•    Risks associated with codeine-containing cough medicine
•    Pediatric acetaminophen dosing
•    Risks associated with propylhexedrine abuse and misuse
•    Nonsteroidal anti-inflammatory drugs (NSAIDS) and oligohydramnios
•    Oral health care in infants and children
•    Risks associated with use of ipecac syrup as OTC poison treatment
•    Pediatric cough/cold dosing
•    Effectiveness of phenylephrine as an oral decongestant ingredient

 

See: https://dps.fda.gov/omuf/forecast?utm_medium=email&utm_source=govdelivery 

 

 

 

Co-processed excipients

 

The European Medicines Agency (EMA) has drafted a document concerning co-processed excipients (CoPEs). The document is available for comment until 31st December 2024.

 

While CoPEs can offer benefits such as improved functionality, they also introduce additional risks compared to using individual excipients. The use of CoPEs in pharmaceutical formulations can present higher risks due to several factors including:

 

• The complexity of composition - inherent variability, unpredictable interactions
• Quality control - challenges for analytical methods, batch to batch consistency
• Formulation development - complexity of optimisation studies, challenges with scaling up production
• Stability issues - due to combination of different materials

 

To access see:  https://www.ema.europa.eu/en/documents/scientific-guideline/questions-answers-regarding-co-processed-excipients-used-solid-oral-dosage-forms-h-v_en.pdf 

 

 

 

UK-wide licensing for medicines comes into effect on 1 January 2025

 

If you work in pharmaceuticals or a related industry, you’ll already know that there are new arrangements for medicines under the Windsor Framework that come into effect on 1 January 2025.  This should make the supply of medicines to the UK market simpler by ensuring they are available across the UK in the same packaging at the same time and on the same basis.

 

This will enable industry to use the same packaging and labelling for medicines UK-wide with a single licence. The EU Falsified Medicines Directive will be disapplied in Northern Ireland.

 

MHRA has just published new guidance building on UK-wide licensing and labelling guidance has already been published. This includes further details on pharmacovigilance, control testing and additional advice for manufacturers and wholesalers.

 

See: https://www.gov.uk/government/collections/mhra-windsor-framework?utm_source=insite&utm_medium=news&utm_id=wf1 

 

 

 

Analytical balances

 

US Pharmacopeia (USP) is updating chapter <41> “Balances for Analytical Purposes”.

 

The following changes have been proposed:

 

1.   Introduce the relationship between calibration and performance checks within the life cycle approach in order to ensure fitness for purpose
2.   Include the concept of a risk-based approach with respect to the frequency of calibration and performance checks
3.   Add a new section on calibration, clarifying its purpose and including considerations for uncertainty and frequency
4.   Introduce clarifications of compliance with respect to the repeatability test
5.   Align the term minimum weight with that in 〈1251〉 and in the European Pharmacopoeia, regarding standard deviation. Include calculation examples
6.   Introduce text that differentiates the minimum weight from the smallest net weight
7.   Clarify criteria to ensure compliance with the required accuracy during performance test checks and calibration. This includes the consideration of the uncertainty of the test weights
8.   Incorporate additional applicable references into the text

 

In addition, the companion chapter 〈1251〉 “Weighing on an Analytical Balance” is being updated.

 

The following changes have been proposed:

 

1.   In the “Introduction”, clarify the group of instruments in which balances are included as per 〈1058〉 “Analytical Instrument Qualification” and its relationship with the analytical target profile described in 〈1220〉 “Analytical Procedure Life Cycle” 
2.    Add a new section, “Principle”, defining weight and units
3.    In ‘Performance Qualification’, the risk of the weighing application is explained with regard to the user’s quality management system. This is in order to define the frequency and the type of performance qualification activities
4.    Discuss the frequency of each of the individual tests included, as well as the relationship between calibration and verification
5.    Delete the section “Balance Checks” and integrate it into “Performance Qualification”
6.    Simplify the definition of minimum weight and add clarifications about the tare vessel, as well as examples to address frequently asked questions
7.    Introduce a safety factor that addresses critical performance changes of the balance during routine usage
8.    Add a glossary to clarify the use of specific terms
9.    Add an additional information section to ensure alignment of concepts and terminology.

 

Access requires registration via USP Online to view.

 

 

 

Microbiology testing

 

USP is updating chapter 〈2022〉 “Microbiological Procedures for Absence of Specified Microorganisms—Nutritional and Dietary Supplements”. This proposal is based on the version of the chapter official as of November 1, 2019. A proposal to revise the companion chapter, 〈2021〉 “Microbial Enumeration Tests—Nutritional and Dietary Supplements”, is also being published in this issue of PF.

 

The Joint Subcommittee for Microbiological Issues in Dietary Supplements and Food Ingredients proposes the following revisions to both chapters:

 

• Revise the title by changing "Nutritional Supplements" to "Dietary Ingredients"
• Include a reference to the validation of alternative microbiological methods
• Update text throughout to use modern terminology that aligns with the current microbiology chapters

 

Access requires registration via USP Online.

 

 

 

Osmolarity

 

The USP is proposing a new chapter: 〈1785〉 “Osmolality and Osmolarity - Practical Considerations”. This will become a companion to 〈785〉 “Osmolality and Osmolarity”.

 

The purpose of the chapter is to provide information and guidance regarding how to evaluate whether an osmolality instrument is suitable for use with certain pharmaceutical formulations. The chapter discusses how to assess the ideal behaviour of a solution, how to determine what nonideal behaviours dominate and how to evaluate whether a freezing point measurement is suitable for an undiluted sample. 

 

Additionally, this chapter provides suggestions and recommendations on situations when the procedure needs to be validated or revalidated due to test condition changes. This chapter also briefly discusses the correlation and difference between tonicity and osmolality.

 

The osmolality of certain solutions may be challenging to measure. The presence of cosolvents, which may be used as solubilisers, may have an antifreeze effect, which can preclude the use of a freezing-point osmometer. Osmolality measurement challenges are often seen in solutions with high protein or polymer concentrations (e.g., >50 mg/mL). Samples of this type are frequently encountered in the development of biopharmaceutical formulations for subcutaneous or intravitreal delivery, which may require the delivery of a large therapeutic dose of protein in a low, patient-acceptable volume.

 

Meanwhile, chapter 〈785〉 is due to be revised, with the following:

 

1.     Types of Osmolality Instruments: Include a cross-reference to the new general chapter, 〈1785〉 “Osmolality and Osmolarity—Practical Considerations”, which contains additional information on the use of different osmometers on the same sample
2.    Procedure for Calibration Check: Clarify the use of single solution or bracketing solutions and include an example
3.    Test Solutions: Add a discussion on the impact of sample dilution
4.    Method: Freezing-Point Osmometry: Under Procedure, remove the rinsing step as it is not consistent with modern instruments that use disposable test cells. Remove the sentence related to sample viscosity from the troubleshooting section
5.    Tonicity: Add a cross-reference to 〈1785〉

 

Access requires registration via USP Online.

 

 

 

Glassware

 

USP is updating chapter 〈660〉 “Containers—Glass”. This is to enhance the evaluation and standards for glass packaging systems used in pharmaceuticals. The key changes being proposed are as follows:

 

• Addition of new glass materials: Two new glass materials have been introduced -aluminosilicate glass and quartz glass. These additions aim to provide more options with varying properties for different pharmaceutical applications

 

• Removal and replacement of tests: The glass grains test has been removed and replaced with a new identification test based on WDXRF (4.1 Elemental Composition by Wavelength Dispersive X-Ray Fluorescence). This modern method enhances the accuracy of identifying and characterising glass materials. The surface etching test has been eliminated, streamlining the testing process and removing redundancies

 

• Revision of existing tests: The determination of inner surface hydrolytic resistance test is retained (4.2 Determination of Inner Surface Hydrolytic Resistance) with added guidance on the application of autoclave instructions based on new studies. This ensures precise and reliable testing procedures. A new extractable arsenic test (4.4 Extractable Elements) has been added using inductively coupled plasma (ICP) technology, providing a more sensitive and accurate measurement of arsenic levels. The spectral transmission test for coloured glass containers has been revised (4.5 Spectral Transmission for Coloured Glass Containers), incorporating data from both borosilicate and soda–lime–silica coloured glass to refine the evaluation of light protection capabilities

 

Also, under review is chapter 〈1660〉 “Evaluation of the Inner Surface Durability of Glass Containers”. The proposed changes are:

 

• The inclusion of various glass types, including aluminosilicate, borosilicate, quartz, and soda–lime–silica glass.

 

Key topics include:

o    Glass composition
o    Formation processes
o    Surface treatments
o    Factors affecting inner surface durability

 

Access requires registration via USP Online.

 

 

 

Pharmaeuropa

 

New European Pharmacopoeia (Ph. Eur.) texts that have undergone technical revisions are published in Pharmeuropa for public consultation.

 

The deadline for comments the latest Pharmeuropa - edition 36.4 - is 31 December 2024.

 

It should be noted that:

 

• Although draft monographs must not be regarded as official standards, they will, once adopted by the Ph. Eur. Commission at a later date, become applicable and legally binding standards for the products concerned in all Ph. Eur. member states
• While general texts are not legally binding per se, they become mandatory when referred to in a monograph. Changes to general texts may therefore impact monographs

The main chapters under revision are:

 

• 2.8.25. High-performance thin-layer chromatography of herbal products. Reference number: PA/PH/Exp. 13B/T (24) 29 ANP. Text number: 20825
• Evaluation of safety of veterinary vaccines and immunosera. Reference number: PA/PH/Exp. 15V/T (24) 9 ANP. Text number: 50206
• 5.38. Quality of data. Reference number: PA/PH/Exp. SDA/T (23) 5 ANP. Text number: 53800

 

Perhaps of greatest interest is the chapter on “Quality of Data”. This connects with both data integrity and advances in artificial intelligence.

 

The rapid recent progress in measurement techniques and data analysis, alongside the ability to generate more data from an ever-increasing number of sources, means that the volume of data that can be collected, stored and analysed is greater than ever before and is still growing. 

 

As such, data is taking on an increasingly important role in the quality assessment of medicines, especially when it is fed into numerical models based on chemometrics, machine learning (ML) or other forms of artificial intelligence (AI) in order to make inferences, decisions and take action (e.g. algorithmic decision-making (ADM) systems). 

 

Because bad or poor-quality data may cause false information or technical errors, data quality requires careful management - this forms the basis of this chapter.

 

Pharmeuropa is free to read, although registration is required: https://www.edqm.eu/en/-/pharmeuropa-36.4-just-released