European Warning Letters? Is there such a thing? Basically, no. Warning Letters are issued by the US-American FDA. However, there is something "comparable" namely the "Non-Compliance Reports" published in the Eudra GMDP database. Now, one may question what the authorites has complained about in the last 3 months.
Water systems are one of the most important systems in the pharmaceutical industry. What are the GMP requirements for the qualification and running of these systems? The US GMP regulations (21 Code of Federal Regulation (CFR) 210/211) do not provide much concrete information on this. There is still a Guide to Inspection for FDA inspectors from the early 90s. So, what does the FDA expect today? A current Warning Letter provides a few answers.
In the USA, combination products are regulated independantly. A draft document from the FDA entitled "Principles of Premarket Pathways for Combination Products" describes the ways in which marketing authorisations are granted in the USA and how the various Centers interact.
With the entry into force of the FDA Reauthorization Act (FDARA) in August 2017, sections on the inspection of medical device manufacturers in the USA and abroad also became effective. A draft document from the FDA on inspections of medical device manufacturers has been issued for some time now to further harmonize and interpret the changes.
In October 2019, the FDA issued guidelines in a draft document regarding the use of a Type V Drug Master File (DMF). In this document, information can be made available to the CDER (if it is in charge of the (project) approval procedure) concerning the medical device proportion of a combination product.
The new ICH Q12 Guideline for Post-Appproval Changes has been adopted in Singapore in November 2019. The document provides guidance on a framework to facilitate the management of post-approval CMC changes.
When it comes to process validation, FDA's Process Validation Guidance from 2011 is state-of-the-art. It is interesting to see how the FDA would like to see the guidance implemented. Here, the findings described in Warning Letters issued after FDA inspections can help. A recent Warning Letter regarding deficiencies to 21 CFR 211.100 from October 2019 mentions the following.
The European Commission has published an aide memoire for Good Distribution Practices (GDP) inspection of wholesalers’ compliance with Commission Delegated Regulation (EU) 2016/161 for safety features.
An USP Stimuli article on Elastomeric Components for Inhalation Packaging / Delivery Systems has been published in Pharmacopeial Forum, proposing to test for nitrosamines in elastomeric components used for inhalation products.
FDA's Warning Letters provide a valuable source of detailed information and can be helpful in preparing for an inspection, making a more detailed analysis worthwhile. Read more here about what FDA inspectors have discovered in recent months regarding frequent weaknesses at GMP-liable pharmaceutical manufacturers.