The qualification of pharmaceutical facilities is a essential requirement to guarantee quality, safety and regulatory compliance in drug production. This technical guide offers a clear and practical comparison among three of the most relevant regulatory frameworks at the international level: the Annex 15 of the Good Manufacturing Practice (GMP) of the European Union, the Guidelines of the International Conference of Harmonization of Technical Requirements for the Registry of Pharmaceutical Products for Human Use (I) and the regulations of the Food and Drug Administration (FDA) of the United States. Our goal is to provide a useful tool for professionals in the pharmaceutical industry and engineers who seek to align their processes with the most demanding standards and understand the similarities and key differences between these regulations.
Definitions
Annex 15 of the EU GMP:
Annex 15 of the GMP standards of the European Union (EU) focuses on the qualification and validation. It establishes the principles to determine and verify that the equipment, facilities, systems, services and processes are adequate for the planned use and work consistently.
Covers the qualification stages (USE, DQ, IQ, OQ, PQ, RECUFICATION) and the validation of processes, analytical methods and cleaning systems. Emphasize the Risk management to determine the scope and extension of the activities.
The revised version highlights the Continuous verification to maintain the qualified state throughout the life cycle. It requires thorough documentation and a scientific approach to demonstrate the aptitude for use.
Normas me:
ICH standards are guidelines developed by experts from the regulatory authorities and the pharmaceutical industry of Europe, Japan and the United States. Your main objective is harmonize the technical requirements for the registration of medicines, reducing the need to carry out tests and evaluations duplicated in different regions. This facilitates and accelerates global access to new medicines, maintaining high standards of quality, safety and efficiency. ICH guides cover various areas, from quality and safety to efficacy and multidisciplinary requirements.
ICH Q8, Q9, Q10 and Q11 guides form a set of guidelines interrelated that seek Modernize and harmonize pharmaceutical manufacturing globally. They focus on a scientific approach and based on the risk for the quality of medicines.
FDA standards:
The FDA standards are a set of regulations and guidelines issued by the United States government agency with the main objective of protect public health.
These standards They govern a wide range of products, including food, medicines (both human and veterinarians), biological products, medical devices, cosmetics and products that emit radiation.
Regulate the whole Life cycle of these products, from its development, manufacture, labeling, distribution to its commercialization and post-commercialization surveillance. The standards seek to ensure that these products are Insurance, effective and of High quality For the consumer.
He Compliance with FDA standards is mandatory For companies that operate in these sectors within the United States or export products to this market. The GMP They are a fundamental part of the FDA regulations to ensure the quality in the manufacture of regulated products. Your breach can entail regulatory actions such as warnings, market retreats, fines and even criminal actions.
The FDA also broadcasts guides (Guidance) that inregulations and provide recommendations on how to fulfill them.
In essence, FDA standards establish the legal frame and technical to guarantee the safety and quality of products that directly impact the health of US citizens.
Key equivalence and differences:
General similarities:
- Common objective: The three documents aim to ensure that pharmaceutical facilities, equipment and systems are adequate for the planned use and that they work consistently to produce quality products.
- Focus on the life cycle: The three recognize the importance of considering the qualification and validation throughout the life cycle of the facilities and equipment.
- Risk Management: The application of risk management principles to determine the scope and extension of qualification activities is a common element.
- Documentation: The three require comprehensive documentation of all qualification activities, including plans, protocols, reports and results.
- Qualification stages: While terminology can vary slightly, the three recognize the logical stages of qualification that progress from design to performance verification.
Annex 15 of the GMP:
- Range: It focuses on qualification and validation on the manufacture of medicines.
- Defined qualification stages: Clearly define the design qualification stages (DQ), installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ).
- Emphasis on continuous verification: The revised version of Annex 15 puts a greater emphasis on continuous verification to ensure that the qualified state is maintained over time.
- Specific details: It provides specific details on the qualification of services (utilities), the validation of cleaning, the validation of analytical methods, and the qualification of computerized systems.
- Minimum number of validation lots: It mentions a minimum number of three lots for processes validation (although this must be justified by risk management).
Normas me:
- ICH Q8: Pharmaceutical Development
- Regulates the content of the pharmaceutical development section of the common technical document (CTD) for the registration of medicines.
- It promotes a scientific approach and risk management for the development of robust products and manufacturing processes.
- Introduce the concept of Design space, which is the multidimensional and interactive combination of input parameters (materials) and process variables that have shown to provide quality guarantee. Working within the design space is not considered a change and does not require prior regulatory approval.
- It seeks to establish a greater understanding of the product and the process, identify and control the critical quality attributes (CQAS) and the critical parameters of the process (CPPS).
- Promotes the concept of Design quality (QBD).
- I Q9: Quality Risk Management
- It provides principles and examples of tools for quality risk management.
- It offers a systematic approach to evaluation, control, communication and review of the risks for the quality of medicines throughout their life cycle (development, manufacturing, distribution, etc.).
- It does not prescribe specific methodologies, but offers examples such as the analysis of failure modes and its effects (FMEA), the analysis of the failure tree (FTA) and the analysis of hazard and critical control points (HACCP).
- It seeks to improve decision -making based on science and risk assessment, contributing to greater quality and safety of the product.
- ICH Q10: Pharmaceutical Quality System (Pharmaceutical Quality System)
- Describe a Pharmaceutical Quality System model (PQS) that is based on the principles of good manufacturing practices (GMP) and complements the Ich Q8 and Q9 guides.
- Promote a life cycle approach for product quality, from development to discontinuation.
- It focuses on four key elements:
- Product and process performance monitoring: Establish systems to monitor and control the processes and product quality.
- Corrective and Preventive Action System (Capa): Implement effective systems to investigate deviations, implement corrective actions to prevent recurrence and preventive actions to avoid problems.
- Change management: Establish a system to evaluate and control changes that may affect product quality.
- Direction review: Perform periodic reviews by the address to evaluate the efficacy of PQS and product quality.
- It encourages continuous improvement.
- ICH Q11: Development and Manufacture of Dr Substances (Chemical Entities and Biotechnological/Biological Entities) (Development and Manufacture of Pharmaceutical Substances (Chemical and Biotechnological/Biological Entities))
- It provides guide for the development and manufacture of pharmaceutical substances (active or APIs).
- Clarifies and complements the principles and concepts described in ICH Q8, Q9 and Q10 in the specific context of APIS manufacturing.
- Describe approaches to develop the understanding of the process and the pharmaceutical substance.
- It offers guidance on what information should be provided in the relevant sections of the CTD (specifically sections 3.2.2.2 to 3.2.s.2.6).
- It helps define the control strategy to ensure the quality of the pharmaceutical substance.
- It addresses aspects such as the selection and justification of the starting materials, the description of the manufacturing process and the controls in process.
FDA standards:
- Range: The FDA CGMPs (mainly found in Title 21 of the CFR, parts 210 and 211) cover the manufacture, processing, packaging and drug retention.
- GENERAL REQUIREMENTS: They establish general requirements for facilities and equipment, including adequate design, construction, location, maintenance and cleaning to prevent pollution and ensure product quality.
- Process validation: They require the validation of the processes to ensure the quality of the finished product. The FDA guide on processes validation (Process Validation: General Principles and Practices) aligns its approach with a life cycle.
- Does not define the stages of qualification explicitly: Although the FDA does not explicitly define the stages of DQ, IQ, OQ and PQ in its regulations, the pharmaceutical industry in the US. UU. It generally adopts these stages as a good practice to demonstrate compliance with the requirements of CGMPs.
- Emphasis on critical quality attributes and critical parameters of the process: The FDA guide on processes validation focuses on the identification and control of the critical quality attributes (CQAS) and the critical parameters of the process (CPPS).
In summary:
- There is one High convergence in the fundamental principles of qualification and validation between these three regulatory frameworks. All seek to ensure that the facilities and equipment are adequate and work reliably.
- He Annex 15 It provides the most detailed and structured guide on the qualification stages (DQ, IQ, OQ, PQ) for the manufacture of medications.
- The I, although it does not formally define the stages of qualification, the underlying principles are consistent. It offers more flexibility in its application.
- The FDA regulations They establish general requirements and the industry often adopts the stages of qualification as a way to meet these requirements. The FDA guide on processes validation has a life cycle approach similar to Annex 15.
It is important to keep in mind that, although there are equivalences, The specific requirements of the regulatory authority corresponding to the market where the product will be marketed must always be met. In a global environment, many pharmaceutical companies seek to implement qualification and validation systems that meet the requirements of multiple authorities to facilitate access to different markets.