Cleaning Validation Procedure in pharmaceuticals

Cleaning Validation Procedure in pharmaceuticals

Cleaning validation procedure in pharmaceuticals

Cleaning Validation criteria:

  • Equipments shall be cleaned as per the respective cleaning SOPs.
  • Swab samples are collected from the predefined locations of all the equipments.
  • The quantity per swab is analyzed by using validated Analytical method.
  • Calculate the total content for sampled area per swab.
  • Recovery: A correction factor based on the Spike Recovery Studies shall be applied for the swab results. Minimum Recovery shall be include in calculation
  • Cleaning validation shall be performed on worst-case product.
  • In case worst case product is not manufactured; the 2nd Worst-case product shall be taken for study.
  • As and when the worst-case product is changed or the acceptance limits are changed (decreased), the same shall be validated.
  • If acceptance criteria is more than 10 ppm/swab than to make acceptance criteria more stringent, 10 ppm/swab shall be considered as acceptance criteria.
  • Cleaning agent: Purified water shall be used as cleaning agent.

  • Advantage of purified water as cleaning agent: Solubility of material, easy to remove, easy to detect, suitable with construction of equipment surface.

  • Approved purified water by QC shall be used for cleaning purpose. Purified water used shall be in-House grade which complies with USP/Ph.eur grade. Attach water testing reports with cleaning validation. 
  • Verify critically following points during cleaning: This verification shall be done by quality assurance
  • Disassembly of System, Pre-cleaning of equipment, Rinsing of Equipment
  • Water Quality, Pressure of water, Temperature of Water
  • Nozzle diameter of Gun, Flow rate of water, Cleaning Time
  • For all these variables attach the Batch cleaning Record of all equipments of all three validation bathes. 


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Variables
  • Operators negligence
  • Distance of cleaning
  • Temperature of water
  • Pressure of water
These variables shall be considered during cleaning validation.

SAMPLING METHOD

Selection of sampling method

Swab sampling shall be considered as sampling method.
Justification for swab sampling: Looking to the Design and Size of equipment, swab sampling shall be considered main method for validation. Most difficult to clean locations are selected for sampling.

 Advantage of swab sampling: 
  • Direct evaluation of surface contamination
  • Insoluble and poorly soluble substance may be physically removed


Hard to clean but accessible areas are easily incorporated in final result.

Scientific rational for selecting sampling point

     The product contact surface area which is most difficult to clean shall be selected as sampling point. The location selected for swabbing are generally those locations that are most difficult to clean representative of different materials (e.g. Stainless steel, glass, gasket etc.) and   representative of different functional locations (Side corners, valve, agitator, blades etc.). If these locations are swabbed and if residues in these materials are acceptable then residues on another location shall also be acceptable. Performing swab on these locations and materials can be helpful in terms of providing higher assurance in validation results. The location from which sample is taken into consideration is the composite of equipment (e.g. glass/steel).
          
Sampling Procedure

Visual Inspection
After cleaning of the garments visual inspection shall be done. This should be done under viewing conditions (Lighting, angle, Distance). Attach the eye test report of concerned personals who performed visual inspection and lux meter certificate with cleaning validation report.
The visual inspection shall be done from one fit distance of the surface of garments because greater the distance a less sensitive visual examination will be.

Swab Sampling for Chemical analysis:
Description of swab:
•         Make                    :  Texwipe Swab ,USA
•         Model                   :  TX714A
•         Head Material      :  Knitted Alp halite Polyester.
•         Handle Material   :  Polypropylene
•         Selection              :  Due to benefit and application for cleaning validation.

 Attach swab certificate with cleaning validation protocol.
  •  Swab samples shall be taken after the final cleaning of garment, and once the garment qualifies the visual inspection test. The swab shall be wet in purified water. Swab samples from different areas of garments shall be collected. Swab area shall be measured for swabbing.
  • Sampling error: During swab sampling following care to be taken: area of sampling (should not be less than 25 cm2), apply proper force during collection of sample.

  • Sampling area: 5 x 5 cm. = 25 cm2

  • Sampling patterns: Wipe the defined area in zigzag directions as shown in the figure.  Apply only one times. Collect the swab by application of manual force and after collection of swab in one direction flip the swab and collect the sample at 90°C.
Note: Do not lift the swab stick from contact surface during collection of swab.
Refer the typical diagram to collect the sample-using swab.


Handling of swab Samples: Swab shall be prepared by quality control. The test tubes shall be covered with paraffin film, proper precaution shall be taken during handling of swab. After swabbing, each sample shall be placed inside the test tube duly labelled and covered with paraffin film and should be sent to QC Laboratory for testing of determination.

Swab sampling for Microbial analysis:

For microbiological testing sterile cotton swab shall be used for swabbing. The swab shall be wet in sterile saline. After swabbing each swab sample shall be placed inside a properly labelled sterile test tube. Each swab sample shall then be analyzed to find out bio burden as per the method mentioned in SOP.

Sampling Location:
Prior to swab sampling, garments shall meet “Visual Clean” criteria. Chemical and microbial sampling location shall be different from each other.

 ANALYTICAL PROCEDURES:
Analytical methods for Specific analysis were validated as per Analytical Method Validation Protocol. Specific analysis shall be carried out using UV method. Validated methods shall be employed to analyse the cleaning validation samples. Recovery results of garments shall be included in swab results. For analytical method validation and recovery results refer respective analytical method validation and recovery study protocol.                                 

ESTABLISHMENT OF ACCEPTANCE CRITERIA:

The acceptance residual limit will be calculated as follows:
  • Maximum Allowable Residue (MAR) for any combination of products changeover in the subsequent product will be calculated by considering the smallest batch size, smallest strength and maximum daily dose among all the products manufactured in the Tablet Section.
  • Considering obtained Maximum Allowable Residue, acceptance limit mg / swab will be calculated according to the equipment surface area. Subsequently the final allowable acceptance limit will be calculated for sampled surface area of individual equipment.
  • Maximum surface area is taken in calculation.
  • Hardest to clean area shall be selected in sampling.
  • Recovery study of different product contact shall be taken into consideration
Variables shall be covered that during sampling, non distribution of residue.
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