Dimensional analysis of container and package system components can play a critical role in the selection and qualification process. Determining optimal fit of married components – for example a rubber stopper to a glass vial or a screw top closure to a plastic HDPE container – can help to ensure the integrity of the drug product package. The FDA issued Guidance for Industry on Container Closure Systems for Packaging Human Drugs and Biologics clearly states that as part of the quality control data package, the dimensional drawings and relevant performance criteria be included as part of the approval submission dataset. Numerous studies have shown that ill-fitting components can clearly impact the USP 1207 Container Closure Integrity requirements.
Based upon our comprehensive and complimentary approach to container qualification testing, at CS Analytical, dimensional testing is a routine service offering. The CS Analytical Team has many years of experience designing and implementing dimensional analysis test programs that help clients ensure the optimal selection of components. In this article we will review the technology used to execute a successful dimensional program for a drug product package system and key factors for consideration in the development of an effective test program.
The majority of dimensional testing will typically be completed using an optical comparator. As the name implies, an optical comparator is an optical measuring instrument. The measurement principle is similar to that of optical microscopes. The target is placed on the stage and a light is shined on the target from underneath. This causes the target’s profile, or shadow, to be projected on the screen. A telecentric optical system is used to enable accurate measurements. Optical comparators were originally developed to inspect the outlines of targets. Models equipped with measurement functions appeared later. Optical comparators are also commonly known as a profile projector or shadowgraph. An optical system called a “telecentric optical system” is used in the optical comparator so that it can be projected with accurate magnification from any position on the stage. This telecentric lens allows you to cast the shadow of an object at the correct magnification without warping the image.
At CS Analytical we use the Keyence IM Series Optical Comparison. This system offers high-definition imaging and boasts of having triple the detection performance of conventional optical comparator. It features a 20-megapixel CMOS sensor and an algorithm that ensures stable edge detection and high-accuracy measurement on multiple dimensional features simultaneously. Running on Keyence Part 11 compliant software, the instrument can read mechanical drawings and generate precise measurements that can provide specific pass/fail results.
In the development of an effective dimensional analysis test program, the component’s engineering specification sheet is the ideal place to start. This document will establish the key dimensions and assigned tolerances for that specific part. As an example, a common and routine dimensional request for container and package system components typically include the following:
|HDPE Container||Glass Vials||Syringe Barrels||Elastometric Stoppers||Aluminum Seals|
|Height||Height||Overall Length||Overall Height||Overall Height|
|Width||External Diameter||Barrel Length||Overall Width||Flange Height|
|Depth||Bottom Concavity||Barrel Inner Diameter||Outside Top Diameter||Metal Thickness|
|Wall Thickness||Flange Height||Flange Length||Flange Thickness||Inside Diameter|
|Inner Diameter||Internal Diameter||Flange Width||Plug Height|
|Dimension T||Outside Diameter||Flange Thickness|
|Dimension H||Weight||Exposed Needle|
|Dimension E||Overflow Capacity|
The next key factors deals with total number of samples to be tested. In many cases the ISO / ANSI / Military Standard for Sample Procedures and Tables for Inspection Attributes serves as the basic guideline for selection of sample size. The total number of samples to be tested is typically based upon the lot size, the intent of the testing program and the assigned quality level the program is designed to achieve.
Dimensional test programs for package components can play a critical role as part of a material selection and qualification process for a container / package system used for drug and medical products. With many years of experience designing and executing small and large scale dimensional test programs, CS Analytical has the ability to tie a dimensional test program into the overall qualification plan for a wide variety of package system components.