How to Prepare a "Contamination Control Strategy" Document?

After the GMP Annex1 revision in August 2022, one of the most common questions we all asked was: "How to develop a contamination control strategy?". In the pharma world, we have been implementing contamination control measures for decades as part of our routine. However, the new GMP Annex 1 came with another definition; CCS; Contamination Control Strategy.

What is Contamination Control Strategy?

According to GMP Annex1, CCS is a planned set of controls for microorganisms, endotoxin/pyrogen, and particles, derived from current product and process understanding that assures process performance and product quality. The controls can include parameters and attributes related to active substances, excipient and drug product materials and components, facility and equipment operating conditions, in-process controls, finished product specifications, and the associated methods and frequency of monitoring and control.

What we should understand from this definition?

The CCS document is an umbrella document; a summary of all our activities to identify, control and prevent contamination at every critical control point so that the document can guide your audience (inspectors, auditors, your GMP site employees etc.) on our process. Like IKEA instructions; nothing more nothing less, easy to understand, and can guide us from the first piece till the end of our process.

3 Easy Steps to Prepare CCS

Let's start with the easiest and the most "catchy" way;

1. Identify your contamination sources,
2. Define critical control points, process risks & prevent
3. Build your strategy to monitor and control

What do you need to build a proper Contamination Control Strategy?

• Process and technical knowledge,
• Define the entire process workflow,
• Define critical control points
• Define risk and identify risk levels,
• Minimize the risk of contamination
• Assess, control, and monitor individually ?
• Consider collective effectiveness together.

Template of a proper Contamination Control Strategy Document

First think first; keep it simple and lean. The best CCS document will be around 30-40 pages only. Remember, this is your summary document, no need to add all your SOPs, measures, and technical & site knowledge into this file. Don't say "shall may" etc. This is a proof document of the activities that you have already done.

Sections for your CCS document;

1. Purpose

Say something like "..to protect product quality from viable and non-viable particulate, pyrogens, endotoxin and any sort of viral contamination" Make your statement here clearly.

2. Background

Describe what you have learned from CCS requirement, why we need it, and how we execute through this document

3. Scope

(where and how you achieve your CCS targets. Describe the product, process, facility, etc. Write down your controls here).

4. Responsibility

(Who is involved and what are their responsibility? Example; Quality – to ensure that the policy remains current )

5. CCS Elements

Address control parameters that are mentioned in your scope section items one by one here

6. Glossary

Relevant site definitions and abbreviations are here

7. Reference Documents

(SOPs, site validation, risk assessments, and other docs that are mentioned in this document. Do not put the entire document as an annexure/attachment. Just mention their doc number/title here. The auditor will know where to find it :)

8. Revision History

Table showing revision no., Date, and Summary of Changes. Keep in mind, CCS is a living organism so there should be several revisions with a valid rationale behind it.

Is there any guide that we can use while preparing the CCS?

PDA, Parenteral Drug Association, recently published a nice Technical Report; "TR No.90 CCS Development in Pharmaceutical Manufacturing"

I highly recommend this Technical Report. You can find it at the PDA Bookstore. Simply click on an image to review and purchase.

If you are a member of PDA, or your organization is a corporate member, you can download it for free depending on your membership tier.

Latest Webinar "How to classify cleanrooms?"

On our webinar series, the topic for this month was "How to classify cleanrooms?". This was a very well-attended event with over 300 attendees and with 90/100 Average Interest Rating. The topic was quite hot, especially right after GMP Annex1 major revision on the classification table, with significant changes in min. sample volume etc. If you are not able to attend, feel free to watch it again with an on-demand link here;

Watch the Webinar; Fill in the GAP Good Application Practices – How to classify cleanrooms?

I got this question right before my webinar yesterday;

Which particle sizes must be measured during the re-classification of Grade A and Grade B cleanrooms used for manufacturing sterile products (at rest and in operation conditions)? Taking into consideration that no limits are defined in Annex 1 for 5.0μm particles for Grade A nd Grade B In-Operation. What is the minimum limit that we can use during re-classification?

Excellent question indeed! Especially, while GMP revision takes us from the 5-micron limit and 1000-liter sample to the single size, 0.5 microns with 5.6 liters only! This is quite a major change! Imagine, your July 2022 re-qualification was on 1000 liters, -assuming that you are using a 1CFM (28.3LPM) device- that will take 36 minutes in each and every location. A month later, a 1-minute sample with the same particle counter is now enough, plus, no need to sample 5 microns for classification (still exists for monitoring BTW) anymore! Considering the iterative and incremental approach in the pharma industry, it is too much to digest! We should not take that risk and as suggested in the new GMP Annex1, we should have our own particle size (could be 5 microns or 1 micron, depending on your risk level) and limit defined in the contamination control strategy file. Also, the sample volume to be taken in each location (Vs) should not be dropped from 1000 liters to 5.6 liters in one day. We can consider changing that with reasonable steps. If you will add 1 micron, Vs will be around 25 liters, 40 times less than 1000 liters, which will be still risky for our operation. Please note, this is my personal advice only. But a scientifically valid one :)

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