GMP Compliance Adviser Update No. 1/2018

GMP Regulations

Chapter C EU Directives and Guidelines

C.6.1.1 Annex 1 – Draft Manufacture of Sterile Medicinal Products

On 20 December 2017, the European Commission has published the long awaited draft of Annex 1 of the EU GMP Guide. The comprehensive revision includes a focus on Quality Risk Management (QRM) and PQS (Pharmaceutical Quality System) as introduced with the implementation of ICH Q9 and ICH Q10.
Some of the further key changes in short:

• Single use technologies
• Aseptic operator qualification
• Application of quality risk management
• Cleaning validation for cleanroom surfaces
• Water systems – biofilm strategy
• Pure steam
• Utilities
• Cooling systems
• Compressed gasses
• Closed systems.

A public consultation period will run until 20 March 2018.

C.22 Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products

On 24 November 2017, the European Commission has published the final version of the document. The term “Advanced Therapy Medicinal Products” (ATMPs) is used to designate gene therapies, somatic cell therapies and tissue engineered products.

According to the European Commission, the 90-page document shall facilitate the development and authorisation of these products as they offer groundbreaking new opportunities for the treatment of diseases and injuries. They are particularly important for severe, untreatable or chronic diseases for which conventional approaches have proven to be inadequate.

The new guidelines adapt the European Union GMP requirements to the specific characteristics of ATMPs and address the novel and complex manufacturing scenarios utilised for these products. The guidelines foster a risk-based approach to manufacture and testing of such products. They shall ensure that these novel medicinal products are consistently produced and controlled according to highquality standards, for the benefit and the safety of patients.

It is particularly emphasised that the guidelines are specific to ATMPs. Other documents developing GMP requirements for medicinal products which are contained in Eudralex Vol 4 are not applicable to AMPs, unless specific reference is made.

Chapter D USA: CFR and FDA Guidelines

D.26 Non-Penicillin Beta-Lactam Drugs: A CGMP Framework for Preventing Cross-Contamination

This guidance

• describes the importance of implementing manufacturing controls to prevent cross-contamination of finished pharmaceuticals and active pharmaceutical ingredients (APIs) with non-penicillin beta-lactam drugs.
• provides information regarding the relative health risk of, and the potential for, cross-reactivity in the classes of sensitizing beta-lactams (including both penicillins and non-penicillin beta-lactams).
• clarifies that manufacturers generally should utilize separate facilities for the manufacture of non-penicillin beta-lactams because those compounds pose health risks associated with cross-reactivity.

It is intended for manufacturers of finished pharmaceuticals and APIs, including repackagers.