Optimizing Package integrity operations for multiproduct CDMO facilities.
By: Tyler Harris, Application Engineer, PTI Inspection Systems
A growing pipeline of new and complex therapeutics has led to a monumental shift in business
strategy across the pharmaceutical industry. The
traditional approach of targeting one blockbuster
drug to drive sales is a thing of the past, pushed to the
wayside long ago by a combination of addressing unmet
medical needs in smaller patient populations and an increased
focus on efficiency and flexibility. Now, multiproduct
manufacturing allows CDMOs to serve a wide range
of clients and products, ultimately accelerating production
and improving capacity utilization. Doing so successfully,
though, while maintaining quality throughout the product’s
life cycle until delivery can be challenging.
A critical component to achieving this is container closure
integrity testing (CCIT), which offers assurance of a package’s
ability to prevent loss and maintain product sterility.¹
However, the effectiveness of any CCIT method is based
on physics and the interaction of the product and package
characteristics. Thus, with so many product and package
combinations in use, how do you as a CDMO optimize
operations in your multiproduct facility while also ensuring
the technology you invest in can meet the needs of pharma
manufacturers and their products?
PROBABILISTIC VS. DETERMINISTIC:
A critical component to achieving this is container closure
integrity testing (CCIT), which offers assurance of a package’s
ability to prevent loss and maintain product sterility.¹
However, the effectiveness of any CCIT method is based
on physics and the interaction of the product and package
characteristics. Thus, with so many product and package
combinations in use, how do you as a CDMO optimize
operations in your multiproduct facility while also ensuring
the technology you invest in can meet the needs of pharma
manufacturers and their products?
PROBABILISTIC VS. DETERMINISTIC:
IDENTIFYING YOUR PATH TO
QUALITY AND COMPLIANCE
To understand the complexity of this issue, it is important
to identify the key differences between the two categories
of CCIT methods ? probabilistic and deterministic ? and
what impact selecting one over the other has from both
an efficacy and a regulatory perspective. Several guidance
documents are available to help you with this task, yet USP
<1207> provides one of the more thorough overviews, including
what is available on today’s market and what the
critical differences are between them.
Probabilistic methods rely on a series of sequential and/or simultaneous
events, each associated with uncertainties, yielding
random outcomes described by probability distributions.²
They often require a large sample size and are only visually
assessed by a technician, leading to qualitative and subjective
results. While USP <1207> does not warn against using these
methods, it does stress the need for reliable and accurate test
data. Therefore, using probabilistic methods could put the
manufacturers you serve at risk of facing scrutiny from regulators
about why a method that offers more definitive results
about package integrity wasn’t used instead.
The alternative is deterministic methodology, which follows
a predictable chain of events, and leakage is measured using
physiochemical technologies that are readily controlled and
monitored, yielding objective quantitative data.² The investment
in a deterministic method can be more significant, but
the ROI this type of CCIT method offers is high when taking
the benefits of deterministic into consideration, which can be particularly beneficial for a CDMO seeking increased
efficiency in a multiproduct facility. This includes not only
consistently reliable, science-based data but also several advantages,
including a non-destructive approach to testing
and easy changeover.
When faced with selecting a CCIT method to implement, you
must weigh the difference between the investment and longterm
benefits. Quality assurance has always been an investment
that provides little measurable short-term ROI but always
wins out in long-term performance. Ask yourself ? which option
will help elevate your service above your competitors’?
SELECTING A CCIT METHOD
WITH OPTIMIZATION IN MIND
If you’ve decided that an accurate, reliable, and repeatable CCIT
testing method is the best way to maintain quality and differentiate
your service from others’, then it’s time to gain a better
understanding about CCIT and, most importantly, what deterministic
method is the best fit for each application. The first
question you will need to ask is – what is the level of detection
required? This is identified through the customer’s own internal
assessment based on the product and the risk associated
with contamination. There are many types of breaches possible
in a manufacturing environment and understanding what they
are and how to prevent them offers manufacturers protection
against a wide range of issues, such as lot-holds and costly recalls.
Using the most appropriate CCIT method can help achieve
consistent quality as well as sustainable compliance.
The next factors to consider are the products they want to
manufacture and the package format intended for the application.
As mentioned previously, the physics and the interaction
of the product and package combination are critical. Other
factors, such as the head space within a container and product
viscosity and chemistry, can also impact how successful one
method is over another. With this information in mind, you’ll
then need to look at the options for deterministic methods
available on today’s market, of which there are several.
For example, vacuum decay is a versatile deterministic method
that works well for not only lyophilized products but also small
molecule liquids in a wide variety of package formats. It offers
defect detection of under 1 micron, making it the gold standard
for package integrity testing in the industry today. The
level of sensitivity used in a vacuum decay test is a function of
the package design, the package test fixture, and critical test
parameters of time and pressure, all of which are determined
by the scope of the project and product needs. There is also
the ability to have multiple test chambers in one instrument,
with each test chamber designed to contain the package to
be tested, offering the flexibility and efficiency a CDMO with
a multiproduct facility needs to reduce costs but also maintain
a high level of quality.
While vacuum decay can cover a large percentage of applications,
it is not a fit for all. Project scope must remain the primary
criteria for selecting the right CCIT method. There is never a one-size-fits-all solution, but there are inspection methods
that can cover multiple applications without significant added
investments. An experienced and knowledgeable technology
provider can help you with your decision-making process, using
only the most critical factors of a product’s needs as your
guide. Be wary of decisions made on a price tag only and not
the overall ROI, as this could result in selecting a method that
leads you down a path toward high costs, poor results, and
potentially, non-compliance.
RELIABILITY AND FLEXIBILITY
FOR MULTIPRODUCT
MANUFACTURING
The pharmaceutical industry today ? like the world it resides
in ? is a fast-changing and unpredictable environment.Customers look to their outsourcing partners for an optimized
manufacturing strategy that offers reliability and flexibility
throughout the life cycle of their product. They want
to be sure you can provide them the highest level of service
and commitment, regardless of how many manufacturers
you serve. One common pitfall that can deter this effort
and push a company and its timeline off course is a reactive
approach to quality control. However, by selecting a CCIT
method that holds up to the quality standards of the industry,
you can provide them with high-quality delivery systems
that can withstand the rigors of the journey from the lab to
the patient. As you continue to navigate the challenges of
this evolving landscape, choose a supplier that is dedicated
to helping you achieve your goals through all-encompassing
solutions designed to deliver on the promise of science and
your commitment to improving patient care.
REFERENCES
- US Pharmacopeia. Chapter <1207>. Package Integrity Evaluation – Sterile Products. http://www.pharmacopeia.cn/v29240/usp29nf24s0_c1207.html
- Stauffer, Oliver and Mullan, Juliet. (September/October 2019). Shifts in Container Closure Integrity Test Methods. Pharmaceutical Engineering.https://ispe.org/pharmaceutical-engineering/september-october-2019/shifts-container-closure-integrity-test-methods