Rationale for the omission of the "well-closed" specification from USP general chapter <671>

In Pharmacopeial Forum 42(4) [Jun-Jul 2016] a stimuli article on the rationale for the proposed omission of the "well-closed" specification from the general chapter <671> Containers-Performance Testing has been published.

The present stimuli article "outlines the rationale for the omission of the Packaging and Storage statement from certain monographs in the USP–NF, the omission of the “well-closed” acceptance criterion from the USP–NF, and establishing the “tight” definition in Packaging and Storage Requirements <659> and acceptance criterion in <671> as the default for those products and materials that do not go through formal stability testing."

Package integrity is necessary to maintain a drug product’s quality throughout its shelf life. As reported in our news on the Effect of primary packaging on the drug stability of solid dosage forms package moisture permeation is a critical quality attribute for solid oral dosage forms, with moisture uptake being a common cause for product package failures. Current methods for the measurement of water permeation in container–closure systems (cap/bottle and blister packs) are found in Containers—Performance Testing <671>.

In addition to the tests and specifications provided in chapter <671> USP general chapter <659> Packaging and storage Requirements contains the following definitions:

Hermetic container:
A packaging system that is impervious to air or any other gas under the ordinary or customary conditions of handling, shipment, storage, and distribution.

Tight container:
A packaging system that protects the contents from contamination by extraneous liquids, solids, or vapors; from loss of the article; and from efflorescence, deliquescence, or evaporation under the ordinary or customary conditions of handling, shipment, storage, and distribution and is capable of tight reclosure. Where a tight container is specified, it may be replaced by a hermetic container for a single dose of an article. [Note—Where packaging and storage in a tight container or well-closed container is specified in the individual monograph, the container used for an article when dispensed on prescription meets the requirements in Containers-Performance Testing <671>.] 

Well-closed container:
A packaging system that protects the contents from contamination by extraneous solids and from loss of the article under the ordinary or customary conditions of handling, shipment, storage, and distribution. See Containers-Performance Testing <671>.

Currently, the method for measuring water vapor permeation in multiple-unit containers for capsules and tablets in <671> provides two acceptance criteria for containers, defined as “tight” and “well-closed”. Of the two, “tight” is referenced in the Packaging and Storage statement of >2600 USP monographs and has been applied to drug products such as solutions, suspensions, creams, ointments, suppositories, tablets, capsules, and injections. The “well-closed” definition is referenced in >1300 USP monographs and has been applied to all the same drug product categories as “tight”. Although <671> was initially intended for solid oral dosage forms, it has been applied to all USP dosage forms and USP monographs (excipients, drug substances, dietary supplements, and compounding), which puts into question the discernibility of the two container types. The blister classes (A, B, C, and D), which are defined in <671>, are up to now not referenced in any USP monograph.

The stimuli article emphasizes that "The only way to determine the level of moisture protection necessary for a drug substance or product, as well as the suitability and safety of a packaging system, is through stability testing. The stability of a drug substance or product, until its expiration date, is determined through its testing in a specific packaging system."

"Although stability data are used to determine the packaging system and storage requirements for drug substances and products, this is not the case for excipients. Few excipient manufacturers undertake formal stability testing; if an excipient is not stable, then stability testing might be used to determine the shelf-life of the material, based on a defined condition of storage. Similar to excipient manufacturers, dietary supplement manufacturers and compounders also do not preform formal stability testing to determine the packaging and storage requirements of their product."

In this context, the USP Packaging and Distribution Expert Committee is proposing the following:

  • Removal of the Packaging and Storage statement from drug product and drug substance monographs, with the addition of language to the General Notices and Requirements, 10. Preservation, Packaging, Storage, and Labeling that packaging systems and storage requirements for drug products and drug substances should be based on data generated from stability studies.
  • The Packaging and Storage statement will be retained in excipient, dietary supplement, and compounding monographs, but the “tight” definition and criteria should be the default.
  • Revise <671> by separating the chapter into two parts; 1) one part for packaging systems used by drug substance and product manufacturers and repackagers; and 2) a second part in the chapter for packaging systems used for excipients, dietary supplements, compounded products, and in dispensing practices.
  • Omit the “well-closed” definition and specification from <659> and <671>.

Due the impact of such changes (e.g. number of monographs to be changed) USP is seeking stakeholder feedback and how to best move forward in omitting and revising packaging and storage specifications in USP–NF monographs.

After registration on the USP Pharmacopeial Forum website you can read the complete stimuli article about the Rationale for the Omission of the Packaging and Storage Statement from USP-NF Monographs and the Omission of the "Well-Closed" Specification from Containers-Performance Testing <671>.

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