New EU GMP Annex 1: Compliant Aseptic Operations

In August 2022, (14 years after its last publication), the long-awaited EU GMP guide Annex 1 was published and comes into force on 25 August 2023.  Annex 1, which includes new expectations as well as detailing the existing requirements in the 2008 publication, has been aimed to be harmonized with other updated guides. The Annex 1 guide is a versatile document that outlines the various aspects of the aseptic process as well as personnel, facilities, equipment, production, and robust technologies. Maintaining a sterile production environment on an ongoing basis is critical in the production of sterile pharmaceuticals, and strict adherence to guidelines and relevant standards is required to minimize contamination risks and ensure product quality and safety. It is very important that the production equipment, the production environment, the production process, and the criteria to be met by personnel are clearly and comprehensibly evaluated in the main GMP documents.

During this training, all changes in Annex 1 will be evaluated, and the minimum requirements that aseptic operations must meet will be discussed and presented to the participants through examples.

This course will address all current aseptic process guidance and it will provide participants with the opportunity to refresh their knowledge. How to minimize the risks of quality risk management principles will be discussed and the basics of microbiology will be explained. Environmental monitoring, bioburden and sterility assurance will be evaluated through examples, and the terms of cleaning, disinfection, sanitation and decontamination will be explained.

In Annex 1, the principles of Contamination Control Strategy (CCS), which is one of the most important expectations, will be evaluated and guidance will be given on how to prepare a sample CCS. Examples of the expectations of the health authorities regarding sterilization and visual control will be presented, and the points to be considered in Heating, Ventilation and Air Conditioning (HVAC), Water, Steam, and Gas systems will be covered.

Clean room classification, Personal Air Lock (PAL), Material Air Lock (MAL) concepts, and critical aspects in Restricted Access Barrier Systems (RABS) and Isolator systems that are starting to replace clean rooms will be evaluated. In addition, robust production techniques such as Blow Fill Seal (BFS) and Form Fill Seal (FFS) will be emphasized. The inconveniences encountered due to the violation of the microbial rules that must be followed in sterile environments due to various reasons will be conveyed with sample applications.

Important aspects of critical aseptic process simulation operations, previously known as media fill, airflow visualization study, aseptic filling, and closure will be shared with the participants.

In the last part of the training, the expectations of the health authorities of quality assurance and aseptic operations will be included, and the expectations of regulatory authorities such as FDA, MHRA, TGA, WHO, PIC/S from aseptic operations and the new Annex 1 will be addressed, and the most common deviations will be evaluated with recommendations.