Last week’s round -up;
04 -08 October 2021
EU extension of GMP and GDP certificates through 2022
EU regulators have automatically extended GMP and GDP certificates and other time-limited authorisations (manufacturing, import and wholesale authorisations) through 2022 due to COVID-19 safety and travel restrictions. This has been done to ensure the availability of medicines throughout the EU during the pandemic. For sites within the EEA, the extensions should occur without any action on the part of the certificate holder, unless any restrictions on the validity period are stated in the clarifying remarks of the certificate or the issuing/supervisory authority takes action that affects the validity of the certificate. The automatic extension does not apply to changes in the scope of the certificate. Distant assessments by an EEA supervisory authority may be required for new sites in third countries when no applicable mutual recognition agreement (MRA) exists with local regulators.
Risk of the presence of mutagenic azido impurities in losartan API
Following a report about the possible presence of potentially mutagenic azido impurities in certain sartan active substances, the EDQM has taken a number of measures to ensure that any active substances containing these impurities above the acceptable level would not be released onto the market. Holders of impacted CEPs were also requested to take corrective action to ensure that such impurities do not exceed their acceptable limits in the future. The EDQM’s recent investigations identified another azido impurity that has so far only been detected in losartan potassium (losartan azido impurity). This impurity has tested positive in a bacterial mutagenicity (Ames) test. The Directorate has advised that this azido impurity should be controlled at or below the Threshold of Toxicological Concern (ICH M7) due to the lack of additional information from in vivo studies. CEP holders were advised of their obligation to provide appropriate information relating to azido impurities to MAHs, therefore, enabling them to fulfil their legal responsibilities.
FDA: Microbial contamination in non-sterile drugs
The FDA has issued draft guidance to help manufacturers control microbiological contamination of non-sterile drugs (NSDs) due to concerns over a high number of adverse events and recalls associated with contaminated products. The draft guidance covers product development considerations, risk assessments, and GMP requirements that are relevant to control microbiological contamination in the manufacturing of a non-sterile drug. Solid non-sterile dosage forms as well as semi-solid forms and liquid non-sterile dosage forms including topically applied creams, lotions and swabs; and oral solutions and suspensions are covered in the guidance. The draft guidance applies to prescription or non-prescription drugs and approved NDAs or ANDAs as well as over-the-counter monograph drugs. Adverse events and recalls of drug products due to Burkholderia cepacia complex (BCC) contamination are included in the guidance, and prevention and testing for BCC in aqueous dosage forms of NSDs are also described. Further information on the draft guidance may be found in the link below and the deadline for comments is the 30th December.
Updated EMA Nitrosamines Q&A
A new draft Ph. Eur. monograph on Particle Size and Shape Determination by Image Analysis has been published in Pharmeuropa 33.4 for public consultation until the 31st December 2021. Image analysis is a computer-based technique used to determine the size and shape of particles from digital images efficiently and reliably. The images may be obtained by several techniques including optical microscopy, chemical imaging or electron microscopy. The measuring principle is based on a discretisation of an image into ‘pixels’, which are calibrated with respect to size and a software algorithm assigns the pixels to individual particles, which are thus characterised by a defined number of pixels of known size. The new guidance covers both static and dynamic image analysis. The dynamic technique can measure more particles than in static image analysis and is more reliable for wide size distributions, however, the technique is prone to systematic errors with respect to size.