Originally published on Jan 30, 2019.
Wholesalers serving the hospital market and other point-of-care locations are often requested to “break case packs” – in other words, to take a manufacturer-sealed pack of 25 vials, open the pack, and then sell the vials separately. The reason behind the practice is simply to facilitate logistics for their customers: buying and storing 25 pieces is much more difficult than just buying products on an as-needed basis, just a few at a time.
So a few open questions remain: how to manage only receiving one product insert? Is this considered repackaging, on a Federal and/or State level? And how will it be affected by serialization requirements?
FDA Regulation of Repackaging: Splitting Hairs Between Container and Package
First, let us get to the definitions.
The FDA defines Repackaging as:
“the act of taking a finished drug product from the container in which it was distributed by the original manufacturer and placing it into a different container without further manipulation of the drug.”
The FDA defines a Container Closure System as:
“the sum of packaging components that together contain and protect the dosage form.
The FDA defines a Packaging Component as:
“any single part of a container closure system. Typical components are containers (e.g., ampules, vials, bottles), container liners (e.g., tube liners), closures (e.g., screw caps, stoppers), closure liners, stopper overseals, container inner seals, administration ports (e.g., on large-volume parenterals (LVPs)), overwraps, administration accessories, and container labels.”
This is where semantics become very important, especially as Arizona defines things slightly differently (more on that later).
The argument, on the Federal level, revolves around whether a case pack is the container or insignificant packaging.
Industry is mostly adamant that merely removing a vial from the case or box in which the manufacturer packaged it in does not amount to repackaging – the manufacturer’s label remains on each individual vial and no relabeling occurs. Although not shipped in the original package, the manufacturer’s container (vial) is never opened or relabeled.
Because the manufacturer package of 25 vials is shipped with only one product insert, and FDA requires a product insert be sent with product, wholesalers are happy to comply by either making copies of the original insert and/or printing inserts from the manufacturer website.
The current “state patchwork” for regulation of the pharmaceutical supply chain means that every state (1) has their own laws and (2) implements those laws according to the individuals that are at the state agency in charge of enforcing those laws. This, of course, can lead to a lot of confusion.
Diving into State Law
Per the Arizona Board of Pharmacy’s interpretation of AZ Rule R4-23-605(G)(2)(a)(i) & (ii), if the item is packaged by the manufacturer/repackager in a pack of 25 with one package insert, then that pack is the original package; therefore, breaking case packs is repackaging and requires a manufacturer permit.
Specifically, the fact that there is only one product insert is what makes the case for Arizona considering the practice manufacturing.
AZ Rule R4-23-605(G)(2)(a)(i) & (ii):
A full-service drug wholesale permittee shall:
Not sell, distribute, give away, or dispose of, any narcotic or other controlled substance, prescription-only drug or device, nonprescription drug, precursor chemical, or regulated chemical, except in the original container packaged and labeled by the manufacturer or repackager;
ii. Not package, repackage, label, or relabel any narcotic or other controlled substance, prescription-only drug or device, nonprescription drug, precursor chemical, or regulated chemical;
At the very least, those wholesalers engaging in the practice and shipping that product from/into Arizona, should be cautious.
One of the requirements of obtaining an Arizona Manufacturer Permit is that the applicant must process Establishment Registration with
“Drug packager or drug prepackager permit to an individual or establishment that is currently listed by the United States Federal Food and Drug Administration and has met the requirements of that agency to purchase, repackage, relabel or otherwise alter the manufacturer’s original package of an approved drug product with the intent of reselling these items to persons or businesses authorized to possess or resell the repackaged, prepackaged or relabeled drug.”
The Curveball: Serialization
In the (currently) messy world of Serialization, how manufacturers will ultimately decide to execute their packaging requirements on vials is relatively unknown. However, it is likely what will give the most clarity on wholesaler requirements: if individual vials have unique serial numbers, then it will reinforce the current status quo of the practice being classified as wholesale activity; if individual vials do not have unique serial numbers, wholesalers will be forced to either relabel the product with their own serial number, attempt a 3PL model or abandon the practice altogether.
Because of the importance, Five Rivers RX performed anecdotal research and this is what we found:
A Hospira case pack at a wholesaler warehouse location has a 2D barcode, GTIN & serial number; but the vial pulled only has an NDC.
A Pfizer case pack at a wholesaler warehouse location has a 2D barcode, GTIN & serial number; the vial has a GTIN and 2D barcode but not a serial number.
It is important to remember that the packaging referenced is likely not the most recent or final iteration of the manufacturer’s packaging. Specifically, a number of US facilities – including, the McPherson, KS plant that Pfizer acquired from Hospira – received a one-year extension for DSCSA compliance from the FDA.
More information as it breaks!
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