From The Editor | July 1, 2024

Embrace Packaging and Delivery Systems Designed for Today's Standards

Fran DeGrazio Headshot

By Fran DeGrazio, executive editor, Drug Delivery Leader


Pharmaceutical companies love to tout innovation but don’t always implement actual change. This is particularly true when it comes to innovation or change in their approaches to sterile packaging, delivery systems, or, ultimately, combination products comprising various components and constituent parts. The tendency is to stick with what has worked in the past. Doing so can seem to minimize risk and maximize efficiency. But does it?

Pharmaceutical companies often fail to recognize the hidden or looming downsides of product development stasis:  unexpected costs, loss of resources to areas of low value, and negative impacts to drug quality and compliance. Frankly, all of these can – and likely will – result from falling back on how things have always been done rather than implementing best practices for the future.

Resistance to the New is Not New

Let’s look at the day-to-day reality of what commonly happens when a pharmaceutical company is choosing, for example, the packaging components or delivery system for an injectable drug product, such as a prefillable syringe. Quite often, the company will choose components or systems it has previously used, believing it is minimizing risk regarding suitability factors it must consider: compatibility, performance, protection, and safety. Choosing a previously used component leverages prior analytical work and provides a reassuring degree of familiarity from a technical and regulatory standpoint. The choice may also leverage long-established and company-friendly pricing.

The company can also face considerable resistance when asking the manufacturer of the product (internal or outsourced) to move on from a component or system it has used for years. Anything new can bring challenges and unknowns into the processing arena, sometimes contributing to manufacturing inefficiencies until issues are addressed.

Moreover, under the guise of continuous improvement, pharma companies can spend tremendous amounts of time and energy engaging suppliers to overcontrol the product they are using rather than choosing a component or system that has been more recently developed to meet the current needs of the industry. While continuous improvement should be an overall part of any product’s lifecycle, it cannot magically change the core nature of an older product and its original characteristics and intent.

Old Products Introduce New Risks

As much as using familiar products can provide a certain level of comfort, the practice can also – and usually will, over time – generate new risks. Perhaps the most concerning is the potentially poor fit between, on the one hand, old products and, on the other, new and evolving regulations. When the fit is poor, the cost of compliance can skyrocket – if companies can even achieve compliance using an older product.

Pharma companies that use, for example, packaging components developed many years ago may do so because they believe (or hope) that the products are good enough to remain acceptable in today’s quality and regulatory environment even though these products may have been originally qualified more than 30 years ago. When a company uses such components on a consistent basis, however, it may discover that the product is too variable or lacks certain quality characteristics. In that common scenario, a pharma company that is unwilling to switch to a new, more recently developed product will ultimately put an incredible amount of time, effort, and resources into trying to “force fit” a product that was not designed to meet current standards. Many of these regulations could not have been imagined or anticipated when the product was originally created.

Regulation Drives Innovation

Frankly, why would anyone trust that a packaging component or a delivery system originally developed and commercialized decades ago will meet today’s and future standards? To illustrate why new, innovative products should be, at least, evaluated, let’s look at how frequently and significantly regulations and standards have developed and advanced through the years (Figure 1).

For example, milestones in the evolution and advancement of EU GMP Annex 1: Manufacturing of Sterile Medicinal Products (or, “European Annex 1”) can be noted for 1997, 2009, and 2023. With time has come significantly higher expectations for pharmaceutical companies, as evidenced simply by the expansion of the previous version’s 16 pages to 58 pages in the 2023-effective iteration. A major expectation in this annex is for a pharmaceutical company to have an effective Contamination Control Strategy (CCS) that, rather than having been developed to fit a historic process, is suitable for an upgraded process designed to improve microbiological and particulate specifications and controls. This newly effective, greatly expanded standard reflects additional, global regulatory input and is, therefore, seen as the current global standard and expectation on this subject.

As another example, USP 382 and USP 661.1 & 661.2 all go into effect in 2025 (Figure 1). USP 382 Elastomeric Closure Functionality in Injectable Pharmaceutical Packaging/Delivery Systems substantially broadens the evaluation of elastomers from components to systems and expands the integrity and functionality testing to be completed just to meet the USP standard. This is a major change from the prior requirement, which was only for USP 381 Elastomer Closures for Injection. USP 661.1 Plastic Materials of Construction & USP 661.2 Plastic Packaging System for Pharmaceutical Use will replace USP 661 Plastic Packaging Systems & Their Materials of Construction. Materials currently qualified by USP 661 will need to be requalified to the new standards, which include expanded testing.

The regulatory bar has clearly been raised. New products may very well be required to clear it. Frankly, every organization should thoughtfully consider if it should continue to invest resources in using an older product with which it may struggle (and potentially fail) to meet current standards or, instead, move on to qualifying and deploying products designed to address prevailing industry quality and regulatory challenges while anticipating the future.