Regulatory Requirements and Guidelines for Cleaning Validation : Pharmaguideline

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Regulatory Requirements and Guidelines for Cleaning Validation

Cleaning validation is an essential regulatory requirement, it includes cleaning procedure, validation protocol, study and acceptance criteria.
Cleaning validation is an important part of pharmaceutical manufacturing and regulatory agencies take it very seriously. FDA issues many warning letters due to improper cleaning of facilities and equipment in various pharmaceutical manufacturing firms every year. Cleaning validation helps to ensure cleanliness to prevent cross-contamination to maintain product quality. 

Various pharmaceutical regulatory agencies like the Food and Drug Administration (FDA), International Council for Harmonization (ICH) and European Medicines Agency (EMA) and other regulatory bodies have established the standard requirements for cleaning procedures. In this article, we will explore the cleaning validation requirements and guidelines provided by these regulatory agencies.

Regulatory Requirements on Cleaning Validation

A. FDA Regulations

1. 21CFR part 211 Section 211:67 of CFR by FDA provides guidance to clean the equipment and utensils used in pharmaceutical manufacturing. It also emphasizes having a written cleaning procedure and assignment of cleaning responsibilities. To prevent the batch from contamination, cleaned equipment must be protected from contamination until they are used in manufacturing.

2. FDA Guide to Inspections Validation of Cleaning Processes: It provides guidance to create a cleaning validation plan and conduct a validation study according to the written cleaning validation protocol. Cleaning procedures, sampling techniques, and establishment of limits for cleaning validation are discussed in detail in this document.

B. International Council for Harmonization (ICH) Regulations

cleaning validation

1. ICH Q7 - Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients: It provides the outline of cleaning validation to prevent the product from cross-contamination on page no 34. It doesn’t address specifically the cleaning validation but it emphasizes the importance of the cleaning procedures in API manufacturing. It guides to monitor the cleaning of equipment regularly.

2. ICH Q9 - Quality Risk Management: It reminds the manufacturers about the risks associated with the manufacturing. It encourages the to have a risk-based approach to cleaning validation. It focuses on critical areas with the highest risk where contamination may occur.

C. European Medicine Agency (EMA)

1. EudraLex Volume 4, Annex 15 - Qualification and Validation: It provides guidance on qualification and validation in pharmaceutical manufacturing. It has recommendations for cleaning validation, validation protocol, acceptance criteria, and their documentation.

2. Guideline on setting health-based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities: This EMA guideline provides the health based exposure limits in shared facilities and also offers the procedure for cleaning validation and determination of acceptance criteria.

Key Components of Cleaning Validation Guidelines

Now let us know the main components of the cleaning validation guidelines by regulatory agencies.

Documentation: All regulatory guidelines highlight the importance of documentation of all activities done during cleaning validation like cleaning procedure, validation protocol, and acceptance criteria in detail and in the sequence they occur.

Risk Assessment: All guidelines recommend to have a risk-based approach to cleaning validation where the companies must assess the potential risk in cleaning procedures of equipment during manufacturing.

Validation Study: A validation study should be conducted on the cleaning procedure to demonstrate the effectiveness of the cleaning procedure. It must show to remove the contamination from the facility and equipment effectively.

Acceptance Criteria: On the basis of safety and regulatory requirements, clear and scientifically justified acceptance criteria should be established before the validation study starts. It should be written in a pre-approved cleaning validation protocol.

Continued Monitoring: It is essential to monitor continuously the effectiveness of the cleaning procedure. It ensures ongoing compliance with regulatory standards.

Frequently Asked Questions (FAQs) on Cleaning Validation

Following are some frequently asked questions and their answers that will help you to understand the topic better.

Q1: Why is cleaning validation important in pharmaceutical manufacturing?

Ans: Cleaning validation has great importance in pharmaceutical manufacturing because it ensures product quality, prevents cross-contamination and helps to comply with regulatory requirements.

Q2: Which regulatory agencies provide guidelines for cleaning validation in pharmaceutical manufacturing?

Ans: Regulatory agencies like the FDA, EMA and ICH offer cleaning validation guidelines and requirements.

Q3: What are the key components of cleaning validation guidelines outlined by regulatory agencies?

Ans: Preparation and documentation of the cleaning procedure, risk assessment related to cleaning, validation study and continued monitoring of the cleaning process are key components of the cleaning validation requirements.

Q4: What are the documentation requirements for cleaning validation according to regulatory agencies?

Ans: In the documentation, documented cleaning procedure, validation protocol, acceptance criteria and validation activities done during validation must be documented properly.

Q5: What are acceptance criteria, and how are they established for cleaning validation?

Ans: Acceptance criteria are the limits specified before doing any test or validation that must be fulfilled by the equipment or product under testing. They are established on the basis of the regulatory requirements and must be scientifically justified.

Q6: How often should cleaning validation studies be conducted in pharmaceutical manufacturing?

Ans: Initially during the establishment of the cleaning procedure the cleaning method should be validated and thereafter its effectiveness must be validated periodically based on product complexity, equipment design and specific regulatory requirements.

Q7: What are the consequences of non-compliance with cleaning validation guidelines?

Ans: Non-compliance in pharmaceuticals is a serious issue and it can result the product recall and loss of company reputation. It is essential to fulfill the regulatory requirements, in such cases FDA issues a warning letter to the manufacturer.

If you still have any questions, please post them in the comment section, we shall answer your questions soon.
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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