Standard Operating Procedure of Validation of Cleaning in Pharmaceuticals SOP is describe in this post.
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1. PURPOSE
To describe a procedure for cleaning validation, preparation of protocol and sampling plan for different equipments / machines used in manufacturing to identify the traces of previous product that may contaminate the batch of subsequent product.
To eliminate chances of contamination or cross contamination of subsequent product manufactured and also to check validity of the procedures used for cleaning of equipments / machines.
2. SCOPE
This procedure is applicable for validation of all cleaning procedures used for equipments/machines present in premises which are in direct contact with product.
3. RESPONSIBILITY
3.1 Production Manager responsible for cleaning of equipments as per standard operating procedure of cleaning and coordinate for cleaning validation activities.
3.2 Production Pharmacist & Q.A Officer monitors the whole activity of Cleaning Validation. Q.A Officer performs sampling of cleaning validation.
3.3 Quality Control Manager is responsible for testing of cleaning validation samples with relevant documentation.
4. MATERIAL & EQUIPMENT
Materials required for sampling:
4.1 Cotton Swabs
4.2 Purified Water/Solvent
4.3 Glass beaker/flask 250ml
4.4 Measuring Tape
4.5 10x10 cm S.S. template
4.6 Cleaning validation label
5. PROCEDURE
5.1 Selection of Products and Equipments for the conduction of Cleaning Validation is carried out as per worst case scenario.
5.2 Worst Case Product is selected on the basis of following criteria
5.2.1 Difficult to Clean
5.2.2 Low Water Solubility/Insoluble in Water and Toxic
5.3 Dedicated equipments for one product are exempted from Cleaning Validation.
5.4 Cleaning validation for each worst case product is conducted to validate the cleaning procedure used for machine/equipment.
5.5 Cleaning validation Schedule is prepared by production officer and reviewed byProduction Manager.
5.6 The agreed schedule is approved by Q.A Manager and shared with all concerned departments.
5.7 A copy of this schedule is kept by production section while original is sent to Q.A department.
5.8 From selected product (having more than one API) that active is selected as worst case, which is least soluble in water and more toxic. In collecting the toxicity data, preference is given to data with similar mode of administration as that of product.
5.9 Cleaning Validation Protocol preparation:
5.9.1 Cleaning Validation Protocol is prepared for the equipment selected for cleaning validation by Q.A Officer with the consultation of Cleaning Validation Team.
5.9.2 Cleaning Validation Protocol includes following:
a. Purpose
b. Scope
c. Responsibilities
d. Product Selection Criteria
e. Acceptance Criteria
f. Equipments, Materials And Samples
g. Cleaning Procedure
h. Sampling Procedure
i. Testing Procedure
j. References
k. Deviation report
l. Any change(s) suggested
m. Summary of Cleaning Validation
5.9.3 Cleaning Validation Protocol (CVP) and Cleaning Validation Report Numbers are assigned by Q.A and mentioned in Log Book after Cleaning Validation Protocol (CVP) approval.
5.9.4 To allot Protocol No. and Report No., a uniform numbering System is followed as CVX/PP/000
CVX = Type of Cleaning Validation (Protocol or Report) e.g. CVP or CVR.
PP = Product Code (product selected for cleaning validation)
000 = Serial Number.
Example:
Protocol No. and Report No. for Cleaning Validation of equipment used for Ibuprofen suspension will be as follow,
Protocol No. = CVP/IB/001, Report No.= CVR/IB/001
5.9.5 Serial Number of Report no. is same as its serial # in Protocol No. Serial # is allotted and Cleaning Validation Log Book is updated.
5.10 Production Pharmacist and Q.A Officer ensure that the cleaning of the equipment is carried out as per approved SOP and by the trained worker(s).
5.11 TYPES OF SAMPLING:
Cleaning validation samples are collected by following two methods, e.g., Direct Surface Sampling (Swab Method) and Indirect Sampling (use of rinse solutions)
5.11.1 DIRECT SURFACE SAMPLING (SWAB METHOD) :
a. Areas which are hardest to clean and their rinse sampling cannot be performed, are evaluated by direct sampling method (i.e. Rotary Machines, Blister Machine etc.) after cleaning.
b. Sampling is done with cotton swabs soaked in purified water or solvent.
c. Before sampling Q.A Officer visually inspects the equipment / machine for Cleanliness, if cleaning is satisfactory (i.e. no visible residue exists) then he / she takes the sample for cleaning validation according to approved sampling points in the protocol.
d. During sampling cotton swab soaked with purified water/solvent is rubbed on selected area of the equipment / machine which is in direct contact with product, after swabbing put the swab back to labeled swab tube.
e. Cotton swab is rubbed on the selected area from one side to another as shown in below diagram by using suitable template ensuring that contaminated swab or part of swab not used for next rubbing. New swab is used for sampling of different specified areas of the selected equipment.Swab is shifted back to labeled swab tube after appropriate sample taking.
f. Equipment parts such as punches, dyes as in case of compression machine are swabbed completely.
g. More than one swab can be used for sampling of machine / equipment and composite sample is prepared for testing.
h. Sampling Area:
For sampling 10x10 cm S.S. template is used. For area where 10x10 cm S.S. template cannot be used (for example curved areas) or where the total product contact surface area is less than 10x10 cm, a measuring tape is used for sampling area measurements.
i. Samples from different locations / spots are collected and analyzed separately.
j. After sampling, sample is sent to Q.C for analysis of any traces of previous product API(s).
5.11.2 INDIRECT SAMPLING (USE OF RINSE SOLUTIONS):
a. Rinse sampling method allows sampling of large surface area which can easily be washed with plenty of water (like Bin Blenders, Film coating machine tablet pan etc.).
b. Before sampling Q.A Officer visually inspects the equipment / machine for Cleanliness, if cleaning is satisfactory (i.e. no visible residue exists) then he / she manages to take the sample for cleaning validation.
c. Equipment / machine is rinsed with required quantity of purified water& sampled as per protocol.
d. Quality Assurance Officer collects about 250 ml rinse sample (in cleaned Stoppard volumetric flask/beaker) and send to Quality Control Department for testing.
5.12 Quality Control Department performs testing of cleaning validation samples and provides test results for report preparation.
5.13 Cleaning Validation Report:
5.13.1 Cleaning Validation Report is prepared by Q.A department.
Cleaning Validation Report is prepared by Q.A Officer and approved by Q.A Manager. Final report finding and shared and discussed with concerned departments.
5.13.2 This report is retained by Q.A. department.
5.13.3 Cleaning Validation team review the need for repeat cleaning validation whenever there is change in;
a. Cleaning Procedure
b. Equipment (modified/replaced)
5.14 Cleaning validation is a specially planned activity and during cleaning validation equipment/machine is not hold till results.
5.15 Incase of cleaning validation sample failure in testing or unsatisfactory results, Q.A Officer and Production Pharmacist investigate the root cause of failure.
5.16 After investigation of the root cause of failure in sample testing or unsatisfactory results appropriate correction/corrective action and preventive actions are taken;
• Change in cleaning procedure • Validity of testing procedure etc.
5.17 Periodic cleaning validation is carried out after every five years for equipment chain of the selected equipments.
6. REPORTING
6.1 Cleaning Validation Log Book
6.2 Schedule for Cleaning Validation
6.3 Cleaning Validation Protocol
6.4 Cleaning Validation Report
7. REFERENCE DOCUMENTS
7.1 WHO Guideline on Validation (May-2016).
7.2 Cleaning Validation Guidelines-Guide-0028
7.3 Supplementary guidelines on good manufacturing practices: 736
WHO Technical Report Series, No. 937, 2006, 737 Annex 4.
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