Fact sheets

Commonly used strains include various types of E. coli such as DH5α, XL1-Blue, Stbl3, and others.

The main challenges include maintaining supercoiled plasmid integrity, minimizing genomic DNA contamination, and efficiently removing endotoxins.

Standard purification methods include alkaline lysis, RNase treatment, anion-exchange chromatography, and tangential flow filtration (TFF).

Applications include gene therapy, vaccine development, CAR-T cell therapy and mRNA manufacturing (as a template for IVT synthesis).

Key considerations include high-yield bacterial strains, fermentation optimization, endotoxin removal, and high-purity chromatographic methods for therapeutic-grade plasmid DNA.

The best expression systems include E. coli or yeast, depending on the required protein complexity and post-translational modifications.

Protein purification is optimized using affinity chromatography, ion-exchange chromatography, and size-exclusion chromatography to achieve high purity.

Protein stability is enhanced through buffer optimization, lyophilization, and the use of stabilizing excipients such as sugars or polyols.

Techniques like SDS-PAGE, Western blot, mass spectrometry, HPLC, and bioassays are used for quality assessment and characterization.

Key steps include plasmid linearization, in vitro transcription (IVT), capping, polyadenylation, purification, and lipid nanoparticle formulation for delivery.

mRNA is highly unstable and requires low-temperature storage (-80°C), stabilizing excipients, and optimized buffer conditions to maintain stability.

Large-scale production involves fermentation in controlled bioreactors, followed by concentration, lyophilization and encapsulation to maintain viability and stability.

Mandatory tests for GMP LBPs include viable cell count (CFU/mL), genomic stability, endotoxin levels and sterility testing.

Bacterial viability is maintained through optimized fermentation conditions, cryoprotectants and freeze-drying techniques.

OMVs are typically produced via controlled bacterial fermentation, followed by filtration and chromatography.

Key purification steps include assessing size distribution (DLS, NTA), protein content (SDS-PAGE, Western blot), sterility and endotoxin levels to ensure product quality.

GMP Fill & Finish follows strict regulatory guidelines for sterility, consistency, and quality control, required for clinical and commercial drug production. Non-GMP Fill & Finish is used for research, preclinical trials, or proof-of-concept studies, where full regulatory compliance is not required.

Sterility is ensured through aseptic processing in cleanrooms, sterile filtration, automated filling lines, and environmental monitoring to minimize contamination risks.

Tests include sterility testing, particulate testing, visual inspection, and container closure integrity (CCI), among others.

GMP Fill & Finish requires validation of the filling procedure (APS/MediaFill) and regular re-validations, while non-GMP Fill & Finish does not require validation.

Yes, but the Fill & Finish process must be validated to meet GMP standards.

Lyophilization adds additional processing time, typically 2-3 days per batch.

Challenges include maintaining product integrity, optimizing the lyophilization cycle, controlling residual moisture levels, and ensuring proper reconstitution of the product.

Lyophilized products are more stable and can be stored at ambient temperatures for extended periods, reducing the need for cold chain logistics. However, proper reconstitution is required before administration to ensure the product is effective. Not all products are best suited for lyophilization.

Spray-drying is used to improve stability during storage, especially for heat-sensitive biologics, vaccines, or therapeutic proteins. It prevents degradation, aggregation, and oxidation by converting the product into a more stable, dry form.

Formulations include dry powder (lyophilization), liposomes, lipid nanoparticles (LNPs), micelles, and polymeric carriers, which are commonly used for encapsulating biologics, such as mRNA, for enhanced delivery and stability.

Challenges include ensuring high encapsulation efficiency, maintaining particle size uniformity, avoiding agglomeration, and preventing leakage or degradation of the encapsulated drug.

The primary challenges are stability (ensuring the active pharmaceutical ingredient (API) doesn't degrade), sterility/low microbial bioburden (to prevent contamination), and accurate filling (ensuring the correct volume is dispensed into each container).

Expect thorough production records, batch records, and a certificate of analysis (COA) for raw materials and final products. Depending on the product, additional documentation such as stability data, validation reports and batch release certificates may also be required.

The contract manufacturer is responsible for maintaining GMP-compliant operations and handling regulatory inspections. They should be prepared to provide inspection-ready documentation, ensure the cleanliness of facilities, and address any corrective actions identified by auditors.

Process validation in GMP manufacturing is essential for ensuring product consistency. Manufacturers typically perform process validation through three stages: installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ). Revalidation occurs periodically or after significant changes to the process, equipment, or materials.

Cleanroom classification determines the maximum allowable particulate levels in the air, which directly impacts contamination control. Higher-class cleanrooms (e.g., Grad A/ISO Class 5) are required for highly sensitive products like sterile pharmaceuticals or biologics. Cleanroom performance must be validated regularly to ensure it meets the required standards.

Regularly updating standard operating procedures (SOPs) to reflect new regulatory requirements, conducting internal audits, and maintaining ongoing communication with regulatory bodies help ensure continuous compliance. Contract manufacturers must also have a system in place for tracking regulatory changes and addressing any gaps in compliance.