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Regulatory Focus™ > News Articles > 2022 > 5 > Euro Roundup: EMA updates annexes on procedures for running GCP inspections

Euro Roundup: EMA updates annexes on procedures for running GCP inspections

Posted 12 May 2022 | By Nick Paul Taylor 

Euro Roundup: EMA updates annexes on procedures for running GCP inspections

The European Medicines Agency (EMA) has updated a set of 15-year-old annexes about the procedures for conducting good clinical practice (GCP) inspections requested by the Committee for Medicinal Products for Human Use (CHMP).
EMA published the five annexes in 2007. Since then, the regulatory landscape has changed, most notably through the adoption and recent implementation of the Clinical Trial Regulation (CTR). Many of the new additions to the annexes relate to CTR, which has provided the basis for the use of a risk-proportionate approach to clinical trial design and conduct that inspectors should consider when reviewing studies.
The five annexes cover the procedures related to investigator sites, clinical laboratories, sponsors and contract research organizations (CROs), record keeping and archiving of documents and bioanalytical part, pharmacokinetic and statistical analyses of bioequivalence trials. EMA is yet to update two other texts in the series that cover computer systems and Phase 1 units.
EMA has retained the structure and much of the content of the older documents while making extensive changes to the details. In the annex focused on sponsors and CROs, the agency has added a subsection on noncompliance, explaining that inspectors should assess the procedures for reviewing and submitting “potential and actual serious breaches, including log, confirmations for decisions, outcomes and CAPAs.”
The agency has also updated existing subsections with new priorities for inspectors. EMA now wants inspectors to evaluate systems for standard operating procedures and associated documents, and to determine if the sponsor or CRO’s procedures include a description of a risk-proportionate approach to monitoring and the rationale for the chosen monitoring strategy in trial-specific monitoring plans.
EMA has made similar changes to the annexes focused on other organizations. The updated annex on investigator sites calls on inspectors to determine if informed consent was obtained in compliance with CTR “by examining an appropriate sample of trial participants (including the trial participants whose medical records are reviewed), or the trial participants' legally acceptable representative, prior to their entry into the study.” The review should now include “documentation in the source data of the process of obtaining the initial informed consent and subsequent consent to updates, including pediatric assent and emergency consent.”
EMA Guidance
EMA establishes rules of procedure for newly created Emergency Task Force
EMA has established the rules of procedure for the Emergency Task Force (ETF) that was created recently as part of the expansion of the powers of the regulator. ETF has taken over from the COVID-19 EMA Pandemic Task Force to give the agency a permanent focus on crisis preparedness.
The rules of procedure document states that ETF was established “in preparation for and during a health emergency to provide scientific advice and to review scientific data on medicinal products targeting the emergency, to provide recommendations with regards to the use of such medicinal products and to provide scientific support to facilitate clinical trials for such medicinal products.”
EMA used the rest of the document to outline how ETF will fulfill that function, starting with an outline of the composition of the task force, details about how it will engage with additional experts, observers and other stakeholders and information about the responsibilities of the chairpersons and coordinator. The procedures permit ETF to access additional expertise and resources if it faces simultaneous crises and empower the co-chairs to initiate the adaptation of the composition of the task force as needed.
Other sections of the document address what ETF will do. EMA has tasked the members with providing scientific advice on developing medicinal products with the potential to treat, prevent or diagnose the public health emergency, and with delivering recommendations to CHMP.
ETF will also provide “information to the public and relevant interest groups” and “scientific support to facilitate clinical trials” of medicinal products to address the public health emergency. EMA foresees the support provided by ETF including advice to “sponsors of similar or linked planned clinical trials on the establishment of joint clinical trials,” potentially covering details about co-sponsoring studies.
ETF Rules
Pfizer recalls hypertension medicines from UK over breach of nitrosamine limit
Pfizer is recalling all batches of Accupro 5mg, 10mg, 20mg and 40mg film-coated tablets from the UK after discovering a nitrosamine above the acceptable limit.
The UK Medicines and Healthcare products Regulatory Agency (MHRA) shared details of the Class 2 recall, which covers 12 batches of the hypertension medication distributed between February 2020 and February 2022. The nitrosamine discovered above the acceptable limit, N-nitroso-quinapril, may raise the risk of cancer if consumed over a long period of time.
MHRA is asking healthcare professionals to quarantine all remaining stock of the affected batches and return them to their suppliers. Patients should continue taking their treatments until they consult with their healthcare professionals.
The UK regulator disclosed details of the recall days before putting out a notice about a labeling error in some batches of GlaxoSmithKline’s Zovirax. MHRA is advising healthcare professionals to refer to the corrected and approved Package Leaflet and discard the incorrect version inside the sealed packs.
MHRA Notice, More
PRAC warns against using Gentium’s Defitelio to prevent veno-occlusive disease
EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has warned healthcare professionals against using Gentium’s Defitelio to prevent veno-occlusive disease after seeing the results of a Phase 3 trial.
Defitelio is approved for use in the European Union as a treatment of severe veno-occlusive disease in patients undergoing haematopoietic stem cell transplantation (HSCT). A clinical trial looked at the effect of using Defitelio to prevent severe veno-occlusive disease after HSCT but stopped after an interim analysis because no benefit was found. Side effects included low blood pressure and bleeding.
After learning of the failure of the study, CHMP saw a need to communicate the findings to healthcare professionals. PRAC concurred with the committee, leading it to propose a direct healthcare professional communication when it met earlier this month. The communication will now pass to CHMP. Once CHMP has reviewed the materials, it will share them with healthcare professionals to warn against off-label use.
PRAC Notice
Spain’s AEMPS asks manufacturers to keep data updated as new feature goes live
The Spanish Agency of Medicines and Medical Products (AEMPS) has asked marketing authorization holders (MAHs) to ensure their data in the SEVeM medication verification system is up to date.
Starting this month, Spain will check that the national code for each medicine corresponds to the record in SEVeM. If there is a mismatch between the information sources, the system will generate an alert and the verification required to dispense the medicine will not take place. The presence of out-of-date data in SEVeM could therefore cause problems.
To avoid that scenario, AEMPS is asking MAHs to check that their national codes have seven digits. The verification process will fail if only the first six digits are included. Medicines that lack national codes, such as products that came to market under special circumstances, should not be uploaded to SEVeM.
AEMPS Notice (Spanish)
Other News:
The Dutch Medicines Evaluation Board (MEB) has published its annual report for 2021. The report sets out how changes to the structure of the regulatory agency and how it collaborates that began last year will continue in 2022. MEB Report


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