The Cleaning Validation Process

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1 The Cleaning Validation Process The Scope of Cleaning Validation The Cleaning Validation Sequence Prerequisites Cleaning Validation Strategy, Plan, and Policy Sampling Recovery Studies Analytical Method Selection and Development Analytical Method Validation Acceptance Criteria Cleaning Method Development Validation Master Plan Cleaning Validation Plan 15

2 Cleaning Process Standard Operating Procedures (SOPs) Cleaning Validation Protocols Protocol Execution Clean and Dirty Hold Times Validation Report Post Validation Monitoring Maintaining the Validated Status Retrospective Cleaning Validation Glossary What You Learned 16

The Scope Of Cleaning Validation Normally, only cleaning procedures for surfaces of the equipment that come into contact with product need to be validated.

3 The Scope Of Cleaning Validation Normally, only cleaning procedures for surfaces of the equipment that come into contact with product need to be validated. To be more effective, however, programs for the elimination of crosscontamination must also address non-product contact surfaces. When establishing prerequisites for non-product contact surfaces, you must review the probable interactions of those areas. Cleaning validation is usually only needed for critical cleaning, e.g. between manufacturing of one product and a different product and is not normally necessarily for non-critical cleaning such as between batches of the same product (or different lots of the same intermediate in a bulk process). In API manufacturing, it may be unnecessary to validate equipment cleaning where residues are removed by subsequent purification steps. Products that simulate the physiochemical properties of the substance to be removed may be used instead of the substances themselves, where such substances are toxic or hazardous. The intervals between use and cleaning, as well as cleaning and reuse, 17

4 should also be validated. Cleaning intervals and methods should be determined. It is the responsibility of the manufacturer to demonstrate that the level of cleaning and validation performed is adequate based on each individual situation and on a justifiable scientific rational. Microbiological aspects should be considered, although they should consist largely of preventative measures rather than the removal of contamination once it has occurred. (WHO) 18

The Cleaning Validation Sequence CLEANING VALIDATION PROCESS (Prospective) Cleaning Validation Strategy Process & Product Development Validation Master Plan Analytical Methods Identified / Developed

5 The Cleaning Validation Sequence CLEANING VALIDATION PROCESS (Prospective) Cleaning Validation Strategy Process & Product Development Validation Master Plan Analytical Methods Identified / Developed Cleaning Agents & Methods Identified Analytical Methods Validated Cleaning Method Developed Recovery Studied Completed Sample technique and Methods of Detection identified Establishment of Acceptable Levels of Carry-over Refining Acceptable Levels of carry-over Cleaning VP Cleaning SOPs Created Cleaning Validation Protocol Validation Summary Report Execution of Protocol Revalidation 19

Pre-requisites Before beginning cleaning validation, the following should be available and completed: Agreed company strategy and policy; Cleaning methodology; Defined sampling methodology; Completed

6 Pre-requisites Before beginning cleaning validation, the following should be available and completed: Agreed company strategy and policy; Cleaning methodology; Defined sampling methodology; Completed analytical method selection / development; Validation of analytical methods; Defined acceptance criteria; Validation Master Plan; Cleaning Validation (Master) Plan; Creation of related SOPs; Cleaning Validation Protocol. 20

Cleaning Validation Strategy, Plan & Policy The cleaning validation policy should incorporate the following: A statement specifying what company policy is on validation of cleaning procedures related

7 Cleaning Validation Strategy, Plan & Policy The cleaning validation policy should incorporate the following: A statement specifying what company policy is on validation of cleaning procedures related to equipment (including ancillary) and processes, such as: Cleaning only after product changeover or between batches in campaigns; Cleaning of major and minor equipment; Company policy on the dedication of all equipment for each product, (if products are deemed too dangerous and / or highly active to manufacture on multi-product equipment); Company policy on the grouping of products or equipment such as: Validate the cleaning of each product individually; Bracketing / grouping products for cleaning validation; Bracketing / grouping equipment for cleaning validation; Selection of worst case products; Sampling Methodology to be used; Analytical validation policy; The rational for the methods by which acceptance criteria is 21

8 determined; Revalidation policy; Glossary / Definition of terms employed during validation (for example, rinse, flush, wash and so on). Campaign Production and Batch Production Campaign production always helps in minimizing cross-contamination issues between lots. In a multiple-product facility, campaign lots of a single product or product family are produced in the same equipment. At times, the production run may be stopped for a partial cleanup of the equipment, which is less stringent than a full cleanup. Once the campaign production is over, an intensive cleaning of the facility and equipment can be performed before starting production of a different product. Minor and Major Equipment Although there is no such terminology as minor equipment in current good manufacturing practices (cgmps), items such as utensils may be regarded as minor equipment. Major equipment represents those that play a central role in production processes. Typically, the cleaning of major equipment will be the subject of specific standard operating procedures (SOPs) and it is important to differentiate those pieces of equipment that are central to the production process from those that perform a secondary role (utensils). 22

Manual: 038. Cleaning and Cleaning Validation of API Plant and Equipment

Manual: 038. Cleaning and Cleaning Validation of API Plant and Equipment Title: Cleaning and Cleaning Validation of API Plant and Equipment Manual Number: 38 Prepared by: Date: Supersedes: Checked by: Date: Date Issued: Approved by: Date: Review Date: Manual: 38 Cleaning and