Step 1: Synthesize the Polymer Backbone

What: Create a water-soluble, biodegradable polymer chain (e.g., PEG-based block copolymer).

How: Use controlled chemical reactions (e.g., ring-opening polymerization).

Equipment:

• Jacketed glass or stainless-steel reactor (with temperature control, stirrer, and nitrogen inlet).
• Condenser and addition funnel for controlled reagent dosing.

🔍 Search term: “chemical reactor for polymer synthesis GMP”

Step 2: Attach Virus-Targeting Ligands

What: Chemically link specific ligands (e.g., peptides that mimic host receptors for orthopoxviruses) to the polymer.

How: Use coupling chemistry (e.g., NHS-ester or click chemistry) in a solvent system.

Equipment:

• Same stirred reactor as above, with precise pH/temperature control.
• In-line analytics (optional): FTIR or Raman probe to monitor reaction progress.

🔍 Search term: “peptide-polymer conjugation reactor”

Step 3: Purify the Conjugate

What: Remove unreacted ligands, solvents, and byproducts.

How: Dialysis or filtration against clean buffer.

Equipment:

• Tangential Flow Filtration (TFF) system – most common in GMP manufacturing. Uses hollow-fiber membranes to separate large polymer-ligand conjugates from small impurities.

🔍 Search term: “TFF system for nanoparticle purification”

Step 4: Form Nanoparticles (Self-Assembly)

What: Trigger the polymer-ligand conjugates to form micelles (~20–50 nm) in water.

How: Add purified conjugate to aqueous buffer under gentle mixing—micelles form spontaneously.

Optional: Use controlled mixing for uniform size.

Equipment: Static mixer or microfluidic nanoparticle assembler (for tighter size control).

🔍 Search term: “nanoparticle self-assembly mixer” or “microfluidic mixer for micelles”

Step 5: Sterile Filtration & Fill

What: Ensure the solution is sterile and ready for lyophilization.

How: Pass through a 0.22-micron filter into sterile vials.

Equipment:

• Sterile filtration unit (in ISO Class 5 cleanroom).
• Aseptic filling machine (for clinical batches).

🔍 Search term: “sterile filtration system pharmaceutical”

Step 6: Lyophilization (Freeze-Drying)

What: Convert liquid drug into stable powder for long-term storage.

How: Freeze solution, then remove water by sublimation under vacuum.

Equipment:

• Industrial lyophilizer (freeze-dryer) with shelves, vacuum pump, and condenser.

🔍 Search term: “pharmaceutical lyophilizer GMP”

Step 7: Quality Control Testing

Tests include:

• Particle size: Dynamic Light Scattering (DLS) instrument
• Purity: HPLC or UPLC system
• Sterility & endotoxins: LAL test kit, microbial culture
• Identity: NMR or mass spectrometry (at development stage)

🔍 Search term: “DLS nanoparticle analyzer Malvern”

[Polymer Synthesis]  
       ↓  
[Ligand Conjugation]  
       ↓  
[Purification (TFF)]  
       ↓  
[Nanoparticle Self-Assembly]  
       ↓  
[Sterile Filtration]  
       ↓  
[Lyophilization → Final Powder]  
       ↓  
[QC Testing → Release]
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