Applying quality by design principles to desiccant selection

A QbD approach to selecting a sorbent is based on strong science, says Adrian Possumato of Multisorb.

At Interpack 2014, Multisorb Technologies hosted the in-booth symposium, “QbD and Sorbent Selection in Pharmaceutical Packaging.” PMP News asked Adrian Possumato, Vice President, Healthcare at Multisorb Technologies, to explain how Quality by Design (QbD) approaches can be put to use when developing active pharmaceutical packaging.

Multisorb will be exhibiting at Booth #3453 at Pharmapack North America June 10-12 in New York City.

Q. How would you define QbD?

A: Quality by Design is a proactive approach to ensuring drug product quality and efficacy throughout its shelf life by defining quality characteristics and designing and building them into the product.

Multisorb’s involvement in QbD dates back to 2004 when we introduced our Calculations through Operations program to the pharmaceutical industry for the selection and use of sorbents to resolve chemical and physical stability challenges in drug substance and drug products at their earliest stages of development. Since then, we have successfully expanded the program to the medical device industry, with a specific focus on in-vitro diagnostic device consumables, as well as the dietary supplement industry.

From a market perspective, the pharmaceutical industry has always been driven by innovation. This innovation is a result of drug and drug/device technology developed in-house or externally obtained through licensing or acquisition. It can also involve complementary technology from vendors in the form of innovations in drug product formulation, delivery, devices, and active packaging (sorbents).

With aggressive strategic procurement efforts offering diminishing returns and access to technology from damaged vendor relationships, the pharmaceutical industry is realizing a return to innovation is necessary to drive their business as a longer-term strategy.

Additionally, the situation with the patent cliff and resulting decreased drug product price points continues to drive pharmaceutical manufacturers, both innovators and generics alike, to consolidate and aggressively reduce cost. This leaves little room for the R&D budgets of yesteryear, so pharmaceutical innovation today needs to offer the promise of a successful drug candidate, but it must also be very efficient.

This environment underscores the benefit offered to the pharmaceutical industry by QbD-based programs, like Multisorb’s Calculations through Operations, and related, innovative technologies, such as StabilOx, Multiform CSF, and IntelliSorb products and formulations. They can quickly and inexpensively resolve drug product stability challenges in an effort to minimize R&D spend, gain faster access to market, and thereby improve a drug company’s cash flow.

Q. How would a QbD approach work in terms of sorbent selection?

A: The Calculations component of this program involves the use of our SimulSorb and SimulOx pseudo-empirical modeling services that take the guesswork out of the selection of all sorbents, including desiccants, IntelliSorb moisture regulators, oxygen absorbers, hydrocarbon scavengers, and multifunctional sorbents.

Working closely with packaging engineers and formulation chemists, SimulSorb and SimulOx modeling involve the use of empirically derived measurements of the drug product or medical device, the packaging presentation, and the sorbent to predict a specific moisture or oxygen management outcome, respectively. Through this process, manufacturers quickly receive a sorbent that has been specifically optimized for their product.

The Operations component of Calculations through Operations program provides manufacturers, for both clinical and commercial packaging operations, with a fully integrated system providing highly efficient and reliable sorbent dispensing. The dispensers are co-engineered specifically with their corresponding sorbents, assuring an output reliability exceeding 99.997%—something greatly appreciated by process engineers in pharmaceutical packaging operations.

As the sorbent directly contributes to the drug product’s stability profile, its capacity must be protected during packaging operations. As in the case with competing sorbent dispensers that do not offer protection or FIFO-controlled dispensing, Multisorb’s systems approach includes dry air purge for desiccants, conditioned air purge for IntelliSorb moisture regulators, or inert gas purge for oxygen absorbers to extend the handling time of the sorbents during packaging operations. These features are directly linked to the specific sorbent formulation and platform and are included in the IQ/OQ documentation to quickly facilitate the dispenser installation and PQ.

Additionally, the quality of the drug/packaging system is further supported by the packet dispenser’s smart dispensing technology, which transmits data, such as lot number, manufacture date, and quantity, from the packet spool to dispenser, easily integrating information into your quality system.

Q. How is such an approach different from traditional approaches to sorbent selection?

A: Formulation chemists often rely on packaging engineers to incorporate sorbent technologies in clinical or commercial packaging to help make the difference between actual and desired stability outcomes. When our customers consult with us early in the development process, it allows their formulators, packaging engineers, and packaging operations groups to work together to quickly identify the required sorbent to ensure the desired stability outcome for their product.

Stability studies involve accelerated and real-time testing. Accelerated stability studies (six months, typically at 40°C and 75% RH) are often run to determine shelf life. Data from acceptable accelerated stability studies are used to prove that the same system (packaging, desiccant, etc.) will pass real-time test stability testing (two years, typically at 25°C and 60% RH). The traditional approach to determining the correct sorbent type and amount to incorporate into the system is by performing sorbent ranging studies. These studies require testing several variations followed by confirmation testing, a process that can be very time consuming and costly.

Q. What benefits are there to taking a QbD approach to sorbent selection?

A: Taking a QbD approach to sorbent selection allows manufacturers to forgo sorbent ranging studies, typically saving from 6-12 months of development time. This time savings can result in an expedited regulatory filing and, consequently, a faster time to market, financial savings, and increased income generated from earlier sales.

Q. Are there any particular product categories that would be ideal for such an approach?

A: Solid oral dose drug products are the most common and can have stability challenges related to multiple pathways of degradation. Without Multisorb’s QbD approach, sorbents selected to solve one problem can create another—often the case in balancing chemical and physical stability needs.

Combination oral dose drug products can be quite complex and have opposing stability issues that need to be carefully balanced via QbD through packaging presentation selection, sorbent formulation type, and mass.

Tamper resistant, rapid-release, sustained-release, and targeted-release solid oral dose formulations each bring their stability issues that can often be easily resolved using the Calculations through Operations program.

Drug-device combination products such as prefilled syringes (PFS), dry-powder inhalers (DPI), aerosol inhalers (pMDI), and active and passive transdermal systems (TTS) can have their specific sorbent requirements for physical and chemical stability problems.

Q. What are the challenges?

A: The main challenge is getting manufacturers to realize the importance of determining sorbent needs early on in the development process. The market is very competitive and getting your product out into the marketplace before your competitors is a critical factor in a successful product launch. A QbD approach employing the Calculations through Operations program is a valuable tool for assisting manufacturers with achieving this goal.

Q. What are common industry questions or concerns with such an approach?

A: Anytime you ask someone to consider a new approach, you are faced with proving its worth. The QbD approach to selecting a sorbent is based on strong science. For more than 10 years, Multisorb has successfully demonstrated that SimulSorb and SimulOx modeling can accurately predict the moisture and oxygen management outcomes for drug product stability requirements through consumer use. The value to drug manufacturers is time saved, earlier regulatory submission, faster time to market, all of which ultimately translates into money saved—and earned.