Tech Bulletin | April 2018

Current regulations for testing that is inherently not stability indicating are vague regarding testing requirements. They are also not specific about what is expected from these beyond use date studies when trying to encompass other product attributes that can be casually included in cGMP requirements.

In the past few years, DYNALABS has taken the Stability Profile as a proactive approach to changing industry standards and foreseen transition of Beyond Use Date studies to Stability Profile studies.

For a product that is run by methodology, such as IC and Titration, DYNALABS recommends, at minimum, a testing regiment that includes not just potency, sterility, and endotoxin but always includes testing such as Particulate Matter (USP <788 or <789>), pH, Visual Inspection, Identification, and Weight Check. Sterility and endotoxin would need to be proven compatible with specific formulation by performing validations/suitabilities. For methodology that is not stability indicating due to limitations to separate degradants (e.g. IC and Titration), Potency Specificity (validation extension) is not required because the methodology does not afford this as an option.

We also recommend USP <51> for Preservative Effectiveness and quantitation of preservatives. For a full list of tests that DYNALABS recommends for Stability Profile Testing see below:

STABILITY PROFILE TESTING

• Potency
• pH
• Endotoxin
• Sterility
• Container Closure Integrity
• Weight Check
• USP <61> / <62>
• USP <51>
• USP <341> preservative assay
• Visual Inspection
• Particulate Matter

For additional information, please see our detailed API list on the link below. Each active is followed by the method type DYNALABS uses along with if it is stability indicating or not. https://www.dynalabs.us/products-services/api-list/

Per USP <1207> container-closure integrity is the ability of a package to prevent product loss, to block microorganisms access, and to limit entry of detrimental gases or other substances, thus ensuring the product meets all necessary safety and quality standards. CCI testing is a package leak test that can detect the presence of any breach or gap in the product.

For performance of the test DYNALABS recommends using USP <71> testing requirements + 4 containers to be used as controls. FDA guidance Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of Stability Protocol for Sterile Products. Encompassing CCIT as part of the stability study can have a positive effect as well as allowing for replacement of endpoint sterility requirements for establishing a BUD.

DYNALABS CCI testing encompasses Dye Ingress methodology. Samples are tested against Methylene Blue and placed in a positive pressure chamber. There must be no evidence of dye inside any sample containers when compared to the negative controls and the positive containers must demonstrate that the dye breached the septum and is observed inside the container. For IV Bags, DYNALABS uses a blood pressure cuff and a required amount of pressure is applied to the bag. The amount of pressure is dependent on the volume of the sample. There must be no evidence of a leak for any sample container under pressure and the positive control must demonstrate the septum was breached and a leak has occurred.
DYNALABS can test on all container types and compounds for CCIT except the following:

• Amber colored vials
• Opaque/white eye dropper vials or bottles
• J-tip syringes (aerosolized syringes)
• Colored compounds (example: Methylcobalamin)

Make sure your browser and operating systems are up to date!

To provide continuous quality improvement and ensure that we follow best practices for website security, DYNALABS will be making changes to our website security on May 1st, 2018.

These changes will only affect a small fraction of our client base.

If you are using Windows 7, Windows 10, or a recent version of Mac OS, you will not be affected by these changes.

Changes that will be made to DYNALABS’ website security include:

• TLS 1.0 will not be supported
• TLS 1.1 will not be supported
• TLS 1.2 will be supported using AES 128/128 and AES 256/256 ciphers only

This will end support for Windows XP/Internet Explorer 8 users. If you are currently using a Windows XP workstation, you will not be able to access the DYNALABS secured website.

What is TLS?

Transport Layer Security (TLS) is a protocol that provides privacy and data integrity between two communicating applications. It’s the most widely deployed security protocol used today and is used for web browsers when data is to be securely exchanged over the internet. TLS 1.2 is the newer and more secure version, and, to ensure the security and data integrity of our customers’ information we are disabling TLS 1.0 and TLS 1.1 on our website.

If you are having issues after the May 1, 2018, security update, please initially consult with your IT professional to update your computer. If you have questions or other issues, please do not hesitate to contact your DYNALABS Customer Support Specialist. sales@dynalabs.us

In the very near future, in an continuing effort to comply to industry standards, DYNALABS will be making updates to the COA.

• In order to meet the standards required by 21 CFR Part 11 and ISO 17025, the COA naming convention will be updated to read as “COA-LotCode-SampleID-MMDDYYHHMMSS -V#”
• DYNALABS’ audit history is being updated to provide more accurate data regarding the downloads of COAs. All COA versions will be stored and records of when each version is downloaded will be accessible.

Any questions regarding these updates can be directed to customer support by calling 888.396.2522 or sales@dynalabs.us