Stability testing services are a growing source of business for contract service providers, both from large and small sponsors. Providers in some cases identify the increase as an adjunct to outsourced product development, and the limited physical resources of small and virtual pharma companies. Among providers with a big pharma client base, the trend may be driven in future by a climate of increased regulatory scrutiny, growing product pipelines and industry consolidation.

Generally speaking, stability testing measures and documents the ability of a product to retain its potency prior to its predicted expiration date. Factors affecting the inherent stability of a product include the natural degradation rate of its APIs; resistance to microbial or fungal intrusion; reactivity with packaging materials; impurity levels imparted by the manufacturing process; and response to the stresses of heat, humidity and light.

Testing protocols vary according to the stage of lifecycle in which the testing is performed. In early development, stress testing is a tool to provoke a reaction or chemical change in the substance. These conditions are devised to verify inherent purity and devise expectations of its degradation after inclusion in a product. By exposing substances to controlled extremes of temperature, light and humidity, labs create an accelerated simulation of the expiration period.

As trials progress toward commercialization, the focus shifts to testing expectations over time. New variables are introduced: packaging, formulation and dosage. At each phase of clinical trials, stability batches must be set aside in long-term storage, and eventually verify the accuracy of the manufacturing process. Test batches become more complex at each step, representing every proposed dosage and package configuration.

Stability testing is inherently painstaking and meticulous; the administrative burden of data collection and reporting over the course of several years can be sizeable. Stability testing programs also require significant investment in the form of certified equipment and laboratory space, personnel, and even specialized tracking and management systems. Traditionally, this is more than a small company is willing (or able) to undertake for its post-commercial products.

Since all new product development carries a stability testing component, it’s understandable that the recent growth in contract development has created a corresponding increase in outsourced stability testing, especially among ‘virtual’ pharmas. Traditionally, smaller companies have relied on providers for stability batch storage of their commercial formulations. However, as CROs have evolved into development partners, they’ve adopted some of the preclinical testing burden, from basic analytical and stress testing, as well as consultative guidance in developing testing protocols in accordance with cGMP requirements. For example, XenoBiotic Laboratories has a significant client base of small pharmas. According to Neil Lewis, the company’s vice president, Pharmaceutical Division, “We find ourselves helping a lot of companies get to Phase I trials. Sometimes it’s simply rapid data collection, and sometimes we’re more involved with early methods development.”

Smaller companies are also seeking more outside help for pre-commercial testing in preparation for the NDA process. “Beyond the ICH guidelines, everyone still has different ways of reporting and administrating test data,” said Tom Handel, vice president of sales for Meridian Medical Technologies. “Controlling and managing the data is big challenge.” Consequently, one of the most important functions the
CROs have taken on is the aggregation and standardizing the data for NDA submissions.

And at no time has the management of this data been more important: the FDA cites stability-related issues as the primary cause of pharmaceutical recalls during the past two years. The explosion of new approval applications, consolidation and globalization of the industry, as well as the rise in contract manufacturing, have all contributed to a greater emphasis on proper reporting and compliance. Is it at all surprising that so many firms are seeking outsourcing relationships for these tests?

In virtual companies, with their slimmer business models centered on R&D, it is sometimes difficult to rationalize assigning top scientists to a task as mundane as stability testing. Many companies prefer to have their best and brightest on the cutting edge, where they create the most potential value.

Similarly, specialty pharma companies also depend heavily on CROs for these services. Companies like Bioglan, Elan and Shire, which strategically acquire product lines or license product lines and reformulate them for ANDA/sNDA applications or apply new delivery technologies, are a strong new source of contract testing business.

Demand has also increased from early-stage biotechnology companies, who bring with them a host of testing challenges. Michael Barron, senior business development scientist for The Pharmaceutical Development Business of Cardinal Health, described the difficulty: “We might be talking about as many as 10 separate tests to understand the biological aspects of a particular protein, because there isn’t any single potency assay.”

Further, biological substances tend to be inherently less stable, making tests more difficult to run. Understandably, Mr. Handel identified early-stage biotech as far and away the largest growth sector for stability services during the past three years, posting a 30% increase.

For a variety of reasons, large companies—even those with the facilities to maintain commercial-level in-house stability programs—are also turning to service providers for project work. As with manufacturing capacity, the pressure on Big Pharma to increase its development operations in recent years has created demand for stability and storage services that may outstrip long-term growth planning in facilities and personnel.

Industry consolidation has also had a significant impact. In some cases, large operations have acquired other pharmas or product lines, and in turn look to CROs for help in assessing volumes of clinical data and validating the acquired company’s processes. In cases where early stage products are integrated into a larger company’s pipeline, a sort of ‘referee testing’ may be required to establish continued compliance during the transition. This is true even in the case of mergers between large companies, each of which has established methods and procedures that only ‘referee testing’ can reconcile.

At the commercial manufacturing level, Mr. Barron has observed a trend “toward decentralized storage and testing, and centralized management and reporting. This creates greater supply chain efficiency for companies with multiple facilities.” Contract relationships now exist based on geographic location and convenience, where sponsors previously conducted their commercial batch stability storage at a single major facility.

One source speculated that the current political climate in the pharmaceutical industry provides a strong incentive for large companies to outsource testing, both in development and post-commercial stages. In light of recent high-profile manufacturing problems, CRO oversight in the form of long-term stability programs can provide an independent, credible and reliable means of achieving clearer compliance and greater accountability. “Regulation has always been tight,” explains Phillip Trager, Consumer Product Testing Co.’s director of analytical services. “The demand now is for better analytical data.”

The move to harmonize international standards has shed light on foreign manufacturing operations. Certainly, with large companies relying on contract manufacturing capacity for swing production, operating through subsidiaries and acquired companies, and locating their facilities throughout the world, centralizing post-commercial testing is often a necessary assurance of ongoing quality in the manufacturing process.

Fortunately, supply of services is strong. Unlike manufacturing capacity, contract providers offered stability services as an a la carte application before demand began to increase. Although individual contractors may have seen capacity bottlenecks, analysts report that provider capacity is readily available industry-wide.

What can be more difficult is finding a provider who meets your needs. As the outsourcing market moves to a longer-term project basis and away from sample work, many providers are being forced to adapt. As Mr. Barron said, “What I hear from customers is that it’s hard to find a provider who treats the business as a partnership.” He recommended examining the suitability of prospective providers in light of long-term relationships. “Look for depth of talent ‘on the bench.’ You want a situation where the departure of one analyst isn’t going to change the face of the company.”

All of the analysts we spoke with stressed continuity in testing relationships, indicating that once a provider has established familiarity with the specific chemistry of a product, it should be utilized for all phases of development. “Every time you change providers, you create additional administrative complications, because everyone formats their reports a little differently,” Mr. Handel remarked. Having one provider for the lifecycle of a development project should also result in a lower cost over time.

In part a reflection of fundamental changes in the pharmaceutical industry, both the volume and basic model of stability services is evolving. Whether due to a shift in sponsor development strategy, steadily increasing production demands, slimmer business models, or more stringent regulatory climate, strong growth is the prognosis for stability service providers.