Everyday Lessons from Extraordinary Circumstances. The business decisions we make often have unforeseen, far-reaching effects wholly unrelated to its original intent.

1. August 2, 2017
By Bryan Cox
The business decisions we make often have unforeseen, far-reaching effects wholly unrelated
to its original intent. These effects can be both intended and unintended, both positive
and negative. Just as a stone cast into the water can make ripples that reach far-flung
shorelines, our decisions can impact many facets of the business. Like everyone, we seek
to maximize the positive and minimize the negative.
In the pharma industry, the phrase “plant within a plant” is sometimes used to describe a
process that requires a greater degree of isolation from other processes within the same
plant. “Plant within a plant” scenarios are seen as most suitable for high potency drugs
produced in a facility that concurrently manufactures products with dissimilar safety and
regulatory requirements.
1
Plant within a Plant
Everyday Lessons from Extraordinary Circumstances

2. August 2, 2017
In late 2016, Pharma Tech Industries was contacted by a potential customer searching for a
manufacturer for its drug-device combination. The product was still in R&D but was
nearly ready for commercialization. The production process was unique, and many of the
analytical methods were customized. As if this were not challenge enough, the timing to
reach stability was very ambitious.
This new business would not be Pharma Tech’s first Rx, medical device, nor combo product,
but did offer several unprecedented challenges. The use of medical gases in the process
posed the first obstacle, one for which a steep learning curve was required. At the crux of
this product’s production is a chemical synthesis process necessitating a chemical
engineering skillset not previously utilized at Pharma Tech. The combination of complex
processes utilizing acids and toxic raw materials called for a new set of tools; The plant
within a plant concept allowed Pharma Tech to deploy these new tools while maintaining
more traditional systems and protocols that have become the lifeblood of our CMO
business model. In other words, we were able to segregate our proven successes from our
bold new venture.
Stacking the deck for success occurred from the earliest stages of the project’s tech transfer
phase. We were able to allocate the appropriate team of Pharma Tech personnel at the
customer location to effectively “pull” the equipment and process out of R&D and drop it
into our organization. This is a notoriously crucial stage, with vital knowledge uncovered
in complex equipment, proprietary processes, and test methods designed specifically for this
new product. It’s a difficult baton to find, let alone pass.
This early learning at the customer location helped us plan for this novel process to be
dropped into a manufacturing site with existing processes with little resemblance to its
former home. We had to decide early on what could be supported with existing systems
and what had to be handled with fresh, innovative approaches. This gave rise to the plant
within a plant concept of manufacturing at Pharma Tech.
First things first: the requirements for safety increased across the board. Personal
monitors found their way onto the list of required Personal Protective Equipment (PPE).
These monitors are used to protect each individual in the pharma suite from exposure to
any harmful gases. A monitor can be found on every lapel of every person that enters the
areas of the suite where there is opportunity for exposure. In addition, gas detectors were
placed at strategic locations throughout the suite. An alarm triggered by one of these
detectors will cause both the exhaust and supply system to ramp-up, resulting in a flushing
of air from the upset area. During normal operation, the system is designed for single pass
air. All of these features were included in the design so as not to compromise safety.
2

3. August 2, 2017
With the use of these specialty gases and other unusual raw materials, environmental impact
also had to be considered. Though environmental considerations are common in all new
products manufactured by Pharma Tech, this new venture entailed guidelines from a
separate set of regulatory bodies. For example, too much of a certain work in process (WIP)
material requires notification to Homeland Security, requiring a heightened level of
inventory management and traceability.
Current good manufacturing practice (cGMP) is familiar to most in our industry.
However, without the ability to effectively apply cGMP to a program, many days of misery
might be in store for those involved. After all, it is not a matter of if one will be audited
but when. All work completed from project conception will potentially be audited by the
Food and Drug Administration (FDA). Basic cGMP does not necessarily change for high
potency products but, understandably, they are held to a higher level of scrutiny. In
addition, applying good validation methodology to the complex processes, test methods,
and required room conditions can be difficult.
Each of the aforementioned moving parts presents unique yet interconnected challenges.
On one hand, there is the challenge of using our flexible systems in some areas to integrate
the new business into our current organization. On the other, there is the challenge of
keeping separate what cannot be commingled and still maintain safety and regulatory
requirements.
The “Plant within a Plant” concept protects less-than-required practices from creeping into
other areas, but many good things come from the challenges presented from this type of
program. Some amount of “mission creep” is invariably a good thing: when financially
feasible, an organization should strive for positive aspects of new endeavors to permeate
other areas. And whenever possible, these new learnings, skills, best practices, systems,
etc. should be sent to other benefitting areas of the organization. The increase in
knowledge and experience for those involved in a program like this will rival many years of
day-to-day work.
When the stone is cast into the water, the ripples will reach every shore. The real
challenge is to encourage the intended ripples to travel and restrict those that should remain
isolated. The great feeling of accomplishment will hopefully maintain the momentum of
the team to do it all again, and will raise the skills and capabilities in the surrounding
businesses to fuel continuous improvement.
3