Risk Assessment in Cleaning Validation – An Overview

The cleaning processes of multiple product use equipment in API facilities are subject to requirements for cleaning validation. The validation effort could be huge. In order to minimize the amount of validation required, a risk assessment based approach for the validation can be used.

Introduction

It is an ethical worldwide acceptable aspect to use clean item / objects for use / consumption. Irrespective of manufacturing process, cleaning is the first aspect which is ensured by the individuals / organizations even in day-to-day life. This article will cover the basics of cleaning concepts employed to ensure how much clean is clean.

Application

Cleaning aspect is employed with a general objective i.e. for removal of contaminants / residue. In case of pharmaceutical industry, pharmaceutical products & APIs can be contaminated by other pharmaceutical products or APIs, by cleaning agents, by other materials (i.e. dust, lubricants, air-borne particles) & by micro-organisms.

In many cases same equipment may be used for processing of different products & to avoid the contamination, adequate cleaning procedures are essential.

Cleaning Validation in Pharmaceutical Industry

Since the pharmaceutical industries are involved in business of vital life saving drugs, hence it is required by law & with aspects of patient safety. Let’s have a quick view on requirements by law:

1. 21 CFR Part 210 & 211, USFDA [$211.67. Equipments & utensils shall be cleaned, maintained & sanitized at appropriate intervals to prevent malfunctions or contaminations that would alter the safety, identity, strength, quality or purity of the drug product beyond the official or other established requirements] & [$211.113 Control of microbiological contamination].

2. Schedule-M [Equipment design, size & Location: $4.2 If the equipment is used for different intermediates & APIs, proper cleaning before switching from one product to another becomes particularly important].

In addition to above mentioned laws there are so many other laws from various regulatory agencies.

Key factors of cleaning validation:

  • Selection of equipments [Based on worst case approach].
  • Appropriate solvent / detergent [Based on Solubility data].
  • Cleaning procedure [Hand scrubbing / solvent wash /Clean In Place / Clean Out of Place / Quantities / time / Pressure / temperature].
  • Level of cleaning required [Based on the risk assessment].
  • What is clean [Acceptance criteria based on the visually clean / Rinse Limit / Swab Limit / Microbiological aspects]

No. of times cleaning required [To achieve acceptance criteria, however “test until clean” is not acceptable].

  • Interval between the end of production & the beginning of the cleaning procedures [Dirty Equipment Hold Time Study].
  • The period and when appropriate, conditions of storage of equipment before cleaning & the time between cleaning and equipment reuse [Clean equipment Hold time study].
  • Analytical Methods / Recovery studies
  • Training of personnel

In addition to all these consideration the Top most requirements are sequential, accurate, scientifically justified & reliable documentation.

Risk assessment in Cleaning validation

In order to minimize the amount of validation required, a worst case approach for the validation can be used; instead of the investigation of each individual cleaning situation similar situation could be grouped.

Worst case rating priority will then support a conclusion that the cleaning procedures are effective for all drug substances within the bracket, including those not individually tested

In order to select the extent of cleaning process formal risk assessment should be carried out based on the factors under considerations i.e. Toxicological / pharmacological activity of the previous product, its side products or degradants, Maximum daily dose of the next product, Microbiological growth, Batch size of the following product, Solubility, experience, difficult to remove previous product etc. This will results in scientific justified rational for cleaning validation in multi product manufacturing facility.

Benefits of Risk Assessment

1. Required extent of cleaning can be evaluated & reduced.
2. Practical, achievable and verifiable limits can be decided based on the grouping into groups of risk (e.g. Very soluble products, similar potency, highly toxic, difficult to detect].
3. Scientific rational based study, hence more convenient to explain during Audits

References

1. 21 CFR Part 210 and 211 [USFDA].
2. Good manufacturing practices and requirements of premises, plant & equipment for pharmaceutical products [Schedule-M].
3. GUIDE-MQA-008-007 “cleaning Validation” Dec-2008 [Health Science Authority].
4. “Guidance on aspects of cleaning validation in active pharmaceutical ingredient plants” Dec-2000 [Active Pharmaceutical Ingredient Committee].

0
shares

  • metalslayer

    It is very helpful information. And, How to do risk assessment for sampling points also should be discussed.

  • metalslayer

    It is very helpful information. And, How to do risk assessment for sampling points also should be discussed.

Similar articles:

The Four Phases of Conducting a Laboratory Investigation [Video]

The process which will be described here is based on the process discussed in the MHRA’s guidance on Out of Specifications Investigation.

When an out of specification, atypical or suspect result is obtained, it is particularly important that all solutions and reagents associated with the test are retained, as this will greatly assist the investigation.

The MHRA advocate laboratory investigations should proceed in four phases as follows:

Phase I(a)

Phase I (a) consists of a preliminary review, by the analyst, to determine whether there has been a clear and obvious error or event that caused the OOS, atypical or suspect result.

Phase I(b)

Phase I (b) occurs after phase 1(a) has failed to identify a clear and obvious cause. This is a more detailed investigation by the analyst and supervisor to identify a laboratory assignable cause.

Phase II

Phase II occurs after the phase I investigation has failed to identify a laboratory assignable cause for the OOS, atypical or suspect result and are driven by written and approved instructions in order to test particular hypothesis.

Phase III

In Phase III all the information obtained during Phases I and II of the laboratory investigation, and any manufacturing investigation, is reviewed and assessed, and a decision is made on the disposition of the batch

Learn More About Laboratory Investigations

If you would like to learn more about laboratory investigations click here for an overview of this course.

0
shares

Similar articles:

New Feature Release: LMS Fully Mobile Responsive

September has been a big month for releases at Learnaboutgmp, with our new fully responsive user interface coming officially out of beta.

If you are a premium member of our platform, you will see first-hand how intuitive and smooth the new UI feels.

Fully Mobile Responsive

We are now fully mobile responsive, giving you flexibility and ensuring you have a great experience on any device, at any time

Tablet

Mobile

A Beautiful New Interface

If you have signed up for our company license (5 or more users) then you can avail of the brand new styling options from the admin panel including:

  1. Customizable Portal Logo
  2. Header Color
  3. Background Color
  4. Link/Active Tab Color
  5. Course Thumbnail Image
  6. Course Info Snapshot

Easy, Consistent Navigation

The primary navigation menu, secondary navigation and page actions are presented consistently throughout the portal, making it easy to find what you need:

  1. Primary Navigation Menu
  2. Page Actions

New Smart Search

Powerful new search capabilities allow you to search for courses, users, and groups.
Smart search saves you time by providing a menu of actions for common Administrator tasks, making updates quick and easy.

Intuitive Settings Menu

The reorganized settings menu groups together related Administrator tasks, e.g. around portal set up and branding, courses, and users, allowing Administrators to easily click through the options and complete their updates.

Online Demo

If you would like to see what our new interface looks like please click the button below to sign up for an online demo today.

DEMO SIGNUP

9
shares

TOP

Similar articles: