Cancer is a leading cause of death worldwide, and the development of more effective, efficient and targeted cancer treatments is both critical and urgent. High potency active pharmaceutical ingredients (HPAPIs) have characteristics that allow the selective targeting of cancer cells, blocking their growth while causing less harm to normal cells.

With new classes of HPAPIs being developed, often better tolerated by patients and available in oral dosage forms, this area has become one of the fastest growing segments in the global pharma industry. According to industry research, their increasing use in oncology and other therapies is expected to drive the global market for HPAPIs to a compounded annual growth rate of 8.4% from 2009 to 2015¹.

Safe Containment is Costly and Complex
Many companies are choosing to outsource the development of these compounds for both strategic and economic reasons in the race to get new therapeutics approved and on the market. By outsourcing, they gain access to highly specialized experts and facilities while avoiding the significant investment and operational costs required for in-house capabilities.

The very thing that makes these HPAPIs so effective — their potency — adds layers of complexity to development and manufacturing processes. High containment facilities and procedures are required to ensure their safe handling by workers, protecting them and the environment, while avoiding any cross-contamination of ingredients that use the same equipment.

From purely a process-development perspective, there is little difference between working with low potency APIs and high potency ingredients. It’s the degree of potency that changes the equation, requiring more stringent precautions. Depending on the Occupational Exposure Limits (OEL), the requirements for personal protective equipment could be as high as astronaut-like suits with personal air-purifying respirators. Even at lower levels, those in analytical labs and manufacturing facilities might need to gown — and de-gown — and to go through decontamination procedures, including showers, when leaving the work area.

Within the containment facility, there must be appropriate levels of pressurized and filtered airflow, while dedicated wastewater systems are needed for safe storage, handling, treatment, and disposal. Every piece of equipment that comes into contact with high potency ingredients must be thoroughly cleaned before being used again. Emergency procedures must be in place as part of extensive risk management plans, both within the facility and in coordination with external responders in the local community.

It’s this increased level of containment operations, on top of the development work itself, that adds complexity and cost — and makes the decision to outsource so appealing to pharma companies watching the bottom line.

Full-Service Capabilities
Outsourcing customers are often virtual small- to mid-scale companies that have limited or no development manufacturing expertise or capabilities, especially with potent APIs. Even large pharma companies may outsource much of this work, mostly as a strategy for managing resources. For them, it can be a decision to defer capital investment or a matter of capacity constraint, as they may be unable to run all of their projects in parallel.

A key consideration for many customers when choosing an outsourcing partner is finding full-service capabilities for process development, analytical services and market supply. An ideal partner is one that can become involved in early formulation development, then see the project through to further process optimization and scale-up, process validation, and transition to commercial manufacturing.

Customers, especially virtual companies, often look for advice from their outsourcing partner, drawing on their expertise in the necessary steps and stringent standards to develop a product for market. They tend to value premium services in which the outsourcing partner can maintain the highest levels of containment and operator safety while delivering the agreed work packages on time.

There are a number of providers in the market that offer contract development and manufacturing services. Some are low-cost options that might initially seem attractive for purely economical reasons; however, many low-cost providers are also limited in their containment activities, with lower levels of occupational and environmental protections.

Outsourcing providers often specialize in certain steps of a product development lifecycle, with few offering a comprehensive full-service approach. Small- to medium-size contract services providers can be active in local markets only; others are global players. Some focus only on early phases of development or on later development; others provide only contract manufacturing.

A number of large pharma companies — GlaxoSmithKline, Hospira, Pfizer CentreSource, and others — have begun to offer their capabilities and experience in the contract development and manufacturing field. With their size, resources, expertise and capabilities, they often are able to provide the comprehensive continuum of services that is in demand.

Prioritizing Key Requirements
While each company may have different priorities when evaluating outsourcing partners for high containment development, the requirements typically fall into these six areas:

• Capability: presenting the right facilities and analytics; offering development and process transfer expertise from the lab to commercial scale; accommodating a portfolio of products; working in a variety of batch sizes; handling different high potency compound classes; providing excellent containment facilities.
• Quality: staffing trained and expert teams; providing full compliance with cGMP; delivering high quality products; meeting all requirements to protect the environment, health and safety.
• Reliability: ensuring safe data storage and transfer; delivering the agreed work packages — both product and services — on time and on budget.
• Flexibility: being able to react quickly to changing customer requirements and still deliver the agreed work packages on time.
• Speed: maintaining cycle times; developing the product even within tight timelines without causing any program delays.
• Cost: remaining cost competitive, or providing extra service and value for premium pricing.

These trends are reflected in the experience at Pfizer’s Freiburg Development/Containment facility, which is now six years old and remains a benchmark in the industry for innovative design and capabilities in the safe handling of high potency APIs, covering five bands of occupational exposure levels.

Strategic Decision-Making
There are many reasons pharma companies consider outsourcing: internal capacity constraints; decision to restrict investments in capital projects or equipment; strategy to remain flexible and agile in manufacturing; lack of expertise in development and manufacturing. Outsourcing can be a way to bring products through their pipeline quicker, access a greater range of technologies and specialized services, and gain a competitive edge.

When it comes to outsourcing high containment development, most companies look for a strategic partner with which to build a long-term relationship. Those that are successful often think beyond a single product or a few months’ development work. They establish a trusted relationship that will last over years and bring many important new patient therapies to market. 

Reference
1. Source: GBI Research, “Global HPAPI Market, Revenue Forecasts, 2009-2015,” published March 2010.

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Dr. Bernd Schümmelfeder, a pharmacist by training, serves as director/team leader PPD Business Development to evolve the new Contract Service business mainly in the high containment product development area.Cristin Grove serves as director, Global Contract Manufacturing for Pfizer CentreSource (PCS). Her organization markets third-party manufacturing capabilities to the pharmaceutical industry. For more information about this article, please contact [email protected]