Cleaning Validation
| Glossary of Terms | ||
| 1 | Acceptable daily intake | An amount of a substance administered or consumed on a daily basis that will not produce a pharmacological or toxic response |
| 2 | Analyte | Substance for which an analysis is being performed |
| 3 | API | Active pharmaceutical ingredient |
| 4 | Automated cleaning | A cleaning procedure which relies on a sequence of programmed, reproducible steps (usually via mechanical and/or electronic devices) |
| 5 | Batch production | A series of unit operations performed according to a single manufacturing order during the same cycle of manufacture to produce a specific quantity of a drug having uniform character and quality within specified limits |
| 6 | Blank | Analytical method control sample used to establish a baseline for the result, e.g., as in a titration where one or two drops of the titrant must be added to the blank to cause an indicator color change |
| 7 | Bulk pharmaceutical | Generally known as bulk pharmaceutical chemicals; also called primary pharmaceuticals or active pharmaceutical ingredients |
| 8 | Campaign | Processing of more than one product in the same facility and/or equipment in a sequential manner; only one product is present in any one manufacturing area of the facility at a time |
| 9 | CGMP | Current Good Manufacturing Practices |
| 10 | Change control | A documented system for reviewing proposed or actual changes that might affect a validated system or process; change control includes the determination of any corrective action required to ensure that the system remains in a validated state |
| 11 | Change-over | Actions required for switching multi-product equipment and facilities from one product to another |
| 12 | Clean (v.) | The implementation of procedures to render a piece of equipment, or a system, free of adulterants and contaminants |
| 13. | Clean (v.) | Visually clean – absence of materials which would adulterate a product when inspected with the eyes |
| Detectably clean – absence of materials which would adulterate a product down to the level of detection | ||
| Chemically clean – absence of all chemicals which would adulterate a product | ||
| 14. | Clean-in-place (CIP) | Cleaning without the need to disassemble equipment (may be either automatic or manual) |
| 15. | CIP system | A system, usually automatic, used to clean equipment in place |
| 16. | Clean-out-of-place (COP) |
the cleaning performed, usually manually, after disassembly of equipment or a system |
| 17. | COP system | A system which may be automatic, semi-automatic or manual, used to clean equipment out of place, e.g., a parts washer |
| 18. | Cleaning agent | Usually a detergent or surfactant that reduces the surface tension of a solvent to increase its effectiveness |
| 19. | Cleaning validation | Demonstrating that cleaning results are consistent and reproducible, usually by sampling critical and representative sites on the equipment after cleaning |
| 20. | Contaminant | Extraneous substance that exists in a product |
| 21. | Continuous process | A series of operations performed according to a manufacturing order so as to provide a steady stream of a drug having uniform character and quality within specified limits |
| 22. | Control parameters | those operating variables that can be assigned values that are used to regulate a process |
| 23. | Coverage | The exposure of equipment surface area to the cleaning process |
| 24. | Critical site | area of a piece of equipment on which residual materials are trapped or concentrated (e.g., because of location, surface or equipment design) and which is likely to contribute all of the contamination to a single dose (i.e., “hot spot”) |
| 25. | Dead leg | A pipe with restricted flow or agitation exceeding the length of six pipe diameters |
| 26. | Dedicated equipment | Equipment that is to be utilized for a single product or product family |
| 27. | Degradation | Breakdown of material during manufacture or after exposure to the cleaning process |
| 28. | depyrogenation | removal or destruction of pyrogens |
| 29. | Detergent | A synthetic wetting agent and emulsifier that can be added to a solvent to improve its cleaning efficiency |
| 30. | Disinfection | To adequately treat equipment, containers, or utensils by a process that is effective in destroying vegetative cells of microorganisms of public health significance, and in substantially reducing numbers of other undesirable microorganisms |
| 31. | Endotoxin | lipopolysaccharide, usually from gram negative bacteria |
| 32. | Equipment grouping | Equipment closely related by design, as to be considered the same for the purposes of cleaning |
| 33. | Equipment train | The sequence of equipment through which a product is produced or processed |
| 34. | Final rinse | The last rinse of a piece of equipment during the cleaning procedure |
| 35. | Impingement | To cause to strike |
| 36. | Impurity | Any extraneous substance or contaminant present in the drug substance or drug product |
| 37. | LD50 | The dose resulting in a fifty percent mortality of the test animal |
| 38. | Largest daily dose | Maximum daily dose of the next product to be produced in the equipment train |
| 39. | Limit | A prescribed maximum and/or minimum tolerance |
| 40. | Limit of detection | The lowest concentration of analyte in a sample that can be detected, but not necessarily quantitated, under the stated experimental conditions |
| 41. | Limit of quantitation | The lowest concentration of analyte in a sample that can be determined with acceptable precision and accuracy under the stated experimental conditions |
| 42. | Major equipment | Any process equipment which is uniquely identified within the drug product batch record (e.g., autoclave, batch tank, blender, encapsulator, filler, tablet press) |
| 43. | Manual cleaning | A cleaning procedure requiring operator performed critical steps (e.g., scrubbing with a brush or rinsing with a hose) |
| 44. | Maximum allowable carryover |
The maximum amount of carryover from one product to the next that will not produce a therapeutic dose, corrected for a safety factor (e.g., 1/1000) |
| 45. | Minimum pharmacological dose |
The minimum dose required to elicit a response in vitro or in vivo |
| 46. | Minimum therapeutic dose |
The minimum dose that will produce a pharmacological response as derived by medical criteria |
| 47. | Minor equipment | Ancillary equipment (e.g., dispensing containers, utensils, scoops) associated with a drug product manufacturing process |
| 48. | Peptizing | To bring into colloidal solution, esp. proteins |
| 49. | Placebo | Inert material or formulation |
| 50. | Placebo scrubbing (or solid washing) | Use of an inert material to mechanically displace and dilute residuals |
| 51. | Process validation | Establishing 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 attributes |
| 52. | Product family | A group of closely formulated products with the same active ingredient(s) |
| 53. | Prospective | Establishing documented evidence that a system validation does what it is supposed to do, based on information generated before actual implementation of the process |
| 54. | Protocol | A document with agreed upon set of standards and tests |
| 55. | Prototyping | Use of a representative drug product and/or piece of equipment to demonstrate a cleaning procedure can achieve adequate levels of cleanliness for similar product and/or equipment families |
| 56. | pyrogen | A material which elicits a pyrogenic response (fever) |
| 57. | Rinse (aqueous/ nonaqueous) | To cleanse or treat an equipment as part of a cleaning procedure |
| 58. | Safety factor | A predetermined value (e.g., 1/1000) used to minimize the uncertainty of a calculated limit |
| 59. | Sanitize | To make physically clean and to remove and destroy, to the maximum degree that is practical, agents injurious to health |
| 60. | Semi-automated | A system controlled partly by mechanical/electronic devices, but requiring some manual intervention |
| 61. | Serial cleaning | Cleaning performed in the midst of a production campaign; serial cleaning is usually less intensive than the procedure used between different products |
| 62. | Swab | An absorptive device used to remove a sample from a surface |
| 63. | Therapeutic dose | An amount of drug that will produce a pharmacological response |
| 64. | Toxic dose | The minimum dose required to produce a harmful, poisonous effect |
| 65. | Visually clean | Absence of visible contaminants |
| 66. | Worst case | The highest or lowest value of a given control parameter, maximum system load, or maximum or minimum environmental conditions actually evaluated in a validation exercise |
Reference: PDA Technical Report No. 29
