104 Definitions

Annual Review – An evaluation, conducted at least annually, that assesses the quality standards of each drug product to determine the need for changes in drug product specifications or manufacturing or control procedures CAPA – Corrective and preventive action: A systematic approach that includes actions needed to correct (“correction”), prevent recurrence (“corrective action”), and eliminate the cause of potential nonconforming product and other quality problems (preventive action) (21CFR 820.100) Continual Improvement – Ongoing activities to evaluate and positively change products, processes, and the quality system to increase effectiveness Correction – Repair, rework, or adjustment relating to the disposition of an existing discrepancy Corrective Action – Action taken to eliminate the causes of an existing discrepancy or other undesirable situation to prevent recurrence Customer – A person or organization (internal or external) that receives a product or service anywhere along the product’s life cycle Discrepancy – Datum or result outside of the expected range; an unfulfilled requirement; may be called non-conformity, defect, deviation, out-of-specification, out-of-limit, out-of-trend Harm – Damage to health, including the damage that can occur from the loss of product quality or availability Non-conformity – A deficiency in a characteristic, product specification, process parameter, record, or procedure that renders the quality of a product unacceptable, indeterminate, or not according to specified requirements Preventive Action – Action taken to eliminate the cause of a potential discrepancy or other undesirable situation to prevent such an occurrence Product/Service – The intended results of activities or processes; products/services can be tangible or intangible Quality – A measure of a product or service’s ability to satisfy the customer’s stated or implied needs Quality Assurance – Proactive and retrospective activities that provide confidence that requirements are fulfilled Quality Control – The steps taken during the generation of a product or service to ensure that it meets requirements and that the product or service is reproducible Quality Management – Accountability for the successful implementation of the quality system Quality Objectives – Specific measurable activities or processes to meet the intentions and directions as defined in the quality policy Quality Plan – The documented result of quality planning that is disseminated to all relevant levels of the organization

www.pharmatechbd.blogspot.com

http://www.pharmatechbd.blogspot.com

almamun

Highlight

Quality Planning – A management activity that sets quality objectives and defines the operational and/or quality system processes and the resources needed to fulfill the objectives Quality Policy – A statement of intentions and direction issued by the highest level of the organization related to satisfying customer needs. It is similar to a strategic direction that communicates quality expectations that the organization is striving to achieve. Quality System – Formalized business practices that define management responsibilities for organizational structure, processes, procedures, and resources needed to fulfill product/service requirements, customer satisfaction, and continual improvement Quality Unit – A group organized within an organization to promote quality in general practice Risk – The combination of the probability of occurrence of harm and the severity of that harm Risk Assessment – A systematic process for organizing information to support a risk decision that is made within a risk management process. The process consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards. Risk Management – The systematic application of quality management policies, procedures, and practices to the tasks of assessing, controlling, communicating, and reviewing risk Senior Management – Top management officials in a firm who have the authority and responsibility to mobilize resources Stakeholder – An individual or organization having an ownership or interest in the delivery, results, and metrics of the quality system framework or business process improvements Verification – Confirmation, through the provision of objective evidence, that specified requirements have been fulfilled. (Reference: The ASQ Auditing Handbook, 3rd edition, ASQ Quality Audit Division, J.P. Russell, and Editor) Validation – Validation is a documented evidence which provides a high degree of assurance that a specific process, method or system will consistently produce to the required specification in accordance with accepted standards of cGMP. Active pharmaceutical ingredient (API) - Any substance or mixture of substances intended to be used in the manufacture of a pharmaceutical dosage form and that, when used in the production of a drug, becomes an active ingredient of that drug. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease, or to affect the structure and function of the body. Contamination - The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into or onto a starting material, or intermediate or finished product during production, sampling, packaging or repackaging, storage or transport. Cross-contamination - Contamination of a starting material, intermediate product or finished product with another starting material or product during production. Excipient- A substance, other than the active ingredient, which has been appropriately evaluated for safety and is included in a drug delivery system to: — aid in the processing of the drug delivery system during its manufacture; — protect, support or enhance stability, bioavailability, or patient acceptability;



— assist in product identification; or — enhance any other attribute of the overall safety and effectiveness of the drug during storage or use. Expiry date - The date given on the individual container (usually on the label) of a drug product up to and including which the product is expected to remain within specifications, if stored correctly. It is established for each batch by adding the shelf-life to the date of manufacture. Labelling - The action involving the selection of the correct label, with the required information, followed by line clearance and application of the label. Manufacture - All operations of purchase of materials and products, production, quality control, release, storage and distribution of finished products, and the related controls. Material - A general term used to denote starting materials (active pharmaceutical ingredients and excipients), reagents, solvents, process aids, intermediates, packaging materials and labelling materials. Packaging material - Any material, including printed material, employed in the packaging of a pharmaceutical product, but excluding any outer packaging used for transportation or shipment. Packaging materials are referred to as primary or secondary according to whether or not they are intended to be in direct contact with the product. Pharmaceutical product - Any medicine intended for human use or veterinary product administered to food-producing animals, presented in its finished dosage form or as a starting material for use in such a dosage form, that is subject to control by pharmaceutical legislation in both the exporting state and the importing state. Production - All operations involved in the preparation of a pharmaceutical product, from receipt of materials, through processing, packaging and repackaging, labelling and relabelling, to completion of the finished product. Retest date - The date when a material should be re-examined to ensure that it is still suitable for use. Storage - The storing of pharmaceutical products and materials up to their point of use. Supplier - A person providing pharmaceutical products and materials on request. Suppliers may be agents, brokers, distributors, manufacturers or traders. Where possible, suppliers should be authorized by a competent authority. Calibration (old) The performance of tests and retests to ensure that measuring equipment (e.g. for temperature, weight, pH) used in a manufacturing process or analytical procedure (in production or quality control) gives measurements that are correct within established limits. Calibration (new) The set of operations that establish, under specified conditions, the relationship between values indicated by an instrument or system for measuring (especially weighing), recording, and controlling, or the values represented by a material measure, and the corresponding known values of a reference standard. Limits for acceptance of the results of measuring should be established. Computer validation



Documented evidence, which provides a high degree of assurance that a computerized system records data correctly and that data processing complies with, predetermined specifications. Concurrent validation Validation carried out during routine production of products intended for sale. Cleaning validation Documented evidence to ensure that cleaning procedures are removing residues to predetermined levels of acceptability, taking into consideration i.e. batch size, dosing, toxicology, equipment size, etc. Design Qualification (DQ) Documented evidence that the premises, supporting utilities, equipment and processes have been designed in accordance with the requirements of GMP. Good Engineering Practices Established engineering methods and standards that are applied throughout the project lifecycle to deliver appropriate, cost-effective solutions. Installation Qualification (IQ)(old) IQ is the documentary evidence to verify that the equipment has been built and installed in compliance with design specifications. Installation Qualification (IQ)(new) The performance of tests to ensure that the installations (such as machines, measuring devices, utilities, manufacturing areas) used in a manufacturing process are appropriately selected and correctly installed and operate in accordance with established specifications. Working document QAS/03.055/Rev.2 Operational Qualification (OQ)(old) OQ is the documentary evidence to verify that the equipment operates in accordance with its design specifications in its normal operating range and performs as intended throughout all anticipated operating ranges. Operational Qualification (OQ)(new) Documented verification that the system or subsystem performs as intended over all anticipated operating ranges. Performance Qualification (PQ) PQ is the documentary evidence, which verifies that the equipment or system operates consistently and gives reproducibility within defined specifications and parameters for prolonged periods. (The term “process validation” may also be used.) Process validation (See Validation) Documented evidence, which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality characteristics. Prospective validation Validation carried out during the development stage by means of a risk analysis of the production process, which is broken down into individual steps; these are then evaluated on the basis of past experience to determine whether they may lead to critical situations. Qualification (new)



Action of proving and documenting that any premises, systems and equipment are properly installed, and/or work correctly and lead to the expected results. Qualification is often a part (Initial stage) of Validation, but the individual qualification steps alone do not constitute process validation. Retrospective validation Involves the examination of past experience of production on the assumption that composition, procedures, and equipment remain unchanged. Revalidation (old) Involves the repeat of the initial process validation to provide assurance that changes in the process and/or in the process environment, whether intentional or unintentional, do not adversely affect process characteristics and product quality. Revalidation (new) Repeated validation of an approved process (or a part thereof) to ensure continued compliance with established requirements. Standard operating procedure (SOP) An authorized written procedure giving instructions for performing operations not necessarily specific to a given product or material but of a more general nature [new] (e.g. equipment Working document QAS/03.055/Rev.2 operation, maintenance and cleaning; validation; cleaning of premises and environmental control; sampling and inspection). Certain SOPs may be used to supplement product-specific master and batch production documentation. Validation (new) Validation is a documented evidence which provides a high degree of assurance that a specific process, method or system will consistently produce to the required specification in accordance with accepted standards of cGMP. Validation Protocol (VP)(old) The VP is a written plan stating how validation will be conducted, including test parameters, product characteristics, production equipment and decision points on what constitutes acceptable test results. Validation Protocol (or plan) (VP)(new) A document describing the activities to be performed in a validation, including the acceptance criteria for the approval of a manufacturing process - or a part thereof - for routine use. Validation Report (VR)(old) The VR is a written report on the validation activities, the validation data and the conclusions drawn. Validation Report (VR)(new) A document in which the records, results and evaluation of a completed validation programmed is assembled. It may also contain proposals for the improvement of processes and/or equipment. Validation Master Plan (VMP) VMP is a high level document that establishes an umbrella validation plan for the entire project and summarizes the manufacturer’s overall philosophy and approach, to be used for establishing performance adequacy. It provides information on the manufacturer’s validation work programmed and defines details of and time-scales for the validation work to be performed, including stating the responsibilities relating to the plan. www.pharmatechbd.blogspot.com


Verification The application of methods, procedures, tests and other evaluations, in addition to monitoring, to determine compliance with the GMP principles. Worst case A condition or set of conditions encompassing upper and lower processing limits and circumstances, within SOPs, which pose the greatest chance of product or process failure when compared to ideal conditions. Such conditions do not necessarily include product or process failure. Air lock- A small room with interlocked doors, constructed to maintain air pressure control between adjoining rooms (generally with different air cleanliness standards). The intent of an aseptic processing airlock is to preclude ingress of particulate matter and microorganism contamination from a lesser-controlled area. Alert Level- An established microbial or airborne particle level giving early warning of potential drift from normal operating conditions and triggers appropriate scrutiny and follow-up to address the potential problem. Alert levels are always lower than action levels. Action Level- An established microbial or airborne particle level that, when exceeded, should trigger appropriate investigation and corrective action based on the investigation. Aseptic Manufacturing Area- The classified part of a facility that includes the aseptic processing room and ancillary clean rooms. For purposes of this document, this term is synonymous with “aseptic processing facility” as used in the segregated segment context. Aseptic Processing Facility- A building, or segregated segment of it, containing clean rooms in which air supply, materials, and equipment are regulated to control microbial and particle contamination. Aseptic Processing Room- A room in which one or more aseptic activities or processes is performed. Asepsis- A state of control attained by using an aseptic work area and performing activities in a manner that precludes microbiological contamination of the exposed sterile product. Bioburden- The total number of microorganisms associated with a specific item prior to sterilization. Barrier- A physical partition that affords aseptic processing area (ISO 5) protection by partially separating it from the surrounding area. Biological Indicator (BI)- A population of microorganisms inoculated onto a suitable medium (e.g., solution, container or closure) and placed within appropriate sterilizer load locations to determine the sterilization cycle efficacy of a physical or chemical process. The challenge microorganism is selected based upon



its resistance to the given process. Incoming lot D-value and microbiological count define the quality of the BI. Clean Area- An area with defined particle and microbiological cleanliness standards. Clean room-

A room designed, maintained, and controlled to prevent particle and microbiological contamination of drug products. Such a room is assigned and reproducibly meets an appropriate air cleanliness classification. Component- Any ingredient intended for use in the manufacture of a drug product, including those that may not appear in the final drug product. Colony Forming Unit (CFU)- A microbiological term that describes the formation of a single macroscopic colony after the introduction of one or more microorganisms to microbiological growth media. One colony-forming unit is expressed as 1 CFU. Critical Area – An area designed to maintain sterility of sterile materials. Sterilized product, containers, closures, and equipment may be exposed in critical areas. Clean Zone- See Clean Area. Critical surfaces- Surfaces that may come into contact with or directly affect a sterilized product or its containers or closures. Critical surfaces are rendered sterile prior to the start of the manufacturing operation, and sterility is maintained throughout processing. Decontamination- A process that eliminates viable Bioburden via use of sporicidal chemical agents. Disinfection- Process by which surface Bioburden is reduced to a safe level or eliminated. Some Disinfection agents are effective only against vegetative microbes, while others possess additional capability to effectively kill bacterial and fungal spores. Depyrogenation- A process used to destroy or remove pyrogens (e.g., endotoxin). D value- The time (in minutes) of exposure at a given temperature that causes a one-log or 90 percent reduction in the population of a specific microorganism. Dynamic- Conditions relating to clean area classification under conditions of normal production. Endotoxin- A Pyrogenic product (e.g., lipopolysaccharide) present in the bacterial cell wall. Endotoxin can lead to reactions in patients receiving injections ranging from fever to death.



Gowning Qualification- A program that establishes, both initially and on a periodic basis, the capability of an individual to don the complete sterile gown in an aseptic manner. HEPA filter- High efficiency particulate air filters with minimum 0.3 µm particle retaining efficiency of 99.97 percent. HVAC- Heating, ventilation, and air conditioning. Intervention- An aseptic manipulation or activity that occurs at the critical area. Isolator- A decontaminated unit, supplied with Class 100 (ISO 5) or higher air quality, that provides uncompromised, continuous isolation of its interior from the external environment (e.g., surrounding cleanroom air and personnel). There are two major types of isolators: Closed isolator systems exclude external contamination from the isolator’s interior by accomplishing material transfer via aseptic connection to auxiliary equipment, rather than use of openings to the surrounding environment. Closed systems remain sealed throughout operations. Open isolator systems are designed to allow for the continuous or semi-continuous ingress and/or egress of materials during operations through one or more openings. Openings are engineered (e.g., using continuous overpressure) to exclude the entry of external contamination into the isolator. Laminar flow- An airflow moving in a single direction and in parallel layers at constant velocity from the beginning to the end of a straight-line vector. Operator- Any individual participating in the aseptic processing operation, including line set-up, filler, maintenance, or other personnel associated with aseptic line activities. Overkill sterilization process- A process that is sufficient to provide at least a 12 log reduction of microorganisms having a minimum D value of 1 minute. Pyrogens- A substance that induces a febrile reaction in a patient. Sterile Product- For purposes of this guidance, sterile product refers to one or more of the elements exposed to aseptic conditions and ultimately making up the sterile finished drug product. These elements include the containers, closures, and components of the finished drug product. Sterilizing grade filter- A filter that, when appropriately validated, will remove all microorganisms from a fluid stream, producing a sterile effluent. Quality Control Unit- An organizational element with authority and responsibility as defined by 211.22. Unidirectional flow- An airflow moving in a single direction, in a robust and uniform manner, and at sufficient speed to reproducibly sweep particles away from the critical processing or testing area. Terminal sterilization-



The application of a lethal agent to sealed, finished drug products for the purpose of achieving a predetermined sterility assurance level (SAL) of usually less than 10-6 (i.e., a probability of a no sterile unit of greater than one in a million). ULPA filter- Ultra-low penetration air filter with minimum 0.3 µm particle retaining efficiency of 99.999 percent. Validation- Establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes.

or Validation is a documented evidence which provides a high degree of assurance that a specific process, method or system will consistently produce to the required specification in accordance with accepted standards of cGMP.



Documents

104 Definitions