The 10 ppm Problem: Why Silicone Antifoam Can Be Challenging for Food Bioprocessing

Silicone-based antifoams such as simethicone are widely used in bioprocessing because they are highly effective at controlling foam. For food applications, however, their use introduces an important regulatory consideration: FDA limits dimethylpolysiloxane (PDMS) to 10 parts per million (ppm) in food.

Under 21 CFR §173.340, dimethylpolysiloxane may be used as a defoaming agent at no more than 10 ppm in food, except for certain specifically identified applications. The regulation also requires defoaming agents to be used only at levels reasonably required to control foam.¹

For bioprocesses in which the cultured biomass itself becomes food—such as cultivated meat—this limit can become relevant surprisingly quickly.

A 2,000 L Bioreactor Example

Consider a 2,000 L bioreactor using a 30% simethicone emulsion. For illustration, we assume an antifoam dosing rate of 75 µL/L/day, equivalent to 150 mL/day in a 2,000 L bioreactor. Actual antifoam demand will vary depending on the cell line, medium, aeration, agitation, and other process conditions.

For a conservative screening calculation, assume:

• Antifoam addition: 150 mL/day

• Antifoam density: 1.027 kg/L

• Simethicone concentration: 30% w/w

• PDMS content of simethicone: 99%

• No degradation or removal of PDMS

This corresponds to approximately:

• 150 mL/day × 1.027 g/mL × 30% × 99% ≈ 45.8 g PDMS/day

4-Day Fed-Batch Process

Over a four-day fed-batch culture:

• 45.8 g/day × 4 days ≈ 183 g PDMS

Assuming approximately 2,000 kg of culture at harvest:

• 183 g ÷ 2,000 kg ≈ 92 ppm PDMS

That is approximately 9× the FDA 10 ppm limit before downstream biomass concentration is considered.

Continuous Process at 0.5 VVD

Now consider the same 2,000 L reactor operated continuously at 0.5 vessel volumes per day (VVD).

Daily harvest is:

• 2,000 L × 0.5 VVD = 1,000 L/day

At steady state, 45.8 g/day of PDMS entering the process corresponds to:

• 45.8 g/day ÷ 1,000 kg/day ≈ 46 ppm PDMS

This is approximately 4.6× the FDA 10 ppm limit, again before downstream biomass concentration is considered.

Process	Estimated PDMS
4-day fed-batch	~92 ppm
Continuous at 0.5 VVD	~46 ppm
FDA limit in food	10 ppm

Can Downstream Processing Solve the Problem?

In your impurity assessment, it should not be assumed that it will.

PDMS is highly hydrophobic, and its partitioning during cell separation is process-dependent. Centrifugation therefore cannot simply be assumed to remove PDMS with the aqueous supernatant.

If PDMS associates with cells, lipids, or other components recovered with the biomass, concentrating the biomass could potentially increase its concentration in the recovered fraction.

For example, consider a 20× biomass concentration step following the continuous process. Under the most conservative assumption that essentially all PDMS follows the recovered biomass:

46 ppm × 20 ≈ 920 ppm PDMS in the concentrated biomass

This represents a worst-case mass-balance scenario, not an experimentally established PDMS partition coefficient. If only 50% of the PDMS followed the biomass, for example, the theoretical enrichment would instead be approximately 10×.

The important point is that PDMS exceeding 10 ppm upstream cannot simply be assumed to disappear during downstream processing. Its partitioning and residual concentration may need to be characterized experimentally.

So with 20× concentration factor in downstream:

PDMS Recovered with Biomass	Potential PDMS Enrichment	Fed-Batch Biomass PDMS	Continuous Biomass PDMS
10%	2×	~184 ppm	~92 ppm
25%	5×	~460 ppm	~230 ppm
50%	10×	~920 ppm	~460 ppm
100%	20×	~1,840 ppm	~920 ppm

What About Dilution in the Final Product?

The concentrated biomass may represent only a portion of the finished food. Final formulation therefore provides some dilution—but depending on the residual PDMS level in the biomass, dilution alone may not be sufficient to meet the 10 ppm limit.

Using the conservative 20× biomass concentration scenario described above:

• 4-day fed-batch biomass: ~1,840 ppm PDMS

• Continuous-process biomass: ~920 ppm PDMS

If the concentrated biomass represents 10%, 20%, or 33% of the final product by weight, the estimated PDMS concentrations would be:

Biomass Inclusion	4-Day Fed-Batch	Continuous (0.5 VVD)
10%	~184 ppm	~92 ppm
20%	~368 ppm	~184 ppm
33%	~607 ppm	~304 ppm
FDA limit in food	10 ppm	10 ppm

Even at only 10% biomass inclusion, the continuous-process example results in approximately 92 ppm PDMS—more than 9× the FDA limit under this conservative scenario.

These calculations assume that no additional PDMS is introduced by other ingredients and, importantly, use the same worst-case downstream assumption that essentially all PDMS follows the biomass during the 20× concentration step. Actual PDMS partitioning and residual levels would need to be determined experimentally.

Nevertheless, the calculation illustrates an important consideration for biomass-based foods: final formulation cannot necessarily be assumed to dilute residual PDMS below the regulatory limit. When silicone-based antifoam is used, its fate through biomass recovery, concentration, and final formulation may therefore need to be understood and controlled.

Why Silicone-Free Antifoam Can Simplify Food Bioprocessing

Using silicone antifoam can therefore introduce an additional process constraint:

Antifoam dosing → PDMS mass balance → downstream partitioning → residual testing → finished-food compliance

For biomass-based food processes, this can become particularly important because the cultured cells or biomass are harvested and concentrated into the food rather than being discarded.

Naturafoam takes a different approach. As a silicone-free antifoam developed for food bioprocessing, Naturafoam does not introduce PDMS into the process. Consequently, the 10 ppm PDMS limitation associated with silicone-based defoamers is not introduced by the antifoam.

At large scale, antifoam selection is therefore about more than controlling foam. What happens to the antifoam after it enters the bioreactor—and ultimately where it ends up in the food—matters too.

References

¹ 21 CFR §173.340 — Defoaming Agents. FDA regulations specify a maximum of 10 ppm dimethylpolysiloxane in food, subject to specified exceptions.21 CFR §173.340 — Defoaming Agents

² Simethicone and PDMS: The USP defines simethicone as a mixture of fully methylated linear siloxane polymers (PDMS) and silicon dioxide. Simethicone contains not less than 90.5% and not more than 99.0% PDMS, as well as 4.0–7.0% silicon dioxide. The calculations above use 99% PDMS as the conservative upper-bound assumption.USP–NF: Simethicone Monograph

The examples above are conservative engineering screening calculations intended to illustrate the potential significance of PDMS in food bioprocessing. Actual PDMS concentrations depend on antifoam formulation, dosing, culture conditions, downstream partitioning, removal steps, and final product formulation. This article is for technical and educational purposes and does not constitute regulatory or legal advice.