Anyone familiar with Annex 11 of Eudralex Annex 4 won’t be surprised by the content, but frankly I expect a lot of folks who have primarily experience on the clinical side will be scratching their heads. The fact that the authors felt the need to have an entire paragraph dedicated to unique user names is telling.
This is a great resource for sponsors who need to figure out just what to evaluate at investigators sites, a requirement this guideline repeats multiple times.
I’ll be very curious how effective sponsors are in ensuring this requirement is met “The investigator should receive an introduction on how to navigate the audit trail of their own data in order to be able to review changes.”
Beyond wishing for an 11 month cycle of writing and approval on my annual reports, there is some valuable information there.
In 2021, three CHMP GCP inspections were conducted entirely remotely, and three inspections were conducted in a hybrid setting. A total of 286 deficiencies, comprising 24 critical, 152 major and 110 minor findings were recorded for the 27 CHMP requested inspections conducted in 2021. This represents an average of 10-11 findings per site inspected. The three top categories were: “General”, “Trial Management” and “Computer System”. An increase in findings related to computer systems (e. g. Audit Trail and Authorized Access, Computer Validation, Physical Security System and Backup) is noted compared to the last reports.
On 20 March the new Annex 21 to the EU-GMP Guidelines was published as a draft. The document is entitled “Importation of medicinal Products”. The “Concept Paper” was published on 13 May 2015 (EMA/238299/2015) and the consultation phase ended in August 2015. The first draft for regulatory consultation was published in November 2016. Since then, no further activities or versions have been issued.
The Guidance is aimed at Manufacturing and Importation Authorisation holders (MIA holders) who import human or veterinary medicinal products from third countries. It does not cover products that do not have a marketing authorisation in the EU/EEA and are directly re-exported. The following points are to be regulated by the new Annex:
Physical transfer from the third country to the EU/EEA
Certification by the Qualified Person (QP) (link with the requirements of Annex 16)
Requirements for equipment and facilities
GMP requirements for manufacturers and exporters in third countries
Qualification and audits under the responsibility of the importing company and the Qualified Person (QP)
Contractual regulations between all companies or persons involved in the import
Last November, officials from the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) met with industry representatives in London to discuss the various quality challenges that arise when the development of investigational products is accelerated .
The report was recently published, and can be found here.
The workshop discussed process validation, control strategies, good manufacturing practice (GMP) compliance, comparability, stability and regulatory tools of early access approaches. Throughout they discussed two elements:
Scientific which includes technologies and scientific concepts or principles for development, manufacture and quality risk management, which may or not be present or implied in existing guidelines. Examples include concurrent validation, new modelling methodologies, new analytical techniques, etc.
Regulatory/procedural tools are described in the legal, regulatory framework and can be specific to PRIME (or Breakthrough Therapies) (e.g. kick-off meetings) or generally applicable [e.g. Post-approval change management protocols (PACMPs), recommendations, scientific advice (SA)].
I strongly recommend reading the report in it’s entirety.