Glass delamination, which is a reaction from a form of glass corrosion, are small, thin, glass fragments, termed “glass lamellae”, which are shed from the interior portion of glass containers and vials. USP 1660 describes a methodology for evaluating various glass vials under simulated conditions. The results from these types of approaches can be difficult to translate to the issue of compatibility of a specific drug product with specific vial types in real-life scenarios.

https://info.gatewayanalytical.com/application_proactive_reactive_glass_delam

 

This function has a great deal of utility when performing materials analysis, whether the goal is product development, failure analysis, or reverse engineering.  Manual analysis certainly has its advantages when a quick, general overview of a sample is effective. However sometimes the end goal of an examination requires a bigger picture of the sample, and automated SEM-EDS analysis can provide a solution.

While taking thousands of measurements may be a tedious, time-consuming task for a microscopist, computers are efficient tools that can be programmed to perform numerous measurements over long periods of time.  Additionally, software can be utilized to pull out the information of interest that the computer collected, providing data such as particle counting, particle size distribution, elemental distribution, and statistical information. The Perception software, by Aspex Corporation © (utilized here at Gateway), can even provide an X-ray map of particle distribution to give a nice visual representation of elemental allocation over a sample.  Additionally, an analyst can use this software to establish elements of interest, size ranges, and “rules” to determine how features are categorized.  This allows the analyst to be very specific in what is analyzed during automated analysis.  This application can be employed on a substantial number of sample types, from elemental distribution in polymers, rubbers and adhesives to particle sizing and counting of powders and sprays.

So before you ask your analyst to collect thousands of datapoints manually, you may want to consider employing automated SEM-EDS analysis to attain both an unbiased, accurate representation of your sample, and to keep your scientists happy.

 

Particulate matter in injections is defined as extraneous particles, unintentionally present in the end product. These contaminants can come from various sources, including the environment, packaging materials and undissolved formulation ingredients. Particulate matter can be harmful when introduced into the bloodstream. Therefore, the US Pharmacopeia places limits on the amount of sub-visible particles that are allowed in both injections and ophthalmic solutions based on these risks, as described in USP<788> and USP <789>.

https://info.gatewayanalytical.com/usp-788-789-particle-id-app-note-download-0

 

 

Contamination in drug products is a common problem in the pharmaceutical industry that can have major impacts on pharmaceutical companies, from both financial and safety aspects. Inhalable drug products are unique with regards to the affects of contamination, due to enduse design. Inhalation of foreign particles can lead to particle settlement in the alveolus, which (depending on the size and distribution of the particles) can lead to such contraindications as allergic reactions, pain, inf lammation, adverse immune responses, aggravated asthma, chronic bronchitis and acute respiratory affects.

The US Food and Drug Administration (FDA) has taken action against companies specifically for violations involving inadequate investigations of contamination failures within products. Warning letters include verbiage such as “…the black particles were not identified and source was not determined. In addition, there was no attempt to determine if the black particles originated from the manufacturing process, or if additional lots were affected…” and “Reddish-brown particulate matter has been a recurring problem…The cause of the particulate matter problem has not been determined.” These statements indicate that merely the detection of foreign particulate contamination is not sufficient in itself, but that the identification and source determination of the contaminants is necessary.

[Download & Read Full Article]

 

Glass delamination⁽¹⁾ has become a bit of a hot topic in the area of parenterals over the past several years. Glass delamination is, indeed, a serious issue which can not only cause pharmaceutical companies millions of dollars in recalls, but also stands as a safety hazard to end users. Delamination is essentially the flaking off of the top layers of a glass surface into the liquid contents of a pharmaceutical vial, syringe, or other container. Numerous companies have experienced this issue, and have had to open investigations⁽²⁾ to address the issue. The question is, how can we be proactive, rather than reactive, in addressing concerns with glass delamination?  How can we minimize the risk of experiencing a delamination issue, in order to protect the welfare of end-users and uphold the quality of our products?

USP <1660> ⁽³⁾ details the testing requirements for the assessing the durability of glass container surfaces. The purpose of this document is to recommend “approaches to predict the potential of a drug product to cause formation of glass particles and delamination and to detect their occurrence.” These methods are not only applicable to the common vials we encounter, but also to syringes, ampules, and other glass containers that house drug products. USP <1660> describes the various types of glass encountered, how molded/tubing glass containers are manufactured, and glass surface chemistry. After discussing the variables that affect the durability of the inner surface of glass containers, both predictive and aggressive screening suggestions are outlined.

These screening methods include utilization of technologies to test the degree of pitting/chemical composition on the glass surface, the conductivity/pH and extractables of elements in solutions, and the size/number/morphology/composition of glass particles (visible and subvisible) in solutions. Techniques include microscopy (DIC, SEM, etc.), pH meters, ICP spectroscopy, and particle size analyzers.

Both pharmaceutical companies and glass manufacturers alike are in a position to benefit from performing screening studies on glass containers used to hold drug products. The benefits and necessity for the pharmaceutical companies are quite obvious (increased safety and quality, decreased risk of costly recalls). Glass container manufacturers also can benefit from such screening as well…predictive and aggressive durability screening of their glass container products can be included as a selling point to their customers. As always, it does not come as a surprise that a focus on quality is key in successful drug product manufacturing.

References:

1. http://rx-360.org/en-us/Alerts-News/Alerts/Glass-Delamination
2. https://gatewayanalytical.com/resources/webinars/evaluation-pharmaceutical-vials-glass-delamination
3. http://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/revisions/c1660.pdf
4. USP <1660> Evaluation of the Inner Surface Durability of Glass Containers, www.usp.org

 

Recently on December 22^nd, Dave Exline, Senior V.P. at Gateway Analytical stopped by the Pittsburgh Technology Council’s TechVibe Radio to talk on-air with Audrey Russo and Jonathan Kersting about Gateway Analytical and its services.

During the show, Dave discussed the various analytical testing and consulting services the company offers for the pharmaceutical, material science, and forensic industries.  Most notably, how Gateway Analytical takes a forensic investigative approach to contamination issues in a company’s pharmaceutical manufacturing process.

You can listen to the Mp3 below:

Gateway Analytical Interview on Pittsburgh Technology Council’s TechVibe Radio

About TechVibe Radio:

The Pittsburgh Technology Council’s Audrey Russo and Jonathan Kersting interview local entrepreneurs, business leaders and stakeholders behind the Pittsburgh region’s fast-moving technology industry.

TechVibe Radio broadcasts on 104.7 FM News Talk every Saturday at Noon. With a crystal-clear FM signal, TechVibe reaches thousands of listeners across all of southwestern Pennsylvania and parts of the tri-state area. To listen to previous broadcasts you can do so here.

TechVibe Radio podcasts can also be found on iTunes. Just search “TechVibe Radio” under the podcast section and have the latest shows ready for download.

Particulate matter, in both parenteral and ophthalmic drug products, consists of extraneous mobile, undissolved particles, other than gas bubbles, unintentionally present in the solutions. These particles can originate from various sources including, but not limited to: the environment, the manufacturing process, packaging materials and undissolved formulation ingredients. This particulate matter can be harmful when introduced to the body. Therefore, the US Pharmacopeia places limits on the amount of sub-visible particles that are allowed in drug products based on these risks.

https://info.gatewayanalytical.com/usp-788-789-particle-counting-app-note-download