In detail
Basis
Chapter 4 of the EU GMP Guide lists the Site Master File as part of the required GMP documentation and describes it as a document describing the GMP-related activities of the manufacturer. Its content and structure are set out in the European Commission's Explanatory Notes on the preparation of a Site Master File (Part III of the EU GMP Guide). Whether an SMF is mandatory depends on national or regional requirements. The notes apply to all kinds of manufacturing operations, including sites that only carry out testing, packaging or relabelling.
Content
The Explanatory Notes provide for the following chapters:
- General information on the manufacturer, authorised activities and GMP inspections in the last five years
- Quality management system, release procedure and role of the Qualified Person, management of suppliers and contractors, quality risk management, product quality reviews
- Personnel, including an organisation chart
- Premises and equipment, including water and ventilation systems
- Documentation, production, quality control
- Distribution, complaints, product defects and recalls
- Self-inspections
These are supplemented by appendices such as the valid manufacturing authorisation, the GMP certificate, organisation charts, layouts with material and personnel flows, schematic drawings of water systems and a list of major production and laboratory equipment.
Length and maintenance
As far as possible, the SMF should not exceed 25 to 30 pages plus appendices and should be readable on A4 paper. Simple plans and schematic layouts are preferred to narrative text. It forms part of the quality management system documentation and has an edition number, an effective date and a review date. Appendices may have their own effective dates and be updated independently.
Common weaknesses
An SMF loses its value when it no longer reflects the actual situation, for example after building work, new products or changed responsibilities. Long narrative passages instead of overviews, or appendices that do not match the main text, are equally unhelpful. It makes sense to link the review of the SMF to change control, so that significant changes at the site are also reflected in the document.
In practice at A&O Pharma
A&O Pharma prepares and maintains GMP documents for its clients, including the Site Master File. We also provide support in preparing for regulatory inspections, for which the SMF is a key basis.
Document PreparationFrequently asked questions
How long should a Site Master File be?
The EU Explanatory Notes recommend that it should, as far as possible, not exceed 25 to 30 pages plus appendices. Plans and schematic layouts are preferred to narrative text.
How often must a Site Master File be updated?
The Explanatory Notes do not set a fixed interval. The SMF must be reviewed regularly, carry a review date and reflect current activities.
Does a testing-only laboratory need a Site Master File?
The Explanatory Notes also apply to sites carrying out only part of the operations, such as analysis or packaging. The SMF then describes only those operations. Whether it is mandatory follows from national requirements.
