6. CLEANING VALIDATION CONSIDERATIONS
6.3 Cleaning Validation Protocols
There should be documentation specifying how cleaning processes will be validated.
GUIDE TO INSPECTIONS OF VALIDATION OF CLEANING PROCESSES (July 1993) III. General Requirements
(para 2) [VIP ID: 1324]
“FDA expects firms to have written general procedures on how cleaning processes will be validated.”
6.3.1 General
Cleaning validation protocols should:
1. not be executed until all of the associated analytical methods have been validated.
PI 006-2
RECOMMENDATIONS ON VALIDATION MASTER PLAN INSTALLATION AND OPERATIONAL QUALIFICATION NON-STERILE PROCESS VALIDATION CLEANING VALIDATION (July 2004)
7. CLEANING VALIDATION 7.10 Analytical Methods 7.10.1
[VIP ID: 188696]
“The analytical methods should be validated before the Cleaning Validation Study is carried out.”
Selected FDA 483 Observations (June 2003) Active Pharmaceutical Ingredient Manufacture [VIP ID: 52760]
“Cleaning validation should include:
(a) the validation of analytical methods prior to use.”
EU GUIDE TO GOOD MANUFACTURING PRACTICE: ANNEX 15 - VALIDATION MASTER PLAN DESIGN QUALIFICATION, INSTALLATION AND OPERATIONAL QUALIFICATION, NON-STERILE PROCESS VALIDATION, CLEANING VALIDATION - SUPERSEDED!! (October 1999)
4. Cleaning Validation 4.10. Analytical Methods 4.10.1.
[VIP ID: 69360]
“The analytical methods should be validated before the Cleaning Validation Study is carried out.”
2. include/reference the analytical methods to be used.
EU GUIDE TO GOOD MANUFACTURING PRACTICE PART II: BASIC REQUIREMENTS FOR ACTIVE SUBSTANCES USED AS STARTING MATERIALS (October 2005)
12. VALIDATION 12.7 Cleaning Validation 12.72
[ViP ID: 24771]
“The cleaning validation protocol should describe the equipment to be cleaned, procedures, materials, acceptable cleaning levels, parameters to be monitored and controlled, and analytical methods. The protocol should also indicate the type of samples to be obtained and how they are collected and labelled.”
Selected FDA 483 Observations (June 1999) Product Manufacture
[VIP ID: 7235]
“Cleaning validation protocols should include:
2) a description of the analytical methods to be used”
REG 07/01/93 GUIDE TO INSPECTIONS OF VALIDATION OF CLEANING PROCESSES (July, 1993) III. General Requirements
(para 4)
“FDA expects firms to prepare specific written validation protocols in advance for the studies to be performed on each manufacturing system or piece of equipment which should address such issues as sampling procedures, and analytical methods to be used including the sensitivity of those methods.”
3. include/reference the limit of detection and the limit of quantitation of the analytical methods to be used.
Selected FDA 483 Observations (March 2001) Laboratories
[VIP ID: 27260]
“Analytical methods used in cleaning validation should be shown to have suitable sample preparation, HPLC operating conditions, and / or limits for quantification and detection.”
EU GUIDE TO GOOD MANUFACTURING PRACTICE: ANNEX 15 - VALIDATION MASTER PLAN DESIGN QUALIFICATION, INSTALLATION AND OPERATIONAL QUALIFICATION, NON-STERILE PROCESS VALIDATION, CLEANING VALIDATION - SUPERSEDED! (October 1999)
4. Cleaning Validation 4.4. Documentation 4.4.1.
(k)
[VIP ID: 69130]
“A Cleaning Validation Protocol is required laying down the procedure on how the cleaning process will be validated. It should include the following:
(k) analytical methods including the limit of detection and the limit of quantitation of those methods,”
4. state the title of the individual(s) responsible for performing and approving the validation study.
CLEANING VALIDATION (July 2004) 7. CLEANING VALIDATION 7.4 Documentation 7.4.1
[VIP ID: 188662]
“A Cleaning Validation Protocol is required laying down the procedure on how the cleaning process will be validated. It should include the following:
- Responsibilities for performing and approving the validation study,”
Selected FDA 483 Observations (January 1999) Product Manufacture
[VIP ID: 7094]
“Cleaning validation protocols should include provisions for:
4) the title of the individual(s) responsible for performing and approving the validation study”
Selected FDA 483 Observations (March 1997) Product Manufacture
[VIP ID: 2550]
“The cleaning validation protocol should address who is responsible for performing and approving the validation study, and address when revalidation will be required.”
GUIDE TO INSPECTIONS OF VALIDATION OF CLEANING PROCESSES (July 1993) III. General Requirements
(para 3) [VIP ID: 1325]
“FDA expects the general validation procedures to address who is responsible for performing and approving the validation study, the acceptance criteria, and when revalidation will be required.”
• The Cleaning Validation Protocol should be formally approved by the Plant Management to ensure that aspects relating to the work defined in the protocol, for example personnel resources, are known and accepted by the management. Quality Assurance should be involved in the approval of protocols and reports.
PI 006-2
RECOMMENDATIONS ON VALIDATION MASTER PLAN INSTALLATION AND OPERATIONAL QUALIFICATION NON-STERILE PROCESS VALIDATION CLEANING VALIDATION (July 2004)
7. CLEANING VALIDATION 7.4 Documentation 7.4.2
[VIP ID: 188664]
“The Cleaning Validation Protocol should be formally approved by the Plant Management, to ensure that aspects relating to the work defined in the protocol, for example personnel resources, are known and accepted by the management. Quality Assurance should be involved in the approval of protocols and reports.”
EU GUIDE TO GOOD MANUFACTURING PRACTICE: ANNEX 15 - VALIDATION MASTER PLAN DESIGN QUALIFICATION, INSTALLATION AND OPERATIONAL QUALIFICATION, NON-STERILE PROCESS VALIDATION, CLEANING VALIDATION - SUPERSEDED! (October 1999)
4. Cleaning Validation 4.4. Documentation 4.4.2.
[VIP ID: 69170]
“The Cleaning Validation Protocol should be formally approved by the Plant Management to ensure that aspects relating to the work defined in the protocol, for example personnel resources, are known and accepted by the management. Quality Assurance should be involved in the approval of protocols and reports.”
5. state the objective of the validation process.
PI 006-2
RECOMMENDATIONS ON VALIDATION MASTER PLAN INSTALLATION AND OPERATIONAL QUALIFICATION NON-STERILE PROCESS VALIDATION CLEANING VALIDATION (July 2004)
7. CLEANING VALIDATION 7.4 Documentation 7.4.1
[VIP ID: 188662]
“A Cleaning Validation Protocol is required laying down the procedure on how the cleaning process will be validated. It should include the following:
- The objective of the validation process,”
EU GUIDE TO GOOD MANUFACTURING PRACTICE: ANNEX 15 - VALIDATION MASTER PLAN DESIGN QUALIFICATION, INSTALLATION AND OPERATIONAL QUALIFICATION, NON-STERILE PROCESS VALIDATION, CLEANING VALIDATION - SUPERSEDED! (October 1999)
4. Cleaning Validation 4.4. Documentation 4.4.1.
(a)
[VIP ID: 69030]
“A Cleaning Validation Protocol is required laying down the procedure on how the cleaning process will be validated. It should include the following:
(a) the objective of the validation process,”
6. include a description of the equipment to be used.
PI 006-2
RECOMMENDATIONS ON VALIDATION MASTER PLAN INSTALLATION AND OPERATIONAL QUALIFICATION NON-STERILE PROCESS VALIDATION CLEANING VALIDATION (July 2004)
7. CLEANING VALIDATION 7.4 Documentation 7.4.1
[VIP ID: 188662]
“A Cleaning Validation Protocol is required laying down the procedure on how the cleaning process will be validated. It should include the following:
- Description of the equipment to be used,”
EU GUIDE TO GOOD MANUFACTURING PRACTICE: ANNEX 15 - VALIDATION MASTER PLAN DESIGN QUALIFICATION, INSTALLATION AND OPERATIONAL QUALIFICATION, NON-STERILE PROCESS VALIDATION, CLEANING VALIDATION - SUPERSEDED!! (October 1999)
4. Cleaning Validation 4.4. Documentation 4.4.1.
(c)
[VIP ID: 69050]
“A Cleaning Validation Protocol is required laying down the procedure on how the cleaning process will be validated. It should include the following:
(c) description of the equipment to be used,”
7. state the cleaning procedures to be used for each product, each manufacturing system or each piece of equipment, including the rationale for use.
PI 006-2
RECOMMENDATIONS ON VALIDATION MASTER PLAN INSTALLATION AND OPERATIONAL QUALIFICATION NON-STERILE PROCESS VALIDATION CLEANING VALIDATION (July 2004)
7. CLEANING VALIDATION 7.4 Documentation 7.4.1
[VIP ID: 188662]
“A Cleaning Validation Protocol is required laying down the procedure on how the cleaning process will be validated. It should include the following:
- Cleaning procedures to be used for each product, each manufacturing system or each piece of equipment,”
EU GUIDE TO GOOD MANUFACTURING PRACTICE PART II: BASIC REQUIREMENTS FOR ACTIVE SUBSTANCES USED AS STARTING MATERIALS (October 2005)
12. VALIDATION 12.7 Cleaning Validation 12.72
[VIP ID: 24771]
“The cleaning validation protocol should describe the equipment to be cleaned, procedures, materials, acceptable cleaning levels, parameters to be monitored and controlled, and analytical methods. The protocol should also indicate the type of samples to be obtained and how they are collected and labelled.”
Extracted from FDA Warning Letter 320-01-06 (December 2000) India
19/04/2001 [VIP ID: 29310]
“4. Cleaning validation studies for multiple use equipment were inadequate in a that the validation protocol did not identify the cleaning procedure, total surface area was not considered during the validation study, recovery studies were not done to validate the swab sampling method or filtering of rinse samples, some rinse samples were not analyzed, dates of analyses were inaccurate, and analytical data on rinse samples were not checked by a second person. [FDA-483 items 9, 10]”
ICH HARMONISED TRIPARTITE GUIDELINE GOOD MANUFACTURING PRACTICE GUIDE FOR ACTIVE PHARMACEUTICAL INGREDIENTS Q7A (November 2000)
12. VALIDATION 12.7 Cleaning Validation 12.72
[VIP ID: 155760]
“The protocol should also indicate the type of samples to be obtained and how they are collected and labelled.”
Selected FDA 483 Observations (December 1999) Product Manufacture
[VIP ID: 14310]
“Cleaning validation protocols should:
(1) include a specific sample collection method”
EU GUIDE TO GOOD MANUFACTURING PRACTICE: ANNEX 15 - VALIDATION MASTER PLAN DESIGN QUALIFICATION, INSTALLATION AND OPERATIONAL QUALIFICATION, NON-STERILE PROCESS VALIDATION, CLEANING VALIDATION - SUPERSEDED! (October 1999)
4. Cleaning Validation 4.4. Documentation 4.4.1.
(e)
[VIP ID: 69070]
“A Cleaning Validation Protocol is required laying down the procedure on how the cleaning process will be validated. It should include the following:
(e) cleaning procedures to be used for each product, each manufacturing system or each piece of equipment,”
Selected FDA 483 Observations (June 1999) Product Manufacture
[VIP ID: 7235]
“Cleaning validation protocols should include:
1) sampling procedures”
REG 07/01/93 GUIDE TO INSPECTIONS OF VALIDATION OF CLEANING PROCESSES (July, 1993) III. General Requirements
(para 4)
“FDA expects firms to prepare specific written validation protocols in advance for the studies to be performed on each manufacturing system or piece of equipment which should address such issues as sampling procedures, and analytical methods to be used including the sensitivity of those methods.”
8. include API cleaning procedures.
Selected FDA 483 Observations (October 2000) Active Pharmaceutical Ingredient Manufacture [VIP ID: 19890]
“Cleaning validation should be completed for API chemical process / synthesis trains and dryer bending / finishing trains.”
Selected FDA 483 Observations (August 2000) Active Pharmaceutical Ingredient Manufacture [VIP ID: 19570]
“API cleaning procedures should be validated.”
9. state the cleaning agent to be used.
Extracted from FDA warning letter 07-NWJ-06 (February 2007) USA
01-Feb-07 7. c)
[VIP ID: 194846]
“Your firm's cleaning validation studies were found to be inadequate and, as a result, there was no assurance that equipment is adequately cleaned between the manufacture of different drug products. [21 CFR 211.67(b)] For example:
c) Cleaning validation studies do not indicate whether a cleaning agent was used when cleaning the equipment process train. Equipment cleaning SOPs prior to March, 2006, indicated that equipment could be cleaned "using hot water or approved cleaning agent and water if necessary.”
10. state the number of cleaning cycles to be performed consecutively.
Selected FDA 483 Observations (January 2006) Active Pharmaceutical Ingredient Manufacture [VIP ID: 180390]
“Cleaning validation studies conducted to prove that cleaning procedures are effective in removing previous peptide, reagent, solvent, cleaning agent, or other potential residues from manufacturing equipment and utensils are deficient if the studies are performed and concluded based on only one validation run.”
CLEANING VALIDATION (July 2004) 7. CLEANING VALIDATION 7.4 Documentation 7.4.1
[VIP ID: 188662]
“A Cleaning Validation Protocol is required laying down the procedure on how the cleaning process will be validated. It should include the following:
- The number of cleaning cycles to be performed consecutively,”
Selected FDA 483 Observations (September 2003) Active Pharmaceutical Ingredient Manufacture [VIP ID: 70330]
“Cleaning validation studies conducted to prove that cleaning procedures are effective should be performed and concluded based on more than one validation run.”
EU GUIDE TO GOOD MANUFACTURING PRACTICE: ANNEX 15 - VALIDATION MASTER PLAN DESIGN QUALIFICATION, INSTALLATION AND OPERATIONAL QUALIFICATION, NON-STERILE PROCESS VALIDATION, CLEANING VALIDATION - SUPERSEDED! (October 1999)
4. Cleaning Validation 4.4. Documentation 4.4.1.
(f)
[VIP ID: 69080]
“A Cleaning Validation Protocol is required laying down the procedure on how the cleaning process will be validated. It should include the following:
(f) the number of cleaning cycles to be performed consecutively,”
11. state the number of batches required to complete the validation.
Selected FDA 483 Observations (July 2004) Active Pharmaceutical Ingredient Manufacture [VIP ID: 123320]
“Cleaning validation studies conducted to prove that cleaning procedures are effective in removing previous peptide, reagent, solvent, cleaning agent, or other potential residues from manufacturing equipment and utensils should be performed and concluded based on multiple validation runs.”
Selected FDA 483 Observations (September 2003) Active Pharmaceutical Ingredient Manufacture [VIP ID: 70330]
“Cleaning validation studies conducted to prove that cleaning procedures are effective should be performed and concluded based on more than one validation run.”
Selected FDA 483 Observations (April 2000) Product Manufacture
[VIP ID: 15420]
“Process validation and cleaning validation protocols should state the number of batches required to complete the validation.”
• Typically three consecutive applications of the cleaning procedure should be performed and shown to be successful in order to prove that the method is validated.
PE 009-5
GUIDE TO GOOD MANUFACTURING PRACTICE FOR MEDICINAL PRODUCTS (August 2006) ANNEX 15 - QUALIFICATION AND VALIDATION
CLEANING VALIDATION 40
[VIP ID: 187110]
“Typically three consecutive applications of the cleaning procedure should be performed and shown to be successful in order to prove that the method is validated.”
PI 006-2
RECOMMENDATIONS ON VALIDATION MASTER PLAN INSTALLATION AND OPERATIONAL QUALIFICATION NON-STERILE PROCESS VALIDATION CLEANING VALIDATION (July 2004)
7. CLEANING VALIDATION 7.3 General
7.3.6
[VIP ID: 188650]
“At least three consecutive applications of the cleaning procedure should be performed and shown to be successful in order to prove that the method is validated.”
EU GUIDE TO GOOD MANUFACTURING PRACTICE: ANNEX 15 - QUALIFICATION AND VALIDATION (September 2001)
CLEANING VALIDATION 40.
[VIP ID: 21400]
“Typically three consecutive applications of the cleaning procedure should be performed and shown to be successful in order to prove that the method is validated.”
EU GUIDE TO GOOD MANUFACTURING PRACTICE: ANNEX 15 - VALIDATION MASTER PLAN DESIGN QUALIFICATION, INSTALLATION AND OPERATIONAL QUALIFICATION, NON-STERILE PROCESS VALIDATION, CLEANING VALIDATION - SUPERSEDED! (October 1999)
4. Cleaning Validation 4.3. General
4.3.6.
[VIP ID: 68970]
“At least three consecutive applications of the cleaning procedure should be performed and shown to be successful in order to prove that the method is validated.”
12. reflect actual worst case production conditions. (e.g. validation after the maximum number of consecutive same product runs and/or the longest production campaigns)
Selected FDA 483 Observations (August 2007) Product Manufacture
[VIP ID: 193904]
“Validation runs should be performed using worst case scenarios (i.e., most difficult to clean drug residues, maximum holding time prior to or after equipment cleaning, etc.) to justify the currently-in-use equipment cleaning procedures.”
Selected FDA 483 Observations (July 2005) Product Manufacture
[VIP ID: 178120]
“Cleaning procedures should be validated to support the longest production campaigns.”
EU GUIDE TO GOOD MANUFACTURING PRACTICE PART II: BASIC REQUIREMENTS FOR ACTIVE SUBSTANCES USED AS STARTING MATERIALS (October 2005)
12. VALIDATION 12.7 Cleaning Validation 12.71
[VIP ID: 24770]
“Validation of cleaning procedures should reflect actual equipment usage patterns.”
ICH HARMONISED TRIPARTITE GUIDELINE GOOD MANUFACTURING PRACTICE GUIDE FOR ACTIVE PHARMACEUTICAL INGREDIENTS Q7A (November 2000)
12. VALIDATION 12.7 Cleaning Validation 12.71
[VIP ID: 155750]
“Validation of cleaning procedures should reflect actual equipment usage patterns.”
Selected FDA 483 Observations (February 1999) Product Manufacture
[VIP ID: 7118]
“Cleaning validation should reflect actual worst case production conditions, e.g. validation after the maximum number of consecutive same product runs.”
Selected FDA 483 Observations (April 1998) Active Pharmaceutical Ingredient Manufacture [VIP ID: 6370]
“Cleaning validation should include cleaning after a campaign.”
13. include any routine monitoring requirements.
CLEANING VALIDATION (July 2004) 7. CLEANING VALIDATION 7.4 Documentation 7.4.1
[VIP ID: 188662]
“A Cleaning Validation Protocol is required laying down the procedure on how the cleaning process will be validated. It should include the following:
- Any routine monitoring requirement,”
EU GUIDE TO GOOD MANUFACTURING PRACTICE: ANNEX 15 - VALIDATION MASTER PLAN DESIGN QUALIFICATION, INSTALLATION AND OPERATIONAL QUALIFICATION, NON-STERILE PROCESS VALIDATION, CLEANING VALIDATION - SUPERSEDED! (October 1999)
4. Cleaning Validation 4.4. Documentation 4.4.1.
(g)
[VIP ID: 69090]
“A Cleaning Validation Protocol is required laying down the procedure on how the cleaning process will be validated. It should include the following: (g) any routine monitoring requirement,”
14. include sampling procedures, including the rationale for why a certain sampling method is used.
PI 006-2
RECOMMENDATIONS ON VALIDATION MASTER PLAN INSTALLATION AND OPERATIONAL QUALIFICATION NON-STERILE PROCESS VALIDATION CLEANING VALIDATION (July 2004)
7. CLEANING VALIDATION 7.4 Documentation 7.4.1
[VIP ID: 188662]
“A Cleaning Validation Protocol is required laying down the procedure on how the cleaning process will be validated. It should include the following:
- Sampling procedures, including the rationale for why a certain sampling method is used,”
Selected FDA 483 Observations (November 2003) Product Manufacture
[VIP ID: 72300]
“Cleaning Validation Protocols should include:
a. Specific instructions for sample collection and their frequency.”
EU GUIDE TO GOOD MANUFACTURING PRACTICE: ANNEX 15 - VALIDATION MASTER PLAN DESIGN QUALIFICATION, INSTALLATION AND OPERATIONAL QUALIFICATION, NON-STERILE PROCESS VALIDATION, CLEANING VALIDATION - SUPERSEDED! (October 1999)
4. Cleaning Validation 4.4. Documentation 4.4.1.
(h)
[VIP ID: 69100]
“A Cleaning Validation Protocol is required laying down the procedure on how the cleaning process will be validated. It should include the following:
(h) sampling procedures, including the rationale for why a certain sampling method is used,”
• include the taking of bioburden samples from sample sites before cleaning.
Selected FDA 483 Observations (February 2006) Sterile Product Manufacture
[VIP ID: 193140]
“Cleaning validation of equipment should include demonstration of worst case conditions such as the taking of bioburden samples from sample sites before cleaning.”
Selected FDA 483 Observations (August 2000) Active Pharmaceutical Ingredient Manufacture [VIP ID: 19580]
“There should be data to support the effectiveness of the cleaning procedures in reducing the bioburden on equipment used to manufacture APIs intended for parenteral use.”
15. clearly define the sample locations.
PI 006-2
RECOMMENDATIONS ON VALIDATION MASTER PLAN INSTALLATION AND OPERATIONAL QUALIFICATION NON-STERILE PROCESS VALIDATION CLEANING VALIDATION (July 2004)
7. CLEANING VALIDATION 7.4 Documentation 7.4.1
[VIP ID: 188662]
“A Cleaning Validation Protocol is required laying down the procedure on how the cleaning process will be validated. It should include the following:
- Clearly defined sampling locations,”
Selected FDA 483 Observations (November 2003) Product Manufacture
[VIP ID: 72300]
“Cleaning Validation Protocols should include:
b. Identification of the exact sampling points for rinse residue tests.”
Selected FDA 483 Observations (January 2003) Active Pharmaceutical Ingredient Manufacture [VIP ID: 51940]
“Cleaning validation should include:
(a) a description of the swab method to include where the samples are taken, how the samples are collected, and the amount of samples collected.
(b) the amount of rinse samples collected, and the location from where they are taken.”
Selected FDA 483 Observations (September 2001) Active Pharmaceutical Ingredient Manufacture [VIP ID: 40930]
“The exact/precise location of swab samples should be documented in cleaning validation studies.”
Selected FDA 483 Observations (November 2000) Product Manufacture
[VIP ID: 26190]
“Cleaning validation should include:
(2) a clear description of all sampling locations”
EU GUIDE TO GOOD MANUFACTURING PRACTICE: ANNEX 15 - VALIDATION MASTER PLAN DESIGN QUALIFICATION, INSTALLATION AND OPERATIONAL QUALIFICATION, NON-STERILE PROCESS VALIDATION, CLEANING VALIDATION - SUPERSEDED! (October 1999)
4. Cleaning Validation 4.4. Documentation 4.4.1.
(i)
[VIP ID: 69110]
“A Cleaning Validation Protocol is required laying down the procedure on how the cleaning process will be validated. It should include the following:
(i) clearly defined sampling locations,”
Selected FDA 483 Observations (October 1998) Product Manufacture
[VIP ID: 6844]
“The exact location of cleaning validation swab samples should clearly identified.”
Selected FDA 483 Observations (August 1998) Active Pharmaceutical Ingredient Manufacture [VIP ID: 6766]
“BPC cleaning validation should include:
4) precise identification of rinse sample locations”
Selected FDA 483 Observations (May 1997) Sterile Product Manufacture
[VIP ID: 2534]
“Cleaning Validation should include:
(7) identification of rinse sample collection locations”
16. include a description of the swab method to include how the samples are collected and the amount of samples collected.
Selected FDA 483 Observations (July 2007) Sterile Product Manufacture
[VIP ID: 193844]
“Validation data should be provided to support the surface monitoring procedure using the swab technique, and recovery data should be available relating to the qualification of laboratory personnel in the execution of this technique.”
Selected FDA 483 Observations (January 2003) Active Pharmaceutical Ingredient Manufacture [VIP ID: 51940]
“Cleaning validation should include:
(a) a description of the swab method to include where the samples are taken, how the samples are collected, and the amount of samples collected.”
17. define and justify the area to be swabbed for sampling.
Selected FDA 483 Observations (December 2006) Product Manufacture
[VIP ID: 194286]
“… The surface area to be swabbed should be specified in the protocol or documented, the total surface area of the equipment should be taken into account when setting the acceptance criterion and there should be written justification for the acceptance criterion.”
Extracted from FDA Warning Letter 320-05-03 (July 2005) Italy
21/07/2005 [VIP ID: 169210]
“3. Test methods and techniques are not adequate for their intended purposes. 21 CFR 211.160
a. Your justification of the use of a swabbing area of [redacted] is not adequate. We acknowledge that the USP section [redacted] includes a sampling area of [redacted]. However, this procedure is for a microbiological test, and your sampling is for chemical residues. We recommend using an area of at least 100 cm2 for this purpose. The swabbing is to detect low-level chemical residues of a sensitizing nature. Smaller sampling areas under these conditions have not been shown to be sufficient to ensure the detection of low levels of chemical residue in a containment monitoring program.”
Selected FDA 483 Observations (June 2003) Active Pharmaceutical Ingredient Manufacture [VIP ID: 52760]
“Cleaning validation should include:
(b) a scientific rationale for the sampling sizes to determine residuals.”
Selected FDA 483 Observations (January 2003) Product Manufacture
[VIP ID: 51880]
“Cleaning validation protocols should define the area to be swabbed for sampling.”
18. data to support sampling procedures with swab techniques for microbiological surface monitoring of equipment.
Selected FDA 483 Observations (March 2006)
Selected FDA 483 Observations (March 2006)