Issue link: https://www.e-digitaleditions.com/i/626800
pen to be, there are several key issues to consider, including the water activity (a w ) of the drug product, the packaging configuration, the MVTR of the packaging material, the storage conditions, and the desired shelf life. Depending on the drug product, the oxygen transmission rate may also require consideration. Traditionally, manufacturers have conducted forced- degradation studies to determine whether a sorbent is required, followed by sorbent-ranging studies to identify and optimize the type and quantity of sorbent required to ensure stability. Now, however, QbD-based pseudo-empiri- cal modeling [2] offers a quick way to predict stability out- comes, including how much desiccant is required to pre- vent moisture- and oxygen-induced degradation. In practice, the pseudo-empirical modeling takes any given set of external conditions and calculates the condi- tions within the drug product's package. The calculations— based on the integration of variable internal and constant external equilibrium relative humidity (ERH) conditions over time—take into account the conditions at the time of packaging (i.e., headspace), the package's MVTR, and isotherms of the sorbent and drug product. The proven accuracy and speed of pseudo-empirical modeling make desiccant ranging studies unnecessary and simulations can shorten development time by 6 to 12 months. That enables pharmaceutical manufacturers to expedite regulatory filings and get their stabilized product to market faster. Pseudo-empirical modeling also allows you to test sor- bents in a variety of formats that accommodate almost any packaging design. Formats include sachets and canisters dropped into the package; low-profile formats that affix to the packaging; and other configurations that are built into the package as a static structural component, such as a con- tainer wall, or as a mechanical component, such as a lever used to dispense the drug product. Like the pharmaceuticals they protect, many of these formats have improved over the years. For example, our company offers a drop-in canister that delivers 2.0 grams of functional silica gel desiccant in a canister that traditionally held only 1.0 gram of desiccant (photo). That enables phar- maceutical manufacturers to protect products even in space- constrained packages. Selecting vendors to avoid supply chain disruptions Supply chain interruptions can delay and disrupt pro- duction and cause your company to lose sales and brand equity. Even a seemingly inconsequential component can delay product deliveries. As development costs continue to rise, don't jeopardize your investment: Make a plan to avoid a broken supply chain and a second plan to mitigate its effects. According to a recent Tufts study, the cost of developing a new branded drug can exceed $2.6 billion [3]. A similar study by the Canadian Generic Pharmaceutical Association estimated that developing a generic drug product costs more than $4 million and takes 3 to 6 years [4]. Whatever the exact numbers, development is time con- suming and costly. Don't squander more time fighting to sustain your supply chain. The first step: Make a business-continuity plan. Next, ask each of your suppliers to do the same or to share their plan for minimizing disruptions. Follow up regularly during your audits to confirm a sound plan is in place. Here are some topics to cover: • Manufacturing sites. How many different manufactur- ing sites do you operate? How quickly can another site produce what I need if a political, economic, or natural disaster disrupts business as usual? • Redundant manufacturing. Can each manufacturing site supply the exact same product? Do the sites meet the same standards and use the same processes? How will turnaround time be affected? • Vendor-managed inventory. Are you willing to maintain and manage reserve inventory to support my operations and/or to accommodate a surge in demand? • Ramping ability. How quickly can you increase produc- tion to supply what we need for new products or an increase in production? Preventing and managing quality mishaps It's costly when quality is called into question. In the biotechnology industry, a single quality mishap is estimated to cost $10,000 to $50,000 [5]. And that doesn't factor in the potential for loss of brand equity, product disruptions, and lower sales and revenue. So it pays both to reduce the chance of a quality upset and to prepare for one. Start by making a plan before you install new equipment. Sorbent dispensers, for example, differ greatly in how they perform. Investigate all the options during procurement to determine which unit will meet your quality requirements and how it will help you during a quality mishap (photo). Pseudo-empircal modeling can predict stability outcomes faster than traditional forced-degradation studies. This drop-in canister delivers 2.0 grams of functional silica gel desiccant in a canister that traditionally held only 1.0 gram of desiccant. Tablets & Capsules January 2016 29