5.2 - Quality Management Guidance
Product Quality Complaint Handling
This Complaint Handling guidance defines practices for establishing and maintaining a product quality complaint handling system, and for monitoring and reporting corrective actions based on the findings
Application of Quality Risk Management to Periodic Review of SOPs
Application of Quality Risk Management to Periodic Review of SOPs is intended to provide a tool for determining the optimal review frequency that will ensure those SOPs which relate to GMP systems or processes and therefore bear the greatest potential for impact on product quality are reviewed/revised in a timely and possibly more frequent manner than those which are determined to be less critical or reflect stable processes.
Statistical Rationale for Raw Material Sampling
The practice of using the √N+1 as a rule for sample size is common in the pharmaceutical industry.
Quality Risk Management Application Critical Instrument Calibration
This document offers a risk assessment approach to document a critical instrument calibration interval change request.
Structured On-the-Job Training System
This document discusses considerations for a site Structured On-the-Job Training system including GMP tasks and knowledge necessary to perform those tasks.
Training system for Aseptic Operators and Support Staff
This document discusses considerations for a robust training system for those working in or in support of a preparation for aseptic processing area.
Disposal of Rejected and Waste Materials
This document provides guidance for the handling, collecting and disposing of waste materials.
Quality Assurance Self-Appraisals
This document provides guidance in the conduct of Quality Assurance Audits to verify and assure the effectiveness of on-going quality systems, practices and programs and to identify potential procedural gaps or system weaknesses at Manufacturing Production and logistic Sites.
Material Status Indication
This document provides guidance on status control of the following materials: Raw Materials (RM); Starting Materials; Packaging Materials including labeling; In-Process Materials; Drug Products; Intermediates; Medical Devices; Components; Active Pharmaceutical Ingredients (API); Returned Goods, including Recalled product; Materials determined to be Acceptable for Rework/Reclaim; Rejected Materials; and Materials with Direct or Potential Indirect Product Contact, including cleaning materials and other items.
Annual Product Records Review
This document provides guidance in the performance of annual product record reviews to evaluate data and trending to: Verify consistency of the process; Identify the need to modify specifications, and Identify any preventive or corrective actions that would lead to product quality improvements.
Receipt, Approval and Use of Labels and Labeling
This document provides guidance on the printing, receipt, storage, use and reconciliation of product labels and labeling for active pharmaceutical ingredients (API), medical devices, and drug products.
Weighing and Measuring Practices In Manufacturing Operations
This document provides guidance in the weighing and measuring of materials used in the manufacture of drug products, active pharmaceutical ingredients (API), medical devices, and intermediates.
Material Supplier Approval
This document provides guidance in the process for identifying suppliers to be audited and the process for conducting and documenting such audits and approving suppliers.
Storage & Distribution of Drug Products, Medical Devices and Related Materials
This document provides guidance the storage and distribution requirements for Drug Products, Medical Devices and related Production Materials from a GMP Site or Logistics Centers, and/or transported between manufacturing and Logistic Sites.
Control of Manufacturing and Packaging Defects Non Sterile
This document provides guidance on the inspection of non-sterile drug products and non-sterile medical devices for manufacturing and packaging defects.
This document provides guidance in the implementation and maintenance of pest control program for buildings and facilities at a GMP Site and Logistics Centers that are used for production, testing, or storage of pharmaceutical ingredients.
Raw Materials and Packaging Materials Receipt
This document provides guidance for receipt and storage of raw materials (RM), components, and packaging materials used in the manufacture and packaging of active pharmaceutical ingredients (API), drug products, and medical devices.
Sampling of Production Materials and Finished Goods
This document provides guidance for a sampling program for Raw Materials (RM), Starting Materials, Packaging Materials, Labeling, In-Process Materials, Intermediates, Active Pharmaceutical Ingredients (API), Drug Products, Biologics, Medical Devices, Medical Device Components and Materials with Direct or Potential Product Contact.
Water Purification, Storage and Distribution For Pharmaceutical Production
This document provides guidance for the purification, storage and distribution of water used for Production including water used for cleaning of product contact equipment, containers, and closures.
Use of a Risk-Based Approach To Establish External Quality Assurance Audit Frequency
The purpose of this document is to provide guidance for GMP Quality Audits stakeholder’s responsibility to utilize a risk-based approach for determining External Quality Assurance Audit prioritization and frequencies.
Reduced Testing Program
This guidance document defines a science and risk-based approach for the evaluation and implementation of a reduced testing program for the release of starting materials, intermediates, APIs, excipients and packaging components at a GMP user site upon receipt from vendors (manufacturer/supplier).
GMP Training System
This document discusses considerations for site GMP Training systems including training on regulations, GMP concepts, GMP tasks and knowledge necessary to perform those tasks.
This document provides guidance for the stability testing for drug products, consumer non-drug products (e.g., cosmetics), Active Pharmaceutical Ingredients (API), API Intermediates for Sale and medical devices manufactured at GMP facilities.
Quality Risk Management Application to Identify Deviations vs. Events
Often times, deviations that occur during the handling, manufacturing, testing or distribution of materials/products have little or no impact on product quality or to its registration filing. The purpose of this guidance is to provide a process for assessing if a deviation does or does not impact the product quality or its filing through the use of a Quality Risk management tool.
Implementation of Real Time Release
This document provides practical guidance on how to implement a Real Time Release (RTR) testing approach as part of a manufacturing control strategy to ensure product quality while enabling the rapid release of API, intermediate and/or finished products.
This document provides guidance in for Preventive Maintenance of direct impact systems and associated critical components used in production, storage, and testing that may affect the safety, identity, strength, quality, or purity of active pharmaceutical ingredients, drug products, drug product raw materials, API starting materials, critical in-process materials, critical intermediates, biologics, or medical devices.
This document provides guidance for the calibration of equipment, instruments, and standards used in production, storage and testing that may affect the identity, strength, quality or purity of Pharmaceutical drug products, active pharmaceutical ingredients and medical devices.
Evaluation Process Supporting Elimination of Defined Shipment Temperature Range
This document provides the scientific and risk management assessment process to support the evaluation and, where appropriate, discontinuation of solid oral dosage form shipment under defined temperature range conditions, dependent upon the results of individual product analyses.
Determining Testing Patterns and Acceptance Criteria for Analytical Method Transfers
This document provides guidance for setting experimental testing patterns and acceptance criteria for Analytical Method Transfer Exercises. This document provides guidance to GLP sites in identifying lots and number of samples for testing, setting appropriate acceptance criteria for conducting transfers.
Quality Risk Management to Establishment of Weighing Device Performance Testing Intervals
Application of Quality Risk Management to performance checks for weighing devices such as balances and scales is intended to provide a tool for determining the acceptability of decreasing the frequency of verifying the performance of a weighing device from the current frequency (e.g. daily) to an alternative schedule.
Analytical Laboratory Management
This document provides guidance for the management of analytical laboratories including the following: Personnel training; Proper handling of samples; Hazardous materials; Control and maintenance of reagents, reference standards, and buffers; Laboratory facilities and equipment; and Documentation and control of test results.
Microbiology Laboratory Management
This document provides guidance for the management of microbiology laboratories including the following Proper handling of samples; Control and maintenance of reagents, reference standards, buffers, microbial cultures, and microbiological culture media; Monitoring and control of the microbiology laboratory environment; Calibration and maintenance of laboratory equipment; and Documentation and control of microbiological test results.
Transfer of Analytical Methods
This document provides guidance for establishing a documented process for the transfer of analytical methods, microbiological and/or bioanalytical methods.
Quality Agreement – a document between buyer site and a contractor or supplier of material which defines the roles and responsibilities for Quality related functions of the two partiesThis document provides general guidance to site Quality Teams responsible for writing, revision and maintenance of Quality Agreements with suppliers of materials.
This document provides guidance in the validation of systems (facilities, utilities, and equipment, including process control systems, and information systems), that support regulatory compliance – practices, validated processes and/or systems used in the production or storage and distribution of Active Pharmaceutical Ingredients (API), intermediates (subsequent to the introduction of the API starting materials), drug products, medical devices or biologics.
This document provides guidance in the installation, use and maintenance of metal detectors in Pharmaceutical and Animal Health solid oral dosage form drug products and medical devices that by design do not contain metal components.
What minimum standards should be considered by an API manufacturing site for the storage, handling and cleaning of hoses used during cleaning or production of Intermediates or final Active Pharmaceutical Ingredients (APIs)?
Use of Process Analytical Technology in Process Validation
This document provides examples of the possible use of Process Analytical Technology (PAT) systems during traditional process validation to demonstrate that a manufacturing process is in a validated state. This guidance is supplemental to guidance ‘Process Validation for Drug Products and Medical Devices’ and ‘Process Validation for Active Pharmaceutical Ingredients (API)’.
Implementation of Process Analytical Technology
The extent of verification testing (incorporating commissioning and qualification), method validation and approach to deviation investigation will depend on the
outcome of the risk assessment and should be commensurate with the risk associated with the both the use of the PAT application and the data generated as result of application use.
Validation of Process Analytical Technology System
This document provides guidance for validation of PAT systems to assure compliance for PAT applications which can be implemented at a GMP site. The scope of this guidance includes PAT systems used in both Drug Product and Active Pharmaceutical Ingredient (API) manufacturing.
5.3 - Aseptic Processing Area Guidance
Alternatives to Formaldehyde Fogging of Clean Rooms
Alternatives to formaldehyde fogging include the use of liquid sanitizers or fogging with an alternate chemical sterilant such as chlorine dioxide, vapor-phase hydrogen peroxide, or atomized peroxyacetic acid-hydrogen peroxide. For biological facilities where viral contamination is a concern, it may be a regulatory expectation to decontaminate via fogging with some frequency.
Clean Steam Systems
This document provides guidance for clean steam used in aseptic applications, and applications where the steam or condensate directly contacts products or materials, or direct product contact surfaces (i.e., equipment, containers, closures).
Cleaning and Sterilization of Aseptic Manufacturing Equipment
This document provides guidance in the cleaning and sterilization of aseptic manufacturing equipment to minimize the risk of particulate and microbiological contamination.
Container Closure Integrity for Sterile Drug Products
This document provides guidance for ensuring that the integrity of the container closure system will protect the product over its shelf life.
Controlling the Microbiological Quality of Solid Oral Dosage Forms
To control the microbial quality of a non-sterile Solid Oral Dosage form, it is recommended to perform a risk assessment of the manufacturing process to identify potential sources of microbial contamination. The intention of this document is to provide guidance to determine and control these sources of microbial contamination.
Defining Worst Case Conditions for Aseptic Process Simulations
Aseptic process simulation tests (e.g. media fills) “are used extensively and are recognized as an effective way to validate aseptic filling” processes for the purpose of complying with regulatory GMP expectations. A media fill begins at the point where the final sterilization of the product takes place (i.e. where aseptic operations are performed) through the completion of filling operations with the sealing of the filled containers.
Explanation of Repeat Testing and Retesting Utilized During Microbiological OOS Investigations
During a laboratory investigation, confusion may arise as to the difference between these terms and their overall purpose. This document provides a more detailed explanation of these differences and the individual importance of these tools during a microbiological OOS laboratory investigation.
Gamma Radiation Sterilization
This document provides guidance for validation of gamma radiation sterilization processes used to sterilize active pharmaceutical ingredients, drug products, medical devices and non-product items, such as, APA gowning articles, containers, and closures with direct or potential contact with sterile raw materials, APIs, drug products or medical devices.
This document provides guidance for design, operation, and commissioning or qualification of lyophilizers and the validation of lyophilization processes.
Lyophilizer Loading and Unloading Recommendations
This guidance should address questions raised by lyophilization (freeze drying) facilities involving in using of automated loading and unloading systems for new lyophilizer installations. The options described in this guidance assume the use of such an automated system.
Microbial Attributes Testing of Non-Sterile Solid Oral Dosage Forms and Materials
The intention of this document is to provide guidance to determine the need for performing microbial attributes testing of drug product raw materials, non-sterile excipients, active pharmaceutical ingredients (APIs), and finished drug products. This guidance is recommended in order to ensure the microbiological quality of any non-sterile solid oral dosage form.
Microbiological Testing in Cleaning Validation for APIs and Drug Products
This document describes the rationale and recommended microbiological methodology for consideration during cleaning validation of product contact surfaces for Active Pharmaceutical Ingredients and drug products.
Overview of Trending of Environmental Monitoring Data for Aseptic Processing Areas
This guidance establishes the need for trending of environmental monitoring data and gives recommendations on aspects of trending such as categorization of data, frequency of trending, trend definition, and content of trend reports.
Packaging System Integrity for Sterile Medical Devices
This document provides guidance for determining the suitability of packaging materials and the evaluation and testing of the integrity of packaging systems for sterile Medical Devices manufactured and/or packaged by GMP sites.
Preventing Cross Contamination
This document provides guidance for the prevention of cross contamination in production processes, warehousing, material transfer, and distribution.
Prevention and Control of Fungal Contamination in Tablets
What steps can be taken to prevent and control of fungal contamination in tablets? The presence of water is the key element in the growth of fungal contamination. This document discusses the prevention and control of fungal contamination in tablets production to include: raw material and API testing, manufacturing processes, environmental monitoring, and final product testing.
Sanitant Rotation in a Routine Sanitization Program
What are the expectations for industry for the inclusion of different sanitization agents within a routine sanitization program? Additionally, are there tangible benefits to routinely rotating sanitization agents? Finally, how is sanitant performance defined?
Sterilization or Depyrogenation Validation - Non Product
This procedure provides guidance for validating sterilization and depyrogenation of equipment and containers and closures with direct or potential contact with sterile medical devices, sterile drug products or sterile active pharmaceutical ingredients.
Unplanned Cleanroom Power Outage Time Limit and Recovery Determinations for Aseptic Processing Areas
How can the time between a cleanroom power outage and loss of environmental control in the critical area be determined? Once the power is restored, how can the time it takes to recover the desired environmental conditions be determined? An interruption of power supply to the HVAC systems may produce a “loss of control” which can be defined as a breech in the integrity of the controlled areas in sterile manufacturing.
Use of Sterilized Goggles Within the Aseptic Processing Area
This document will discuss the requirement for goggle use within Aseptic Processing Areas (APA) as well as products and processes that are available to assist sites in complying with established requirements. Suggested elements of a sterile goggle program are also considered.
Water Activity - What Is It and How Does It Apply To Pharmaceutical Manufacturing
This document discusses the basic principles of water activity and the importance it has in the manufacture of pharmaceuticals. It also provides direction on when and where testing for water activity can be most beneficial.
Assessment of Shipping Processes for Drug Products
This document provides guidance on assessing the transportation of Drug Products (DP). It can be applied to assessment of shipping Bulk DP and finished commercially packaged DP (“finished product”) between any two locations – such as manufacturing sites, wholesale distribution centres, and receiving sites or – within the GMP sites distribution network.
Cold Chain Management of Biopharmaceutical Materials
The risk of compromising biopharmaceutical materials in internal shipping and external distribution is relatively high, as these materials are particularly vulnerable to degradation when exposed to various environmental and handling conditions. The risks can be managed effectively through qualification of transport packing systems, handling, and transport procedures. This guidance summarizes suggested considerations in the cold chain management (CCM) of biopharmaceuticals
Stability Considerations for Planned or Unplanned API Process Changes
This document outlines the considerations site quality organizations should review to assess whether stability data are needed to support planned or unplanned post-approval changes to API or API Intermediate for sale manufacturing processes. This document also recommends customer notification if subsequent intermediate processing or drug product quality may be impacted by the change.
Clean Process - External Vial Capping Operations
This guidance applies to capping operations performed as an aseptic process using sterilized caps or as a “clean process” that is performed outside the aseptic core using clean non-sterilized caps.
Use and Recovery of Solvents in API Manufacturing
This document provides guidance in offloading, use and recovery of solvents used in the commercial manufacture of Active Pharmaceutical Ingredients (API) and intermediates The processing and use of solvents should be established, controlled and monitored based on the potential impact on intermediate or final API product quality.