Has Outsourcing Derailed PAT and QbD?

Quality management requires more effort in a complex supply chain.
Aug 02, 2011
Volume 35, Issue 8

Daniel R. Matlis
In the days when pharmaceutical companies were vertically integrated, industry and regulators began to develop ways to change the paradigm for pharmaceutical manufacturing from "testing quality out" to "building quality in." These collaborations resulted in innovative approaches under FDA's Critical Path Initiative and included process analytical technology (PAT) and quality by design (QbD).

PAT continues to drive industry to gain a deeper understanding of its products and manufacturing processes to allow for tight controls over critical quality attributes (CQAs) and process parameters (CPPs). This approach supports the implementation of control strategies aimed at improving quality while reducing the need for in-process and finished-goods testing. To collect, act, and capitalize on the knowledge gained from identifying and monitoring CQAs and CPPs, many companies have been and continue to invest significant resources in data acquisition, historian, and manufacturing execution systems.

These paradigms were designed to enable life-science organizations to speed time to market, improve quality, and lower costs while facilitating compliance with regulatory requirements.

The outsourcing effect

The pharmaceutical industry is also increasing its level of outsourcing of noncore activities, processes, and supplies as a means to lower costs. As a result of outsourcing, many brand owners have lost their visibility into CQAs and CPPs. When a company does not own the equipment, it is often difficult to collect, act, and capitalize on indicators and parameters. These data are needed to achieve PAT and QbD, and also have a significant effect on drug product safety, efficacy, and quality.

Despite this problem, globalization and outsourcing are here to stay. According to Congressional testimony given by FDA Commissioner Margaret Hamburg, "up to 40% of the drugs Americans take are manufactured outside our borders, and up to 80% of the active pharmaceutical ingredients in those drugs comes from foreign sources" (1).

According to findings from Axendia's Life-Science Global Supply Chain research, 78% of industry executives expect global sourcing to increase, and 76% anticipate their global manufacturing to grow (2). These executives also reported that they expect the top threats in the next five years to stem from these same trends. While 74% identify contract manufacturing as a "significant or moderate risk," 61% view contaminated or nonconforming raw materials as a top threat.

Today, visibility into the pharmaceutical supply chain is largely based on "snapshots in time" with little sharing of common practices and information. According to Axendia's research, more that three quarters (77%) of industry executives responding to the survey indicated that the primary method used to gain visibility into suppliers is a periodic audit. Only 25% stated that they share common practices and information with suppliers and only 3% said they have real-time access to their suppliers' data.

An audit, although required, provides visibility into a specific timeframe. After an on-site visit, the next time a sponsor company is likely to get data from the contract supplier or manufacturer is either when it receives a batch of product along with some form of document such as a quality certificate or a certificate of analysis.

This lack of visibility is illustrated by the low proportion of survey respondents able to gather critical information across their product supply chain in a timely manner. Only 19% of executives reported that they could obtain needed information from critical suppliers within two hours.

Interconnected systems that enable "on-demand-visibility" (i.e., the ability to obtain relevant product information at the appropriate time to enable decisions with a high degree of confidence) within an organization and its suppliers/contract organizations is also limited. Only 28% of survey participants said they could obtain information from their company sites within two hours, and only 43% could obtain the information within a business day.

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