ECA kommentiert FDA Guideline über Visuelle Kontrolle

Die FDA hatte im Dezember 2021 ihre lang erwartete Guideline über die visuelle 100% Kontrolle von Parenteralia als Entwurf veröffentlicht - wie Sie bereits unter FDA veröffentlicht Draft Guidance über Visuelle Kontrolle von Parenteralia lesen konnten. Eine Kommentierung war bis Mitte Februar 2022 möglich. Die Mitglieder des Advisory Boards der ECA Visual Inspection Group haben dies genutzt und zahlreiche Kommentare eingereicht.

Eine Kernaussage der Gruppe war dabei: Der Schwerpunkt des Dokuments liegt zu sehr auf der Partikelgröße. Es gibt dabei keine klaren Hinweise, welche Größen "akzeptabel" sind. Die Empfehlung wäre, repräsentative Partikel aus der Produktion von nicht repräsentativen Partikeln zu trennen.

Einige der Kommentare finden Sie exemplarisch hier:

Line 19-22 We understand that this refers to USP<790> and the section "Sampling at Batch Release" and the reference to single sampling plans for normal inspection with an AQL of 0.65%. We would disagree for the USP<790> section "Product in Distribution". Here the approach has no link to cGMP and is only in order to evaluate product already released and in the market.
This needs to be more specified stating the section!!
USP<790> already states that "Alternative sampling plans with equivalent or better protection are acceptable." This does fully comply with the intention of this draft Guideline.
Line 90-116

The text is to some extend contradictory. It starts with referencing USP General Chapter <1> and its requirement to follow USP General Chapter <790> to conclude that following USP General Chapter <790> alone is not sufficient to point out again to USP General Chapter <1> and its requirements that needs to be taken into consideration.

This twisted argumentation should be replaced by a much shorter explanation that FDA expects both General Chapter should be followed, including the request for a risk-based definition for product specific standards in production and in testing

Lines148 et seqq

A revision of Annex 1 (Manufacture of Sterile Medicinal Products) of the PIC/S and EU GMP Guides has been prepared in co-operation with the European Medicines Agency (EMA), WHO and PIC/S in order to maintain global alignment of standards.
The last targeted stakeholder consultation has ended and the final version is expected to be published within the next months.
FDA, being a member of PIC/S was fully included in the consultation process.
It is irritating that the draft FDA Guideline does not at all include any of the adopted wording and considerations laid down in the Annex to implement a Contamination Control Strategy intended not only to control and limit microorganisms and pyrogens but also particles, based on current product and process understanding. The Annex is very descriptive in its requirements for such a control strategy.

In addition, sections 8.30 and 8.31 are providing what must be considered additional GMP considerations for the visual inspection process.

It would be more than highly appreciated if FDA as a PIC/S member would align any new Guideline with existing or nascent PIC/S guidance documents.

Line 485 - 487:
Typically, the percentage of defective units in a test set should not exceed 10-20 percent, and the
test set quantities should be sufficient to provide an adequate degree of confidence in the test results.

This goes back to J. Knapp, H. Kushner (Generalized Methodology For Evaluation of Parenteral Inspection Procedures, PDA J Pharm Sci and Tech, 1980, 34, p. 14-61) with the focus on particle detection. Correct number: not more than 25% defects...once there are other "obvious" defects within the test set the percent can be higher as the 10-20% are only for the focus of particles within units. 

A better wording would be:
Typically, the percentage of defective units in a test set should not exceed 10-20 (25 percent !! instead of 10-20%) percent, and the test set quantities should be sufficient to provide an adequate degree of confidence in the test results, once only particulate defects (and non-defect units) are within the test set.

Alle ECA Kommentare zum FDA-Entwurf finden Sie in der Stellungnahme der ECA Visual Inspection Group. Auf der Website können Sie sich auch für Benachrichtigungen über Änderungen in den Interessengebieten anmelden.

Informationen zur kostenlosen Mitgliedschaft in der ECA Visual Inspection Group finden Sie auf der Homepage der Gruppe.

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