USP 671 Permeation – Clarification on Changes

A few weeks ago I wrote an article on USP updates and referred to pending changes to USP 671 Container Performance Testing as “the bad”. While I still stand by the assertions made in that article (the lack of specifications, the use of the word ‘may”), I have spent considerable time reviewing methods and supporting scientific articles, interviewing key participants to include UPS committee members and researching previous revisions to this general chapter. In this excerpt, I will attempt to outline the pending changes that will become effective December 14, 2014 and offer insight into how industry companies may utilize the procedures to insure they meet the regulatory (FDA) requirements. Where I feel deficiencies are noticeable, I will be sure to offer my personal insight (criticism) freely.

To begin, the new USP <671> Permeation test procedures go into effect December 1, 2014. By the letter of the law, this means that any quality control testing that is commenced on or after December 1, 2014 must reference the new USP method. It is acceptable to perform and reference the new test method prior to this official date but not an official requirements.

All of the current USP permeations procedures that industry has used for the past few years, still remain as official and acceptable methods. All of them (permeation for solid and liquid holding containers, unit dose methods one and two) are still outlined with no changes. They remain effective procedures for the qualification for your container and package systems. The major change to the new USP <671> chapter centers on the addition of new test options for your permeation testing needs. As I was critical of in the previous article, the USP does not clearly provide direction as to which procedure (old or new) should be used. In discussion with the USP committee, I received the following response when inquiring about this shortfall, “At this time, the option of what test to perform is left up to organization. The addition of the new method (ASTM 7709-12) was based on industry interest in having a method that allowed for MVTR per unit dose testing, thus, allowing for a better comparison of the moisture-barrier properties of different container-closure systems used for packaging finished oral solid dosage forms. There was a discussion to omit the current test for bottles and blisters, but decided to keep due to their wide use.”

Based upon this official response, I feel the criticism was justified. Clearly defined laws, rules, guidelines and directives are much easier to “interpret” over vague ones. The questions as to what test to perform still remains for industry. Some perspective on options to follow are warranted. For the ultra-conservative approach undergoing initial container qualification, the approach would be to perform all current applicable USP <671> procedures in addition to the new and updated procedure. This ultra-conservative options will satisfy any and all questions an FDA inspector may have. Option number two, for the slightly less conservative, would be to perform either the current procedure or the new methods but not both. If this approach is taken, it would be suggested to have some specific reason in place as to why one method was chosen over the other method. A question along these lines would not be uncommon during a routine FDA inspection. There are other combinations and variations of testing that could be utilized. For example, the permeation no closure test is still applicable for PE and PP containers. A company may choose to perform this test along with the new, updated permeation method. Again, having some formal rationale in place to answer method selection questions would be advised.

The final part that industry must understand prior to the December 1st implementation date is the actual new method. Be fair warned that the new method requires a larger sample set, runs for 35 days verses 14 days for current method and testing is done at different environmental conditions (40C°/75% RH vs. 23C°/75% RH). Due to the specific test steps, the new method is also more costly. It is imperative that anyone involved with container qualification testing must take the time to read, review and understand the PF Stimuli Article that accompanies the revised USP 671 chapter. For access to this article please reference please click here

[USP General Chapter 671 Containers].

The introduction of the article provides a very good summary of the thinking behind the new method and how it should be used. “Recently, the U.S. Pharmacopeial Convention (1) published a proposed revision to general USP General Chapter <671> Containers—Performance Testing that incorporates a barrier performance assessment method for container closure systems used in packaging solid oral dosage forms. This method is intended to be used by pharmaceutical manufacturers and aligns with ICH’s accelerated storage conditions for stability testing of pharmaceutical finished products. In addition, this method is applicable to both high- and low-barrier performance packaging systems. The primary intent is to improve accuracy for assessing the performance of high-barrier packaging systems. The method provides a specific moisture vapor transmission value for container closure systems and is intended to be of sufficient sensitivity and precision to allow clear differentiation of the moisture barrier performance across packaging systems. Another advantage of the method is that the conditions used for testing are the same as the ICH accelerated stability conditions for solid oral dosage forms [40°C/75% relative humidity (RH)]. Under these conditions, the method has demonstrated the ability, within a reasonable period of time, to differentiate a wide range of moisture barrier properties for container-closure systems of different solid oral dosage forms. The purpose of this stimuli article is to provide background on the research, development, and potential application of this method.”

Upon your more formal review of the entire article, one key area that is clearly defined centers on the use of permeation testing when changes in container materials are undertaken. The stimuli article clearly defines that the improved robustness and precision of the method can serve as an acceptable path to follow when a change in container or packaging is undertaken and thus prevent more stability testing: “With knowledge of 1) the MVTR for the container-closure system and 2) the performance of the product on stability measures, a proven acceptable range (PAR) for MVTR/m can be established. For container-closure systems that do provide an adequate moisture barrier, the MVTR/m can be used to justify a change in packaging without having to undertake costly stability studies.”

USP <671> Permeation Testing is set to change. While the additional method will offer some improvement with regard to robustness and validity, how your company implements its path forward will take a careful review and understanding of the new options available.