Resolution – RDC Nº 16
Responsabilidad del comprador – bajo análisis de RDC -16
8 de June de 2020
Pamax lança novas Bobinas Tubulares para a área da Saúde
16 de November de 2023
RESOLUTION – RDC No. 16, OF MARCH 28, 2013. Approves the Technical Regulations for Good Manufacturing Practices for Medical Products and Products for Diagnosis of In Vitro Use and other measures.
The Collegiate Directorate of the National Health Surveillance Agency, using the powers conferred on it by item IV of art. 11 of the Regulation approved by Decree No. 3,029, of April 16, 1999, and in view of the provisions of item II and § 1 and § 3 of art. 54 of the Internal Regulation approved under the terms of Annex I of Ordinance 354 of ANVISA, of August 11, 2006, republished in the DOU of August 21, 2006, in a meeting held on March 7, 2013, considering Law no. 6360, of September 23, 1976 and its regulation, Decree No. 79094 of January 5, 1977;
considering the need to internalize MERCOSUR / GMC / RES. No. 20/11, which approved the “MERCOSUR Technical Regulation on Good Manufacturing Practices for Medical Products and Products for Diagnosis of In Vitro Use (repeal of GMC Res. 04/95, 38/96, 65/96 and 131 / 96) “;
whereas the regulation of Good Manufacturing Practices related to medical products and products for in vitro use diagnostics must seek to guarantee the quality, safety and efficacy of products sold in Brazil;
whereas it is essential to promote the improvement of national systems aimed at the regulation and control of medical products and products for diagnosis of in vitro use; adopts the following Collegiate Board Resolution and I, the Chief Executive Officer, determine its publication:
Art. 1 – To approve the “Technical Regulation for Good Manufacturing Practices for Medical Products and Products for Diagnosis of In Vitro Use”, which is included as an Annex and is part of this Resolution.
Single paragraph. This regulation incorporates into the national legal system Resolution GMC MERCOSUR nº 20/2011 “MERCOSUR Technical Regulation of Good Manufacturing Practices for Medical Products and Products for Diagnosis of In Vitro Use (repeal of Res. GMC nº 04/95, 38/96, 65/96 and 131/96) ”.
Art. 2 – Revoke Ordinance No. 686, of August 27, 1998; Resolution RDC No. 59, of June 27, 2000; and RDC Resolution No. 167, of July 2, 2004.
Art. 3 – The distributors and stores of medical products and products for diagnosis of in vitro use must comply with the requirements of this Resolution, as applicable.
Art. 4 – A period of 180 days is allowed, from the date of incorporation of the normative instrument, for the adoption of the necessary measures for the application of the Technical Regulation.
Art. 5 – This Resolution comes into force on the date of its publication.
DIRCEU BRÁS APARECIDO BARBANO
TECHNICAL REGULATION OF GOOD PRACTICES FOR THE MANUFACTURING OF MEDICAL PRODUCTS AND PRODUCTS FOR DIAGNOSIS OF IN VITRO USE
CONTENT
CHAPTER 1 – GENERAL PROVISIONS
CHAPTER 2 – GENERAL QUALITY SYSTEM REQUIREMENTS
2.1. General provisions
2.2. Managerial responsibility
2.3. Folks
2.4. Risk management
2.5. Purchasing Controls
CHAPTER 3 – QUALITY DOCUMENTS AND RECORDS
3.1. General requirements
3.2. Product historical record
3.3. Inspection and test records.
CHAPTER 4 – PROJECT CONTROL AND PRODUCT MASTER RECORD (RMP)
4.1. Project Control
4.2. Product Master Record (RMP)
CHAPTER 5 – PROCESS AND PRODUCTION CONTROLS
5.1. General instructions
5.2. Packaging controls, labeling and instructions for use
5.3. Inspection and testing
5.4. Inspection, measurement and testing equipment.
5.5. Validation
5.6. Change control
CHAPTER 6 – HANDLING, STORAGE, DISTRIBUTION AND TRACEABILITY
6.1. Handling
6.2. Storage
6.3. Distribution
6.4. Identification and traceability
6.5. Non-conforming components and products
CHAPTER 7 – CORRECTIVE AND PREVENTIVE ACTIONS
7.1. Corrective and Preventive Actions
7.2. Complaints management
7.3. Quality audit
CHAPTER 8 – INSTALLATION AND TECHNICAL ASSISTANCE
8.1. Installation
8.2. Technical assistance
CHAPTER 9 – STATISTICS TECHNIQUES
CHAPTER 1 – GENERAL PROVISIONS
1.1 – Applicability
1.1.1. This Technical Regulation establishes requirements applicable to the manufacture of medical products and products for diagnosis of in vitro use. These requirements describe Good Manufacturing Practices (GMP) for methods and controls used in the design, purchasing, manufacturing, packaging, labeling, storage, distribution, installation and technical assistance of medical products and products for in-vitro diagnostic use. The requirements of this Technical Regulation are intended to ensure that medical products and products for diagnosis of in vitro use are safe and effective.
1.1.1.2. The requirements of this Technical Regulation are applicable to manufacturers and importers of medical products and products for in vitro diagnostic use that are marketed in Brazil.
1.1.3. Whenever the manufacturer understands that any of the requirements of this resolution is not applicable to its processes, it must document a justification for this understanding.
1.1.1.4. Importers of medical products and products for diagnosis of in vitro use must comply with the requirements of this Resolution, as applicable.
1.1.2. Definitions
For the purposes of this Technical Regulation, the following definitions apply:
1.2.1. Technical assistance: Maintenance or repair of a finished product in order to return it to its specifications.
1.2.2. Quality audit: means an established, systematic and independent examination of the entire quality system of a manufacturer, performed at regular intervals and with sufficient frequency to ensure that both the activities of the quality system and its results satisfy the procedures specified in its system quality, that these procedures are implemented efficiently and that they are adequate to achieve the objectives of the quality system. The quality audit is different from other activities in the quality system required by this Technical Regulation.
1.2.3. Component: raw material, substance, part, part, software, hardware, packaging, label or instruction for use, used during the manufacture of a medical product and product for diagnosis of in vitro use, intended to be included as part of the finished product.
1.2.4. Project input data: description of physical attributes, indication of use, performance, compatibility, safety, efficacy, ergonomics, usability, information from previous projects and results of risk management, among other requirements of a medical product or product for diagnosis in vitro use that are used as the basis of your project.
1.2.5. Project output data: result of the work in each phase of the project and its final result. The finished project output data is the basis for the product master record (RMP).
1.2.6. Damage: physical injury or damage to the person’s health, or damage to property or the environment.
1.2.7. Specifications: requirements to which products, components, production activities, technical assistance, services, quality system or any other activity must comply.
1.2.8. Establish: define, document (by written or electronic means) and implement.
1.2.9. Manufacturer: any person who designs, manufactures, assembles or processes a finished product, including those who perform functions under a sterilization contract, labeling, packaging.
1.2.10. Executive management: senior management of the company responsible for providing resources and with authority to establish or change the company’s quality policy and system.
1.2.11. Risk management: systematic application of management policies, procedures and practices to the tasks of analyzing, evaluating, controlling and monitoring risks associated with a specific product or process.
1.2.12. Batch or batch: quantity of a product made in a manufacturing or sterilization cycle, whose essential characteristic is homogeneity.
1.2.13. Manufacturing material: material or substance used in the manufacturing process or to facilitate this process, including cleaning agents, mold release agents, lubricating oils, sterilizers, or other by-products of the manufacturing process.
1.2.14. Non-compliance: non-compliance with a previously specified requirement.
1.2.15. Serial or batch number: distinct combination of letters or numbers, or both, from which the complete history of purchases, manufacture, packaging, labeling and distribution of finished products can be determined.
1.2.16. Danger: Potential source of damage.
1.2.17. Quality policy: the totality of an organization’s intentions and guidelines with respect to quality, expressed by executive management.
1.2.18. Special process: any process whose results cannot be fully verified by subsequent inspections and tests.
1.2.19. Production: all operations involved in the manufacture of a given product, from receipt of components, through processing and packaging, to obtaining the finished product.
1.2.20. Finished product: any product or accessory suitable for use, packaged, labeled.
1.2.21. Quality: totality of aspects and characteristics that make it possible for a medical product or product for diagnosis of in vitro use to meet the requirements for suitability for use, including safety and performance.
1.2.22. Complaint: written, oral or electronic communication regarding the non-acceptance of the identity, quality, durability, reliability, safety, efficacy or performance of a product.
1.2.23. Registration: physical or electronic document, which shows data, facts, specific events and results achieved in relation to compliance with procedures and standards of the quality system.
1.2.24. Product historical record: compilation of records containing the complete production history of a finished product.
1.2.25. Historical project record: compilation of documents containing the complete project history of a finished product.
1.2.26. Product master record (RMP): compilation of documents containing specifications, instructions and procedures for obtaining a finished product, as well as installation, technical assistance and maintenance.
1.2.27. Rework: part or all of the manufacturing operation aimed at correcting the non-conformity of a component, intermediate product or a finished product, so that it meets the specifications defined in the RMP.
1.2.28. Project review: documented, systematic and complete examination carried out during the development of the project to assess its suitability for the planning and established objectives.
1.2.29. Risk: combination of probability of occurrence and severity of damage.
1.2.30. Quality system: organizational structure, responsibilities, procedures, specifications, processes and resources necessary for quality management.
1.2.31. Validation: confirmation by analysis and objective evidence that the requirements defined for a given purpose consistently lead to the expected result. With respect to a project, it means establishing and documenting objective evidence that the product specifications meet the user’s needs and their intended use. With respect to a process, it means establishing and documenting objective evidence that the process will consistently produce a result that meets the predetermined specifications.
1.2.32. Verification: confirmation by analysis and presentation of objective evidence that the specified requirements have been met. Verification includes the process of examining the results of an activity to determine compliance with established specifications.
1.2.33. Useful life: period of time estimated by the manufacturer in which a product correctly fulfills the functions for which it was designed.
CHAPTER 2 – GENERAL QUALITY SYSTEM REQUIREMENTS
2.1. General Provisions
2.1.1. Each manufacturer must establish and maintain a quality system to ensure that the requirements of this Technical Regulation are met and that the products manufactured are safe, effective and suitable for their intended use. As part of its activities in the quality system, each manufacturer must:
2.1.1.1. Establish and maintain effective quality system instructions and procedures in accordance with the requirements of this Technical Regulation, and
2.1.1.2. Establish procedures to comply with the legal provisions provided for in the current sanitary legislation.
2.2. Managerial responsibility
2.2.1. Quality policy. The executive management of each manufacturer must establish its policy and its objectives of commitment to quality, which must be measurable and consistent with the established policy. Executive management must maintain the policy at all levels of the organization. Executive management must ensure that this policy is described in a quality manual and that it is understood by all employees who may affect or influence the quality of a product.
2.2.2. Organization. Each manufacturer must establish and maintain an adequate organizational structure, represented by means of an organization chart, with sufficient personnel to ensure that the products are manufactured in accordance with the requirements of this Technical Regulation.
2.2.3. Responsibility and Authority. Each manufacturer must establish, in each chapter of this Technical Regulation, the responsibility, authority and interrelationship of all personnel who manage, execute and verify the work related to quality, with the necessary independence to carry out their responsibilities.
2.2.4. Resources and personnel for verification. Each manufacturer shall establish verification functions and shall provide adequate resources and designation of trained personnel to carry out the verification activities.
2.2.5. Management representative. The executive management of each manufacturer must designate an individual of this, and document this designation, who, regardless of other functions, will have the authority and responsibility to:
2.2.5.1. Ensure that the quality system requirements are established and maintained in accordance with this Technical Regulation;
2.2.5.2. Report the performance of the quality system to executive management for review and provide information on improving the quality system.
2.2.6. Management review. The executive management of each manufacturer must assess the adequacy and effectiveness of the quality system at defined intervals and with sufficient frequency to ensure that the quality system meets the requirements of this Technical Regulation and that it meets the objectives of the established quality policy. The management review must be conducted according to the established review procedures and the results of each review of the quality system must be documented. Issues related to audit results, post-marketing information, process performance and product compliance, status of corrective and preventive actions, changes that may affect the product quality or compliance system, regulatory requirements, should be considered for review.
2.3. Folks
2.3.1. General Instructions. Each manufacturer must have a sufficient number of personnel with instruction, experience, training and practice compatible with the duties of the position, in order to ensure that all activities provided for in this Technical Regulation are correctly performed. Descriptions should be maintained defining the authority, responsibility and requirements necessary for the various tasks of the company.
2.3.2. Treinamento. Cada fabricante deverá assegurar que todo o pessoal seja treinado para executar adequadamente as tarefas a ele designadas. O treinamento deverá ser conduzido de acordo com os procedimentos estabelecidos por pessoas qualificadas para garantir que os empregados tenham uma compreensão adequada de suas funções regulares e dos requisitos deste Regulamento Técnico aplicáveis às suas funções. Como parte de seu treinamento, todos os empregados deverão ser advertidos de defeitos em produtos que poderão ocorrer como resultado do desempenho incorreto de suas funções específicas. O treinamento de empregados deverá ser documentado.
2.3.3. Consultants. Each manufacturer shall ensure that any consultant who advises on methods employed or on the controls used for design, purchasing, manufacturing, packaging, labeling, storage, installation or technical assistance of products has sufficient qualifications (instruction, training and experience) to advise on matters for which he was hired. The hiring of consultants must be conducted in accordance with the purchase control requirements provided for in this Technical Regulation.
2.4. Risk management
2.4.1. Each manufacturer must establish and maintain a continuous risk management process that involves the entire life cycle of the product, from conception to its discontinuation, to identify the hazards associated with a medical product or product for in vitro diagnostic use, estimate and evaluate the risks involved, control them and evaluate the effectiveness of the controls established. This program must include the following elements: risk analysis, assessment, control and monitoring.
2.4.2. The company’s executive management must designate the responsible professionals, establish the policy for determining the criteria for acceptability of the risk, as well as determine a periodic review of the risk management activities in order to guarantee their adequacy and effectiveness.
2.5. Purchasing Controls
2.5.1. Each manufacturer must establish and maintain procedures to ensure that components, manufacturing materials and finished products manufactured, processed, labeled or packaged by third parties or stored by them under contract, comply with the specifications. Each manufacturer must also ensure that services performed by third parties comply with the specifications established by him.
2.5.2. Evaluation of suppliers of products and services. Each manufacturer must establish and maintain, according to the impact on the quality of the final product, criteria for assessing suppliers, specifying the requirements, including quality requirements, which they must satisfy.
2.5.3. Each manufacturer must evaluate and select potential suppliers according to their ability to meet previously established requirements, maintaining a record of approved suppliers. Records of the evaluation, as well as its results, must be kept.
2.5.4. Purchase record. Each manufacturer must maintain records of purchase orders that clearly describe or refer to specifications, including quality requirements, for components, manufacturing materials, finished products or services requested or contracted. The approval of orders, including the date and the person’s manual or electronic signature, must be documented.
2.5.5. An agreement should be documented in which suppliers undertake to notify the manufacturer of any change in the product or service, so that the manufacturer can determine whether the change affects the quality of the finished product.
2.5.6. Each manufacturer must review and approve purchasing documents prior to their release.
CHAPTER 3 – QUALITY DOCUMENTS AND RECORDS
3.1. General requirements.
3.1.1. Each manufacturer must establish and maintain document control procedures to ensure that all documents indicated in this Technical Regulation are correct and suitable for their intended use, and are understood by all employees who may affect or influence the quality of a product.
3.1.2. Approval and issuance of documents. Each manufacturer must designate people to evaluate and approve all documents established in this Technical Regulation for adequacy before their issue. The approval, including date and manual or electronic signature of the person responsible for approving the documents, must be documented.
3.1.3. Distribution of documents. The manufacturer must ensure that all documents are up-to-date and available at the application sites and that all unnecessary or obsolete documents are removed from use, or protected from unintended use.
3.1.4. Change of documents. Changes to specifications, methods or procedures related to the quality system must be evaluated, documented, reviewed and approved by persons whose function and level of responsibility are equivalent to those who performed the original review and approval.
3.1.5. Records of document changes. Each manufacturer must keep records of changes to documents that must include a description of the change, identification of the changed and affected documents, identification of the responsible person, approval date and date when the changes will take effect. A list of current documents must be maintained in order to identify their current status and ensure that only current and approved documents are in use.
3.1.6. Documents and Records Archive. All quality documents and records must be legible and kept in a way to minimize damage, prevent loss and provide rapid recovery. All digitally archived documents and records must be backed up:
3.1.6.1. Confidentiality. Documents and records considered confidential by the manufacturer may be marked to alert the competent health authority;
3.1.6.2 Document and record retention period: all necessary documents and records related to a product must be kept for a period equivalent to the product’s useful life, but in no case for less than two years from the date distribution.
3.2. Product historical record.
3.2.1. Each manufacturer must maintain historical product records. Each manufacturer must establish and maintain procedures to ensure that historical product records are maintained for each batch or series to demonstrate that the products have been manufactured in accordance with the product’s master record and the requirements of this Technical Regulation. The product’s historical record must include or reference the following information:
3.2.1.1. Manufacturing date;
3.2.1.2. Components used;
3.2.1.3. Quantity manufactured;
3.2.1.4. Results of inspections and tests;
3.2.1.5. Special process parameters;
3.2.1.6. Quantity released for distribution;
3.2.1.7. Labeling;
3.2.1.8. Identification of the serial number or production batch; and
3.2.1.9. Final product release.
3.3. Inspection and test records.
3.3.1. Each manufacturer must keep a record of the results of the inspections and tests established, when these are directly related to the critical quality attributes of the product.
These records must include the acceptance criteria, the results, the equipment / instrument used and the date and manual or electronic signature of the person responsible.
CHAPTER 4 – PROJECT CONTROL AND PRODUCT MASTER RECORD (RMP)
4.1. Project Control
4.1.1. General Instructions Each manufacturer must establish and maintain product design control procedures to ensure that the requirements specified for the project are met.
4.1.2. Project and development planning. Each manufacturer must establish and maintain plans that describe or reference the design and development activities and the persons responsible for each activity. The plans should describe or refer to the project development activities, including any interaction between the various organizational and technical groups that may have some interface with it. The plans should be evaluated, updated and approved as the project progresses.
4.1.3. Project input data. Each manufacturer must establish and maintain procedures to ensure that the requirements related to a product are appropriate and meet their intended use, including the needs of the user and patient and applicable legal and regulatory requirements. Procedures should include a mechanism that allows incomplete, ambiguous or conflicting requirements to be identified and addressed. The input data for a project must be documented, evaluated and approved by a qualified designated person. The approval of requirements, including the date and the manual or electronic signature of the person responsible for approval, must be documented.
4.1.4. Design verification. Each manufacturer must establish and maintain procedures for verifying the product design. The design check must be performed by designated personnel and must ensure that the project’s output data matches the input data. The results of the project verification, including the identification of the verified project, verification methods, date and name of the person in charge of the verification, shall be documented in the historical record of the project.
4.1.5. Project output data. Each manufacturer must define and document the project output data in order to allow the assessment of the project’s compliance with the requirements established as input data. The project output data must satisfy the requirements of the input data and must include the acceptance criteria and identify the design characteristics that are essential for the intended use of the product. These must be documented, reviewed and approved prior to their release.
4.1.6. Project Review. Each manufacturer must establish and maintain procedures to ensure that evaluations of project results are planned, conducted and documented at the various stages of the project’s development. The procedures should ensure that representatives of all functions directly related to the stage of the project being reviewed, as well as individuals from related areas and necessary specialists are involved. The results of the project review should be documented in the project’s historical record.
4.1.7. Project transfer. Each manufacturer must establish and maintain procedures to ensure that the product design is correctly translated into production specifications.
4.1.8. Project validation. Each manufacturer must establish and maintain a procedure to validate the product design. The validation of the project must be carried out under predetermined operational conditions, in the initial production of lots or unit. The design validation must ensure that the product meets the user’s needs and indication of use and must include product tests in real or simulated conditions of use. Project validation should include software validation, where appropriate. The results of the project validation, including their identification, methods, date and manual or electronic signature of those responsible must be documented in the historical record of the project. Stability studies should be carried out whenever applicable.
4.1.9. Project release. Each manufacturer must ensure that the project is not released for production until it is approved by the persons designated for that purpose by the manufacturer. Designated persons shall review all records required for the historical registration of the project, to ensure that it is complete and that the final project is compatible with the approved plans, prior to its release. This release, including date and manual or electronic signature of the person responsible, must be documented.
4.1.10. Design changes. Each manufacturer must establish and maintain procedures for the identification, documentation, validation, review and approval of design changes prior to their implementation, including an assessment of risks within the risk management process.
4.1.11. Historical project record. Each manufacturer must establish and maintain a historical project record for each product. The historical project record shall contain or reference all records necessary to demonstrate that the project was developed in accordance with the approved project plan and the requirements of this Technical Regulation.
4.2. Product master record (RMP)
4.2.1. Each manufacturer must maintain master product records (RMP’s). The RMP for each type of product should include or reference the following information:
4.2.1.1. Product specifications, including respective drawings, composition, formulation, component specifications, software design specifications and their source codes;
4.2.1.2. Specifications of the production process, including specifications for infrastructure, equipment, production methods and instructions and environmental production specifications;
4.2.1.3. Packaging and labeling specifications, including methods and processes used;
4.2.1.4 Inspection and testing procedures, with the respective acceptance criteria; and
4.2.1.5. Installation, maintenance and technical assistance methods and procedures.
CHAPTER 5 – PROCESS AND PRODUCTION CONTROLS
5.1. General instructions
5.1.1. Each manufacturer must design, conduct, control and monitor all production processes to ensure that the product complies with its specifications. Where any deviation from product specifications may occur as a result of the manufacturing process, the manufacturer shall establish and maintain process control procedures that describe any process controls necessary to ensure compliance with the specifications. Process controls should include:
5.1.1.1. Documented instructions, standard operating procedures and methods that define and control the form of production, installation and maintenance;
5.1.1.2. Monitoring and control of process parameters;
5.1.1.3. Compliance with technical norms, standards or reference codes; and
5.1.1.4. Instructions for starting the process;
5.1.2. The company’s facilities must be adequately designed in order to provide the performance of all operations, prevent changes or contamination of components, manufacturing materials, intermediate and finished products and ensure their correct handling, including an adequate flow of people.
5.1.3. Environmental control. Each manufacturer must provide adequate environmental conditions for production operations, in order to prevent contamination or other adverse effects on the product. The correct functioning of the established environmental control systems must be monitored, maintaining the corresponding records.
5.1.3.1. Limpeza e sanitização. Cada fabricante deverá estabelecer e manter procedimentos de limpeza e sanitização adequados, bem como uma programação que satisfaça as exigências das especificações do processo de fabricação. Cada fabricante deverá assegurar que os funcionários envolvidos compreendam esses procedimentos.
5.1.3.2. Staff health and hygiene. Each manufacturer must ensure that employees and or others who are in contact with the product or its environment are clean, healthy and dressed appropriately for the activity to be performed. Anyone who, through medical examination or observation of supervisors, appears to be in a health condition that may affect the product, should be removed from operations until it is remedied. Each manufacturer must instruct its personnel to report such conditions to supervisors.
5.1.3.3. Staff habits. Each manufacturer must limit the consumption of food and beverages to specific locations so as not to affect the production areas.
5.1.3.4. Contamination control. Each manufacturer must establish and maintain procedures to avoid contamination of equipment, components, manufacturing materials, intermediates and products finished with cleaning and disinfection materials, including dangerous substances or contaminants generated by the manufacturing process. A pest control program must be established and whenever chemical agents are used, the company must ensure that they do not affect the quality of the product.
5.1.3.5. Removal of garbage and chemical sewage. The treatment and disposal of waste, chemical effluents and by-products must take place in accordance with the applicable legislation.
5.1.3.6. Rules on biological safety must be observed in cases where there is a biological risk.
5.1.4. Worker’s health. Each manufacturer must ensure compliance with applicable standards related to workers’ health, including the use of personal protective equipment by them, which is compatible with work processes.
performed.
5.1.5. Equipment. Each manufacturer must ensure that all equipment used in the manufacturing process is suitable for its intended use and correctly designed, built and installed to facilitate maintenance, adjustments, cleaning and use.
5.1.5.1. Maintenance schedule. Each manufacturer must establish and maintain a schedule for maintenance, adjustments and, where applicable, cleaning of the equipment, to ensure that all manufacturing specifications are being met. The maintenance program must be in an easily accessible place for the personnel responsible for the maintenance and use of the equipment. A record of maintenance activities must be made with the date of completion and the identification of the persons in charge.
5.1.5.2. Settings. Each manufacturer must ensure that any acceptable tolerances or inherent limitations are posted in a visible place or close to the equipment that requires periodic adjustments, or are easily available to the personnel in charge of these adjustments.
5.1.5.3. Manufacturing materials. Each manufacturer must establish and maintain procedures for the use and removal of manufacturing materials, to ensure that such materials are removed from the product or limited to a specified quantity that does not adversely affect the quality of the product.
5.1.6. Special processes must be conducted according to the procedures and parameters established to ensure compliance with the specifications. Critical parameters must be monitored and recorded in the historical product record.
5.2. Packaging controls, labeling and instructions for use
5.2.1. Product packaging. Each manufacturer must establish procedures for packaging the products in order to protect the product from any alteration, damage or contamination during the stages of processing, storage, handling and distribution.
5.2.2. Product labeling
5.2.2.1. Each manufacturer must establish and maintain procedures to ensure integrity and avoid accidental mixing of labels, instructions for use, packaging materials or identifying labels.
5.2.2.2. Each manufacturer must ensure that the labels are designed, printed and, when applicable, applied in such a way that they remain legible and adhered to the product during the stages of processing, storage, handling and use.
5.2.2.3. Inspection of labels and instructions for use. The labels and instructions for use should not be released for use until an authorized person has examined their compliance with the information contained therein. The approval, including date, name and manual or electronic signature of the person responsible, must be documented in the product’s historical record.
5.3. Inspection and testing
5.3.1. General instructions. Each manufacturer must establish and maintain inspection procedures, tests or other means of verification in order to ensure compliance with the requirements specified throughout the manufacturing chain. The results of the acceptance activities during the receipt of components and manufacturing materials, as well as intermediate stages of production and final acceptance of the finished product must be documented, including its completion (acceptance or rejection).
5.3.2. The authority and responsibility for such activities should be defined by the manufacturer.
5.3.3. The components and manufacturing materials received, as well as components, intermediate products, and returned products, must not be used or processed until their compliance with established requirements is verified. Each manufacturer shall establish and maintain procedures for the retention of components, manufacturing materials, intermediate products, and returned products until the inspections, tests or other established checks have been completed and documented.
5.3.4. Finished products should not be released until the activities specified in the RMP have been completed and the documentation and associated data have been reviewed by a designated person to ensure that all acceptance criteria have been met. The release, including the date and the person’s manual or electronic signature, must be documented.
5.4. Inspection, measurement and testing equipment.
5.4.1. Each manufacturer must ensure that all measurement and test equipment, including mechanical, automated or electronic equipment, is suitable for its intended purpose and is capable of producing valid results. Each manufacturer must establish and maintain procedures to ensure that the equipment is routinely calibrated, inspected and controlled. The measuring equipment must be identified in a way that allows the calibration situation to be determined.
5.4.2. Calibration. Each manufacturer must establish and maintain calibration procedures that include specific guidelines and limits of precision and accuracy, as well as prescriptions for corrective actions when the limits of precision and accuracy are not reached. Calibration must be performed by personnel who have the necessary education, training, practice and experience.
5.4.3. Calibration standards. Each manufacturer must establish and maintain calibration standards for measuring equipment that are traceable to official national or international standards. If there is no applicable standard available, the manufacturer must establish and maintain a standard of its own.
5.4.4. Calibration records. Each manufacturer must ensure that records of calibration dates, measurements obtained, of the employee in charge of this task and the next date for this operation are kept. The records must be kept by the manufacturer, and must be available to the personnel who use this equipment and to those responsible for calibrating it.
5.4.5. Maintenance. Each manufacturer must establish and maintain procedures to ensure that the handling, preservation and storage of test, inspection and measurement equipment is carried out in order to preserve its accuracy and suitability for use.
5.4.6. Installations. Each manufacturer shall protect inspection, test and measurement facilities and equipment, including test hardware and software, from adjustments that could invalidate the calibration.
5.4.7. The manufacturer must establish procedures to assess the impact of the results of previous measurements when he finds non-conformities in the measurement and test equipment. The result of the assessment must be documented.
5.5. Validation
5.5.1. Special processes must be validated according to previously established protocols. The results of the validations, including the date and identification of the person responsible for their approval, must be recorded.
5.5.2. Analytical methods, auxiliary systems to support the process or environmental control, automated computerized systems and software that may adversely affect product quality or the quality system must be validated.
5.5.3. The manufacturer must establish procedures to periodically check its processes, analytical methods, auxiliary systems to support the process or environmental control, automated computerized systems and validated software and, when applicable, establish the frequency for revalidation.
5.6. Change Control. The manufacturer must establish a change control procedure in order to control changes in auxiliary systems, software, equipment, processes, methods or other changes that may influence the quality of products, including an assessment of risks within the risk management process. .
5.6.1. The procedure should describe the actions to be taken, including, when applicable, the need for re-qualification or re-validation.
5.6.2. Changes must be formally requested, documented and approved prior to implementation.
CHAPTER 6 – HANDLING, STORAGE, DISTRIBUTION AND TRACEABILITY
6.1. Handling
6.1.1. Each manufacturer must establish and maintain procedures to ensure that inversions (exchanges), damages, deterioration or other adverse effects affecting components, manufacturing materials, intermediate products, finished products and samples for quality control do not occur during any stage of handling.
6.1.2. Each manufacturer must establish and maintain procedures to identify the conformity of components, manufacturing materials, intermediate products and finished products, in order to ensure that only those duly approved are used or distributed.
6.1.3. The procedures should ensure that when the quality or condition of the use of a component, manufacturing material, intermediate product or finished product deteriorates over time, it is not used or distributed.
6.1.4. Procedures should ensure that components, manufacturing materials, intermediate products or finished products closest to expiration are distributed or used first and that those that are out of date are not distributed or used.
6.2. Storage
6.2.1. Each manufacturer must establish and maintain procedures for the identification of components, manufacturing materials, intermediate products, finished products and samples for quality control in order to prevent inversions (exchanges). These must be stored in physical and environmental conditions that prevent damage, deterioration or other adverse effects during the period in which they remain stored.
6.3. Distribution
6.3.1. Each manufacturer must maintain distribution records that include or refer to:
6.3.1.1. Consignee’s name and address;
6.3.1.2. Identification and quantity of products shipped, with shipping date; and
6.3.1.3. Any numerical control used for traceability.
6.4. Identification and traceability
6.4.1. Each manufacturer must establish and maintain procedures for the identification of components, manufacturing materials, intermediate products and finished products during all phases of storage, production, distribution and installation to avoid confusion and to ensure correct order fulfillment.
6.4.2. Each manufacturer must identify each unit, batch or batch of products with a serial or batch number. This identification
must be registered in the product’s historical record.
6.5. Non-conforming components and products
6.5.1. Each manufacturer must establish and maintain procedures to ensure that components, manufacturing materials, intermediate products, finished products and returned products that do not comply with established requirements are not used or installed inadvertently. The procedures must contain prescriptions for the identification, documentation, evaluation, segregation and disposition about components, manufacturing materials, intermediate products and non-compliant finished products. The assessment of non-compliance should include the need for investigation and notification of the persons and or organizations involved in the non-compliance. The results of the evaluations and possible investigations must be recorded.
6.5.2. The responsibility for the review and the authority to dispose of components, manufacturing materials, intermediate products, finished products and returned products that do not conform must be defined. The review and disposition process must be described in an established procedure. The provision must be documented, and a record of the justification and manual or electronic signature of the person (s) responsible for it must be kept. In case of authorization of use, the decision must be based on a technically justified risk assessment.
6.5.3. Each manufacturer must establish and maintain procedures for reworking, re-inspection and reevaluation of intermediate or finished products after rework, to ensure that they meet their original specifications. Activities related to rework and reevaluation of the product, including problems with rework, must be documented in the historical product record.
CHAPTER 7 – CORRECTIVE AND PREVENTIVE ACTIONS
7.1. Corrective and preventive actions.
7.1.1. Each manufacturer must establish and maintain procedures for:
7.1.1.1. Analyze processes, work operations, quality audit reports, quality records, technical assistance records, complaints, returned products and other sources of quality data in order to identify existing and potential causes of non-conformities related to the product, process or quality system. When applicable, the analysis should be based on a valid statistical technique for detecting recurring quality problems;
7.1.1.2. Investigate the cause of non-conformities related to the product, process or quality system;
7.1.1.3. Identify and execute the necessary actions to prevent the occurrence, correct the occurrence and prevent the recurrence of non-conformities;
7.1.1.4. Check or validate the effectiveness of the corrective action and ensure that it does not adversely affect the product. To this end, any changes made, when applicable, must comply with change control procedures and established validation protocols;
7.1.1.5. Record the activities related to corrective and preventive actions;
7.1.1.6. Ensure that information about quality problems or non-compliant products is properly disseminated to those directly involved in maintaining product quality or preventing the occurrence of such problems;
7.1.1.7. Submit relevant information about identified quality problems and preventive and corrective actions to executive management for knowledge and monitoring, as well as to the competent health authority, when applicable;
7.1.1.8. Determine the collection of products and other field actions that are relevant in the case of products already distributed.
7.2. Complaints management.
7.2.1. Each manufacturer must establish and maintain procedures for receiving, examining, evaluating, investigating and filing complaints. Such procedures should ensure that:
7.2.1.1. Complaints are received, documented, examined,
evaluated, investigated and filed by a formally designated unit;
7.2.1.2. When applicable, complaints are notified to the competent health authority;
7.2.1.3. Complaints are examined to see if an investigation is necessary. When an investigation is not carried out, the unit must keep a record that includes the reason why the investigation was not carried out and the names of those responsible for the decision not to investigate;
7.2.1.4. Each manufacturer must examine, evaluate and investigate all complaints involving possible product non-compliance. Any claim relating to death, injury or threat to public health must be immediately examined, evaluated and investigated.
7.2.1.5. When an investigation is made, a record must be kept that includes:
7.2.1.5.1. Product’s name;
7.2.1.5.2. Date of receipt of the complaint;
7.2.1.5.3. Any control number used;
7.2.1.5.4. Complainant’s name, address and telephone number;
7.2.1.5.5. Nature of the complaint; and
7.2.1.5.6. Date and results of the investigation including actions taken.
7.3. Quality audit.
7.3.1. Each manufacturer must conduct and document quality audits to assess the conformity of the quality system with established requirements.
7.3.2. Quality audits should be conducted by people who have been proven to be trained, in accordance with established audit procedures, but who have no direct responsibility for the matters being audited.
7.3.3. Those responsible for the audited areas must be notified of identified non-conformities.
CHAPTER 8 – INSTALLATION AND TECHNICAL ASSISTANCE
8.1. Installation. Each manufacturer must establish and maintain appropriate instructions and procedures for the correct installation of the products. When the manufacturer or its authorized representative installs a product, it must verify that it works according to established criteria. The results of this check must be recorded. The manufacturer must ensure that installation instructions and procedures are distributed with the product or that they are otherwise available to the person responsible for installing the product.
8.2. Technical assistance. Each manufacturer must establish and maintain procedures to ensure that finished products, which are subject to technical assistance by the manufacturer or its representative, meet specifications.
8.2.1. Technical assistance records. Each manufacturer shall establish and maintain procedures to ensure that technical assistance records are maintained and that they identify:
8.2.1.1. Product object of the service;
8.2.1.2. Control number used;
8.2.1.3. Date of performance of the service;
8.2.1.4. Identification of the service provider;
8.2.1.5. Description of the service performed; and
8.2.1.6. Results of inspections and tests for approval of the service.
8.2.2. Each manufacturer must periodically review the technical assistance records. In cases where the analysis identifies failure trends that represent danger or records involving death or serious injury, corrective / preventive action should be initiated according to the requirements of this Technical Regulation.
CHAPTER 9 – STATISTICAL TECHNIQUES
9.1. Each manufacturer must establish and maintain procedures to identify valid statistical techniques to verify the performance of the quality system and the capacity of the process to meet the established specifications.
RESOLUTION – RDC No. 16, OF MARCH 28, 2013. Approves the Technical Regulations for Good Manufacturing Practices for Medical Products and Products for Diagnosis of In Vitro Use and other measures.
The Collegiate Directorate of the National Health Surveillance Agency, using the powers conferred on it by item IV of art. 11 of the Regulation approved by Decree No. 3,029, of April 16, 1999, and in view of the provisions of item II and § 1 and § 3 of art. 54 of the Internal Regulation approved under the terms of Annex I of Ordinance 354 of ANVISA, of August 11, 2006, republished in the DOU of August 21, 2006, in a meeting held on March 7, 2013, considering Law no. 6360, of September 23, 1976 and its regulation, Decree No. 79094 of January 5, 1977;
considering the need to internalize MERCOSUR / GMC / RES. No. 20/11, which approved the “MERCOSUR Technical Regulation on Good Manufacturing Practices for Medical Products and Products for Diagnosis of In Vitro Use (repeal of GMC Res. 04/95, 38/96, 65/96 and 131 / 96) “;
whereas the regulation of Good Manufacturing Practices related to medical products and products for in vitro use diagnostics must seek to guarantee the quality, safety and efficacy of products sold in Brazil;
whereas it is essential to promote the improvement of national systems aimed at the regulation and control of medical products and products for diagnosis of in vitro use; adopts the following Collegiate Board Resolution and I, the Chief Executive Officer, determine its publication:
Art. 1 – To approve the “Technical Regulation for Good Manufacturing Practices for Medical Products and Products for Diagnosis of In Vitro Use”, which is included as an Annex and is part of this Resolution.
Single paragraph. This regulation incorporates into the national legal system Resolution GMC MERCOSUR nº 20/2011 “MERCOSUR Technical Regulation of Good Manufacturing Practices for Medical Products and Products for Diagnosis of In Vitro Use (repeal of Res. GMC nº 04/95, 38/96, 65/96 and 131/96) ”.
Art. 2 – Revoke Ordinance No. 686, of August 27, 1998; Resolution RDC No. 59, of June 27, 2000; and RDC Resolution No. 167, of July 2, 2004.
Art. 3 – The distributors and stores of medical products and products for diagnosis of in vitro use must comply with the requirements of this Resolution, as applicable.
Art. 4 – A period of 180 days is allowed, from the date of incorporation of the normative instrument, for the adoption of the necessary measures for the application of the Technical Regulation.
Art. 5 – This Resolution comes into force on the date of its publication.
DIRCEU BRÁS APARECIDO BARBANO
TECHNICAL REGULATION OF GOOD PRACTICES FOR THE MANUFACTURING OF MEDICAL PRODUCTS AND PRODUCTS FOR DIAGNOSIS OF IN VITRO USE
CONTENT
CHAPTER 1 – GENERAL PROVISIONS
CHAPTER 2 – GENERAL QUALITY SYSTEM REQUIREMENTS
2.1. General provisions
2.2. Managerial responsibility
2.3. Folks
2.4. Risk management
2.5. Purchasing Controls
CHAPTER 3 – QUALITY DOCUMENTS AND RECORDS
3.1. General requirements
3.2. Product historical record
3.3. Inspection and test records.
CHAPTER 4 – PROJECT CONTROL AND PRODUCT MASTER RECORD (RMP)
4.1. Project Control
4.2. Product Master Record (RMP)
CHAPTER 5 – PROCESS AND PRODUCTION CONTROLS
5.1. General instructions
5.2. Packaging controls, labeling and instructions for use
5.3. Inspection and testing
5.4. Inspection, measurement and testing equipment.
5.5. Validation
5.6. Change control
CHAPTER 6 – HANDLING, STORAGE, DISTRIBUTION AND TRACEABILITY
6.1. Handling
6.2. Storage
6.3. Distribution
6.4. Identification and traceability
6.5. Non-conforming components and products
CHAPTER 7 – CORRECTIVE AND PREVENTIVE ACTIONS
7.1. Corrective and Preventive Actions
7.2. Complaints management
7.3. Quality audit
CHAPTER 8 – INSTALLATION AND TECHNICAL ASSISTANCE
8.1. Installation
8.2. Technical assistance
CHAPTER 9 – STATISTICS TECHNIQUES
CHAPTER 1 – GENERAL PROVISIONS
1.1 – Applicability
1.1.1. This Technical Regulation establishes requirements applicable to the manufacture of medical products and products for diagnosis of in vitro use. These requirements describe Good Manufacturing Practices (GMP) for methods and controls used in the design, purchasing, manufacturing, packaging, labeling, storage, distribution, installation and technical assistance of medical products and products for in-vitro diagnostic use. The requirements of this Technical Regulation are intended to ensure that medical products and products for diagnosis of in vitro use are safe and effective.
1.1.1.2. The requirements of this Technical Regulation are applicable to manufacturers and importers of medical products and products for in vitro diagnostic use that are marketed in Brazil.
1.1.3. Whenever the manufacturer understands that any of the requirements of this resolution is not applicable to its processes, it must document a justification for this understanding.
1.1.1.4. Importers of medical products and products for diagnosis of in vitro use must comply with the requirements of this Resolution, as applicable.
1.1.2. Definitions
For the purposes of this Technical Regulation, the following definitions apply:
1.2.1. Technical assistance: Maintenance or repair of a finished product in order to return it to its specifications.
1.2.2. Quality audit: means an established, systematic and independent examination of the entire quality system of a manufacturer, performed at regular intervals and with sufficient frequency to ensure that both the activities of the quality system and its results satisfy the procedures specified in its system quality, that these procedures are implemented efficiently and that they are adequate to achieve the objectives of the quality system. The quality audit is different from other activities in the quality system required by this Technical Regulation.
1.2.3. Component: raw material, substance, part, part, software, hardware, packaging, label or instruction for use, used during the manufacture of a medical product and product for diagnosis of in vitro use, intended to be included as part of the finished product.
1.2.4. Project input data: description of physical attributes, indication of use, performance, compatibility, safety, efficacy, ergonomics, usability, information from previous projects and results of risk management, among other requirements of a medical product or product for diagnosis in vitro use that are used as the basis of your project.
1.2.5. Project output data: result of the work in each phase of the project and its final result. The finished project output data is the basis for the product master record (RMP).
1.2.6. Damage: physical injury or damage to the person’s health, or damage to property or the environment.
1.2.7. Specifications: requirements to which products, components, production activities, technical assistance, services, quality system or any other activity must comply.
1.2.8. Establish: define, document (by written or electronic means) and implement.
1.2.9. Manufacturer: any person who designs, manufactures, assembles or processes a finished product, including those who perform functions under a sterilization contract, labeling, packaging.
1.2.10. Executive management: senior management of the company responsible for providing resources and with authority to establish or change the company’s quality policy and system.
1.2.11. Risk management: systematic application of management policies, procedures and practices to the tasks of analyzing, evaluating, controlling and monitoring risks associated with a specific product or process.
1.2.12. Batch or batch: quantity of a product made in a manufacturing or sterilization cycle, whose essential characteristic is homogeneity.
1.2.13. Manufacturing material: material or substance used in the manufacturing process or to facilitate this process, including cleaning agents, mold release agents, lubricating oils, sterilizers, or other by-products of the manufacturing process.
1.2.14. Non-compliance: non-compliance with a previously specified requirement.
1.2.15. Serial or batch number: distinct combination of letters or numbers, or both, from which the complete history of purchases, manufacture, packaging, labeling and distribution of finished products can be determined.
1.2.16. Danger: Potential source of damage.
1.2.17. Quality policy: the totality of an organization’s intentions and guidelines with respect to quality, expressed by executive management.
1.2.18. Special process: any process whose results cannot be fully verified by subsequent inspections and tests.
1.2.19. Production: all operations involved in the manufacture of a given product, from receipt of components, through processing and packaging, to obtaining the finished product.
1.2.20. Finished product: any product or accessory suitable for use, packaged, labeled.
1.2.21. Quality: totality of aspects and characteristics that make it possible for a medical product or product for diagnosis of in vitro use to meet the requirements for suitability for use, including safety and performance.
1.2.22. Complaint: written, oral or electronic communication regarding the non-acceptance of the identity, quality, durability, reliability, safety, efficacy or performance of a product.
1.2.23. Registration: physical or electronic document, which shows data, facts, specific events and results achieved in relation to compliance with procedures and standards of the quality system.
1.2.24. Product historical record: compilation of records containing the complete production history of a finished product.
1.2.25. Historical project record: compilation of documents containing the complete project history of a finished product.
1.2.26. Product master record (RMP): compilation of documents containing specifications, instructions and procedures for obtaining a finished product, as well as installation, technical assistance and maintenance.
1.2.27. Rework: part or all of the manufacturing operation aimed at correcting the non-conformity of a component, intermediate product or a finished product, so that it meets the specifications defined in the RMP.
1.2.28. Project review: documented, systematic and complete examination carried out during the development of the project to assess its suitability for the planning and established objectives.
1.2.29. Risk: combination of probability of occurrence and severity of damage.
1.2.30. Quality system: organizational structure, responsibilities, procedures, specifications, processes and resources necessary for quality management.
1.2.31. Validation: confirmation by analysis and objective evidence that the requirements defined for a given purpose consistently lead to the expected result. With respect to a project, it means establishing and documenting objective evidence that the product specifications meet the user’s needs and their intended use. With respect to a process, it means establishing and documenting objective evidence that the process will consistently produce a result that meets the predetermined specifications.
1.2.32. Verification: confirmation by analysis and presentation of objective evidence that the specified requirements have been met. Verification includes the process of examining the results of an activity to determine compliance with established specifications.
1.2.33. Useful life: period of time estimated by the manufacturer in which a product correctly fulfills the functions for which it was designed.
CHAPTER 2 – GENERAL QUALITY SYSTEM REQUIREMENTS
2.1. General Provisions
2.1.1. Each manufacturer must establish and maintain a quality system to ensure that the requirements of this Technical Regulation are met and that the products manufactured are safe, effective and suitable for their intended use. As part of its activities in the quality system, each manufacturer must:
2.1.1.1. Establish and maintain effective quality system instructions and procedures in accordance with the requirements of this Technical Regulation, and
2.1.1.2. Establish procedures to comply with the legal provisions provided for in the current sanitary legislation.
2.2. Managerial responsibility
2.2.1. Quality policy. The executive management of each manufacturer must establish its policy and its objectives of commitment to quality, which must be measurable and consistent with the established policy. Executive management must maintain the policy at all levels of the organization. Executive management must ensure that this policy is described in a quality manual and that it is understood by all employees who may affect or influence the quality of a product.
2.2.2. Organization. Each manufacturer must establish and maintain an adequate organizational structure, represented by means of an organization chart, with sufficient personnel to ensure that the products are manufactured in accordance with the requirements of this Technical Regulation.
2.2.3. Responsibility and Authority. Each manufacturer must establish, in each chapter of this Technical Regulation, the responsibility, authority and interrelationship of all personnel who manage, execute and verify the work related to quality, with the necessary independence to carry out their responsibilities.
2.2.4. Resources and personnel for verification. Each manufacturer shall establish verification functions and shall provide adequate resources and designation of trained personnel to carry out the verification activities.
2.2.5. Management representative. The executive management of each manufacturer must designate an individual of this, and document this designation, who, regardless of other functions, will have the authority and responsibility to:
2.2.5.1. Ensure that the quality system requirements are established and maintained in accordance with this Technical Regulation;
2.2.5.2. Report the performance of the quality system to executive management for review and provide information on improving the quality system.
2.2.6. Management review. The executive management of each manufacturer must assess the adequacy and effectiveness of the quality system at defined intervals and with sufficient frequency to ensure that the quality system meets the requirements of this Technical Regulation and that it meets the objectives of the established quality policy. The management review must be conducted according to the established review procedures and the results of each review of the quality system must be documented. Issues related to audit results, post-marketing information, process performance and product compliance, status of corrective and preventive actions, changes that may affect the product quality or compliance system, regulatory requirements, should be considered for review.
2.3. Folks
2.3.1. General Instructions. Each manufacturer must have a sufficient number of personnel with instruction, experience, training and practice compatible with the duties of the position, in order to ensure that all activities provided for in this Technical Regulation are correctly performed. Descriptions should be maintained defining the authority, responsibility and requirements necessary for the various tasks of the company.
2.3.2. Treinamento. Cada fabricante deverá assegurar que todo o pessoal seja treinado para executar adequadamente as tarefas a ele designadas. O treinamento deverá ser conduzido de acordo com os procedimentos estabelecidos por pessoas qualificadas para garantir que os empregados tenham uma compreensão adequada de suas funções regulares e dos requisitos deste Regulamento Técnico aplicáveis às suas funções. Como parte de seu treinamento, todos os empregados deverão ser advertidos de defeitos em produtos que poderão ocorrer como resultado do desempenho incorreto de suas funções específicas. O treinamento de empregados deverá ser documentado.
2.3.3. Consultants. Each manufacturer shall ensure that any consultant who advises on methods employed or on the controls used for design, purchasing, manufacturing, packaging, labeling, storage, installation or technical assistance of products has sufficient qualifications (instruction, training and experience) to advise on matters for which he was hired. The hiring of consultants must be conducted in accordance with the purchase control requirements provided for in this Technical Regulation.
2.4. Risk management
2.4.1. Each manufacturer must establish and maintain a continuous risk management process that involves the entire life cycle of the product, from conception to its discontinuation, to identify the hazards associated with a medical product or product for in vitro diagnostic use, estimate and evaluate the risks involved, control them and evaluate the effectiveness of the controls established. This program must include the following elements: risk analysis, assessment, control and monitoring.
2.4.2. The company’s executive management must designate the responsible professionals, establish the policy for determining the criteria for acceptability of the risk, as well as determine a periodic review of the risk management activities in order to guarantee their adequacy and effectiveness.
2.5. Purchasing Controls
2.5.1. Each manufacturer must establish and maintain procedures to ensure that components, manufacturing materials and finished products manufactured, processed, labeled or packaged by third parties or stored by them under contract, comply with the specifications. Each manufacturer must also ensure that services performed by third parties comply with the specifications established by him.
2.5.2. Evaluation of suppliers of products and services. Each manufacturer must establish and maintain, according to the impact on the quality of the final product, criteria for assessing suppliers, specifying the requirements, including quality requirements, which they must satisfy.
2.5.3. Each manufacturer must evaluate and select potential suppliers according to their ability to meet previously established requirements, maintaining a record of approved suppliers. Records of the evaluation, as well as its results, must be kept.
2.5.4. Purchase record. Each manufacturer must maintain records of purchase orders that clearly describe or refer to specifications, including quality requirements, for components, manufacturing materials, finished products or services requested or contracted. The approval of orders, including the date and the person’s manual or electronic signature, must be documented.
2.5.5. An agreement should be documented in which suppliers undertake to notify the manufacturer of any change in the product or service, so that the manufacturer can determine whether the change affects the quality of the finished product.
2.5.6. Each manufacturer must review and approve purchasing documents prior to their release.
CHAPTER 3 – QUALITY DOCUMENTS AND RECORDS
3.1. General requirements.
3.1.1. Each manufacturer must establish and maintain document control procedures to ensure that all documents indicated in this Technical Regulation are correct and suitable for their intended use, and are understood by all employees who may affect or influence the quality of a product.
3.1.2. Approval and issuance of documents. Each manufacturer must designate people to evaluate and approve all documents established in this Technical Regulation for adequacy before their issue. The approval, including date and manual or electronic signature of the person responsible for approving the documents, must be documented.
3.1.3. Distribution of documents. The manufacturer must ensure that all documents are up-to-date and available at the application sites and that all unnecessary or obsolete documents are removed from use, or protected from unintended use.
3.1.4. Change of documents. Changes to specifications, methods or procedures related to the quality system must be evaluated, documented, reviewed and approved by persons whose function and level of responsibility are equivalent to those who performed the original review and approval.
3.1.5. Records of document changes. Each manufacturer must keep records of changes to documents that must include a description of the change, identification of the changed and affected documents, identification of the responsible person, approval date and date when the changes will take effect. A list of current documents must be maintained in order to identify their current status and ensure that only current and approved documents are in use.
3.1.6. Documents and Records Archive. All quality documents and records must be legible and kept in a way to minimize damage, prevent loss and provide rapid recovery. All digitally archived documents and records must be backed up:
3.1.6.1. Confidentiality. Documents and records considered confidential by the manufacturer may be marked to alert the competent health authority;
3.1.6.2 Document and record retention period: all necessary documents and records related to a product must be kept for a period equivalent to the product’s useful life, but in no case for less than two years from the date distribution.
3.2. Product historical record.
3.2.1. Each manufacturer must maintain historical product records. Each manufacturer must establish and maintain procedures to ensure that historical product records are maintained for each batch or series to demonstrate that the products have been manufactured in accordance with the product’s master record and the requirements of this Technical Regulation. The product’s historical record must include or reference the following information:
3.2.1.1. Manufacturing date;
3.2.1.2. Components used;
3.2.1.3. Quantity manufactured;
3.2.1.4. Results of inspections and tests;
3.2.1.5. Special process parameters;
3.2.1.6. Quantity released for distribution;
3.2.1.7. Labeling;
3.2.1.8. Identification of the serial number or production batch; and
3.2.1.9. Final product release.
3.3. Inspection and test records.
3.3.1. Each manufacturer must keep a record of the results of the inspections and tests established, when these are directly related to the critical quality attributes of the product.
These records must include the acceptance criteria, the results, the equipment / instrument used and the date and manual or electronic signature of the person responsible.
CHAPTER 4 – PROJECT CONTROL AND PRODUCT MASTER RECORD (RMP)
4.1. Project Control
4.1.1. General Instructions Each manufacturer must establish and maintain product design control procedures to ensure that the requirements specified for the project are met.
4.1.2. Project and development planning. Each manufacturer must establish and maintain plans that describe or reference the design and development activities and the persons responsible for each activity. The plans should describe or refer to the project development activities, including any interaction between the various organizational and technical groups that may have some interface with it. The plans should be evaluated, updated and approved as the project progresses.
4.1.3. Project input data. Each manufacturer must establish and maintain procedures to ensure that the requirements related to a product are appropriate and meet their intended use, including the needs of the user and patient and applicable legal and regulatory requirements. Procedures should include a mechanism that allows incomplete, ambiguous or conflicting requirements to be identified and addressed. The input data for a project must be documented, evaluated and approved by a qualified designated person. The approval of requirements, including the date and the manual or electronic signature of the person responsible for approval, must be documented.
4.1.4. Design verification. Each manufacturer must establish and maintain procedures for verifying the product design. The design check must be performed by designated personnel and must ensure that the project’s output data matches the input data. The results of the project verification, including the identification of the verified project, verification methods, date and name of the person in charge of the verification, shall be documented in the historical record of the project.
4.1.5. Project output data. Each manufacturer must define and document the project output data in order to allow the assessment of the project’s compliance with the requirements established as input data. The project output data must satisfy the requirements of the input data and must include the acceptance criteria and identify the design characteristics that are essential for the intended use of the product. These must be documented, reviewed and approved prior to their release.
4.1.6. Project Review. Each manufacturer must establish and maintain procedures to ensure that evaluations of project results are planned, conducted and documented at the various stages of the project’s development. The procedures should ensure that representatives of all functions directly related to the stage of the project being reviewed, as well as individuals from related areas and necessary specialists are involved. The results of the project review should be documented in the project’s historical record.
4.1.7. Project transfer. Each manufacturer must establish and maintain procedures to ensure that the product design is correctly translated into production specifications.
4.1.8. Project validation. Each manufacturer must establish and maintain a procedure to validate the product design. The validation of the project must be carried out under predetermined operational conditions, in the initial production of lots or unit. The design validation must ensure that the product meets the user’s needs and indication of use and must include product tests in real or simulated conditions of use. Project validation should include software validation, where appropriate. The results of the project validation, including their identification, methods, date and manual or electronic signature of those responsible must be documented in the historical record of the project. Stability studies should be carried out whenever applicable.
4.1.9. Project release. Each manufacturer must ensure that the project is not released for production until it is approved by the persons designated for that purpose by the manufacturer. Designated persons shall review all records required for the historical registration of the project, to ensure that it is complete and that the final project is compatible with the approved plans, prior to its release. This release, including date and manual or electronic signature of the person responsible, must be documented.
4.1.10. Design changes. Each manufacturer must establish and maintain procedures for the identification, documentation, validation, review and approval of design changes prior to their implementation, including an assessment of risks within the risk management process.
4.1.11. Historical project record. Each manufacturer must establish and maintain a historical project record for each product. The historical project record shall contain or reference all records necessary to demonstrate that the project was developed in accordance with the approved project plan and the requirements of this Technical Regulation.
4.2. Product master record (RMP)
4.2.1. Each manufacturer must maintain master product records (RMP’s). The RMP for each type of product should include or reference the following information:
4.2.1.1. Product specifications, including respective drawings, composition, formulation, component specifications, software design specifications and their source codes;
4.2.1.2. Specifications of the production process, including specifications for infrastructure, equipment, production methods and instructions and environmental production specifications;
4.2.1.3. Packaging and labeling specifications, including methods and processes used;
4.2.1.4 Inspection and testing procedures, with the respective acceptance criteria; and
4.2.1.5. Installation, maintenance and technical assistance methods and procedures.
CHAPTER 5 – PROCESS AND PRODUCTION CONTROLS
5.1. General instructions
5.1.1. Each manufacturer must design, conduct, control and monitor all production processes to ensure that the product complies with its specifications. Where any deviation from product specifications may occur as a result of the manufacturing process, the manufacturer shall establish and maintain process control procedures that describe any process controls necessary to ensure compliance with the specifications. Process controls should include:
5.1.1.1. Documented instructions, standard operating procedures and methods that define and control the form of production, installation and maintenance;
5.1.1.2. Monitoring and control of process parameters;
5.1.1.3. Compliance with technical norms, standards or reference codes; and
5.1.1.4. Instructions for starting the process;
5.1.2. The company’s facilities must be adequately designed in order to provide the performance of all operations, prevent changes or contamination of components, manufacturing materials, intermediate and finished products and ensure their correct handling, including an adequate flow of people.
5.1.3. Environmental control. Each manufacturer must provide adequate environmental conditions for production operations, in order to prevent contamination or other adverse effects on the product. The correct functioning of the established environmental control systems must be monitored, maintaining the corresponding records.
5.1.3.1. Limpeza e sanitização. Cada fabricante deverá estabelecer e manter procedimentos de limpeza e sanitização adequados, bem como uma programação que satisfaça as exigências das especificações do processo de fabricação. Cada fabricante deverá assegurar que os funcionários envolvidos compreendam esses procedimentos.
5.1.3.2. Staff health and hygiene. Each manufacturer must ensure that employees and or others who are in contact with the product or its environment are clean, healthy and dressed appropriately for the activity to be performed. Anyone who, through medical examination or observation of supervisors, appears to be in a health condition that may affect the product, should be removed from operations until it is remedied. Each manufacturer must instruct its personnel to report such conditions to supervisors.
5.1.3.3. Staff habits. Each manufacturer must limit the consumption of food and beverages to specific locations so as not to affect the production areas.
5.1.3.4. Contamination control. Each manufacturer must establish and maintain procedures to avoid contamination of equipment, components, manufacturing materials, intermediates and products finished with cleaning and disinfection materials, including dangerous substances or contaminants generated by the manufacturing process. A pest control program must be established and whenever chemical agents are used, the company must ensure that they do not affect the quality of the product.
5.1.3.5. Removal of garbage and chemical sewage. The treatment and disposal of waste, chemical effluents and by-products must take place in accordance with the applicable legislation.
5.1.3.6. Rules on biological safety must be observed in cases where there is a biological risk.
5.1.4. Worker’s health. Each manufacturer must ensure compliance with applicable standards related to workers’ health, including the use of personal protective equipment by them, which is compatible with work processes.
performed.
5.1.5. Equipment. Each manufacturer must ensure that all equipment used in the manufacturing process is suitable for its intended use and correctly designed, built and installed to facilitate maintenance, adjustments, cleaning and use.
5.1.5.1. Maintenance schedule. Each manufacturer must establish and maintain a schedule for maintenance, adjustments and, where applicable, cleaning of the equipment, to ensure that all manufacturing specifications are being met. The maintenance program must be in an easily accessible place for the personnel responsible for the maintenance and use of the equipment. A record of maintenance activities must be made with the date of completion and the identification of the persons in charge.
5.1.5.2. Settings. Each manufacturer must ensure that any acceptable tolerances or inherent limitations are posted in a visible place or close to the equipment that requires periodic adjustments, or are easily available to the personnel in charge of these adjustments.
5.1.5.3. Manufacturing materials. Each manufacturer must establish and maintain procedures for the use and removal of manufacturing materials, to ensure that such materials are removed from the product or limited to a specified quantity that does not adversely affect the quality of the product.
5.1.6. Special processes must be conducted according to the procedures and parameters established to ensure compliance with the specifications. Critical parameters must be monitored and recorded in the historical product record.
5.2. Packaging controls, labeling and instructions for use
5.2.1. Product packaging. Each manufacturer must establish procedures for packaging the products in order to protect the product from any alteration, damage or contamination during the stages of processing, storage, handling and distribution.
5.2.2. Product labeling
5.2.2.1. Each manufacturer must establish and maintain procedures to ensure integrity and avoid accidental mixing of labels, instructions for use, packaging materials or identifying labels.
5.2.2.2. Each manufacturer must ensure that the labels are designed, printed and, when applicable, applied in such a way that they remain legible and adhered to the product during the stages of processing, storage, handling and use.
5.2.2.3. Inspection of labels and instructions for use. The labels and instructions for use should not be released for use until an authorized person has examined their compliance with the information contained therein. The approval, including date, name and manual or electronic signature of the person responsible, must be documented in the product’s historical record.
5.3. Inspection and testing
5.3.1. General instructions. Each manufacturer must establish and maintain inspection procedures, tests or other means of verification in order to ensure compliance with the requirements specified throughout the manufacturing chain. The results of the acceptance activities during the receipt of components and manufacturing materials, as well as intermediate stages of production and final acceptance of the finished product must be documented, including its completion (acceptance or rejection).
5.3.2. The authority and responsibility for such activities should be defined by the manufacturer.
5.3.3. The components and manufacturing materials received, as well as components, intermediate products, and returned products, must not be used or processed until their compliance with established requirements is verified. Each manufacturer shall establish and maintain procedures for the retention of components, manufacturing materials, intermediate products, and returned products until the inspections, tests or other established checks have been completed and documented.
5.3.4. Finished products should not be released until the activities specified in the RMP have been completed and the documentation and associated data have been reviewed by a designated person to ensure that all acceptance criteria have been met. The release, including the date and the person’s manual or electronic signature, must be documented.
5.4. Inspection, measurement and testing equipment.
5.4.1. Each manufacturer must ensure that all measurement and test equipment, including mechanical, automated or electronic equipment, is suitable for its intended purpose and is capable of producing valid results. Each manufacturer must establish and maintain procedures to ensure that the equipment is routinely calibrated, inspected and controlled. The measuring equipment must be identified in a way that allows the calibration situation to be determined.
5.4.2. Calibration. Each manufacturer must establish and maintain calibration procedures that include specific guidelines and limits of precision and accuracy, as well as prescriptions for corrective actions when the limits of precision and accuracy are not reached. Calibration must be performed by personnel who have the necessary education, training, practice and experience.
5.4.3. Calibration standards. Each manufacturer must establish and maintain calibration standards for measuring equipment that are traceable to official national or international standards. If there is no applicable standard available, the manufacturer must establish and maintain a standard of its own.
5.4.4. Calibration records. Each manufacturer must ensure that records of calibration dates, measurements obtained, of the employee in charge of this task and the next date for this operation are kept. The records must be kept by the manufacturer, and must be available to the personnel who use this equipment and to those responsible for calibrating it.
5.4.5. Maintenance. Each manufacturer must establish and maintain procedures to ensure that the handling, preservation and storage of test, inspection and measurement equipment is carried out in order to preserve its accuracy and suitability for use.
5.4.6. Installations. Each manufacturer shall protect inspection, test and measurement facilities and equipment, including test hardware and software, from adjustments that could invalidate the calibration.
5.4.7. The manufacturer must establish procedures to assess the impact of the results of previous measurements when he finds non-conformities in the measurement and test equipment. The result of the assessment must be documented.
5.5. Validation
5.5.1. Special processes must be validated according to previously established protocols. The results of the validations, including the date and identification of the person responsible for their approval, must be recorded.
5.5.2. Analytical methods, auxiliary systems to support the process or environmental control, automated computerized systems and software that may adversely affect product quality or the quality system must be validated.
5.5.3. The manufacturer must establish procedures to periodically check its processes, analytical methods, auxiliary systems to support the process or environmental control, automated computerized systems and validated software and, when applicable, establish the frequency for revalidation.
5.6. Change Control. The manufacturer must establish a change control procedure in order to control changes in auxiliary systems, software, equipment, processes, methods or other changes that may influence the quality of products, including an assessment of risks within the risk management process. .
5.6.1. The procedure should describe the actions to be taken, including, when applicable, the need for re-qualification or re-validation.
5.6.2. Changes must be formally requested, documented and approved prior to implementation.
CHAPTER 6 – HANDLING, STORAGE, DISTRIBUTION AND TRACEABILITY
6.1. Handling
6.1.1. Each manufacturer must establish and maintain procedures to ensure that inversions (exchanges), damages, deterioration or other adverse effects affecting components, manufacturing materials, intermediate products, finished products and samples for quality control do not occur during any stage of handling.
6.1.2. Each manufacturer must establish and maintain procedures to identify the conformity of components, manufacturing materials, intermediate products and finished products, in order to ensure that only those duly approved are used or distributed.
6.1.3. The procedures should ensure that when the quality or condition of the use of a component, manufacturing material, intermediate product or finished product deteriorates over time, it is not used or distributed.
6.1.4. Procedures should ensure that components, manufacturing materials, intermediate products or finished products closest to expiration are distributed or used first and that those that are out of date are not distributed or used.
6.2. Storage
6.2.1. Each manufacturer must establish and maintain procedures for the identification of components, manufacturing materials, intermediate products, finished products and samples for quality control in order to prevent inversions (exchanges). These must be stored in physical and environmental conditions that prevent damage, deterioration or other adverse effects during the period in which they remain stored.
6.3. Distribution
6.3.1. Each manufacturer must maintain distribution records that include or refer to:
6.3.1.1. Consignee’s name and address;
6.3.1.2. Identification and quantity of products shipped, with shipping date; and
6.3.1.3. Any numerical control used for traceability.
6.4. Identification and traceability
6.4.1. Each manufacturer must establish and maintain procedures for the identification of components, manufacturing materials, intermediate products and finished products during all phases of storage, production, distribution and installation to avoid confusion and to ensure correct order fulfillment.
6.4.2. Each manufacturer must identify each unit, batch or batch of products with a serial or batch number. This identification
must be registered in the product’s historical record.
6.5. Non-conforming components and products
6.5.1. Each manufacturer must establish and maintain procedures to ensure that components, manufacturing materials, intermediate products, finished products and returned products that do not comply with established requirements are not used or installed inadvertently. The procedures must contain prescriptions for the identification, documentation, evaluation, segregation and disposition about components, manufacturing materials, intermediate products and non-compliant finished products. The assessment of non-compliance should include the need for investigation and notification of the persons and or organizations involved in the non-compliance. The results of the evaluations and possible investigations must be recorded.
6.5.2. The responsibility for the review and the authority to dispose of components, manufacturing materials, intermediate products, finished products and returned products that do not conform must be defined. The review and disposition process must be described in an established procedure. The provision must be documented, and a record of the justification and manual or electronic signature of the person (s) responsible for it must be kept. In case of authorization of use, the decision must be based on a technically justified risk assessment.
6.5.3. Each manufacturer must establish and maintain procedures for reworking, re-inspection and reevaluation of intermediate or finished products after rework, to ensure that they meet their original specifications. Activities related to rework and reevaluation of the product, including problems with rework, must be documented in the historical product record.
CHAPTER 7 – CORRECTIVE AND PREVENTIVE ACTIONS
7.1. Corrective and preventive actions.
7.1.1. Each manufacturer must establish and maintain procedures for:
7.1.1.1. Analyze processes, work operations, quality audit reports, quality records, technical assistance records, complaints, returned products and other sources of quality data in order to identify existing and potential causes of non-conformities related to the product, process or quality system. When applicable, the analysis should be based on a valid statistical technique for detecting recurring quality problems;
7.1.1.2. Investigate the cause of non-conformities related to the product, process or quality system;
7.1.1.3. Identify and execute the necessary actions to prevent the occurrence, correct the occurrence and prevent the recurrence of non-conformities;
7.1.1.4. Check or validate the effectiveness of the corrective action and ensure that it does not adversely affect the product. To this end, any changes made, when applicable, must comply with change control procedures and established validation protocols;
7.1.1.5. Record the activities related to corrective and preventive actions;
7.1.1.6. Ensure that information about quality problems or non-compliant products is properly disseminated to those directly involved in maintaining product quality or preventing the occurrence of such problems;
7.1.1.7. Submit relevant information about identified quality problems and preventive and corrective actions to executive management for knowledge and monitoring, as well as to the competent health authority, when applicable;
7.1.1.8. Determine the collection of products and other field actions that are relevant in the case of products already distributed.
7.2. Complaints management.
7.2.1. Each manufacturer must establish and maintain procedures for receiving, examining, evaluating, investigating and filing complaints. Such procedures should ensure that:
7.2.1.1. Complaints are received, documented, examined,
evaluated, investigated and filed by a formally designated unit;
7.2.1.2. When applicable, complaints are notified to the competent health authority;
7.2.1.3. Complaints are examined to see if an investigation is necessary. When an investigation is not carried out, the unit must keep a record that includes the reason why the investigation was not carried out and the names of those responsible for the decision not to investigate;
7.2.1.4. Each manufacturer must examine, evaluate and investigate all complaints involving possible product non-compliance. Any claim relating to death, injury or threat to public health must be immediately examined, evaluated and investigated.
7.2.1.5. When an investigation is made, a record must be kept that includes:
7.2.1.5.1. Product’s name;
7.2.1.5.2. Date of receipt of the complaint;
7.2.1.5.3. Any control number used;
7.2.1.5.4. Complainant’s name, address and telephone number;
7.2.1.5.5. Nature of the complaint; and
7.2.1.5.6. Date and results of the investigation including actions taken.
7.3. Quality audit.
7.3.1. Each manufacturer must conduct and document quality audits to assess the conformity of the quality system with established requirements.
7.3.2. Quality audits should be conducted by people who have been proven to be trained, in accordance with established audit procedures, but who have no direct responsibility for the matters being audited.
7.3.3. Those responsible for the audited areas must be notified of identified non-conformities.
CHAPTER 8 – INSTALLATION AND TECHNICAL ASSISTANCE
8.1. Installation. Each manufacturer must establish and maintain appropriate instructions and procedures for the correct installation of the products. When the manufacturer or its authorized representative installs a product, it must verify that it works according to established criteria. The results of this check must be recorded. The manufacturer must ensure that installation instructions and procedures are distributed with the product or that they are otherwise available to the person responsible for installing the product.
8.2. Technical assistance. Each manufacturer must establish and maintain procedures to ensure that finished products, which are subject to technical assistance by the manufacturer or its representative, meet specifications.
8.2.1. Technical assistance records. Each manufacturer shall establish and maintain procedures to ensure that technical assistance records are maintained and that they identify:
8.2.1.1. Product object of the service;
8.2.1.2. Control number used;
8.2.1.3. Date of performance of the service;
8.2.1.4. Identification of the service provider;
8.2.1.5. Description of the service performed; and
8.2.1.6. Results of inspections and tests for approval of the service.
8.2.2. Each manufacturer must periodically review the technical assistance records. In cases where the analysis identifies failure trends that represent danger or records involving death or serious injury, corrective / preventive action should be initiated according to the requirements of this Technical Regulation.
CHAPTER 9 – STATISTICAL TECHNIQUES
9.1. Each manufacturer must establish and maintain procedures to identify valid statistical techniques to verify the performance of the quality system and the capacity of the process to meet the established specifications.
9.2. Sampling plans must be formalized in writing and based on valid statistical logic. Each manufacturer should establish and maintain procedures to ensure that the sampling methods are suitable for their intended use and that they are regularly reviewed. The review of the sampling plans should consider the occurrence of product non-conformities, quality audit reports, complaints and other indicators.
