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).
Daniel R. Matlis
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'
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.