Cleaning Validation Master Plan - Non Sterile Solid
Table of Content:
1 Introduction
2 Responsibilities
3 Rationale and General Principles
3.1 Rationale
3.2 General Principles
3.3 Cleaning SOP or Instructions
3.4 Risk Based Approach
3.5 Selection of “Worst Case” – Product Bracketing Strategy
3.6 Assessment of New Products
3.7 Preparation and Approval of Protocols and Reports
3.8 Acceptance Criteria
3.9 Priority, Schedules and Documentation
3.10 Cleaning Strategies
3.11 Clean Hold Time
3.12 Dirty Hold Time
3.13 Campaign Cleaning
3.14 Re – Validation
3.15 Manual Cleaning Procedures – Monitoring
3.16 Cleaning Validation Program – Required Documents Table
4 References
Sample Content
[Enter company name] manufactures and distributes a range of sterile and non-sterile, liquid, veterinary biological and pharmaceutical products from their sites [address].
The GMP facility has Code of Good Manufacturing Practice (cGMP) licenses with the [List all licenses].
[Enter company name] core business focus is manufacturing and packaging pharmaceuticals and veterinary medicines in various forms. These include oral and pour–on drenches, powders, creams, ointments, lotions, pastes and tablets.
This document aims to summarise the overall intentions and approach to the validation of the facility, equipment and processes.
It is intended to be a working document and will be periodically updated by site management responsible for the execution of validation.
Validation study design
Identifying and providing the appropriate level of resource in order to execute the cleaning validation exercises
Identification of process equipment trains and selection of worst case products for validation
Calculation of cleaning limits for equipment / processes
Training of Operators in Cleaning SOPs
Writing and execution of protocols
Review of QC results and final report writing
Rinse and Swab Sampling
Conduct analytical test method validation
Testing of swab and rinse samples
Validation cleaning studies discrepancy resolution
Update of this CVMP when required
Pharmaceutical products can be contaminated by other products (cross contamination), by cleaning agents, by micro-organisms or by foreign matter. In a multipurpose facility the same (common) equipment may be used for many different products and therefore to avoid cross contamination of the next product adequate cleaning is essential.
The objective of cleaning validation is to verify the effectiveness of the documented 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. In addition, one needs to ensure there is no risk associated with cross contamination of active ingredients.
The following general principles apply to cleaning validation:
Only cleaning procedures for product contact surfaces are subject to validation. Only cleaning procedures for “product to product” changeover (common equipment) will be fully validated.
Cleaning procedures for products and processes which are very similar do not need to be individually validated. Documented grouping or bracketing of similar products and similar equipment trains is acceptable provided a documented risk assessment is undertaken.
Dedicated equipment is confirmed as visually clean following “same product to same product” cleaning procedures. The verification is documented on the batch record prior to commencing subsequent batches.
Cleaning validation must, where relevant, address removal of cleaning agents and micro-organisms as well as active drug substances/products.
Where cleaning validation is required, a combination of analytical testing for residues on equipment surfaces, analysis of flush volumes and visual inspection is required. A successful validation must pass all three criteria.
Equipment cleaning validation may be performed concurrently with actual production steps during process development and clinical manufacturing. Validation programs should be continued through full scale commercial production.
The primary methods of analytical testing will be based on swab analysis (of predefined “worst case” locations) and or rinse sampling. It will be assumed that all contamination detected will be incorporated into the subsequent batch and that it will be uniformly distributed.
Where sampling detects no residues, calculations of residue will assume residues to be at the limit of detection of the test method. This “worst case” value will be used in residue calculations.
Bracketing of products may be used to validate a common cleaning procedure. In such cases, the acceptance criteria and swab analysis will be based on “worst case” combinations as detailed below.
A maximum (dirty hold) time between end of use of equipment and cleaning must be defined and included in the validation study.