Site Master Files and Quality Manuals…Do Manufacturers Really Need Both?

Site Master Files and Quality Manuals…Do Manufacturers Really Need Both?

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 both documents and are they both mandatory requirements for all manufacturers?

Site Master Files

What does the 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.

Who uses it?

The principle audience for the SMF is the regulator, who highly recommend including the SMF as part of the application to manufacture medicinal products. This allows the TGA to plan GMP inspections before getting to site. However, the SMF is not currently a mandatory requirement but highly appreciated by the TGA. Consequently, most Australian medicinal manufacturers have one.

This approach is consistent with the current 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 has 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.

Quality Manuals

What does the 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).

Who uses it?

The audience for the Quality Manual is the internal company staff and for manufacturers working to ISO 13485, also the regulator.

How is it managed?

As the overarching document of the QMS, the Quality Manual is managed and controlled in the same way as all QMS documents.

What Do the Different Regulations Require?

The following table compares different regulations that have criteria for the SMF and/or a Quality Manual within the QMS.

Regulation or StandardSite Master FileQuality Manual
PIC/S GMP version 8 (in use in Australia)PIC/S GMP version 8 (in use in Australia)PIC/S GMP version 8 (in use in Australia)
PIC/S GMP version 9No (but preferred)No specific requirement
EU GMPEU GMPEU GMP
PIC/S GMP version 10Yes (mandated in Ch 4.)No specific requirement
EU and PIC/S SMF guidance documentEU and PIC/S SMF guidance documentEU 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 guidanceYesYes
ISO 9001NoYes (mandatory)
ISO 13485 (device manufacturers)NoYes (mandatory)
ICH Q10 (strongly ISO 9001-centric)NoYes


So what’s the bottom line?

For medicinal products, the SMF will become a mandatory requirement for a TGA manufacturing license when PIC/S version 10 is adopted. Until then, it is highly appreciated and is included on the TGA Application for a Licence to Manufacture Therapeutic Goods.

The Quality Manual is a requirement for all QMS 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.

References

  1. EU Good Manufacturing Practice Vol 4. Explanatory Notes for Pharmaceutical Manufacturers on the Preparation of a Site Master File (2010)
  2. EU Good Manufacturing Practice Vol 4. Medicinal Products for Human and Veterinary Use – Chapter 4: Documentation (2010)
  3. ICH Q10 Pharmaceutical Quality System (2008)
  4. ISO 9001:2008 Quality Management Systems
  5. ISO 13485:1996 Quality Systems – Medical Devices – Particular requirements for the application of ISO 9001.
  6. PIC/S Explanatory Notes for Pharmaceutical Manufacturers on the Preparation of a Site Master File (2011)
  7. PIC/S Guide to Good Manufacturing Practice for Medicinal Products – Part I Version 8 PE009-8 (15 Jan 2009)
  8. PIC/S Guide to Good Manufacturing Practice for Medicinal Products – Part I Version 9 PE009-9 (1 Sept 2009)
  9. PIC/S Guide to Good Manufacturing Practice for Medicinal Products – Part I Version 10 PE009-10 (1 Jan 2013)
  10. TGA Application for a Licence to Manufacture Therapeutic Goods – 1413 (0406) (application form)
  11. WHO Guidelines for Drafting a Site Master File (Draft) (2010)
(4) Comments
  1. Very nice article,
    This blog helps the manufactures to understand what to do with Site Master Files and Quality Manuals for there product

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