Guide to elaboration of Site Master File (SMF) according to ANVISA- BRAZIL
Guide to elaboration of Site Master File (SMF)
according to ANVISA- BRAZIL
Priscilla Viana Palhano Lima (GPKOL Consultant)
컨설팅 분야 : RA, PM
거주국가 : 브라질
- Argo Consulting (2018~) / CEO
- Vital Brazil Institute/Regulatory Affairs an Special Project Department/ Biomedicine Specialist/(2016-2017)
- Vital Brazil Institute/Biomedicines Department/Biomedicine Specialist/ (2013-2015)
- Technological Life Science Park/Business Incubator/New Business Specialist/ (2010-2013)
* 세부 전문분야 및 컨설팅 내용
- Regulatory affairs: Register of products in ANVISA, including the obtaining of necessary license and certificates
- PM: Technology transfer project in pharmaceutical industry
The proposal of this article is to expresses Anvisa's understanding of best practices regarding procedures, routines and methods deemed adequate to comply with the technical or administrative requirements required by the legislation. It does not confer or creates new obligations and should be used by public and private agents as a reference for compliance with legislation.
Alternative approaches are possible, so that their non-compliance does not characterize sanitary infraction, nor does it constitute grounds for rejecting petitions, provided they comply with the requirements required by the legislation, albeit by means other than that provided for in this recommendation.
□ Table of Contents
2. LEGAL BASIS
3. CONTENTS OF THE SITE MASTER FILE
3.1 GENERAL INFORMATION ABOUT THE MANUFACTURER .
3.2 MANUFACTURER QUALITY MANAGEMENT SYSTEM
3.3 QUALITY RISK MANAGEMENT
3.4 PRODUCT QUALITY REVISIONS
3.6 INSTALLATIONS AND EQUIPMENT
3.10 QUALITY CONTROL (QC)
3.11 DISTRIBUTION, CLAIMS, DEFECTS IN PRODUCTS AND COLLECTIONS
3.12 AUTO INSPECTIONS
5. BIBLIOGRAPHICAL REFERENCES
The Site Master File is prepared by the manufacturer of active pharmaceutical ingredients and should contain specific information on quality management policies, plant activities, production and / or quality control operations performed and any integrated operations performed on adjacent buildings or nearby. If only part of the production operations is performed at the plant, the SMF only needs to describe the step performed, for example, secondary packaging step, granulation, purification, etc.
The Site Master File should contain adequate information, but should not exceed 25-30 pages, including annexes, as far as possible. Simple plans, designs, or schemes are preferable to narratives instead. The Site Master File and its attachments must be legible when printed on A4 size sheets of paper.
It is recommended that the SMF be part of the documentation pertaining to the manufacturer's quality management system (have an edition / version number, effectiveness date and revision date) and is easy to read and prioritize clear and direct communication without the need for additional explanations or descriptions of rational decisions The SMF and its annexes should provide clear information about the manufacturer's Good Manufacturing Practices (GMP) activities that may be useful in the overall supervision and efficient planning and execution of GMP verification.
It is recommended that the SMF be updated periodically and be representative of current activities, including recording changes to each version. Each attachment can have an individual effectiveness date, allowing for independent updates.
2. Legal Basis
The recommendations for the preparation of an MPA are described in several documents, and for the preparation of this guide by ANVISA, the document "WHO guidelines for drafting a site master file" published by the World Health Organization was used.
3. Contents of The Site Master File
3.1 General Information About the Manufacturer
Manufacturer's Contact Information
₋ Name and official (corporate) address of the manufacturer;
₋ If the address of the plant differs from the manufacturer's corporate address, state the name and address of the plants, distinguishing the buildings and units;
₋ Name of the contact person of the manufacturer, including telephone, e-mail and telephone number 24h of responsible personnel in case of defects in products and collections;
₋ Plant identification number: duns number (universal universal numbering System), which is a unique identification number provided by Dun & Bradstreet or any other geographic location system. Likewise, the numbering of Anvisa's International Registry of International Companies may be used in this identification.
Authorized site activities
₋ Copy of operating authorization and activities licensed by the competent health authority;
₋ Brief description of the manufacturing, import, export, distribution and other activities as authorized by ANVISA or other competent authority, with the pharmaceutical forms / pharmaceutical inputs that are subject to certification;
₋ Names, therapeutic classes and pharmaceutical forms of products manufactured in the plant listed by production line (list in Annex 2, specify the respective areas / buildings where they are produced and those in which the production is dedicated);
₋ List of GMP inspections of the plant in the last 5 years, including dates and name / country of the competent authority that carried out the inspection. A copy of the current GMP certificate should be included, if available (Annex 3).
Other manufacturing activities carried out at the plant
₋ Brief description of the manufacturing activities not correlated with the manufacture of active pharmaceutical drugs and consumables, if any.
3.2 Manufacturer Quality Management System
The manufacturer's quality management system
₋ Brief description of existing quality management systems in the company, with reference to the standards used;
₋ Responsibilities related to the maintenance of quality systems, including the senior management;
₋ Information about the activities for which the plant is accredited,
Release Procedure for Finished Products
₋ Detailed description of qualification requirements (training and work experience) of those responsible for batch release;
₋ General description of the batch release procedure;
₋ Role of the person responsible for release into quarantine and release of finished products and assessment of compliance with the registration;
₋ Agreements between those responsible for the release of finished products where more than one person is responsible for this step;
₋ Information on the control strategy employed when the facility adopts Process Analytical Technology (PAT) and / or Real Time Release or Parametric Release.
Supplier and contractor management
₋ Brief description of the establishment, the supply chain and the external audit program;
₋ Brief description of the qualification system for contractors, manufacturers of active pharmaceutical inputs, starting materials and other suppliers of critical materials;
₋ Measures taken to ensure that the products manufactured are in compliance with the guidelines on BSE (bovine spongiform encephalopathy);
₋ Measures taken in case of suspected or identified finished products, bulk, counterfeit / adulterated active inputs;
₋ List of contracted manufacturers and laboratories including addresses and contact information and supply chain flowcharts from outsourced activities related to manufacturing or quality control, eg sterilization of primary packaging material for aseptic processes, raw material analysis , etc. (Annex 4);
3.3 Quality Risk Management
₋ Brief description of the methodology used by the manufacturer in quality risk management (QRM);
₋ Scope and focus of risk management, including a brief description of any activities that are carried out at the corporate level and those carried out locally.
3.4 Product Quality Revisions
₋ Brief description of the methodologies used.
₋ Organization chart containing the distribution of quality management, production and quality control posts, including top management and Technical Manager (Annex 5);
₋ Number of employees involved in quality management, production, quality control, warehousing and distribution, respectively.
3.6 Installations And Equipment
₋ Brief description of the plant; size of land and list of buildings. If production for different markets is carried out in different buildings within the plant (i.e., Europe, United States), buildings should be listed with the respective destination markets identified (if not identified in item 1.1);
₋ Sketches and flowcharts of sampling areas;
₋ Simplified plan or description of manufacturing areas with scale indication (architectural or engineering drawings are not required);
₋ Sketches and flowcharts of the production areas, showing the classification of rooms and pressure differentials between adjacent areas, with indication of room production activities (eg formulation, filling, storage, packaging, etc.);
₋ Nature of construction and finishing;
₋ Disposal of warehouses and storage areas, indicating the special areas for storage and handling of highly toxic, sensitizing and hazardous materials, if applicable;
₋ Brief description of specific storage conditions, if any, that are not indicated in the drawings.
Brief description of the heating, ventilation and air conditioning system (HVAC)
₋ Description of air handling system components (including filter types used), temperature, humidity, pressure differentials and air exchange rates, air recirculation policy (%). It is desirable to include schematic drawings of the systems and mention the classification of the rooms.
Brief description of water systems
₋ Description of the water treatment system, including online controls and quality references of the water produced (schematic drawings of the systems are desirable) (Annex 7);
₋ Sanitation procedures.
Breve descrição de outras utilidades relevantes, tais como vapor, ar comprimido, nitrogênio, etc.
- The company defines how it will describe the other systems
List of the main production equipment and quality control laboratory with identification of the critical parts of the production equipment (Annex 8).
Cleaning and sanitation
₋ Brief description of methods for cleaning and sanitizing surfaces that come into contact with products (eg manual, automatic cleaning - Clean in Place, etc.).
Computer systems critical to GMP
₋ List of computer systems critical to GMP and its main features (with the exception of Programmable Logic Controllers - equipment-specific PLCs).
₋ Description of the documentation system (eg manual, electronic);
₋ In the case of documents and records stored or filed off-site (including pharmacovigilance data, where applicable): list of document / record types; name and address of the storage location and estimated time required to retrieve documents from the external file.
Layouts and activities
We recommend the presentation of layouts of buildings and productive areas with a brief description of the activities carried out at each location.
Types of products
₋ Types of products manufactured including:
List of pharmaceutical inputs produced, with a brief description of the production flow, preferably using a flowchart, indicating the starting material (s), production forms and the buildings / areas where they are produced.
List with the pharmaceutical forms of human and veterinary products manufactured in the plant specifying the buildings / areas where they are produced.
List with the pharmaceutical forms of products in development manufactured for clinical studies and information of production areas and personnel, when different from the commercial manufacture.
Toxic or dangerous substances handled (eg with high pharmacological activity and / or sensitizing properties);
Types of products manufactured in a dedicated area or in a field, if applicable;
Process Analytical Technology (PAT), if applicable: general statement of relevant technology and associated computer systems.
₋ Brief description of the general process validation policy;
₋ Policy for reprocessing or rework;
₋ Policy for recovery of solvents and other materials.
Material and warehouse management
₋ Mechanisms for the handling of raw materials, packaging materials, bulk and finished products including sampling, quarantine, release and storage;
₋ Mechanisms for the handling of rejected materials and products.
3.10 Quality Control (Qc)
₋ Description of the quality control activities performed in the plant in terms of physical, chemical, microbiological and biological tests.
3.11 Distribution, Claims, Defects In Products And Collections
Distribution (part under manufacturer's responsibility)
₋ Types (distributors, manufacturers, etc.) and locations (Brazil, Europe, etc.) of the companies to which the products are sent;
₋ Description of the system used to verify that each customer is legally authorized to receive the manufacturer's products;
₋ Brief description of the system ensuring appropriate environmental conditions during transit, eg temperature monitoring / control;
₋ Rules on the distribution of products and methods to ensure the traceability of products;
₋ Measures taken to prevent products being diverted to the illegal market;
Complaints, defects in products and recall
₋ Brief description of the claims, product defects and recall management system.
3.12 Auto Inspections
₋ Brief description of the system of self-inspections focusing on the criteria used to select the areas to be covered during the planning of inspections, practical arrangements and follow-up activities. It is recommended to mention the references used to define the criteria, the procedure used, etc.
3.13annexes of the Site Master File
Annex 1: Copy of valid manufacturing authorization
Annex 2: Names, therapeutic classes and pharmaceutical forms of products manufactured in the plant listed by production line (list in Annex 2, specify the respective areas / buildings where they are produced and those in which the production is dedicated);
Exemple of table:
Production Area / Building
Dedicated production? Detail
Annex 3: Copy of the valid BPF certificate
Annex 4: List of contracted manufacturers and laboratories, including addresses and contact information and supply chain flowcharts for these outsourced activities
Annex 5: Organizational charts
Annex 6: Design of production areas, including flow of material and people, general process flow diagrams of each type of product (pharmaceutical forms)
Annex 7: Schematic drawings of water systems
Annex 8: List of main production equipment and laboratory
The development of the SMF by pharmaceutical manufacturers and active pharmaceutical inputs is expected to assist the national regulatory authority in planning and conducting risk-based inspections. Using the information provided in this document, the health authority may also decide to shorten the duration of a sanitary inspection and reduce the time required for the preparation of inspection reports which are currently extensive and rich in detail, as it will not be necessary to describe procedures and facilities already detailed in the SMF.
The information provided in the SMF is subject to on-site verification by health inspectors. Further clarification by the health authority may be requested at any time.
1. BRASIL. ANVISA. Agência Nacional de Vigilância Sanitária. Guia para elaboração de Arquivos Mestres de Plantas – AMP (Site Master File - SMF), publicada em http://portal.anvisa.gov.br/ em fevereiro de 2019.
[BRAZIL, ANVISA - Brazilian Health Surveillance Agency. Guia para elaboração de Arquivos Mestres de Plantas – AMP (Site Master File – SMF), published in http://portal.anvisa.gov.br/ in 2019 february].
Priscilla Viana Palhano Lima was Manager of Regulatory Affairs and Special Projects of the Brazilian public laboratory. He was directly in charge of the legal compliance of technology transfers with foreign companies from France, Poland, the United States and South Korea. He has experience in dossier analysis and elaboration of Partnership for Productive Development projects for the Ministry of Health. She is currently a consultant in Regulatory Affairs and Project Management of Partnership Projects for Productive Development for the Ministry of Health. Priscilla is the founder of the Argo Consulting company that promotes consulting in the areas of regulatory affairs, business development, project management international partnerships and technology transfers in partnership with MM Assessoria Industrial company.
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