The following article is the second in a series on design verification. Part I, “Design Verification: Ensure Product Protection throughout the Supply Chain,” is the first article. 

1: Validation of manufacturing equipment and processes in advance

Prior to building the functional product or packaging any of the products for the design verification (DV) testing, fully validate all manufacturing equipment and processes, including the sealing equipment. Typically, validation of sealing equipment begins with a screening designed experiment, such as a Taguchi fractional factorial designed experiment, in which you select the specifications of the sealing parameters and subsequently optimize them in a formal process validation study.¹ The DV test protocol should contain a list of the key process parameters for the verification and a statement to use the manufacturing settings for the sealing and other build equipment in the production of the packaged product (Note: You may choose to conduct the product design verification testing separately from the package design verification testing. This paper suggests a partial combination of functional product and dummy product to demonstrate the package is capable of protecting the product’s functionality throughout its distribution cycle and over its shelf life). Furthermore, trained production operators should conduct all product builds and packaging operations using validated equipment and released manufacturing procedures, or equivalent.

2: Validation of test methods used in manufacturing and in receiving inspection and final testing

In recent years, the FDA and Notified Bodies have focused attention on the reliability (precision and accuracy) of the test methods we rely on to discern conforming from non-conforming results. It is logical that if the test method lacks the precision or ability to detect a defect, then using that test method to search for that defect is meaningless. Beyond the test equipment itself, we also must ensure that properly trained operators are conducting the tests, with enough dexterity or visual acuity, for example, to interpret the results accurately. The formal evaluation of the ability of the test system (the equipment, operator and written test procedure) to distinguish conforming from non-conforming materials, is known as test method validation. It applies to the tests performed to inspect components and raw materials at incoming inspection, to the in-process testing used on the line, to final release testing, to the test methods applied in the prototype lab as well as in design verification and validation. Therefore, prior to beginning the packaged product design verification, validate the performance test methods. State this fact in the test protocol, and attach the production operators’ training records to the test protocol or report.

3: Design verification = Future opportunity

The design verification of packaged product presents a unique opportunity to ensure the release of product in future production situations that might otherwise render them useless. For example, consider a device sterilized by ethylene oxide (EO) prior to shipping. If the biological indicators within the shipping carton reveal a failure of the sterilizing gas to render the product sterile, the manufacturer must scrap the product. If only the product could be re-sterilized, it might be salvageable. However, unless we know the effects of a second EO cycle, the product cannot simply be subject to a second course of sterilization. For this reason, best practice is to expose the packaged product to multiple sterilization cycles (e.g., two EO cycles or a maximum dose of gamma irradiation) prior to package and product testing, in order to validate that practice in case it should be necessary to salvage a future production lot.

4: Determine types of available shippers for packing

The next step is to determine the types of shippers available for packing (full or partially full, with or without dunnage, combinations of products allowed within one shipper, etc.). It is often very helpful to visit the distribution and packaging center before writing the DV protocol in order to see firsthand how the shipping cartons are filled. The DV study should simulate the actual box-filling combinations used by the distribution center, which may include:

• Full shippers in many sizes
• Partially full shippers in many sizes, some with dunnage
• Combinations of different products packaged in the same shipping carton, both full and partial, some with dunnage and some without

It may not be practical or necessary to capture every combination of packaged product in the DV study; however, make every attempt to at least “bookend” the combinations of products within shippers, such as full and partially full, and small and large cartons with heavy and light contents. An often-unexpected benefit of this exercise is the insight to improve efficiency of distribution center by optimizing the number and combinations of shipping containers and product.

The next article in this series addresses the steps involved in the testing phase.

Reference

1. Goode, R.D., (November 1999). “The Taguchi Approach to Fractional Factorial Experimental Design,” Journal of Validation Technology, Vol. 6, No. 1.