pics

• PHARMACEUTICAL INSPECTION CO-OPERATION SCHEME
• Document History Adoption by the PIC Committee of Officials of PH 4/93 22-23 April 1993 Entry into force of PH 4/93 April 1993 Entry into force of PE 008-1 1 November 2002
• SCOPE These Explanatory Notes apply to the preparation and content of the Site Master File. Manufacturers should refer to regional / national regulatory requirements to establish whether it is mandatory for manufacturers of medicinal products to prepare a Site Master File. These Explanatory Notes apply for all kind of manufacturing operations such as production, packaging and labelling, testing, relabelling and repackaging of all types of medicinal products. The outlines of this guide could also be used in the preparation of a Site Master File or corresponding document by Blood and Tissue Establishments and manufacturers of Active Pharmaceutical Ingredients.
• PE 008-4

  1 January 2011
• TABLE OF CONTENTS
• PE 008-4

  1 December 2010
• PHARMACEUTICAL INSPECTION CONVENTION
• REVISION HISTORY Date Version Number 1 November 2002 PE 008-1 Revision of format (in line with SOP on SOPs) and introduction; delete reference to
• PURPOSE The aim of these Explanatory Notes is to guide the manufacturer of medicinal products in the preparation of a Site Master File that is useful to the regulatory authority in planning and conducting GMP inspections.
• Introduction The Site Master File is prepared by the pharmaceutical manufacturer and should contain specific information about the quality management policies and activities of the site, the production and/or quality control of pharmaceutical manufacturing operations carried out at the named site and any closely integrated operations at adjacent and nearby buildings. If only part of a pharmaceutical operation is carried out on the site, a Site Master File need only describe those operations, e.g. analysis, packaging, etc. When submitted to a regulatory authority, the Site Master File should provide clear information on the manufacturer’s GMP related activities that can be useful in general supervision and in the efficient planning and undertaking of GMP inspections. A Site Master File should contain adequate information but, as far as possible, not exceed 25-30 pages plus appendices. Simple plans, outline drawings or schematic layouts are preferred instead of narratives. The Site Master File, including appendices, should be readable when printed on A4 paper sheets. The Site Master File should be a part of documentation belonging to the quality management system of the manufacturer and kept updated accordingly. The Site Master File should have an edition number, the date it becomes effective and the date by which it has to be reviewed. It should be subject to regular review to ensure that it is up to date and representative of current activities. Each Appendix can have an individual effective date, allowing for independent updating.
• CONTENT OF SITE MASTER FILE Refer to Annex for the format to be used.
• © PIC/S January 2011 Reproduction prohibited for commercial purposes. Reproduction for internal use is authorised, provided that the source is acknowledged. Editor: PIC/S Secretariat e-mail: [e-mail] web site: http://www.picscheme.org
• EXPLANATORY NOTES FOR PHARMACEUTICAL MANUFACTURERS ON THE PREPARATION OF A SITE MASTER FILE
• Change in the Editor’s co-ordinates

  25 September 2007
• Establishments and manufacturers of Active Pharmaceutical Ingredients

  • Refer to Annex for the format to be used
• 1. GENERAL INFORMATION ON THE MANUFACTURER

  • Contact information on the manufacturer
  • Authorised pharmaceutical manufacturing activities of the site
  • Any other manufacturing activities carried out on the site
• 2.2 Release procedure of finished products

  • Detailed description of qualification requirements (education and work experience) of the Authorised Person(s) / Qualified Person(s) responsible for batch certification and releasing procedures; General description of batch certification and releasing procedure; Role of Authorised Person / Qualified Person in quarantine and release of finished products and in assessment of compliance with the Marketing Authorisation; The arrangements between Authorised Persons / Qualified Persons when several Authorised Persons / Qualified Persons are involved; Statement on whether the control strategy employs Process Analytical Technology (PAT) and/or Real Time Release or Parametric Release
• Revision of format (in line with SOP on SOPs) and introduction; delete reference to the Site Master File as being Part B of the PIC/S inspection report; new point C.5.3 on reprocessing/rework; better distinction between Quality Assurance and Quality Control; explanation of abbreviations; minor editorial changes. All changes adopted at PIC/S Committee meeting on 8 October 2002

  1 November 2002
• 1.3 Any other manufacturing activities carried out on the site

  • Description of non-pharmaceutical activities on-site, if any
• 1.1 Contact information on the manufacturer

  • Name and official address of the manufacturer; Names and street addresses of the site, buildings and production units located on the site; Contact information of the manufacturer including 24 hrs telephone number of the contact personnel in the case of product defects or recalls; Identification number of the site as e.g. GPS details, D-U-N-S (Data Universal Numbering System) Number (a unique identification number provided by Dun & Bradstreet) of the site or any other geographic location system
• 2.3 Management of suppliers and contractors

  • A brief summary of the establishment/knowledge of supply chain and the external audit program
• 2. QUALITY MANAGEMENT SYSTEM OF THE MANUFACTURER

  • The quality management system of the manufacturer
  • Release procedure of finished products
  • Management of suppliers and contractors
• Simplification of the document and implementation of requirements related to quality risk assessment policy

  1 January 2011
• CONTENT OF SITE MASTER FILE

  • General information on the manufacturer
  • Authorised pharmaceutical manufacturing activities of the site
  • Any other manufacturing activities carried out on the site
  • Quality management system of the manufacturer
  • Release procedure of finished products
  • Management of suppliers and contractors
• Change in the Editor’s co-ordinates

  1 July 2004
• 1.2 Authorised pharmaceutical manufacturing activities of the site

  • Copy of the valid manufacturing authorisation issued by the relevant Competent Authority in Appendix 1; or when applicable, reference to the EudraGMP database. If the Competent Authority does not issue manufacturing authorisations, this should be stated; Brief description of manufacture, import, export, distribution and other activities as authorised by the relevant Competent Authorities including foreign authorities with authorised dosage forms/activities, respectively; where not covered by the manufacturing authorisation; Type of products currently manufactured on-site (list in Appendix 2) where not covered by Appendix 1 or the EudraGMP database; List of GMP inspections of the site within the last 5 years; including dates and name/country of the Competent Authority having performed the inspection. A copy of current GMP certificate (Appendix 3) or reference to the EudraGMP database should be included, if available
• 2.1 The quality management system of the manufacturer

  • Brief description of the quality management systems run by the company and reference to the standards used; Responsibilities related to the maintaining of quality system including senior management; Information of activities for which the site is accredited and certified, including dates and contents of accreditations, names of accrediting bodies
• Control strategy

  Statement on whether the control strategy employs Process Analytical Technology (PAT) and/or Real Time Release or Parametric Release
• Product Quality Reviews

  Brief description of methodologies used
• Equipment

  1. Listing of major production and control laboratory equipment with critical pieces of equipment identified

  2. Brief description of cleaning and sanitation methods of product contact surfaces

  3. Description of GMP critical computerised systems
• Management of suppliers and contractors

  1. Brief summary of the establishment/knowledge of supply chain and the external audit program

  2. Brief description of the qualification system of contractors, manufacturers of active pharmaceutical ingredients (API) and other critical materials suppliers

  3. Measures taken to ensure that products manufactured are compliant with TSE (Transmitting animal spongiform encephalopathy) guidelines

  4. Measures adopted where counterfeit/falsified products, bulk products (i.e. unpacked tablets), active pharmaceutical ingredients or excipients are suspected or identified

  5. Use of outside scientific, analytical or other technical assistance in relation to manufacture and analysis

  6. List of contract manufacturers and laboratories including the addresses and contact information and flow charts of supply-chains for outsourced manufacturing and Quality Control activities

  7. Brief overview of the responsibility sharing between the contract giver and acceptor with respect to compliance with the Marketing Authorisation
• Personnel

  1. Organisation chart showing the arrangements for quality management, production and quality control positions/titles in Appendix 5, including senior management and Authorised Person(s) / Qualified Person(s)

  2. Number of employees engaged in the quality management, production, quality control, storage and distribution respectively
• Description of documentation system
• Quality Risk Management (QRM)

  1. Brief description of QRM methodologies used by the manufacturer

  2. Scope and focus of QRM including brief description of any activities which are performed at corporate level, and those which are performed locally. Any application of the QRM system to assess continuity of supply should be mentioned
• Premises

  1. Short description of plant; size of the site and list of buildings

  2. Simple plan or description of manufacturing areas with indication of scale

  3. Lay outs and flow charts of the production areas showing the room classification and pressure differentials between adjoining areas and indicating the production activities in the rooms

  4. Lay-outs of warehouses and storage areas

  5. Brief description of specific storage conditions if applicable

  6. Brief description of heating, ventilation and air conditioning (HVAC) systems

  7. Brief description of water systems

  8. Brief description of other relevant utilities, such as steam, compressed air, nitrogen, etc
• Quality Control (QC)

  Description of the Quality Control activities carried out on the site in terms of physical, chemical, and microbiological and biological testing
• Self Inspections


  Short description of the self-inspection system with focus on criteria used for selection of the areas to be covered during planned inspections, practical arrangements and follow-up activities
• Production

  Type of products manufactured including list of dosage forms of both human and veterinary products which are manufactured on the site; list of dosage forms of investigational medicinal products (IMP) manufactured for any clinical trials on the site, and when different from the commercial manufacturing, information of production areas and personnel; Toxic or hazardous substances handled; Product types manufactured in a dedicated facility or on a campaign basis, if applicable; Process Analytical Technology (PAT) applications, if applicable: general statement of the relevant technology, and associated computerised systems
• Documentation

  Description of documentation system (i.e. electronic, manual)
• Process validation

  Brief description of general policy for process validation; Policy for reprocessing or reworking