Campaign Cleaning



How to we validate the number of batches of the same product that can be campaigned? What would I evaluate?

I understand that there is no validation required between batches of the same product.


Dear Mr Jay,

In my opinion your question doesn’t have a straight forward answer.

Number of batches (of the same product) that could be included in a campaign (i.e. number of times the batches of same product could be run on the equipment/manufacturing train consecutively without performing full cleaning procedures in between the runs) depends on the product and equipment characteristics and processing parameters. I would recommend you to carry out a thorough “risk analysis (e.g. FMEA, FTA etc.)”, consider and evaluate all the risks involved. This involves having complete understanding of the product, equipment and the process. Following are some of the concerns (or risks) which may be evaluated:

Microbial growth (accumulation and cross-contamination to subsequently manufactured batch): it has to be proven with evidence that the number batches produced consecutively on the same equipment doesn’t involve the risk of microbial growth thereby affecting the safety and efficacy of the subsequently manufactured batch. The issue might not be so critical in case of solid dosage forms as compared to liquid dosage forms.
Degradation products: Evaluate the possibility of decomposition of API or excipients to more toxic (and less water soluble) degradants. The risk is higher with processes involving high temperatures such as in the case of fluid bed dryer, cream mixers etc. where the drug substances are subjected to high temperatures. Toxic degradants if produced would significantly alter the safety and efficacy of subsequently manufactured batch. You need to consider the solubility of the toxic degradants also. For evaluation purpose, you may conduct a simulation study by selecting worst case product (or the product in concern) and processing parameters. Spike API/formulation on to stainless steel (or any other material) coupons and subject the coupons to the worst case conditions. Analyze for degradation products (if any). Include the possibility of degradants interaction with the active/excipients in risk analysis.
Cross-contamination with contaminants from other products: Consider the possibility of contamination of the dirty equipment (after completion of one batch) with the contaminants from any other product manufactured in the facility. Evaluate possible sources of contamination which may be HVAC system, personnel (movement of personnel from one location to another), water etc.
Integrity of the equipment: Assure that the integrity of the equipment (dirty equipment) is maintained during the campaign i.e. assure that between runs no contaminant is going inside the dirty equipment and no contaminant is coming out of it which can possibly contaminate other products. This can be obtained by properly covering the equipment when not in use (i.e. while preparing for next batch), restricting the flow of personnel etc.
Effect/impact on the final full cleaning procedure: Usually campaigns (based on degree of cleaning used) may be categorized into two types (1) A campaign in which there is “partial cleaning” (such as rinsing with water, scrapping and vacuuming) between each batch and the full cleaning (usually validated procedure) is performed at the end of campaign; and (2) A campaign in which there is no cleaning performed between each batch, and the full cleaning (usually validated procedure) is performed at the end of campaign. Evaluate the effect of running batches consecutively in a campaign on the final full cleaning procedure. For example: if I use a granulator for wet granulation and perform “partial cleaning” between the batches the impact on the final cleaning will not be so high as compared to a campaign where I don’t include any partial cleaning in between batches. The possibility is, irrespective of the fact what type of cleaning (partial or no cleaning) I am using in a campaign, that the residues tend to build up in the equipment thereby causing a significant impact on the final cleaning procedure. If the estimated risk is high then consider this as your worst case and perform cleaning validation (i.e. run a campaign for said number of batches, perform the cleaning validation on this type dirty equipment rather than conducting cleaning validation on the equipment which was used for running only single batch).

Use the risk analysis to evaluate the type and degree of validation required. Apply worst case approach where possible.

For campaign cleaning, the FDA requirement is visually clean between batches ('93 FDA Guidance). The advantage is you can usually perform reduced cleanings in-between the batches. What you’re testing for is that there is no build-up of residue when you switch to the next product that you’re cleaning can’t handle. What I did is tested campaigns of varying length for the worst-case active in that Cleaning Family at the end of each campaign using full cleaning and submitting for Absence of Active (HPLC) testing. So if Product A is the campaign,
A-followed by reduced cleaning to visually clean level, no testing
A-same as above
A-followed by full cleaning, testing for absence of active
B-ensure prior testing is acceptable before proceeding

Some tips, if you introduce detergent for the reduced cleanings you still need to show or justify removal…carryover of active between the same product is different than carryover of detergent. If possible, use as simple a cleaning as you can. I try and not use detergent if water soluble and the cleaning itself can provide the appropriate level of cleanliness.
Also, when we did it, a build-up of residue occurred from an excipient in our mixing vessel’s piping valves. So you may want to do some enhanced visual checks of your equipment in-between your batches to ensure residue is not occurring or change your cleaning a bit.

Thank you for your comprehensive notes. Ovais

tjw : How do you intepret visually clean? A partial clean between batches will not remove residue to a visually clean level when for eg using a vacuum cleaner or scraping a granulator.