelloy, and stainless steel reactors.
• Four dedicated pressure-rated vessels for hydrogenation capable of operating up to 90 psig.
• Eight jacketed pressure filter-dryers (1.5 m2 – 6.0 m2).
• Additional drying capabilities include cone dryers, tumble dryers, and vacuum tray dryers.
• Highly-experienced Technical Services, Chemistry and Engineering Services for process evaluation, implementation, use-testing, reaction monitoring and trouble-shooting.
• Full-service GMP-warehousing with ambient, USP, refrigerated and freezer storage conditions.
Backing up and providing an essential service to all of this pilot plant, scale-up, high potency and production capacity is the site’s quality control lab. According to Brian Haney, Ph.D., Section Head Commercial Manufacturing, one of the benefits to having all of that analytical capability on-site is for rapid troubleshooting. “If we are conducting early scale-up work and something goes wrong we can immediately assign resources to the problem. Our scientists can usually figure out what the problem is very quickly, which gives us ideas how to adjust the scale-up process.”
“That’s where the power of these labs comes in handy– the immediate response to situations as they arise.” Haney concludes.
From analytical and quality control services, to compound and process development, pilot plant and scale-up through commercial manufacturing, AMRI offers a wide range of capabilities to the pharmaceutical customer looking for an outsourcing partner.
“We have everything a large pharma company has, but without that large pharma culture,” says Saffee. “We deliver on the costs, the quality, and consistency of service and we are focused on our customers’ deadlines and success.”
“When we demonstrate how thorough we are in our operations – we gain our customers trust and they keep coming back.”
“For a customer the value/benefit is that they can stay with AMRI the whole way. In addition, customers get a very capable project management team. Most members of our project management teams are scientists, they have come through the development function, so they can speak the language, and they understand the chemistry and serve as the go-between and the voice of the customer when they are not around. Our customers are global – and we are available 24 hours a day.”
With a worldwide operation backed by the technical expertise needed to provide exemplary service to a global customer base, one might think that the company would be content to rest on its laurels, but that’s not the case. AMRI recently launched a new program called SMARTSOURCING™ which is a series of strategic sourcing options for its current and future customers to reach more successful outcomes.
SMARTSOURCING™ is a pioneering approach for the industry that is fit for purpose in today’s world and puts the power of decision making, without compromise, in the hands of the customer.
According to Thomas E. D’Ambra, Ph.D., President and CEO of AMRI, “Pharma companies are looking for more supplier accountability, greater trust and consultation. They want a better balance of risk, but also greater flexibility and tailored business models that address their unique needs. We wouldn’t be in business without our customers and we take this seriously. Our goal is to continue to improve our operations and performance because helping our customers to succeed is our mission.”