Streamlining oral dose packaging design

June 18, 2024
Adrian Possumato and Chris Gilmor from Sanner of America discuss the practical implementation of QbD and how these strategies are driving innovation in oral dose packaging design.

Drugmakers are continuously seeking ways to enhance efficiency, and packaging plays a crucial role. Traditionally, the packaging development process involves extensive stability testing to ensure medications remain effective throughout their shelf life, but the process can be time-consuming and costly.

By integrating a Quality by Design (QbD) approach, developers can design robust packaging from the outset,  drastically reducing development time and costs. Understanding how moisture affects a product is key, allowing developers to use industry-accepted and validated models to predict and address potential stability issues early in the design phase, thereby reducing the need for prolonged probe stability testing and potential reformulations or packaging redesign. 

To understand more about the issues at hand, Pharma Manufacturing recently spoke with Adrian Possumato, president and Chris Gilmor, director of sales, at Sanner of America.

Q: How are current trends in pharma manufacturing impacting the design and production of oral dose packaging?

Adrian Possumato: There is a move towards sustainability across the board in the pharmaceutical industry, including both prescription and OTC products. This involves material selection and regionalization of supply as customers aim to minimize their carbon footprint and de-risk the supply chain. This shift is partly due to concerns exposed during the COVID-19 pandemic.

While the current major drugs are small-volume, high-value biologics in parenteral form, small molecule oral solid dose (OSD) formulations still represent about 38% of the drugs in phase 3 clinical trials. From 2017 to 2022, 182 of the 293 (close to 62% ) of the new chemical entities approved by the FDA were small molecule drugs. Formulators are now focusing on using small molecule drug substances to directly bind to proteins in the body to produce a therapeutic effect, rather than injecting a prepared biologically active protein therapy. Essentially, they aim to get the small molecule drug substance to synthesize therapeutic proteins in the body.

Chris Gilmor: Small molecules still hold significant potential. Formulators are using them innovatively, like binding to proteins in the body for therapeutic effects rather than injecting biologically active proteins.

AP: Because biologically active materials like peptides and proteins can’t be delivered orally as they’re destroyed by the gastrointestinal system, pharma companies are using small molecules to synthesize therapeutic proteins in the body. This maintains the relevance of small molecule drugs. We see many requests for packaging presentations that stabilize these drugs for a two-year shelf life.

Q: What are some critical components as well as challenges for OSD packaging?

AP: OSD remains a focus for the pharmaceutical industry. Stability challenges, both physical and chemical, persist. Consequently, passive and active packaging continues to be necessary. There’s no avoiding the use of HDPE or PVC and related desiccants in packaging presentations.

CG: Because ensuring the physical and chemical stability of drugs is challenging, mathematical models can help streamline these processes.

Q: How has the industry adopted QbD in drug packaging, and what are the main advantages?

AP: Twenty years ago, there was little QbD applied at this development level. Now, QbD is used increasingly to quickly select successful packaging during phase 2B clinical trials. Historically, probe stability studies were used, but now empirical modeling  models like ASAPprime (FreeThink Technologies, Inc.) predicts outcomes, saving 6-12 months of development time and $225,000 per stability test. The first to market gains significant advantages, especially in the generic industry, where exclusivity can yield 60% of profits in the first six months.

Industry scientists have advanced predictive stability modeling programs that operate across a comprehensive range of ICH stability conditions, utilizing a QbD approach.

These programs determine moisture management outcomes by integrating empirical measurements, such as moisture adsorption/desorption isotherms, on the drug product, the moisture vapor transmission rate (MVTR) of the primary packaging, and desiccant isotherms. By collaborating closely with formulation chemists, these moisture management outcomes can accurately predict stability results for the drug product within the modeled packaging presentation.

CG: Using QbD, Sanner’s ‘advance with agility’ proposition determines stability outcomes quickly, designs optimal packaging, and ensures proper use in commercial operations. This comprehensive approach involves all key stakeholders, improving efficiency and reducing costs.

Q: What are the typical cost savings with QbD for OSD packaging?

AP: Our QbD-based approach saves time and money by eliminating probe stability testing and optimizing packaging. This saves 6-12 months of development time, allowing earlier market access and improving cash flow. The design and designate steps reduce package design time and related stability testing, again leading to earlier market access and better cash flow. In the dispense step, we optimize the use of materials, reducing quality costs, packaging waste, and improving operational efficiencies.

CG: Involving all stakeholders ensures that needs are addressed, enhancing the overall efficiency and effectiveness of the process.

Q: What technological innovations does Sanner employ for moisture control in OSD packaging?

AP: We offer standard desiccants, both moderate and aggressive, moisture regulators, and odor/volatile absorbers.

These are used in:

  • Drop-in solutions for conventional bottle and pouch packaging presentations
  • Built-in solutions, which are integrated into Sanner’s stock or custom-designed rigid packaging presentations with child-resistant closures

CG: Built-in solutions prevent desiccants from being mistaken for drugs and simplify packaging processes. This approach is increasingly favored by pharmaceutical companies for its efficiency and safety.

AP: Built-in solutions also streamline commercial packaging operations and are identifiable with a brand. We’re seeing more custom built-in packaging used even at the prescription level for chronic use drugs, preserving stability and efficacy without needing additional pill carriers. 

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