Cleaning Validation of Equipment

1.0 Objective
To lay down a procedure for cleaning validation of equipment.
2.0 Scope
2.1 This Standard Operating Procedure is applicable for cleaning validation of equipment

to be followed at formulation plants of ABC Pvt. Ltd.
3.0 Responsibility
3.1 Officer / Executive QA shall be responsible for cleaning validation of equipment.
3.2 Head QA / his designee shall be responsible for compliance of this SOP.
4.0 Abbreviations and Definitions
SOP : Standard Operating Procedure
MAR : Maximum Allowable Residue
QA : Quality Assurance
No. : Number
5.0 Procedure:
5.1 Precaution
5.1.1 Wear hand gloves during sampling.
5.1.2 During the validation studies, organic solvent shall not be handled at any stage.
5.1.3 All sampling aids shall be handled carefully to eliminate the risk of contamination.
5.2 Cleaning of equipment are done according to respective SOPs.
5.3 Equipment and accessories shall be cleaned as directed by the relevant SOP of equipment cleaning.
5.4 The worst case from the categories shall be selected on solubility of molecule, potency of molecule and

lethality of molecule. The study shall be taken on priority for that product; successively other products

shall be taken. The study shall be applicable to (batches may not be successive) using the same set of, equipment.
5.5 The study should include inspection of external surface for visual cleanliness, though the dangers

of the residue of the previous product contaminating the next product are considered to be negligible.
5.6 Sampling :
5.6.1 Points / areas of the equipment from where the samples for residue testing are to be collected shall

be based on considerations of hard to clean surfaces of the equipment. These locations shall be

specified in relevant cleaning validation protocol.
5.6.2 In case of piping or tubing, sampling shall be performed from the open end.
5.6.3 Check the equipment visually for cleanliness.
5.6.4 The samples shall be collected against a template sheet as specified in relevant protocol.
5.6.5 Samples shall be taken with either of the below swabs or may be used in combination during study.

The type of swab used depends on the sampling location that will be specified in relevant protocol.
5.6.5.1 Large Alphawipe
5.6.6 Template is available in one sizes .The size of the template to be used for the study shall be defined

in the relevant protocols. The sizes are as follows
5.6.6.1 10 x 10 cm: 100 cm2
5.6.7 Put the template on sampling locations of equipment as specified in the protocol. Swab along the

length unidirectional in such a way that swabbing covers complete surface area, taking care not to swipe the already swabbed surface.
5.6.8 Apply appropriate pressure during swabbing to ensure that all the material (if any) is extracted with the swab.
5.6.9 Alpha wipe swab : For Large Alpha wipe swab sampling shall be performed by the following method
5.6.9.1 Fill about 10 ml of water/suitable aqueous medium in a cleaned test tube.
5.6.9.2 Hold the swab from its handle and carefully insert the swab in upside position, in the test tube

such that its head is completely immersed in the zero water/ suitable aqueous medium.
5.6.9.3 Stopper the above test tube, label it and take the sample for the defined location.
5.6.9.4 Send it to the Quality Control Department for analysis.
5.7 Testing :
5.7.1 Swabs & rinse samples shall be tested for the residue by the HPLC. Analytical Method which

consist of limit of detection (LOD) & limit of qualification (LOQ) shall be develop prior to the testing.
5.8 Swab recovery studies :
5.8.1 Perform the swab recovery studies as defined in the relevant protocol.
5.8.2 The swab recovery shall be NLT 70%.
5.8.3 This is a one time exercise, for all subsequent studies related to that category of product data shall be used.
5.9 Computations
5.9.1 It shall be assumed that all the residue of the “immediately preceding” product shall
“contaminate” the first Batch of the succeeding product, and this residue shall be evenly

distributed in the whole batch. An arbitrary safety factor has been considered depending upon toxicity of the product.
5.9.2 A recovery correction is applied for respective methods.
5.9.3 Results of the testing of sampling(s) from each equipment shall be extrapolated to

account for the entire contact surface of the equipment with which the next product may come in contact.
5.9.4 A blank correction value is already established for above mentioned swabs in a separate protocol.
5.9.5 Maximum Allowable Residue (MAR) shall be calculated by considering
5.9.6 Minimum human adult dose has been referred from Martindale, The extra Pharmacopoeia,

Physician desk reference & other literature.
5.10 Evaluation: The results (residue) should be compared with the respective MAR value.
5.11 Acceptance Criteria
5.11.1 Cleanliness of equipment
5.11.1.1 Equipment must be visually inspected (externally and internally) and found to be acceptably clean.
5.11.1.2 The total residue found in the swabs from the cleaning operations shall not exceed the

maximum allowable residue (MAR) or equivalent TC value as specified in acceptance criteria of respective protocols.
5.11.1.3 If MAR value is exceeded, the contamination of the subsequent product must be

regarded as too high. The equipment must not be released for subsequent product and a

revalidation of cleaning procedure shall be carried out.
5.12 Hold time study
5.12.1 Hold time studies of equipment will be based on microbiological aspects of equipment cleaning.

This will largely consist of preventive.
5.12.2 Time – frames for storage of uncleaned equipment, prior to commencement of cleaning, as well

as time frames and conditions for storage of cleaned equipment will be established and documented in protocol.
5.12.3 Acceptance Citeri (Hold Time)- The limits for acceptance criteria for surface sampling duing hold

time studies for equipment shall be as follows:
5.12.3.1 Appearance – There should be no visible signs of microbial growth on the equipments.
5.12.3.2 Bio-Burden – More than 50 cfu/ 25 cm2
5.12.3.3 Coilforms – Coliform bacteria should be absent
5.12.3.4 Fungi – Fungi should be absent
5.12.3.5 Pathogens – Absent
5.12.4 The limit for acceptance criteria for environmental monitoring during hold time studies

shall be as follow: Total count- More than 100 cfu / hr.
5.13 Revalidation: At least 3 categories in a year.
5.14 Documentation: Report must contain all relevant document & records.
6.0 Forms and Records
6.1 None.
7.0 Distribution
7.1 Master copy – Documentation Cell (Quality Assurance)
7.2 Controlled copies – Quality Assurance, Quality Control, Production and Engineering Department.
8.0 History