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Sunday, January 29, 2012

Cleaning Validation Protocol

Cleaning Validation Protocol



1.0 Introduction:

The Validation of the Cleaning Procedures is establishing documented evidence that the procedure is effective and capable for removing the contaminants associated with previous products, residues of cleaning agents as well as the control of potential microbial contaminants.



The Cleaning Validation is not only ensuring the compliance of the regulatory requirements, but a more important benefit for performing cleaning procedure validation is the identification and the correction of the potential problems which could compromise the safety, efficacy or quality of the subsequent batches of drug product.



2.0 Objective:

The objective of the Cleaning Validation is to verify the effectiveness of the cleaning procedure for removal of product residues, degradation products, preservatives, excipients and/or cleaning agents so that the analytical monitoring may be reduced to a minimum in the routine phase, and to ensure that there is no risk associated with cross-contamination of active ingredients.



The objective of Validation of the Cleaning Procedure (SOP No._______________) being used for the cleaning of Machine Name (Machine No. ________________) is to prove that the product contact parts of the Machine Name (Machine No. ________________) have been cleaned and that the contamination level (Chemical and Microbial Contaminants) has been reduced below to an acceptable level.



To achieve these acceptable levels, cleaning procedure (SOP No._______________) need to be established and validated; sampling and analysis will be carried out for this purpose to assure that the cleaning of Machine complies with specified limits.

Cleaning Validation will verify the effectiveness of cleaning procedure.



3.0 Scope:

i. This document on cleaning validation is intended to address special consideration and issues pertaining to validation of cleaning procedure (SOP No._______________) of Machine Name (Machine No. ________________) used for Tablets Compression of Pharmaceutical products.



ii. This document is also intended to establish inspection consistency and uniformity with respect to equipment cleaning procedures.



iii. This document is intended to cover validation of equipment cleaning for the removal of contaminants associated to the previous product, residues of cleaning agents as well as the control of potential microbial contaminants.



4.0 Responsibility:



i. QA/ QC Manager

ii. Validation Team Leader

iii. Validation Officer.

iv. Representative of Production Department.

v. Analyst

vi. Microbiologist



5.0 Validation Program:

Equipment cleaning validation may be performed concurrently with actual production steps during process development and bulk manufacturing. Validation programs should be continued through full scale commercial production



The concept “Test-Until-Clean” will be applied. This concept involves cleaning, sampling and testing with repetition of this sequence until an acceptable residue limit is attained.



A validation program generally encompasses at least three consecutive successful replicate to establish that the procedure is reproducibly effective.



If the equipment of the similar size, design and construction is cleaned by the same procedure, studies need not to be conducted on each unit as long as a total of three successful replicates are done on similar piece of equipment; this concept is known as equipment grouping.



6.0 Change Control:

Any of the following proposed changes are evaluated fully for their impact on the validated state of the procedure. changes may be,



i. Changing in Machine

ii. Change in cleaning agents used (if applicable)

iii. Change in cleaning procedures



If any of the above-cited changes are required it should be performed in accordance with the change control procedure (SOP No. _________________).



After the approval of any change according to procedure, it is required to revalidate the Cleaning Procedure.



7.0 Acceptance Criteria:





S. #


Testing Parameter


Acceptance Criteria

1


Physical determination




The visual examination of the equipment verifying that visible residues or particulate matters.

2.


Chemical Determination


a) NMT 0.1 % of the normal therapeutic dose of any product to appear in the maximum daily dose of the subsequent product.

b) NMT 10 ppm of any product to appear in the next product.

c) For certain allergic ingredients, penicillines cephalosporin of steroids and cytotoxic, the limit should be below the limit of detection.

3.


Microbial Contamination


Total aerobic Counts

a) Bacterial Counts = NMT 20 CFU

b) Molds = NMT 02 CFU



8.0 Sampling Procedure:



Direct Surface Sampling (Swab Method):



a) Area difficult to clean and which are reasonably clean can be evaluated by direct surface sampling method (Swab Method), leading to establish a level of contamination or residue per given area i.e. 60 – 100 in2. The residue that are dried out or are insoluble can be sampled by Swab Method.



b) The suitability of the method to be used for sampling and of sampling medium should be determined. The ability to recover the sample accurately may be affected by the choice of sampling method. It is important to assure the sampling medium and solvent (used for extraction from the medium) are satisfactory and can be readily used.



c) For determination of the Microbiological Contamination on surfaces is to use sterile cotton swabs moistened with sterile peptone water, WFI, or Phosphate Buffer. Using sterile forceps and aseptic technique, an area of predetermined size, e.g. 60 - 100 in2, is wiped with a sterile swab. The swab is then aseptically transferred to a sterile tube containing a suitable diluent. The tube is then agitated to suspend any viable microorganisms and aliquots are placed in a semisolid medium to obtain quantitative results.

9.0 Cleaning Procedure: SOP No. ________________



i. Switch Off the Machine

ii. Write down complete cleaning procedure step wise

iii. After cleaning paste Cleaning Status Label and enter in Logbook

10.0 Testing Procedure :

i. Physical Testing:

Along with taking samples, it is important to perform visual inspection as well to ensure the process acceptability



ii. Chemical Testing:

Write down the analytical procedure for determination of traces at least three Active Pharmaceutical Ingredients.



iii. Microbiological Testing:



Swab Test

· Cotton Swabs prepared on S.S sticks are sterilized.

· Phosphate buffer pH 7.2 prepared and dispensed 5 ml in each screw capped test

tubes is sterilized.

· Material is transferred into sterile area for swab test after disinfection.

· Remove the sterilized swab, soak in phosphate buffer and touch to the surface to be checked

· 2 ½ x 2 ½ inch2 area is touched against each soaked swab.

· Place back the swab into the tube containing phosphate buffer and label the tube with the

testing part and date.

· Transfer the tested swab to micro lab. for microbiological test.

· Pour plate method is used to check the contaminants.

· Plates are incubated for 48 hours, the results are declared as number of CFU per

part or surface.





11.0 Overall Validation Procedure:



i. Intimate the Production Department for the Cleaning Validation of Machine Name (Machine No. ________________) before starting the activity through Cleaning Validation Schedule.



ii. After Cleaning of the Machine Name (Machine No. ________________) according to procedure (SOP No. ____________) Production Department inform the Validation Section for conducting the Validation activities.



iii. Validation Officer takes the Swab Sample for Chemical Determination, whereas Microbiologist takes the Swab Sample for Microbiological Determination.



iv. Send the Samples to Quality Control along with Technical Information Sheet for analysis.



v. QCD analyzes the sample according to procedure and provide the results to Validation Section.



vi. Repeat the steps ii, iii and iv after the change of consecutive three different products.



vii. Validation Section analyzes all the results and compiles the report.



viii. If the results comply with the specified limits than the Machine Name (Machine No.

________________) is considered as cleaned and the Cleaning Procedure (SOP No. _____________) is considered as Validated.



ix. If the results do not comply with the specified limits, then repeat the overall Validation actives for further two consecutive changes of different products i.e. to provide the validation data of three consecutive API’s



x. If the validation results do not comply with the specification, improve the cleaning procedure and continue it until all the results comply with the specified limits.



12.0 Inspection Criteria: (For three consecutive products)





12.1 Previous Product





Batch No.






While taking samples from Machine Name (Machine No. ________________), note down the following points.



· Description of machine/equipment/area:

· Major Product contact components:

· Product Contact Area:

· Previous Batch completed on:

· Equipment cleaned on:

· Detergent / Solvent used:

· Composition of the detergent used:

· Cleaning Tools:

· Ancillary Utilities:

· Cleaning Cycles:

· Cleaned by:

· Supervised by:

· Sampled by (Chemical)

· Sampled by (Microbiological)

· After cleaning the Equipment used on:

· Subsequent Product:

· Batch No.

· Name of API:

· Batch Size of the subsequent product:

· Maximum daily dose of the subsequent Product:

12.2 Previous Product





Batch No.






While taking samples from Machine Name (Machine No. ________________), note down the following points.



· Description of machine/equipment/area:

· Major Product contact components:
· Product Contact Area:

· Previous Batch completed on:
· Equipment cleaned on:

· Detergent / Solvent used:
· Composition of the detergent used:

· Cleaning Tools:
· Ancillary Utilities:

· Cleaning Cycles:

· Cleaned by:

· Supervised by:

· Sampled by (Chemical)

· Sampled by (Microbiological)

· After cleaning the Equipment used on:
· Subsequent Product:

· Batch No.

· Name of API:

· Batch Size of the subsequent product:

· Maximum daily dose of the subsequent Product:











12.3 Previous Product





Batch No.






While taking samples from Machine Name (Machine No. ________________), note down the following points.



· Description of machine/equipment/area: ____________

· Major Product contact components: ______

· Product Contact Area: ______

· Previous Batch completed on: ______

· Equipment cleaned on: ______

· Detergent / Solvent used: ______

· Composition of the detergent used: ______

· Cleaning Tools: ______

· Ancillary Utilities:

· Cleaning Cycles:

· Cleaned by:

· Supervised by:

· Sampled by (Chemical)

· Sampled by (Microbiological)

· After cleaning the Equipment used on: ______

· Subsequent Product: ______

· Batch No.

· Name of API: ______

· Batch Size of the subsequent product: ______

· Maximum daily dose of the subsequent Product: ______



13.0 Facilities/Responsible Personnel & Documentation:



13.1 Facilities:



The Validation of Cleaning procedure being used for the cleaning of Machine Name (Machine No. ________________) was performed in ____________ Section of _________ Production at Company Name and Address.





13.2 Identification of Responsible Personnel:







Name


Job Title


Signature



















13.3 Identification of Documentation:





Document Title


SOP/QF Number

Validation Master Plan




Cleaning Validation (SOP)




Cleaning Validation Report




Machine Operating/ Cleaning Procedure (SOP)




Analytical Result Sheet






13.4 Other Information: (if any)

6 comments:

  1. A validation program generally encompasses at least three consecutive successful replicate to establish that the procedure is reproducibly effective.
    Cleaning Validation Protocol

    ReplyDelete
  2. Software validation is a part of the design validation for a finished device, but is not separately defined in the Quality System regulation.more information

    ReplyDelete
  3. The objective of the Cleaning Validation is to verify the effectiveness of the cleaning procedure for removal of product residues, degradation products, preservatives, excipients and/or cleaning agents so that the analytical monitoring may be reduced to a minimum in the routine phase, and to ensure that there is no risk associated with cross-contamination of active ingredients.
    more information

    ReplyDelete
  4. The suitability of the method to be utilized for sampling and also of sampling medium must be determined. The ability to recuperate the sample precisely can be affected by the choice of sampling system. It is vital to guarantee the sampling moderate and additionally solution (used in extraction from the medium) are really great and also can be readily utilized.automateandvalidate

    ReplyDelete
  5. As an effective means to gain approval, the FDA recommends that medical device software development take an integrated SDLC strategy that merges validation and verification activities, including defect prevention practices such as unit testing, peer code reviews, static analysis, manual testing, and regression testing, throughout the SDLC. The result of such an approach is an emphasis on planning, verification, testing, traceability, and configuration management.submission

    ReplyDelete
  6. Lancaster Laboratories has been providing analytical testing services to the Pharmaceutical, Medical Device and Food industries since 1986. Now, under the expert guidance and management of the same team who bring you excellence in service and innovation at Lancaster Laboratories, we are now pleased to offer our equipment validation services.
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    ReplyDelete