cleaning validation "part 1"

MEDIZEN FOR PHARM. IND.By Ibrahim Ghareeb

CLEANING VALIDATIONPART 1

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WHAT IS VALIDATION ? The process of providing documented evidences, that provides a high degree of assurance that specific process, method, will consistently produce a result with pre – determined acceptance criteria.

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EFFECTIVENESS OF CLEANING4

REGULATIONS

“Particular attention should be accorded to the validation of … cleaning procedures” (WHO)

“Cleaning validation should be performed in order to confirm the effectiveness of a cleaning procedure” (PIC/S)

“The data should support a conclusion that residues have been reduced to an ‘acceptable’ level” (FDA)

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21 CFR 211.65 a) Equipment …. surfaces which contact components, in-

process materials, or drug products shall not be reactive, additive or absorptive…..

21 CFR 211.67 Equipment and utensil …. cleaned, maintained, and

sanitized at appropriate intervals to prevent …or contamination that would alter the safety, identity, strength, quality, or purity ……

21 CFR 211.182 Written cleaning Procedure Cleaning and use log

Guidance Guide to Inspection for Validation of Cleaning Processes. FDA, 1993

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Objective

The objective of the Cleaning Validation is the confirmation of a reliable cleaning procedure so that the analytical monitoring may be omitted or reduced to a minimum in the routine phase.

SO, Cleaning procedures must strictly follow carefully established

and validated methods of execution. This applies equally to the manufacture of pharmaceutical products and active pharmaceutical ingredients (APIs). In any case, manufacturing processes have to be designed and carried out in a way that contamination is reduced to an acceptable level.

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PRINCIPLES

CLEANING SOPPRODUCT GROUPINGWORST CASE SELECTIONSETTING ACCEPTANCE CRITERIASAMPLING METHODS

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CLEANING SOP

TWO CONSIDERATION ARE TAKEN:1- CLEANSING AGENTChemistry,temperature and time

2- EQUIPMENTMechanics and cleaning tools

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CLEANSING AGENT10

1- Chemistry- Solubility of both excipients and API.- Detrmining solubility of API in different

PHs.2- Temperature-Accelerating agent and for microbial aspect-Assuring the temperature constancy-Assuring the temperature control

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3- Time-Minimizing the time required to take effect

using optimum arrangement of chemical, temperature and mechanical factors

Critical inspection of working procedures within the total process (pre-cleaning,assembly/disassembly, rinsing, drying)

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EQUIPMENT

1- Mechanics:

-Type of cleaning:CIP,COP and manual- Difficult to clean locations in equipment

should be determined that they will be sampling location during CV.

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2- Selection of suitable tools (e.g. sponges, brushes, high-pressure cleaners) while considering material and surface compatibility.

ConditionsDo not produce fibers.Disposable as possible.

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Once all the details of the cleaning procedure have been firmly established, a written cleaning instruction (SOP) has to be established.

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The following specifications must be contained in SOP:

Cleansing agents and concentration of the cleaning solution

Quantity and temperature of the cleaning solution Mechanics(non accessible areas) Cleaning time and cleaning cycles Rinsing and secondary treatment Assembly and disassembly procedures required for

cleaning

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PRODUCT GROUPING

Bracketing(grouping)"Cleaning procedures for products and processes

which are very similar, do not need to be individually validated. It is considered acceptable to select a representative range of similar products and processes concerned and to justify a validation programme which addresses the critical issues relating to the selected products and processes. A single validation study under consideration of the `worst case' can then be carried out which takes account of the relevant criteria. This practice is termed `Bracketing'." (PIC/S PI006)

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Bracketing for products: According to risk groups that are:-Risk factor "solubility" :The product contains a

poorly soluble active pharmaceutical ingredient.-Risk factor “Potency“: The product contains a highly

potent active pharmaceutical ingredient(lowest API conc./dose).

-Risk factor "formulation”:The product contains formulation components that are difficult to remove, such

as grease matrices, dyes or flavors.

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CASE STUDY19

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WORST CASE SELECTION

Two possible approaches

product-specific implementation equipment-specific implementation

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For the product-specific approach, a validation protocol is compiled for every critical product that includes all types of equipment necessary for the production process.

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For the equipment-specific approach, a validation protocol is compiled that includes all critical products manufactured on this equipment.

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