22 MARCH 2015 ◗ pharmpro.com
ORAL SOLID DOSAGE TECHNOLOGIES
may emphasize schedule, if an organization aims to capitalize on a
time to market opportunity, or cost, if an opportunity to gain market
share or profitability via lower pricing or greater profit margin exists.
Reality dictates that constraints exist. Project constraints must be
identified as early as possible, either to define project scope boundaries or, perhaps, to introduce a new business driver, if it is deemed
necessary to aim capital at the elimination of a constraint. Existing
utilities generation or distribution capacities are examples of potential
constraints that could be eliminated, if justified or required, to meet the
business needs of the project. Other facilities related constraints might
include waste or solvent handling capabilities, HVAC systems limitations, site size or local code restrictions. Operational constraints include
maximum staffing and allowable working hours. Business related constraints include capital budget and project timeline.
Once drivers and constraints have been set, the product portfolio,
volume demand forecast, and potency profile for the range of compounds to be handled must be established. Occupational Exposure
Levels (OELs) and Acceptable Daily Exposures (ADEs) must be assigned
to potent products, so that project containment and cleaning philosophies can be drafted. Many organizations have documented banding
systems that govern how process and equipment containment, room
pressurization, air handling methods, personnel gowning and personal protective equipment are employed, based on varying levels of
product potency. OELs are needed to categorize products in bands,
and ADEs are required to assess cross-contamination risk as it relates to
cleaning, and the potential decision to dedicate equipment or areas to
special class products. It must be unmistakably clear when engineering
controls are necessary, in lieu of procedural solutions. If the organization does not have established rules of containment, then these must
be developed, prior to any significant expenditure of design or construction resources.
Once the production volumes, containment and segrega-
tion requirements have been determined, the process can be
designed. The team will work through each unit operation and
consider containment measures where potent products may be
exposed, such as in sampling or dispensing, or during material
transfers between unit operations. The analysis will be used to
identify the inputs, outputs, and corresponding work-in-pro-
cess (WIP) staging requirements of each unit operation. This is
also the time to address cleaning requirements and equipment,
which will depend greatly on containment needs.
Organizations will confront highly complex decisions at this
stage of the project. Recently, a new facility was designed for a
generics company to manufacture both established non-potent
products and future highly potent products. The following are
examples of issues that the project team faced during the plan-
• Can the same process rooms and equipment be used to manufacture both potent and non-potent products if they require common unit operations and have similar batch size ranges?
• Will equipment be specified for high containment, even though it
is not required initially?
• Will the profitability of non-potent, established products be
adversely affected if they are manufactured using sophisticated
equipment and components with containment features?
• Can the investment in containment technology be deferred without sacrificing the ability to manufacture potent products in the
• Will separate physically segregated areas be required to manufacture special class products, such as hormones or cytotoxic drugs?
• How will the above decisions to share or dedicate manufacturing
resources according to potency classification affect the design
and sizing of cleaning equipment and areas?
The size, cost and complexity of the facility can
vary tremendously depending on how these issues
are addressed. Potential solutions will vary among
unit operations, as well as equipment manufacturers.
For example, several major tablet press manufacturers offer equipment capable of achieving OELs
down to 1.0 microgram/cubic meter or below, but
their approaches to containment and cleaning are
quite different. Some companies offer washable
presses with separate cleaning skids, which are typically located in a mechanical area. Another supplier
offers a unique system where product contact parts
are removed in the form of a sealed compression
module, placed on a custom cart with wash fittings
and taken to a cleaning skid to be cleaned-out-of-place. Although it is certainly desirable to have these
options, having to select from among them adds yet
another layer of complexity.
The opportunities for generic OSD manufacturers
and CMOs to grow their businesses have never been
greater, nor have the challenges that accompany
these opportunities. It is more important now than
ever for these organizations to align themselves with resources expe-
rienced in confronting the vast complexities inherent to designing a
flexible potent-compound multi-product generic OSD facility.