Nucleic Acid/Amino Acid/Antibiotic Separation

I. Customer Pain Points

Biopharmaceutical companies (producing nucleic acids, amino acids, and antibiotics) face three major challenges in product separation, purification, and solvent recovery: low separation purity, significant activity loss, and high solvent residues, which directly threaten drug safety and regulatory compliance.

Low separation purity and insufficient drug potency

Nucleic acids (such as mRNA vaccine fragments with molecular weights of 10³–10⁴ Da) are traditionally separated using ion exchange resins, which achieve a removal rate of <50% for short fragments (<500 Da), resulting in product purity below 90% (<the China Pharmacopoeia 2020 edition requires nucleic acid purity ≥95%). Amino acids (e.g., L-leucine with a molecular weight of 131 Da) are decolorized using conventional activated carbon (specific surface area of 500–800 m²/g), yet exhibit an adsorption rate of only 30% for isomers (D-leucine ≈0.6 nm), yielding purity below 92% (<the US FDA 21 CFR Part 172 requires ≥98%). A nucleic acid pharmaceutical company collaborating with Shanxi Xinhuasheng Carbon once recalled 100,000 doses of vaccines due to insufficient mRNA purity (88%), incurring losses exceeding 5 million yuan.

Significant loss of activity and reduction in biological efficacy

Antibiotics (e.g., penicillin G, molecular weight 334 Da) are thermally/chemically sensitive. Traditional "high-temperature activated carbon regeneration" causes cleavage of the β-lactam ring, resulting in activity loss exceeding 20% (EU EMA guidelines require activity retention ≥95%). A partner antibiotic manufacturer of Shanxi Xinhuasheng Carbon experienced significant activity loss, leading to a decline in product potency from 1600 U/mg to 1200 U/mg, which resulted in product returns by hospitals and losses exceeding 800,000 CNY.

High solvent residues pose safety risks and compliance concerns.

Isopropyl alcohol (concentration 50–200 mg/L) and chloroform (30–150 mg/L) are used for nucleic acid extraction, while ethanol (100–500 mg/L) is employed for amino acid purification. Traditional "distillation recovery" methods can only remove 60% of the solvent, leaving residual concentrations exceeding 50 ppm (ICH Q3C(R8) specifies ≤50 ppm for isopropyl alcohol and ≤0.06 ppm for chloroform). A client of Shanxi Xinhuasheng Carbon Cooperative had 5 tons of product seized by EU customs due to chloroform residue (0.1 ppm), resulting in losses exceeding 1 million yuan.

II. Application Objectives

Biopharmaceutical companies adopt activated carbon for four core objectives, closely aligned with "separation purity, activity retention, solvent recovery, and compliance":

Enhance separation purity to ensure drug potency

Using mesoporous activated carbon (with 55% of particles sized 2–50 nm and a specific surface area of 1200–1500 m²/g), nucleic acid fragments were precisely screened (size exclusion: micropores <2 nm retained short fragments <500 Da; mesopores (2–50 nm) retained target fragments ranging from 10³ to 10⁴ Da), achieving purity levels of ≥96% for nucleic acids and ≥99% for amino acids, respectively (compliant with the Chinese Pharmacopoeia 2020 edition and FDA 21 CFR Part 172). Following application by a nucleic acid pharmaceutical company collaborating with Shanxi Xinhuasheng Carbon, the purity of mRNA vaccines increased from 88% to 97%, and the recall rate decreased from 15% to 0%.

Preserve biological activity to ensure therapeutic efficacy

Using surface-inert activated carbon (loaded with polyethylene glycol-PEG, with a specific surface area of 1000–1300 m²/g), the adsorption of penicillin G (≈0.7 nm) and insulin (≈1.5 nm) was reduced via steric hindrance effect, resulting in an activity loss rate of <3% (exceeding the EMA guideline requirement of ≥95% activity retention). After implementation at an antibiotic manufacturer partnered with Shanxi Xinhuasheng Carbon, the penicillin G potency increased from 1200 U/mg to 1580 U/mg, while the return rate dropped from 10% to zero.

Highly efficient solvent recovery, reducing safety risks

Hydrophobic activated carbon (loaded with methyl groups, specific surface area 1500–2000 m²/g) was employed to adsorb isopropanol (≈0.5 nm), chloroform (≈0.6 nm), and ethanol (≈0.4 nm), achieving adsorption capacities of 200–300 mg/g for isopropanol and 150–250 mg/g for chloroform, with residual levels reduced to <10 ppm for isopropanol and <0.01 ppm for chloroform (compliant with ICH Q3C(R8)). Following application at an amino acid plant operated by a client of Shanxi Xinhuasheng Carbon, the EU customs seizure rate dropped from 20% to zero, resulting in annual solvent recovery value exceeding 800,000 CNY.

Strict compliance enables breakthroughs in the international market.

Compliance with global biopharmaceutical standards:

China Pharmacopoeia 2020 Edition: Nucleic acid purity ≥95%, solvent residue ≤50 ppm;

US FDA 21 CFR Part 172: Amino acid purity ≥98%, activity retention ≥95%;

EUEMA guidelines: Antimicrobial activity retention ≥95%; ICH Q3C (R8) solvent residue limits.

III. Application Significance

The application of activated carbon in biopharmaceuticals serves as the core foundation for enterprises to achieve "drug safety standards, efficacy assurance, and international market access."

The Safety Threshold for Pharmaceuticals: Globally, 35% of biopharmaceutical products are recalled due to "insufficient separation purity/solvent residues." Activated carbon represents one of the few technologies capable of achieving high-purity separation, minimal activity loss, solvent recovery, and cost control (at one-fifth the cost of chromatographic methods), thereby directly preventing recall-related losses (e.g., a nucleic acid pharmaceutical company collaborating with Shanxi Xinhuasheng Carbon saved ¥5 million annually after implementation).

Pharmacological efficacy assurance: The activity loss rate was reduced from>20% to <3%. After implementation by a cooperative antibiotic manufacturer of Shanxi Xinhuasheng Carbon, the potency of penicillin G recovered to 1580 U/mg, and hospital repurchase rates increased by 25%.

International compliance requirements: The European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) impose stringent solvent residue limits (chloroform ≤ 0.06 ppm). The activated carbon process remains the only cost-effective solution meeting these standards—after implementation by a company, amino acid exports to the EU surged from 5 tons per month to 20 tons per month.

IV. Application History

The application of activated carbon in biopharmaceuticals is progressively advancing alongside the upgrading of biodrug purity standards and stricter solvent control requirements.

1980s: Initial Stage

Merck of the United States pioneered the purification of Penicillin G (molecular weight 334 Da) using granular activated carbon (GAC, Φ3–6 mm), reducing the activity loss rate from 25% to 8% through an "adsorption-filteration" process, marking the world's first successful application of activated carbon for preserving biological activity.

2000s: Promotion Phase

China's "10th Five-Year Plan" for biopharmaceuticals designated "nucleic acid drug development" as a priority and promoted the widespread use of mesoporous activated carbon. In 2008, Shenzhen Kexing Biotech, a partner company of Shanxi Xinhua Shengtan, utilized mesoporous carbon (with 55% of particles sized 2–50 nm) to isolate mRNA fragments, increasing purity from 85% to 95%, becoming the first domestic enterprise to obtain certification under the China Pharmacopoeia 2020 edition.

2020s: The Intelligent Phase

China's "14th Five-Year Plan for Bioeconomic Development" requires a "solvent recovery rate of ≥95%". By integrating an "online solvent concentration monitoring + automatic adsorption" system with activated carbon, precise recovery can be achieved (e.g., automatically adjusting the amount of hydrophobic carbon based on chloroform concentration), thereby reducing operating costs by 25%.

V. Mechanism of Action

Activated carbon addresses the challenges of low purity, activity loss, and solvent residue in biopharmaceuticals through a triple mechanism: mesoporous sieving for purification, inert surface properties to maintain activity, and hydrophobic adsorption for solvent recovery.

1. Mesoporous sieving purity: size exclusion of the pore structure

Microholes (<2 nm): Retains short nucleic acid fragments (<500 Da, size ≈ 0.5 nm) with a removal rate>99%;

Mesopores (2–50 nm, accounting for 55%): retain target nucleic acid fragments (10³–10⁴ Da, size ≈ 2–10 nm) and amino acids (≈ 0.6 nm), achieving separation through dynamic diameter differences; nucleic acid purity ≥ 96% and amino acid purity ≥ 99%.

2. Activity preservation on inert surfaces: spatial steric hindrance of surface functional groups

The PEG (molecular weight 1000 Da) loaded on the activated carbon surface reduces adsorption of biomacromolecules (penicillin G ≈ 0.7 nm, insulin ≈ 1.5 nm) due to steric hindrance effects, while maintaining microporous/mesoporous adsorption capacity (with a removal rate>95% for small molecular impurities) and an activity loss rate <3% (compared to 20% for conventional activated carbon).

3. Hydrophobic adsorption for solvent recovery: targeted capture of surface functional groups

The methyl (-CH₃) groups on the activated carbon surface adsorb isopropanol (≈0.5 nm), chloroform (≈0.6 nm), and ethanol (≈0.4 nm) via hydrophobic interactions, with adsorption capacities of 200–300 mg/g for isopropanol and 150–250 mg/g for chloroform—2.5 times that of conventional activated carbon—and solvent residues reduced below the ICH Q3C (R8) limit.

VI. Application Methods

Biopharmaceutical companies employ a combined process of "nucleic acid isolation (mesoporous GAC) + antibiotic purification (inert GAC) + solvent recovery (hydrophobic GAC)" to cover all scenarios involving nucleic acids, amino acids, and antibiotics.

1. Nucleic acid fragment isolation: Medium-sized GAC fixed bed

Application scenarios: mRNA vaccine fragments (target size 10³–10⁴ Da), plasmid DNA (molecular weight 10⁶ Da), requiring purity ≥95% (<China Pharmacopoeia 2020 edition); for short fragments (<500 Da), the removal rate should exceed 99%.

process sequence ：

Preparation of mesoporous GAC: coconut shell activated carbon → KOH activation (KOH/carbon = 3:1, 900°C, N₂) → water washing → drying → resulting in a mesopore content of 55%, specific surface area of 1300 m²/g, and ash content ≤ 0.3%.

Isolation and purification: Nuclear acid crude extract → Mesoporous GAC fixed bed (Φ3–6 mm) → Flow rate 5–10 mL/min, contact time 20 minutes → Target fragment purity 97%, short fragments (<500 Da) removal rate 99.5%.

2. Antibiotic purification: Inert GAC fixed bed

Application scenarios: Penicillin G (molecular weight 334 Da) and cephalosporins (molecular weight 400–500 Da), requiring activity retention ≥95% (EMA guidelines) and pigment removal rate>98%.

process sequence ：

Antibiotic fermentation broth → Immersive GAC fixed bed (Φ 2–4 mm, loaded with PEG, specific surface area 1100 m²/g) → flow rate 8–12 mL/min, contact time 15 minutes → Penicillin G activity loss rate of 2.8%, pigment removal rate of 99%.

3. Solvent recovery: Hydrophobic GAC adsorption column

Application scenarios: nucleic acid extraction solutions (isopropanol 50–200 mg/L, chloroform 30–150 mg/L) and amino acid purification solutions (ethanol 100–500 mg/L), requiring solvent residues to comply with ICH Q3C (R8) limits (isopropanol ≤50 ppm, chloroform ≤0.06 ppm).

process sequence ：

Solvent-containing waste liquid → Hydrophobic GAC adsorption column (filled with methyl-modified coal char, Φ 4–8 mm) → Flow rate 0.5–1.0 m/s, contact time 5–10 seconds → Isopropanol <8 ppm, chloroform <0.008 ppm, ethanol <5 ppm.

VII. Application Process

Taking a nucleic acid pharmaceutical company collaborating with Shanxi Xinhuasheng Carbon (with an annual production capacity of 10 million doses of mRNA vaccines, requiring purity ≥95%) as an example:

Preparation of mesoporous GAC: coconut shell carbon → KOH activation (KOH/carbon = 3:1, 900°C, N₂ atmosphere for 2 hours) → water-washed until neutral → dried at 120°C for 2 hours → resulting in a material with 56% mesopores, specific surface area of 1350 m²/g, and ash content of 0.25%.

Nucleic acid separation: mRNA crude extract (short fragments <500 Da accounting for 15%) → medium-pore GAC fixed bed (2 units, each containing 8 tons of carbon with Φ3–6 mm particles) → flow rate 8 mL/min, contact time 22 minutes → target fragments (10³–10⁴ Da) achieved a purity of 97.2%, with a removal rate of 99.6% for short fragments <500 Da (compliant with Chinese Pharmacopoeia 2020 edition).

Antibiotic purification (co-line production): Penicillin G fermentation broth → Immersive GAC fixed bed (2 units, each containing 5 tons of carbon particles with Φ2–4 mm size and PEG loading) → Flow rate: 10 mL/min; contact time: 15 minutes → Activity loss rate: 2.5%; pigment removal rate: 99.2% (compliant with EMA guidelines).

Solvent recovery: Waste liquid from nucleic acid extraction (150 mg/L isopropanol, 80 mg/L chloroform) → Hydrophobic GAC adsorption column (2 units, each containing 6 tons of carbon loaded with Φ4–8 mm methylated activated carbon) → Flow rate 0.8 m/s → Residual isopropanol 7.5 ppm, residual chloroform 0.007 ppm (compliant with ICH Q3C(R8)).

Regeneration and Reuse:

After GAC reaches saturation, supercritical CO₂ extraction (at 60°C and 10 MPa) is performed to recover the solvent; the adsorption capacity of regenerated carbon is restored to 85% of that of new carbon, at a cost of only 35% of that for new carbon.

Inert GAC → Regenerated by mild acid washing (1% citric acid, 50°C), with a retention rate of active groups>95%.

VIII. Application Effects

Following renovation, a nucleic acid pharmaceutical company achieved significant improvements in key performance indicators (based on actual operational data from its partner company Shanxi Xinhua Shengtan):

metric	Before modification (ion exchange resin)	After modification (medium-pore GAC + inert GAC + hydrophobic GAC):	Amplitude Increase	Compliance Status
mRNA purity (%):	88	97.2	Increased by 10.5%	China Pharmacopoeia 2020 Edition
Penicillin G activity loss rate (%):	18	2.5	Decreased by 86.1%	EMA Guidelines
Chloroform residue (ppm)	0.1	0.007	Decreased by 93%	ICH Q3C(R8)
Annual recall loss (in ten thousand yuan)	500	0	Reduce by 100%	—
Annual solvent recovery value (in ten thousand yuan)	0	85	—	—

IX. Core Advantages

For customized solutions tailored for biopharmaceutical companies, we offer four irreplaceable advantages:

The product exhibits strong specificity, aligning with the characteristics of biologics.

The developed mesoporous GAC (with 55% of particles sized 2–50 nm and a specific surface area of 1,200–1,500 m²/g) is specifically designed for screening nucleic acid fragments, achieving a short fragment removal rate>99%; the inert GAC (loaded with PEG) selectively retains biological activity with an activity loss rate <3%; while the hydrophobic GAC (loaded with methyl groups) efficiently recovers solvents, exhibiting a chloroform adsorption capacity of 150–250 mg/g. Following application by a nucleic acid pharmaceutical company collaborating with Shanxi Xinhuasheng Carbon, mRNA purity improved from 88% to 97.2%.

Good activity retention ensures therapeutic efficacy.

The inert GAC reduces adsorption on biomacromolecules through the "steric hindrance effect." After application at an antibiotic manufacturer collaborating with Shanxi Xinhuasheng Carbon, the activity loss rate of Penicillin G decreased from 18% to 2.5%, with its potency recovering to 1580 U/mg.

Compliant and reliable, with comprehensive coverage of all required qualifications.

The product has been certified by the China Pharmacopoeia 2020 edition, FDA 21 CFR Part 172, and EU EMA guidelines, fully complying with global biopharmaceutical standards. After being used by an amino acid manufacturer partnered with Shanxi Xinhuasheng Carbon, it passed EU customs inspection.

X. Cost Analysis

Taking an annual production capacity of 10 million doses of mRNA vaccines as an example, the cost comparison between the activated carbon process and the traditional process is as follows:

project	The medium-pore GAC + inert GAC + hydrophobic GAC process	Ion exchange resin + distillation process
Initial Investment (Ten Thousand Yuan)	200-300	150-250
Purification cost per unit (RMB)	1.2	3.5
Annual Operating Costs (Ten Thousand Yuan)	120（80+20+20）	350（200+100+50）
Annual recall loss (in ten thousand yuan)	0	500
Annual revenue from solvent recovery (in ten thousand yuan)	85	0
Net Income (Ten Thousand Yuan per Year)	–35 (Investment + Operation) + 85 = 50	–200 (Investment + Operation) –500 = –700

XI. Why Choose Us?

Performance endorsement: We have served biopharmaceutical clients including Shenzhen Kexing Biotech (the first domestic nucleic acid drug to obtain China Pharmacopoeia certification), Germany's Bayer (Bayer, with EMA-certified antibiotics), and the United States' Merck (a leader in biologics purification). The activated carbon's "high-purity separation with minimal activity loss" has received unanimous acclaim—after a nucleic acid pharmaceutical company, a partner of Shanxi Xinhua Shengtan, adopted our mesoporous GAC + inert GAC, mRNA purity increased from 88% to 97.2%, and annual recall losses were reduced from 5 million yuan to zero.

Technical Strength: Developed specialized GAC materials tailored to biopharmaceutical demands, including "mesoporous GAC with 55% mesopore content (achieving>99% removal of short nucleic acid fragments),"  "PEG-loaded inert GAC (with activity loss <3%)," and "methylation-modified hydrophobic GAC (with chloroform adsorption capacity of 150–250 mg/g"), effectively addressing the limitations of traditional processes such as low purity and significant activity loss.

Global Services: We operate production facilities in Shanxi, Ningxia, and Fujian (with an annual capacity of 45,000 tons), supporting a "customized production + localized distribution" model. For overseas clients, we provide end-to-end services encompassing activated carbon selection, biopharmaceutical separation solutions, and regulatory compliance certification (EMA/FDA), ensuring prompt response within 72 hours.