End of the pyrogen test looms in Europe!

On 28^th June 2021 EDQM declared that rabbit pyrogen testing will end in Europe by 2026. Although most companies have moved away from the test, a few continue and some monographs continue to provide the option. This is a further development of the EU ‘3Rs’ process: Replacement,Reduction and Refinement of the use of animals for test purposes.

Here is the link: https://www.edqm.eu/en/news/european-pharmacopoeia-put-end-rabbit-pyrogen-test

The European Commission states:

The majority of pyrogens are bacterial endotoxins and these can be detected using the bacterial endotoxins test (BET) described in Ph. Eur. general chapters 2.6.14. Bacterial endotoxins and 2.6.32. Test for bacterial endotoxins using recombinant factor C. However, in some cases, non-endotoxin pyrogens may also be present and these are not detected by the BET. A test covering all types of pyrogens is therefore required to confirm the absence of non-endotoxin pyrogens.

General chapter 2.6.30. Monocyte-activation test (MAT) was added to the Ph. Eur. in 2009, providing an in-vitro alternative to the RPT that is capable of detecting both endotoxin and non-endotoxin pyrogens. The publication of this chapter was a significant step forward in terms of animal welfare, in accordance with the Council of Europe’s European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes.

However, despite multiple efforts since then to encourage developers to apply the MAT instead of the RPT, rabbits continue to be used extensively to detect pyrogenic substances.

There are currently 59 Ph. Eur. texts – covering a variety of topics including vaccines for human use, blood products, antibiotics, radiopharmaceuticals and containers – that refer to the RPT and will be affected. The Ph. Eur. is committed, for all these texts, to replacing the test for pyrogens with a suitable in-vitro alternative, ultimately leading to the complete elimination of the RPT. In the meantime, users are actively encouraged to seek alternatives to chapter 2.6.8, the best option being the MAT.

Aside from the complexities, this is something  I’ve long been advocate of. LAL is specific, superior and does not breed rabbits to be killed. In addiion, where non-endotoxin pyrogens are of a concern, the Monocyet Activation Test is available.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

PIC/S issues final data integrity guidance (July 2021)

 

Data Integrityis defined as “the degree to which data are complete, consistent, accurate, trustworthy,andreliable and that these characteristics of the data are maintained throughout the data life cycle”.

This is a fundamental requirement for an effective Pharmaceutical Quality System which ensures that medicines are of the required quality. Poor data integrity practices and vulnerabilities undermine the quality of records and evidence,and may ultimately undermine the quality of medicinal products. 

On 1st July PIC/S issued its final data integrity guidance document for GMP inspectors. The objectives of the doucmernt are:

• Providing guidance for Inspectorates in the interpretation of GMP/GDP requirements in relation to good data management and the conduct of inspections.
• Providing consolidated, illustrative guidance on risk-based control strategies which enable the existing requirements for data to be valid, complete and reliable as described in PIC/S Guides for GMP and GDP to be implemented in the context of modern industry practices and globalised supply chains.
• Facilitating the effective implementation of good data management elements into the routine planning and conduct of GMP/GDP inspections; to provide a tool to harmonise GMP/GDP inspections and to ensure the quality of inspections with regards to data integrity expectations.
  

The doucment can be accessed here: PIC/S

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Polymer approaches to reduce coronavirus infections

 

Polymers have been designed for effective virus inhibition and as antiviral drug delivery carriers. A new review summarizes recent progress and provides a perspective on polymer-based approaches for the treatment and prevention of coronavirus infection. 

 

 

Polymers can:

 

• Prevent or inhibit the spread of a virus by providing a semipermeable barrier (e.g. mask or face-shield).
• Interfere with binding to the glycoprotein surface of host cells.
• Augment small molecular antiviral drug therapies.
• Enhance the response of the immune system as a vaccine adjuvant.
• At as a vehicle for other therapeutic molecules to improve the water solubility or stability of antiviral therapeutics.

 

Applications include integrating functional polymers into personal protective equipment (PPE) to prevent the entrance of virus into the respiratory system; the cellular binding of viral particles at the alveoli can be inhibited using polyanion and polycation against viral S protein or angiotensin-converting enzyme 2 (ACE2) receptors; and polymers could also be used to deliver antivirus drugs.

 

In addition, polymers could also be useful when being covalently combined with small-molecule drugs to form macromolecular prodrugs.

 

Furthermore, polymer-based vaccines or vaccine adjuvants can be used to prevent virus infection or even to boost the immune response during infection.

 

These polymer-based partners include polyanion/polycations, dendritic polymers, macromolecular prodrugs, and polymeric drug delivery systems that have the potential to significantly improve the efficacy of antiviral therapeutics.

 

For further information about the research, see Materials Today.

 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)