To discuss principles and approaches to cleaning validation
including
Validation of cleaning methods provides documented evidence that an approved cleaning procedure will provide clean equipment, suitable for its intended use.
2.0 SCOPE
2.1 This procedure applies to all the employees of the ZYX company
2.2 Adequate cleaning procedures play an important role in preventing contamination and cross-contamination. Validation of cleaning methods provides documented evidence that an approved cleaning procedure will provide clean equipment, suitable for its intended use.
2.3 The objective of cleaning validation is to prove that the equipment is consistently cleaned of product, detergent, and microbial residues to an acceptable level to prevent possible contamination and cross-contamination.
2.4 Cleaning validation is not necessarily required for non-critical cleaning such as that which takes place between batches of the same product(or different lots of the same intermediate in a bulk process), or of floors, walls, the outside of vessels, and following some intermediate steps.
3. Procedure of Cleaning Validation
3.1. At least three consecutive applications of the cleaning procedure should be performed and shown to be successful to prove that the method is validated.
3.2 Cleaning validation protocols and reports
4. Cleaning validation protocols
4.1 Cleaning validation should be described in cleaning validation protocols, which Should be formally approved, e.g. by the quality control or quality assurance unit. make, model, serial number or other unique code, cleaning procedure (interval may be part of the validation challenge study itself) as the establishment of the time that should elapse after cleaning and before use; any automated process) to be used for each product, each manufacturing system or each piece of equipment, meters and total organic carbon analyzers, in-process monitoring and sampling locations) and the rationale for their use, the technique should be established) and the limit of quantification the margin for error and for sampling efficiency quality unit and should be scientifically justified on the basis of, e.g. Need to be individually validated.
A validation study of the “worst-case” may Be considered acceptable. There should be a justified validation program for this approach is referred to as “bracketing”, addressing critical issues relating to the selected product, equipment, or process
4.2 In preparing the cleaning validation protocol, the following should be considered: disassembly of system precleaning cleaning agent, concentration, solution volume, water quality;
4.3 The cleaning validation protocol should include:
- The objectives of the validation process.
- The people are responsible for performing and approving the validation study.
- The description of the equipment to be used, including a list of the equipment.
- The interval between the end of production and the commencement o the maximum period that equipment may be left dirty before being cleaned as well.
- The levels of microorganisms (bioburden).
- The cleaning procedures (documented in an existing SOP, including the definition of all the equipment used for routine monitoring, e.g. conductivity meters, pH
- The number of cleaning cycles to be performed consecutively.
- The sampling procedures to be used (direct sampling, rinse sampling.
- The data on recovery studies (efficiency of the recovery of the sampling.
- The analytical methods (specificity and sensitivity) including the limit of detection.
- The acceptance criteria (with rationale for setting the specific limits) including.
- The choice of the cleaning agent should be documented and approved.
4.4 Cleaning procedures for products and processes which are very similar do not Need to be individually validated. A validation study of the “worst-case” may Be considered acceptable. There should be a justified validation program for this approach referred to as “bracketing”, addressing critical issues relating to the selected product, equipment, or process
4.5 Where “bracketing” of products is done, consideration should be given to the type of products and equipment.
4.4 Bracketing by-product should be done only when the products concerned are similar in nature or property and will be processed using the same equipment. Identical cleaning procedures should then be used for these products.
4.5 When a representative product is chosen, this should be the one that is most difficult to clean.
4.6 Bracketing by the equipment should be done only when it is similar equipment, or the same equipment in different sizes (e.g. 300-L, 500-L, and 1000-L tanks). An alternative approach may be to validate the smallest and the largest sizes separately.
4.7 Cleaning validation reports
4.8 The relevant cleaning records (signed by the operator, checked by production and reviewed by quality assurance) and source data (original results) should be kept.
4.9 The results of the cleaning validation should be presented in cleaning validation reports stating the outcome and conclusion.
5. Personnel
5.1 Personnel or operators who perform cleaning routinely should be trained and should be effectively supervised.
6. Equipment
6.1 Normally only procedures for the cleaning of surfaces of the equipment that come Into contact with the product need to be validated. Consideration should be given to “non-contact” parts of the equipment into which the product or any process material may migrate. Critical areas should be identified (independently from the method of cleaning), particularly in large systems employing semi-automatic or fully automatic clean-in-place systems. equipment that is difficult to clean, or for products with a high safety risk where it is not possible to achieve the required cleaning acceptance limits using a validated cleaning procedure.
This will depend on the products being produced, whether the cleaning occurs between batches of the same product (as in a large campaign), or whether the cleaning occurs between batches of different products.
6.4 The design of equipment may influence the effectiveness of the cleaning process. Consideration should therefore be given to the design of the equipment when preparing the cleaning validation protocol, e.g. V-blenders, transfer pumps, or filling lines.
7. Detergents
7.1 Detergents should facilitate the cleaning process and be easily removable. Detergents that have persistent residues such as cationic detergents which adhere very strongly to glass and are difficult to remove, should be avoided where possible. during rinsing, demonstrated. possibility of detergent breakdown should also be considered when validating cleaning procedures. local food standards or regulations.
8. Microbiology
8.1 The need to include measures to prevent microbial growth and remove contamination where it has occurred should be considered. equipment does not allow microbial proliferation. the time between cleaning and equipment reuse should form part of the validation of cleaning procedures.
Allowed to remain in equipment after cleaning. equipment is important to ensure that subsequent sterilization or sanitization procedures achieve the necessary assurance of sterility, and the control of pyroxenes in sterile processing. Equipment sterilization processes may not be adequate to achieve significance.
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9. Sampling
especially important for operations with topical products, suspensions, and bulk drugs or where the drying of residues will directly affect the efficiency of a cleaning procedure. sampling and rinse samples. A combination of the two methods is generally the most desirable. and is acceptable only in rare cases. Constant retesting and resembling can show that the cleaning process is not validated because these retests actually document the presence of unacceptable residue and contaminants resulting from an ineffective cleaning process.
Note: This method of sampling is the most commonly used and involves taking an inert material (e.g. cotton wool) on the end of a probe (referred to as a “swab”) and rubbing it methodically across a surface. The type of sampling material used and its potential impact on the test data is important as the sampling material may interfere with the test.
(For example, the adhesive used in swabs has been found to interfere with the analysis of samples.)several swabs used, whether they are wet or dry swabs, swab handling and swabbing techniques. composition of the equipment (e.g. glass or steel) and the location (e.g. blades, tank walls, or fittings). Worst-case locations should be considered. The protocol should identify the sampling locations. systems that employ semi-automatic or fully automatic clean-in-place systems.
Note: This method allows sampling of a large surface, of areas that are inaccessible or that cannot be routinely disassembled and provides an overall picture. Rinse samples may give sufficient evidence of adequate cleaning where accessibility of equipment parts can preclude direct surface sampling and may be useful for checking for residues of cleaning agents, e.g. detergent
9.10 Rinse samples should be used in combination with other sampling methods such as surface sampling. For example, recovery of > 80% is considered good, > 50% reasonable and < 50% questionable.
Note: This method relies on the manufacture of a placebo batch which is then checked for carry-over of the previous product. It is an expensive and laborious process.
It is difficult to provide assurance that the contaminants will be dislodged from the equipment surface uniformly. Additionally, if the particles of the contaminant or residue are large enough, they may not be uniformly dispersed in the placebo batch. sampling method(s). preceding products should be sought in these samples. (Note that the sensitivity of
5.0 ABBREVIATIONS
SOP: Standard Operating Procedure
QA: Quality Assurance
No. : Number
IPA: Iso
Propyl Alcohol