The bio/pharmaceutical industry is witnessing two important manufacturing trends. First is the increasing adoption of quality-by-design
(QbD) approaches to enhance process understanding, which results in a long list of consumer, regulatory, and business benefits.
The second trend is the increased use of contract manufacturing organizations (CMOs) to better manage plant capacity and control
production volumes.
According to the 2012 BioPlan Associates' 9th Annual Report and Survey of Biomanufacturing, "Relatively few companies have
outsourced all of their manufacturing, but nearly one-half of surveyed manufacturers expect to increase their budgets for
biopharmaceutical CMO outsourcing (in 2012)" (1). As relationships with CMO relationships increase and expand, and QbD becomes
more essential to business strategy, it is important to examine best practices for determining quality metrics across CMO
and sponsor networks.
A CHALLENGING INTERSECTION
At the intersection of QbD and CMOs is the challenge for sponsor organizations, who have invested time, technology, and resources
into QbD programs for their own manufacturing sites, to ensure that products manufactured by CMOs meet similar quality expectations
for safety and efficacy. With QbD in mind, many biopharmaceutical manufacturing teams have integrated process intelligence
technology tools and practices into their working approaches to collaborate across company-owned (or captive) global sites.
Such tools can help teams access large amounts of process data stored in disparate systems (e.g., laboratory information management
systems, enterprise resource planning systems, manufacturing execution systems, and records stored in paper formats) for proactive
process monitoring and investigative analysis.
As part of the QbD process, many sponsors have developed sets of critical process parameters (CPPs) and key performance indicators
(KPIs) to routinely monitor processes and increase inhouse process understanding. When it comes to outsourcing, sponsor companies
desire a similar level of monitoring and understanding from their CMO partners.
The complexities of data sharing across sponsors and third party CMOs—many of which may be geographically dispersed—include
the following challenges:
- Sponsors and CMOs have different operational models and, therefore, different interests when it comes to data. Sponsors are
looking for quality assurance of the product, while CMOs most often use process data to compare one batch with another at
a local level. The manufacturing processes of CMOs can also vary greatly between plants, which means that direct site-to-site
data comparisons may not be appropriate.
- Most existing sponsor–CMO contracts do not fully specify which data must be shared, or what mechanism should be used for sharing
it. In addition, contracts often do not incorporate enough flexibility to take advantage of improvements in process or data
sharing technologies that may become available during the life of the agreement. Data sharing is usually limited to release
data for regulatory requirements, and does not include data that are comprehensive enough for the proactive monitoring and
investigational analysis required for QbD and continuous process verification. In addition, CMOs tend to produce products
for several customers and can be cautions when it comes to allowing sponsors to tap into existing IT systems to retrieve data.
- CMO records are frequently stored and communicated to sponsors as paper-based documents, making access and analysis difficult.
Sponsors need to collaborate with CMOs to develop monitoring programs that assist in process understanding and verification
at CMO sites, similar to the programs sponsors have developed for use across their own global manufacturing networks.
