CLEANING VALIDATION IN PHARMACEUTICAL INDUSTRY: A COMPREHENSIVE APPROACH

 

 

ABOUT AUTHORS:
Sharma A*, Vaghela J.S, Sharma P, Sharma B, Agrawal M, Jagiwala S
Department of Quality Assurance, Bhupal Nobles’ College of Pharmacy,
Udaipur- 313002, Rajasthan, India
*life4abhishek@gmail.com

ABSTRACT
Pharmaceutical manufacturers must validate their cleaning process to ensure compliance with standard regulatory authorities. Manufacturing and cleaning equipment must be designed for effective and consistent cleaning to avoid cross-contamination and the cleaning processes must be verified as effective. An effective cleaning shall be in place to provide documented evidence that the cleaning methods employed within a facility consistently controls potential carryover of product including intermediates and impurities), cleaning agents and extraneous material into subsequent product to a level which is below predetermined levels. This article provide introduction on cleaning validation and the associated regulations, level/degree of cleaning, approaches to cleaning validation, elements of cleaning validation, acceptance criteria, validation protocols, validation reports.


REFERENCE ID: PHARMATUTOR-ART-1755

1. INTRODUCTION
It is documented evidence with a high degree of assurance that one can consistently clean a system or a piece of equipment to predetermined and acceptable limits. The validation of procedures used to clean the equipment employed during the various steps of a manufacturing process is a clear requirement of current Good Manufacturing Practice (cGMP). Cleaning validation is primarily applicable to the cleaning of process manufacturing equipment in the pharmaceutical industry. Cleaning validation is the process of assuring that cleaning procedure effectively removes the residue from manufacturing equipment/facilities below a predetermined level.Cleaning validation is primarily used for the cleaning of process manufacturing equipment in the pharmaceutical industries. The main purpose of validating a cleaning process is to ensure compliance with standard regulatory authorities and the identification and correction of potential problems previously unsuspected, which could compromise the safety, efficacy or quality of subsequent batches of drug product produced within the equipment.

The term cleaning validation is to be used to describe the analytical investigation of a cleaning procedure or cycle. The validation protocols should reference background documentation relating to the rationale for worst case testing, where this is proposed. It should also explain the development of the acceptance criteria, including chemical and microbial specifications, limits of detection and the selection of sampling methods.

The basic reason for having good, effective, consistent cleaning procedures is to prevent the contamination of products made subsequently in the same equipment. The goal is to provide pharmaceutical products of the highest quality to our patients. This is the basic regulatory requirement as well as the goal of all of those suppliers of products and services.

The focus of cleaning validation is those cleaned surfaces that, if inadequately cleaned, could potentially contaminate the product subsequently manufactured in that same equipment. This primarily covers product contact surfaces in the cleaned equipment. Cleaning validation is not performed only to satisfy regulatory authorities. The safety of patients is the primary objective, and product contamination presents serious liability issues for any pharmaceutical manufacturer or contract organization. The basic mechanisms involved in removing the residues and contaminants from the equipment are mechanical action, dissolution, detergency and chemical reaction.

  • Mechanical action – It refers to the removal of residues and contaminants through physical actions such as brushing, scrubbing and using pressurized water.
  • Dissolution – It involves dissolving the residues with a suitable solvent. The most common and practical solvent is water being non-toxic, economical, environment friendly and does not leave any residues. Alkaline and acidic solvents are sometimes preferred as it enhances the dissolution of the material, which are difficult to remove.
  • Detergency-Detergent acts in four ways as wetting agent, solubilizer, emulsifier and dispersant in removing the residues and contaminants from the equipment.
  • Chemical reaction- Oxidation and hydrolysis reaction chemically breaks the organic residues.

2. OBJECTIVE OF CLEANING VALIDATION
The objective of the cleaning validation is to verify the effectiveness of the cleaning procedure for removal of product residues, degradation products, preservatives, excipients, and/or cleaning agents as well as the control of potential microbial contaminants. In addition one need to ensure there is no risk associated with crosscontamination of active ingredients. Cleaning procedures must strictly follow carefully established and validated methods.

It is necessary to Validate Cleaning procedures for the following reasons:

  • Pharmaceutical products and API can be contaminated by other pharmaceutical products, cleaning agent & microbial contamination.
  • It is regulatory requirement in pharmaceutical product manufacture the concern is the same-assurance that equipment is clean and that product quality and safety are maintained.
  • It is also assure from an internal control and compliance point of view the quality of manufacture.
  • To protect product integrity
  • To reuse the equipment

Other Objectives
- Solvent reduction,
- Shorter cleaning times, increased equipment
- Utilization, extension of equipment life, multiproduct
- Facilities, worker safety, and cost-effectiveness.

“Equipment and utensils shall be cleaned, maintained, and sanitized 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”.

The main objective of cleaning validation of equipment / utensils / components is to demonstrate sufficient documented evidence to ensure that the cleaning process can consistently remove residue of the subjected product below the established Acceptance Criteria.

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