This presentation consist a consolidated list all Regulatory Guidelines for Cleaning Validation. Hyperlink of the applicable guidelines are also given in the presentation.

1. List of Cleaning
Validation
Guidelines

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3. Agency Name : U.S Food & Drug Asminstartion
Summary : Equipment and utensils shall be cleaned, maintained, and, as
appropriate for the nature of the drug, sanitized and/or sterilized at appropriate
intervals to prevent malfunctions or contamination that would alter the
safety, identity, strength, quality, or purity of the drug product beyond the
official or other established requirements.
 No Residue limit or specific acceptance criteria is mentioned.
 TOC is accepted as an acceptable method for monitoring residues
Guidelines Reference :
- 211.67 Equipment cleaning and maintenance ( April-19)
- Validation of Cleaning Processes (Aug-2014)
- Questions and Answers on Current Good Manufacturing Practices—
Equipment(July 2019)
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4. Agency Name : European Medicines Agency (EMA)
Summary : Review and evaluate pharmacological and toxicological data of
individual active substances and thus enable determination of threshold
levels as referred to in the GMP guideline. These levels can be used as a risk
identification tool and can also be used to justify carry over limits used in
cleaning validation.
 Calculation of PDE value form NAOEL
 No guidance how to calculate cleaning limit.
Guidelines Reference :
- Guideline on setting health based exposure limits (June 2015)
- Questions and answers on Guideline on setting health based exposure
limits (April-2018)
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5. Agency Name : Active Pharmaceutical Ingredients Committee (APIC)
Summary :The criteria of Acceptable Daily Exposure (ADE) or Permitted
Daily Exposure (PDE) are recommended to be used by companies to decide if
Dedicated Facilities are required or not and to define the Maximum
Acceptable Carry Over (MACO) of API’s in particular, in Multipurpose
Equipment.
 Applicable for Active Pharmaceutical Ingredients
 No guidance how to calculate cleaning limit.
 Inline with EMA & ISPE guideline
Guidelines Reference :
- Guidance on Aspects of Cleaning Validation In Active Pharmaceutical
Ingredient Plants (Sep 2016)
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6. Agency Name : World Health Organization (WHO)
Summary :The criteria of Acceptable Daily Exposure (ADE) or Permitted Daily
Exposure (PDE) are recommended to be used by companies to decide if
Dedicated Facilities are required or not and to define the Maximum Acceptable
Carry Over (MACO) of API’s in particular, in Multipurpose Equipment.
 Accepts the worst case approach to select representative approach
 Working Draft released in May 2020- Points to consider on the different
approaches – including HBEL– to establish carryover limits in 6 cleaning
validation…
Guidelines Reference :
- WHO good manufacturing practices for active pharmaceutical ingredients-
Annex 2 (2010)
- HEBL Related working draft (Aug 2020)
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7. Agency Name : Pharmaceutical Inspection Co-operation Scheme (PIC/S)
Summary :During an inspection attention should be paid to the risk
management of cross-contamination; however, the amount of time allocated
will depend upon the hazard level of the molecules, the type and number of
products handled, and the degree to which facilities are proven to be separated
and dedicated.
 PIC guideline exactly inline of EMA guideline
Guidelines Reference :
• Guideline on Setting Health Based Exposure Limits-PI 046-1 (July 2018)
• Cross-contamination in Shared Facilities PI-043-1(July 2018)
• Guide to Good Manufacturing Practice For Medicinal Products Part I-PI 009-
14(July 2018)
• Inspection Of Health Based Exposure Limit (HBEL) Assessments-PI 052-1
(June 2020)
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8. Agency Name : Therapeutic Goods Administration (TGA)
 No separate Guideline for TGA
 TGA adopts PICs Cleaning Validation Guideline PE009-13 (PIC/S Guide to
GMP)
Guidelines Reference :
- TGA interpretation and expectations for demonstrating compliance(Sep-
2020)
- Cleaning Validation Presentation-A regulatory perspective
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9. Agency Name : Health Canada (HC)
Summary : Cleaning procedures for products and processes which are very
similar do not need to be individually validated. This could be dependent on
what is common, equipment and surface area, or an environment involving all
product-contact equipment.
 Promotes Cleaning Validation by evaluation of worst case scenario.
 Clear instruction related to cleaning revalidation criteria.
Guidelines Reference :
- Cleaning Validation Guidelines -GUIDE-0028(January-2008)
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10. Agency Name : Parenteral Drug Association (PDA)
Summary : PDA has published two separate documents related to Cleaning
Validation. PDA Technical Report 29 for Actives and PDA Technical Report 49
for Biotechnology products. PDA Cleaning Validation Technical Reports are
the most comprehensive guides when it comes to going into the depths of the
Cleaning Validations and establishing a Cleaning Validation SOP for your
firm.
Guidelines Reference :
- PDA Technical Report 29: Points to Consider for Cleaning Validation (Dec
2012)
- PDA Technical Report 49: Points to Consider for Biotechnology Cleaning
Validation
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11. Agency Name : International Society For Pharmaceutical Engineering
(ISPE)
Summary :ISPE also revised its Baseline Guide on Risk-MaPP (Risk-Based
Manufacture of Pharmaceutical Products) and published in 2nd edition in
2017. The revisions are mostly in line with the 2015 EMA guideline on setting
HBELs.
Guidelines Reference :
- Baseline Guide Vol 7: Risk-Based Manufacture of Pharma Products 2nd
Edition
- Cleaning Validation Lifecycle - Applications, Methods, and Controls -Sep-
2020
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12. Agency Name : American Society For Testing and Materials(ASTM)
Summary :A unique thing about these standards is that it incorporates many
of the science-based, risk-based, and statistical concepts and principles
introduced in the FDA’s Guidance for Industry Process Validation. This guide
supports and is consistent with, elements from ICH Q8, ICH Q9, ICH Q10, and
ICH Q11.
Guidelines Reference :
- Standard Guide for Science-Based and Risk-Based Cleaning Process
Development and Validation-2018-ASTM-E3106
- Standard Guide for Derivation of Health-Based Exposure Limits (HBELs)-
2020-ASTM E3219
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Any questions?
You can find me at
avishek.sensarma8336055587@gmail.com