TC12: Pharma Packaging

TC12 has the main general objective to verify the “weaknesses” of glass containers for pharmaceutical products in front of the demands of new drugs and new drug delivery systems, and to identify the R&D needs in this field. The project is aimed to better understand the interaction of the glass surface with pharmaceutical products, including “delamination” phenomena, adsorption effects and the influence of big molecules.

The first objective of TC12 was to find an experimental method for the evaluation of the propensity to delamination, which was reliable and accepted by most important actors in the field. The delamination problem was a major concern at the time TC12 started its activity. It is nowadays considered with great attention by both glass and pharma industries, and many activities have been started for a better comprehension of the mechanisms, the most important parameters involved (from composition to processing), the strategies to solve the problem.

After an extensive experimental work on delamination, which brought to two scientific publications, TC12 has recently started an experimental activity aimed to check the criticality of the depyrogenation process on the chemical performance of glass vials.

Activities and planned actions

Activities in 2022

At the beginning of the year the Committee agreed to conduct an experimental activity on the effect of the depyrogenation treatment of vials.

Several papers in the literature mention the possible effect of depyrogenation on the delamination propensity. However, only very experimental data are reported in the literature, with contrasting results.

The Committee’s interest in this type of study was stimulated by the fact that, under certain circumstances that can sometimes occur in industrial practice, vials can remain in the depyrogenation phase for more than 50 hours, and nothing is known about the effect of this prolonged and unwanted treatment.

Based on a recent study published by Ditter et al. in 2018, it was decided to expand and diversify the experiments with the aim to investigate the phenomenon by including longer periods of depyrogenation, the comparison of more vials, a comparison between labs, and the use of a different protocol for evaluating the delamination propensity.

During the year, the experimental protocol was defined, the vials to be tested were decided, and they were collected at the SG lab. At the end of the year four type of vials, 75 vials for each type, were shipped to the eight labs which will perform the experimental activity.

Plans for 2023

The experimental activity planned during 2022 will be performed in eight labs and the results will be collected during the first half of the 2023.

The experimental activity will be based on the agreed protocol, which includes the following activities:

• Determination of the filling volume of each sample category
• Washing and spiking with three amounts of water
• Thermal heating process (two temperatures, four times)
• Autoclaving process of treated and untreated samples
• ICP-OES analysis

The analysis of data and their dissemination will be done during the second half of 2023.

Activities in 2020/2021

The activities planned for 2020 were:

• Publication of the results obtained, after the publication of the first paper, on the propensity to delamination.
• Checking the possibility to have common and synergic activities with TC02.
• Coordinating, if possible, the TC12 actions with the pharmacopoeias regulatory bodies.
• Trying to attract other members from the pharma world.
• Starting new experimental activities on the topics of modernization of compendial testing on Glass for Pharma and / or Extractable and Leachables.

Of the above activities, only the first was successfully completed, with the publication, in June 2020, of the following scientific article:

Massimo Guglielmi, Nicola Bessegato, Juan Cerdan-Diaz, Ken Choju, Dave Lisman, Carol Rea Flynn, Emanuel Guadagnino, Amy Meysner, Joachim Pfeifer, Holger Roehl, Volker Rupertus, Martina Scarpa, Huimin Sun, Jingwei Zhang, Daniele Zuccato, Laboratory intercomparison for the evaluation of the delamination propensity of glass containers for pharmaceutical use, Int. J. Appl. Glass Sci., 2021;12:135–144

The other activities could not be completed for several reasons, including the difficulties generated by the pandemic.

However, the main reason for which the activities of the TC have undergone an abrupt slowdown is the inability to agree on the objectives to be pursued.

The discussion within the TC started soon in 2020, and continued by email. Several possible topics were suggested, but no decision could be taken in 2020 because of lack of opinions by the members. This could be interpreted as a lack of interest to continue the activity of the TC. Therefore the specific request for interest in continuing to participate in TC activities was sent to all members in March 2021. The answer was immediate and all members expressed their interest to continue.

On the base of this expression of interest the discussion continued, and a telematic meeting was organized on September 8. Unfortunately, once again no decision was taken, although some although some cues were generated.

For the reasons outlined above, the future of TC12 is still uncertainty, and no specific plan  and still no specific plan for 2022 can be outlined, although there are issues of general interest to the companies that produce the glass containers for pharmaceutical use and the pharmaceutical companies that use them.

TC12 is a particular technical committee among the ICG TCs, as it is mainly composed of members belonging to companies. This fact gives the possibility to deal with issues of great practical relevance, but at the same time makes the risk of having to manage competitiveness very high. Therefore, a balance must be found in identifying the activities to be pursued.

Plans for 2022

The plan for 2022 is to continue the efforts to find activities of interest for all the members. In the unfortunate event that an agreement cannot be reached, consideration will be given to closing the committee

Activities in 2019

The activities planned for 2019 were:

1. Completion of the testing activity on delamination.

2. Organization of an Open Session on Glasses for Pharma at the 25^th International Congress on Glass.

3. Presentation of the results at the 25^th International Congress on Glass.

4. Planning of future activities.

1. In 2018 a new testing activity on delamination was started with the aim to test, using the TC12 protocol for predicting the delamination propensity, the Low delamination propensity Vials available by the members of the TC, and to compare them with a set of “positive” vials (Vials with high delamination propensity). Nuova Ompi, Schott, Nipro, Corning and Bormioli Rocco provided 10 R vials with the desired low delamination propensity. Nipro provided also “positive” vials, i.e. made with 33 expansion borosilicate glass treated with ammonium sulfate. The results were mostly collected at the beginning of 2019 and were discussed in a teleconference in January. The preliminary conclusions were:

• There is clear evidence of the difference among actual “good” vials and “positive” vials.
• The percentage relative standard deviation (RSD%) is in general good. Considering the data for SiO₂, 39 over 48 are below 15%, only 3 are over 20%.
• One lab reported, in general, more dispersed data.
• No delamination was observed, even in positive vials.
• The use of a more aggressive test is fundamental to draw conclusions on the correlation with delamination.

The discussion within the TC brought to the decision to initiate a further round robin activity testing the same type of vials used in the previous experiment, but using a different protocol with the minimum objective to provoke delamination at least in the “positive” vials.

It was decided to use the Accelerated Lamellae Formation protocol proposed by Sloey in 2013. It is based on a pre-treatment, to make the inner surface of vials more sensitive to the chemical attack, and the use of pH  and temperature conditions able to induce delamination while avoiding the dissolution of flakes.

This activity involved 8 laboratories and was completed in November 2019. The results can be resumed as follows:

• Most labs could observe flakes only in “positive” vials.
• “Positive” vials  reached very fast saturation (100% vials with lamellae) and maintained it till the end of the experiment (day 30).
• 2 labs observed lamellae also in “good” vials, but with a number of lamellae one to two orders of magnitude smaller than “positive” vials.
• The correlation between the TC12 protocol and delamination is demonstrated.

2. TC12 organized an Open Session on Glasses for Pharma at the 25^th International Congress on Glass, in June in Boston. The organizers of the session were Daniele Zuccato, Holger Roehl and Massimo Guglielmi. The following six presentations were given:

N. Bessegato, Investigating the effects of the chemical composition on glass corrosion. A case study for Type I vials

E. Guadagnino, New challenges for Pharma glasses: Characterization updates, elemental impurities detection and data quality improvement (Invited)

M. Guglielmi, Delamination in pharmaceutical glasses: An update

M. Guglielmi (substituting D. Zuccato), TC12 “Pharma Packaging”: An update on the activities looking for a Delamination propensity predictive test

V. Rupertus, Dependency of Drug-Container-Interaction on filling volume

R. Schaut, Glass corrosion principles applied to pharmaceutical containers to predict extracted metal concentrations (Invited)

A Round Table followed, with a discussion on the most important and updated topics.

The Session was successful, with several active participants, many discussions and the generation of many interesting ideas.

3. The second presentation given by M. Guglielmi at the Open Session in Boston was devoted to explain the activity of TC12, and it was the first opportunity of divulgation of the preliminary results of the two round robins run in 2018 and 2019.

4. TC12 has now to plan the new activity steps. At the TC meeting held in Boston in June the discussion started and during the following months the opinions of the members were collected, but no decision has been taken yet. Several proposals are on the table, and will be afforded in detail in 2020, but modernization of compendial testing on Glass for Pharma and Extractables and Leacheables are the most shared themes.

Plans for 2020

January:

• Preparation of a paper to be submitted to a scientific journal, on the results obtained after the publication of the first paper on the propensity to delamination
• Submission of the first draft to the members and collection of opinions

February: Submission of the paper to the Journal of American Ceramic Society.

March 24: Meeting of the TC in Murano – Venice to decide the future activities.

May : Starting of a new experimental activity.

September: Teleconference.

General plans for 2020 are:

1. Check the possibility to have common and synergic activities with TC02.

2. coordinate, if possible,  the TC12 actions with the pharmacopoeias regulatory bodies (i.e. the United States Pharmacopeia, USP).

3. Trying to attract other members from the pharma world.

4. start new experimental activities on the topics of modernization of compendial testing on Glass for Pharma and / or Extractable and Leachables.

Committee Members

Satoshi Arai, NEG, Member, sarai@neg.co.jp
Juan Cerdan-Diaz, Consultant, Member, juancerdandiaz@gmail.com
Carol Flynn, Corning, Member, flynnc2@corning.com
Massimo Guglielmi, UNIPD, Chairman, massimo.guglielmi@unipd.it
Peter Otton, Nipro, Member, Peter.Otton@nipro-group.com
Amy Meysner, Glass Technology Services Ltd (GTS), Member, a.meysner@glass-ts.com
Serena Panighello, Stevanato Group, Member, serena.panighello@stevanatogroup.com
Joachim Pfeifer, Amgen, Member, joachimp@amgen.com
Holger Roehl, Roche, Vice Chair, holger.roehl@roche.com
Volker Rupertus, Schott, Member, volker.rupertus@schott.com
Martina Scarpa, SSV, Member, mscarpa@spevetro.it
Huimin Sun, China National Pharma Packaging Association, Member, sunhm@126.com
Jingwei Zhang, SGD, Member, Jingwei.Zhang@sgdgroup.com
Daniele Zuccato, Schott, Secretary, daniele.zuccato@schott.com
Peggy Georges, Corning Europe, Member, GeorgesP@corning.com
Taygun Akar, Sisecam, Researcher, taakar@sisecam.com

Committee Contact Details

TC12: Pharma Packaging