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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.


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.


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


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].


  • 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.

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The same methodology needs to be dedicated when choosing a vendor for your business. Not only will you be purchasing their products or services, but you will also be dealing with them on a regular basis hence your personal relationship most also be strong.

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About Us

Learnaboutgmp is a cloud based learning management system (LMS) designed specifically for life science and regulatory organizations. Our LMS contains the courses you need to help you achieve regulatory compliance. With new courses published every month and existing courses updated in line with regulatory changes we are your true continuous learning platform.


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Choosing the correct software for your organisation is a tricky task and even more so when you are working in a regulated environment.

It’s one thing finding a great software package but if the vendor does not take their quality system seriously this could have a dramatic effect on the evolution and robustness of the solution.

They need to take their quality efforts as seriously as you take yours otherwise product quality and patient safety could be compromised.

An overall quality audit should be performed on each vendor before a decision is made, below are a list of questions that you could ask each vendor specifically on their quality system.

If the software vendor does not take their Quality System seriously you need to walk away.

Quality System Questionnaire

  1. Does the company have an established and Documented Quality System?
  2. Does the Quality System adequately reflect the client’s quality engineering policies?
  3. Is the responsibility for Quality defined (SOP)? What are their qualifications?
  4. Is Quality System documentation adequately controlled in terms of review, approvals and distribution
  5. Is the QS documentation regularly updated and otherwise maintained appropriately? (frequency)
  6. Are there procedures for reviewing the performance of the QS e.g. Internal Audit, Management Review?
  7. Are there training procedures and Job specifications? Are these adequate for the Maintenance of the QS
  8. Is there a Quality Plan for the Design, Development and Implementation of the products?
  9. Do the company use Sub Contractor’s?
  10. Do the company have control over any Sub Contractor’s QS? e.g. Vendor Assessment, Specification, Documentation review and approval?
  11. Do the company have access to relevant Sub-contractor Quality documentation?
  12. Is Sub Contractor’s Quality System compatible with the previous questions of this section?
  13. Have the Sub Contractors been audited? Review the report?
  14. Has accreditation/registration been achieved for: BS 5750 Pt. 1 or 2, TickIT, ISO 9000, Other (name
  15. Does the company operate to GAMP for computer systems?
  16. Are there SOPs for QC? Is there a release procedure?
  17. Is there an out-of-specification procedure?

Choosing the correct software application for your organization is a very tricky task and one that takes alot of upfront planning in order to make the correct choice.

The task has even got more difficult with the emergence of cloud based technology and how that impacts the overall validation process.

Remember to outline your requirements clearly and get buy-in from the other business owners.



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