Site Master Files and Quality Manuals: Differences
I am often asked by new Australian-based manufacturers seeking a TGA manufacturing license and implementing a Quality Management System (QMS) what the difference is between a Site Master File (SMF) and a Quality Manual. The confusion is understandable given that both documents appear to contain similar information.
So what is the intent of a Site Master File vs a Quality Manual? And are they both mandatory requirements for all manufacturers?
Site Master Files (SMF)
What does the Site Master File document contain?
- A SMF contains information about the GMP activities occurring specifically at a site – quality management, production and/or QC operations, or any closely integrated operations at nearby buildings.
- It doesn’t contain information about GMP operations completed elsewhere.
- PIC/S guidance on the Site Master File (SMF)
Who uses the Site Master File (SMF)?
- The principal audience for the Site Master File (SMF) is the regulator/regulatory authority.
- Regulators recommend including the SMF as part of the application to manufacture medicinal products.
- Consequently, most manufacturers will have a Site Master File (SMF).
- Explanatory publications/documentation guidelines from regulators that reference the SMF:
- TGA information regarding the Site Master File (SMF)/inclusion in applications/submissions (TGA explanatory notes).
- EU requirements for Site Master File (SMF)/inclusion in applications/submissions (European Union Explanatory Notes on the preparation of a Site Master File).
- However, the SMF may not always be a mandatory requirement for product applications in every jurisdiction.
A previous regulatory approach, where having a Site Master File (SMF) was recommended but not necessarily mandatory during applications/submissions, was consistent with European regulations, where the SMF is contained in Part III of the GMPs; that is, not typically mandatory elements of the Code of GMP.
- Previously, the US required a Drug Master File (DMF) Type I as an equivalent document to the SMF.
- However, the mandatory requirement in the US for a DMF ceased in about 2000.
Manufacturers of other therapeutic goods in Australia do not need SMFs (such as medical devices, IVDs, blood and tissue).
Stay tuned for further blogs on their requirements!
How is it managed?
The SMF is a document type within the QMS and must be managed according to GMP and Good Documentation Practices (GDP). Facility changes should trigger an update to the SMF and the regulator should be kept up to date with the most recent version.
What does a Quality Manual document contain?
The Quality Manual is the overarching document of the QMS used to describe:
- the quality policy of the business entity
- the boundaries, operations and process improvement of the QMS throughout the product lifecycle
- management responsibilities
- the road map of the key processes of the QMS and their relationship to each other
- The Quality Manual may encompass multiple sites or a business entity operating within a larger site.
- Larger companies may not have a single document, or even call it a Quality Manual, but implement the quality policy using a series of individual documents – this is perfectly acceptable.
- Smaller companies may use the Quality Manual alone to describe their QMS (particularly in ISO 9001, though not so much in pharmaceutical companies).
FDA guidance relating to the Quality Manual
Who uses the Quality Manual?
The audience for the Quality Manual is generally:
- Internal company personnel
- For manufacturers working to ISO 13485, also the regulator
How are Quality Manuals managed?
As the overarching document of the Quality Management System (QMS), the Quality Manual is managed and controlled in the same way as all QMS documents.
What do GMP Regulations in different countries require?
The following table compares different regulations that have criteria for the SMF and/or a Quality Manual within the QMS.
|-||Regulation or Standard||Site Master File||Quality Manual|
|PIC/S GMP Version 15 (in use in Australia)||PIC/S GMP Version 15 (in use in Australia)||PIC/S GMP version 15 (in use in Australia)|
|PIC/S GMP Version 16||No (but preferred)||No specific requirement|
|EU GMP - Volume 4||EU GMP - Volume 4||EU GMP - Volume 4|
|PIC/S GMP version 10||Version where SMF became mandated (Ch 4.)||No specific requirement|
|EU and PIC/S SMF guidance document||EU and PIC/S SMF guidance document||EU and PIC/S SMF guidance document|
|(essentially identical)||Yes||(essentially identical)|
|(PIC/S used by TGA)||No specific requirement||(PIC/S used by TGA)|
|WHO SMF guidance||Yes||Yes|
|ISO 9001||No||Yes (mandatory)|
|ISO 13485 (device manufacturers)||No||Yes (mandatory)|
|ICH Q10 (strongly ISO 9001-centric)||No||Yes|
So what’s the bottom line?
- For medicinal products, the Site Master File (SMF) became a mandatory requirement for a TGA manufacturing license when PIC/S Version 10 was adopted (Note: the TGA now refers to PIC/S version PE 009-16, as of 1 July 2022).
- Even before it became mandatory to have an SMF, it was a much appreciated document by Regulators and was included on the TGA Application for a Licence to Manufacture Therapeutic Goods.
- The Quality Manual is a requirement for all Quality Management Systems (QMSs) that must meet either ICH Q10 or ISO 9001/ISO 13485, but not for other QMS.
- However, the Quality Manual is also seen as industry best practice for capturing the underpinning information describing a pharmaceutical quality system – but this may take a variety of forms, may not be a single document and does not need to meet the same sort of structured requirements like the SMF.
- EU Good Manufacturing Practice Vol 4. Explanatory Notes for Pharmaceutical Manufacturers on the Preparation of a Site Master File (2010) SANCO/C8/AM/sl/ares(2010)1064603
- EU Good Manufacturing Practice Vol 4. Medicinal Products for Human and Veterinary Use – Chapter 4: Documentation (February 2022)
- ICH Q10 Pharmaceutical Quality System (4 June 2008)
- ISO 9001:2008 Quality Management Systems
- ISO 13485:2016 Quality Systems – Medical Devices – Particular requirements for the application of ISO 9001.
- PIC/S Explanatory Notes for Pharmaceutical Manufacturers on the Preparation of a Site Master File (2011)
- PIC/S Guide to Good Manufacturing Practice for Medicinal Products – Part I Version 8 PE009-8 (15 Jan 2009)
- PIC/S Guide to Good Manufacturing Practice for Medicinal Products – Part I Version 9 PE009-9 (1 Sept 2009)
- PIC/S Guide to Good Manufacturing Practice for Medicinal Products – Part I Version 10 PE009-10 (1 Jan 2013)
- PIC/S Guide to Good Manufacturing Practice for Medicinal Products – Part I Version 16 PE009-16 (1 Feb 2022)
- TGA Application for a Licence to Manufacture Therapeutic Goods – 1413 (0406) (application form)
- TGA – Preparation of the Site Master File (PIC/S guidance)
- WHO Guidelines for Drafting a Site Master File (30 September 2011)
Page originally published April 22, 2013 (22 April 2013).
Page last updated on September 13, 2022 (13 September 2022).