Critical to Quality physical dimensions of pharma glass vials – Part 4. Flange ID

Hello everyone – welcome to Part 4 of my series on Critical to Quality (CTQ) physical dimensions of pharmaceutical glass vials.? Today’s CTQ dimension of interest is the inner diameter (ID) of the flange, sometimes referred to as the “mouth” of the vial.? In Part 2 of this series, we reviewed how the external jaws of a caliper could be used to measure the outer diameter of the flange.? We’re now going to shift our attention to the internal jaws that can be used to measure the ID of a hole.

Figure 1 shows a close-up view of the internal jaws of my digital caliper.? I’ve labeled the section of each internal jaw possessing a single beveled knife edge that should be used when making an ID measurement.? These knife edges allow the internal jaws to approximate point contact with the internal surface of the hole being measured (as opposed to a flattened blunt edge that would cause an undermeasurement of the ID as shown in Figure 2).

With those basics out of the way, let’s measure the ID of a vial flange.? Figure 3 shows the internal jaws of my digital caliper inserted into the mouth of the same 2R vial that I used in Part 2 of this series.? Note the use of the knife edges.? I would actually get a different (larger) measurement by inserting the internal jaws too far into the vial (refer back to Figure 1 and notice the offset shape of the internal jaws to understand why).? As with all of our physical dimension measurements, we would repeat this process multiple times to determine if the flange ID is within specification.? And because we’re dealing with the flange, it’s easy to remember the ID specs for ISO format converted tubular glass vials – it will be either 7 mm ± 0.2 mm (for 2R, 3R, and 4R vials) or 12.6 mm ± 0.2 mm (for everything else).

I previously alluded to the idea that multiple methods can often be used to measure a given physical dimension in Part 3 of this series concerning vial height.? The same is true for flange ID.? For example, go/no-go gauges can be used to quickly determine if the entirety of a vial mouth meets a given spec.? Figure 4 shows an example of a go/no-go plug gauge (see Footnote 1).? It consists of two cylinders of a given nominal size.? One cylinder (color coded green) corresponds to the minimum end of the allowable ID range; the other cylinder (color coded red) is the maximum end.? A vial that meets the flange ID spec should always allow the green end to be inserted into the vial mouth (a GO condition) and should not allow the red end to be inserted (a NO GO condition).? Just like my calipers, the calibrated cylinders used in a go/no-go plug gauge have an associated tolerance, and so it’s theoretically possible that a gauge/vial combination at the extremes of the allowable range could result in a false accept or reject (see Footnote 2). ?Go/no-go gauges can be quick, convenient tools, but it’s also important to recognize that they are performing a different measurement from a tool such as a caliper.? The go/no-go gauge is just checking if a part falls within a given dimensional range – it doesn’t measure the actual physical dimension of the feature of interest.? As a result, you lose the ability to monitor for trends in the data that could be used as an early indicator of process drift in vial manufacturing (see Footnote 3).

I should also remind you about blowbacks.? I covered this topic in a previous post, and so please check that out for general info on the topic.? In brief, blowbacks are a feature within the interior of vial necks that are meant to facilitate retention of stoppers, thereby preventing “pop up” and supporting the maintenance of container-closure integrity (CCI).? Within the context of measuring flange ID, just recognize that the blowback type can contribute to the result.? The first “bump” of a European- or American-style blowback can reduce the flange ID relative to a vial that is not designed with a blowback.? With that said, I’m not aware of vials designed with a blowback having a greater likelihood of failing the flange ID spec relative to vials without a blowback.? I also just realized that I’ve previously forgotten to mention one other physical dimension of a vial that’s relevant to this discussion.? The “choke” of a vial refers to the ID of the vial neck.? The flange ID and choke of a vial should be the same for a vial without a blowback.? Vials designed with a blowback should have a flange ID that is less than the choke.

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Let’s close by considering why this is worthy of our attention.? The most obvious importance of maintaining the flange ID of a vial within specs is to ensure compatibility with the inserted elastomeric stopper and, by extension, to ensure CCI.? However, the discussion doesn’t stop here.? The flange ID of a vial matters any time that the fill-finish process involves entering the mouth of the vial – this includes washing and filling needles (a.k.a. nozzles) that “dive” into the vial to dispense hot water or drug product, respectively.? In an ideal world, the deviations in flange ID for a well-controlled vial manufacturing process should be relatively minor compared to a centered washing/filling needle.? And so while it’s rare, I have seen instances in which undetected bent needles can strike the flange of a vial (an in spec vial, by the way) to cause varying degrees of damage, including checks, chips, and breakage.

Questions or comments?? Please leave them below or feel free to directly contact me.

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Footnotes

1.?????? There are many different types of go/no-go gauges available for performing various dimensional checks, including but not limited to: plug gauges, thread gauges, snap gauges, ring gauges, etc.

2.?????? There are multiple tolerances available for plug gauges – they can be found ASME B89.1.5 (Measurement of Plain External Diameters for Use as Master Discs or Cylindrical Plug Gauges).? Selection of a gauge with an appropriately sized tolerance relies on the same “Rule of 10” that was described in Part 2 of this series.

3.?????? I’ve mentioned this before, but it’s worth repeating here. ?Vial manufacturers employing industry best practices will be monitoring physical dimensions of vials in real time to detect process drift instead of using offline measurements with hand tools.? The methods that I’m describing in this series are more likely to be used as additional quality checks.