As you all know it is a systematic process of generation of documents and evidence that the pharmaceuticals manufactured by a particular process ,with use of particular machines , in particular facility adhere to the standards laid down by FDA’S around the world.
I will like to provide you all a very good guide lines on Validations in pharmaceuticals manufacturing, before i am giving some basic definitions pertaining to validation process in pharmaceuticals manufacturing , as well as information about different phases of validation,
so that you can easily and systematically refer or teach topic .
DefinitionsChange Control: A written procedure that describes the action to be taken if a change is proposed (a) to facilities, materials, equipment, and/or processes used in the fabrication, packaging, and testing of drugs, or (b) that may affect the operation of the quality or support system.
Cleaning Validation: The documented act of demonstrating that cleaning procedures for the equipment used in fabricating/packaging will reduce to an acceptable level all residues (products/cleaning agents) and to demonstrate that routine cleaning and storage of equipment does not allow microbial proliferation.
Concurrent Validation: A process where current production batches are used to monitor processing parameters. It gives assurance of the present batch being studied, and offers limited assurance regarding consistency of quality from batch to batch.
Critical Process Parameter: A parameter which if not controlled will contribute to the variability of the end product.
Equipment Qualification: Studies which establish with confidence that the process equipment and ancillary systems are capable of consistently operating within established limits and tolerances. The studies must include equipment specifications, installation qualification, and operational qualification of all major equipment to be used in the manufacture of commercial scale batches. Equipment Qualification should simulate actual production conditions, including “worst case”/ stressed conditions.
Installation Qualification: The documented act of demonstrating that process equipment and ancillary systems are appropriately selected and correctly installed.
Major Equipment: A piece of equipment which performs significant processing steps in the sequence of operations required for fabrication/packaging of drug products. Some examples of major equipment include tablet compression machines, mills, blenders, fluid bed dryers, heaters, drying ovens, tablet caters, encapsulators, fermentors, centrifuges, etc.
Master Production Document: A document that includes specifications for raw material, for packaging material and for packaged dosage form, master formula, sampling procedures, and critical processing related SOPs, whether or not these SOPs are specifically referenced in the master formula.
Measuring Devices: A device used in monitoring or measuring process parameters.
Operational Qualification: The documented action of demonstrating that process equipment and ancillary systems work correctly and operate consistently in accordance with established specifications.
Process Capability: Studies conducted to identify the critical process parameters that yield a resultant quality, and their acceptable specification ranges, based on the established +/- 3 sigma deviations of the process, under stressed conditions but when free of any assignable causes.
Process Qualification: The phase of validation dealing with sampling and testing at various stages of the manufacturing process to ensure that product specifications are met.
Process Re-validation: Required when there is a change in any of the critical process parameters, formulation, primary packaging components, raw material fabricators, major equipment or premises. Failure to meet product and process specifications in sequential batches would also require process re-validation.
Process Validation: Establishing documented evidence with a high degree of assurance, that a specific process will consistently produce a product meeting its predetermined specifications and quality characteristics. Process validation may take the form of Prospective, Concurrent or Retrospective Validation and Process Qualification or Re-validation.
Prospective Validation: Conducted prior to the distribution of either a new product or a product made under a modified production process, where the modifications are significant and may affect the product’s characteristics. It is a pre-planned scientific approach and includes the initial stages of formulation development, process development, setting of process specifications, developing in-process tests, sampling plans, designing of batch records, defining raw material specifications, completion of pilot runs, transfer of technology from scale-up batches to commercial size batches, listing major process equipment and environmental controls.
Retrospective Validation: Conducted for a product already being marketed, and is based on extensive data accumulated over several lots and over time. Retrospective Validation may be used for older products which were not validated by the fabricator at the time that they were first marketed, and which are now to be validated to conform to the requirements of Division 2, Part C of the Regulations to the Food and Drugs Act.
Validation (validation): The documented act of demonstrating that any procedure, process, and activity will consistently lead to the expected results. Includes the qualification of systems and equipment.
Validation Master Plan: An approved written plan of objectives and actions stating how and when a company will achieve compliance with the GMP requirements regarding validation.
Validation Protocol: A written plan of actions stating how process validation will be conducted; it will specify who will conduct the various tasks and define testing parameters; sampling plans, testing methods and specifications; will specify product characteristics, and equipment to be used. It must specify the minimum number of batches to be used for validation studies; it must specify the acceptance criteria and who will sign/approve/ disapprove the conclusions derived from such a scientific study.
Validation Team: A multi-disciplinary team of personnel primarily responsible for conducting and/or supervising validation studies. Such studies may be conducted by person(s) qualified by training and experience in a relevant discipline.
Worst Case Condition: The highest and /or lowest value of a given parameter actually evaluated in the validation exercise.
5.0 Phases of Validation
The activities relating to validation studies may be classified into three phases:
Pre-Validation Phase or the Qualification Phase, which covers all activities relating to product research and development, formulation, pilot batch studies, scale-up studies, transfer of technology to commercial scale batches, establishing stability conditions, storage and handling of in-process and finished dosage forms, Equipment Qualification, Installation Qualification, master production documents, Operational Qualification, Process Capability.
Process Validation Phase (Process Qualification phase) designed to verify that all established limits of the Critical Process Parameters are valid and that satisfactory products can be produced even under the “worst case” conditions.
Validation Maintenance Phase requiring frequent review of all process related documents, including validation audit reports to assure that there have been no changes, deviations, failures, modifications to the production process, and that all SOP’s have been followed, including Change Control procedures.
At this stage the Validation Team also assures that there have been no changes/ deviations that should have resulted in Re qualification and Re validation.
We are giving here a link to a word file for a document where there is complete and detailed information given about validations in pharmaceuticals manufacturing process.
Here you will find very good and helpful documents on this page, this page is dedicated to peoples who are associated with regulatory affairs and want to keep them selves updated with different things happening in the field ,there are some actual documents and SOPS for Microbiology departments too are available there.
Following are some of articles which;will be useful for you in further understanding of aspects of sterile dosage form manufacturing
1 thought on “Guidelines Validations Pharmaceuticals Manufacturing Process”