OBJAVLJENA PIC/S TUMAČENJA ZAHTJEVA EU GMP ANNEX 1

PIC/S (Pharmaceutical Inspection Co-operation Scheme) je 28.10.2026. objavio novi dokument PI 058-1 – Interpretation of the Most Important Changes in the Annex 1 on the Manufacture of Sterile Products (2022). Ovaj dokument ne uvodi nove GMP zahtjeve s obzirom na proizvodnju sterilnih oblika lijekova, već donosi odgovore na niz praktičnih pitanja koja proizlaze iz zahtjeva EU GMP Annex 1 MANUFACTURE OF STERILE MEDICINAL PRODUCTS.  

Dokument je napisan u praktičnom formatu pitanja i odgovora, a slijedi strukturu i poglavlja trenutno važećeg EU GMP Annex 1 te svako pitanje sadrži i referencu na originalni EU GMP Annex 1 zahtjev.

Iako su prikazane informacije primarno namijenjene proizvođačima sterilnih lijekova, pojašnjenja pojedinih GMP zahtjeva i regulatornih očekivanja mogu biti vrlo korisna i kompanijama koje ne proizvode sterilne lijekove, posebno u kontekstu načina razmišljanja o pojedinim situacijama, upravljanja rizicima, kontrole kontaminacije i razvoja učinkovitog farmaceutskog sustava kvalitete. Također, dokument će sigurno biti vrlo koristan svima koji provode audite ugovornih proizvođača sterilnih lijekova ili rade na ugovorima o kvaliteti s takvim proizvođačima.

Evo i nekoliko konkretnih primjera zanimljivih pitanja koja su obrađena u dokumentu:

Does the CCS need to be one document? What should be the structure of the CCS?

What should be the duration of the APS used to simulate a very long filling process (e.g. 96 hours filling process)?

What does “same container/closure configuration” mean?

What are the circumstances where PUPSIT may not be possible?

What should be considered when determining which loading patterns should be used for initial and periodic autoclave (re) validations?

Is there any requirement for room classification of a QC Microbiological laboratory when isolators are used for testing?

Zanimljivo je i to da dokument donosi vrlo jasne stavove za neke specifične situacije, a što može pomoći u donošenju internih oduka oko dizajna aseptičkog procesa, definiranja opsega kvalifikacije i validacije i sl. Evo nekoliko primjera:

Is it acceptable for barrier technology systems with unidirectional air flow to have air speed at the work position outside the range of 0.36 – 0.54 m/s (guidance value) provided in Annex 1?

Yes, where this is scientifically justified in the CCS and meets the requirements for unidirectional air flow, as described in Annex 1. Furthermore, airflow visualization studies should correlate with the air speed measurement and demonstrate protection of the critical process operations (first air protection).

In the case of aseptic processing, would it be acceptable for the dispensing room to be grade D rather than grade C, provided that the materials are dispensed under laminar flow located in this room?

No, according to Annex 1, sampling and dispensing for aseptic processing, should be performed in, at least, a grade C environment. This is a minimum requirement for processes that include a sterile filtration step.

Are other disinfectants acceptable, other than H2O2?

Yes, Annex 1 leaves room for novel disinfectants and sporicides with appropriate validation of their effectiveness.

Is a bracketing approach possible for the APS with more than one lyophiliser?

No. If there are multiple lyophilisers for one filling line, no bracketing approach can be applied. Each lyophiliser and its transfer path needs to be covered by APS. In case of multiple lyophilisers combined with multiple filling lines, the APS program has to cover all lyophilisers and all filling lines. If supported by QRM based on a sound scientific rational, a bracketing approach may be possible, considering risks related to different transfer paths between different filling lines and different lyophilisers. However, it has to be ensured that all lyophilisers, their worst-case transfer paths and all filling lines are covered by the APS programme with a minimal frequency every half yearly as defined by Annex 1.

Pogledajte objavljena PIC/S tumačenja specifičnih zahtjeva EU GMP Annex 1.