Radiopharmaceutical Production Quality Manual STOP

Quality Manual Contents Purpose of the Quality Manual Contents of the Quality Manual Relationship of the Quality Manual to the Validation Master Plan Examples of Quality Manuals A Quality Manual documents the policies, procedures, responsibilities, and documentation, that must be in place for the facility to comply with their regulatory responsibilities. STOP

Purpose of the Quality Manual The organization should establish and maintain a quality manual that includes the quality policy the scope of the quality management system, including details of and justification for any exclusions the documented procedures established for the quality management system, or reference to them, and a description of the interaction between the processes of the quality management system.

Contents of the Quality Manual A quality manual is a document that a facility writes to explain which regulations are applicable to the facility (i.e. which regulations will be followed by the facility.) The regulations that are to be followed are based on the process(es) that are performed at the facility. The facility’s Quality Manual should outline which regulations are going to be followed, how they are going to be followed, who is responsible for ensuring that the regulations are followed, and which of the companies approved procedures address the regulations to be followed. If all parts of a regulation are not going to be followed, a facility may want to include a brief explanation as to why a part of a regulation is not applicable to the facility and therefore will not be outlined in the Quality Manual. The Quality Manual should be written in general terms with minimal specifics. The format of a Quality Manual is usually different than the format used for the facility’s other approved documents. The format should still include such things as a facility’s name, version control, and approval signatures.

Contents of the Quality Manual The following are examples of sections that a Quality Manual should contain: Table of Contents Introduction Facility Background Purpose Scope Quality Policies and Objectives Organization and Structure of Documentation Facility’s Products References Quality Policies for Specific Regulation Elements Table of Contents: A list of the sections contained within the Quality Manuel and the page each section begins on. Introduction: A brief description of the facility, the facility’s purpose for writing a Quality Manual, and a brief description of the scope of the Quality Manual.

Contents of the Quality Manual Background: List the name of the facility, where the facility is located, what radiopharmaceutical products are produced at the facility, and how these will be distributed. Purpose: Provide general statements explaining why and how the Quality Manual will be used. Example: “This Quality Manual describes the quality management system that has been established by facility X in order to meet regulatory requirements for the production of PET radiopharmaceuticals in the United State.” Scope: List the regulations that will be followed by the facility as well as any portions of the regulations that will not be followed. Provide a justification for why those portions of the regulations are not going to be followed. Example: “The system described in this manual is intended to meet general requirements set forth in the United States Food and Drug Administration (FDA) Regulation according to 21CFR Part 210, 21CFR Part 211 and 21CFR Part 212 as well as the relevant section of 21CFR Part 823.”

Contents of the Quality Manual Quality Policies and Objectives: Include a brief statement about the approach that the facility is taking in regards to quality, (i.e. a Quality Mission Statement) and list the quality objectives of the facility. The quality objectives should not be numerous (five to seven is a typical number) and should be briefly stated. Example: Customer issues are addressed in a timely, professional, and thorough manner. Example: Personnel are adequately trained in the job they perform Example: Products and Services provided by our facility are designed, manufactured, and delivered to our customers and meet or exceed our customer requirements. Organization and Structure of Documentation: Provide an explanation as to how the documentation structure at your facility is organized and managed in relation to the applicable regulations. Example: Documents related to the quality system are organized in a hierarchy structure, are maintained in accordance with applicable regulatory requirements and our facility record retention policy, and are managed through a document change control system.

Contents of the Quality Manual Products: This section should include a brief description of the products that are made and distributed by the facility including what the intended use of the products is to be. This description should be similar to a marketing type summary in that it does not list proprietary or explicit product information that would be detrimental to the facility if persons outside the facility read the description. This section should provide enough detail to justify the sections of the regulations that are and are not going to be followed. References: A list of all the different regulations that were sited within the Quality Manual. Example: FDA Title 21, Code of Federal Regulations Part 210 & 211, Current Good Manufacturing Practice in Manufacturing, Processing, Packing, or Holding of Drugs and Finished Pharmaceuticals, FDA Title 21, Code of Federal Regulations Part 212 PET Drugs — Current Good Manufacturing Practice (cGMP),

Contents of the Quality Manual Quality Policies for Specific Regulation Elements: This section will encompass the majority of the manual. It will include each regulation that will be followed by the facility, a brief description of how the facility intends to follow the regulation, and a list of the approved documents (by document name and number) that the facility has in place which specifically address/discuss the facility’s policies and objectives as stated in this section of the Quality Manual. Example: Purchasing Controls; Procedures are established and maintained to ensure that materials, supplies, and services impacting the Quality System and procured by facility X purchasing department, conform to specified requirements. Receiving Procedure SOP # XX. 01 Vendor Qualification Procedure SOP # XX. 01 Release of In-coming Goods Procedure SOP # XX. 01 ...... Example: Corrective and Preventive Action; At facility X, Corrective and Preventive Actions are integral in a variety of programs. Whenever possible, these programs make an effort to determine the root cause of the incident and to implement appropriate actions to prevent the reoccurrence of the incident. Quality Assurance approves all Corrective and Preventive plans and tracks their completion and effectiveness. CAPA Procedure SOP # XX. 01 Material Review Board SOP # XX. 01 Failure Investigation Procedure SOP # XX. 01 .......

Contents of the Quality Manual Topics that should be covered in the final section on Quality Policies for Specific Regulation Elements Deviations and Events Event Recording Reviews and Investigations Remediation Change Control Change Initiation and Approval Change Execution and Tracking Change Verification and Closure Audit Management Planning Execution Review and Remediation Document Management Storing and Classification Access and Viewing Creating New Documents Lifecycle Managements Printing Training Management Employee Course Management Training Request and Approval Gap Management and Records Equipment Management Inventory Management Preventative Maintenance Remedial Maintenance

Contents of the Quality Manual Topics that should be covered in the final section on Quality Policies for Specific Regulation Elements General Requirements Security and Access Control Facility Management Corrective Action Preventive Action (CAPA) CAPA Initiation Investigations and Action Plan CAPA Closure Validation Documentation Structure and Formats Change Control Planning and Scheduling Roles and Responsibilities Regulatory Requirements for Testing A list of SOPs, Forms, Validation Documentation and other appendicies

Relationship of the Quality Manual to the Validation Master Plan Quality Manual: The quality manual is a document that a facility writes to explain which portions of which regulations are applicable to the facility and which documents the policies, procedures, responsibilities, and documentation, that must be in place for the facility to comply with these regulatory responsibilities Validation Master Plan: The Validation Master Plan is a summary plan which communicates management’s expectations and commitments to be followed for the sites validation program including the responsibilities and is therefore a key document at a site. It describes the program to be conducted to get the items in question in a validated manner. The plan lists all of the validation activities to be completed, as well as the schedule for their completion. The term validation is used to demonstrate with written evidence that the item under consideration, e.g. process does what it purports to do. Validation includes but is not limited to: equipment, computer systems, production processes, cleaning procedures, facilities, utilities as well as analytical methods.

Example of a Quality Manual One approach to the Quality Manual is to delineate the quality policies for specific regulation elements by making a flow chart of every process and then assigning the SOP or other document which addresses that process to ensure that everything is covered with an SOP. An example of this is shown on the next slide. Note that each process or activity has an SOP number or document associated with it. The SOP numbers starting with A are the administrative SOPs while those starting with Q are the quality assurance SOPs.

Example of a Quality Manual

Example of a Quality Manual Another example of a Quality Manual with less detail but covering the major elements can be found by following the arrow. More Quality Manual Example

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