Comprehensive Release
The release standard for every batch a company sells under an American Peptide Association designation, and for lots supplied to 503A and 503B pharmacies.
Safety
Control what can cause harm.
01SterilityAbsence of viable microorganisms over a 14-day incubation.
Samples are incubated in two media for fourteen days. This is the compendial method and sets the minimum turnaround for any program that includes it.
- Method
- Membrane filtration, 14-day incubation
- Reference
- USP <71>
02Bacterial endotoxinsEndotoxin in EU/mg against a product-specific limit.
Endotoxin is measured in EU per milligram and compared with a limit calculated for the product and dose.
- Method
- Kinetic chromogenic LAL
- Reference
- USP <85>
03Visible particulatesVisible foreign and product-related particles in the reconstituted vial.
Each vial is inspected under controlled lighting after reconstitution. Any visible particle is recorded and photographed.
- Method
- Visual inspection against black and white backgrounds
- Reference
- USP <790>
04Residual solventsClass 1, 2 and 3 synthesis solvents against their limits.
Acetonitrile, DMF, dichloromethane and the other common synthesis solvents are quantified against their class limits.
- Method
- Headspace GC-MS
- Reference
- USP <467>
05Elemental impurities and catalyst residuesHeavy metals and residual catalysts against parenteral limits.Route-level; re-verified periodically and after changes
Lead, arsenic, cadmium, mercury and residual synthesis catalysts are quantified against parenteral permitted daily exposures. Established per synthesis route and re-verified periodically and after any change.
- Method
- ICP-MS
- Reference
- USP <232> and <233>, ICH Q3D
Holistic peptide quality
Is it what the label says, at labeled strength?
06Identity (intact mass)Confirms the molecular weight of the declared peptide.
High-resolution mass spectrometry measures the molecular weight to within a few parts per million and compares it with the theoretical mass of the declared peptide.
- Method
- LC-HRMS
07Purity and related substancesMain peak purity, with each impurity above the reporting threshold listed.
Reverse-phase chromatography separates the peptide from everything that resembles it. Purity is reported as main peak area percent, and each impurity at or above the reporting threshold is listed with its relative retention time and, where the mass allows, a tentative assignment.
- Method
- RP-UPLC, UV 214 nm, with MS
- Reference
- ICH Q3 reporting thresholds
08Net peptide contentPeptide content per vial against label claim.
The amount of peptide in the vial is quantified against a qualified reference standard and reported in milligrams and as a percentage of label claim, net of water and counterion.
- Method
- UPLC assay against reference standard
09Counterion identity and contentAcetate or trifluoroacetate identity and content.
Synthetic peptides carry acetate or trifluoroacetate from manufacturing. The counterion is identified and quantified so the net peptide content is known.
- Method
- Ion chromatography
10Structural and conformational screenSolution conformation compared with a reference spectrum.
Chiroptical spectroscopy compares the solution structure of the sample with a reference. Two lots can match on mass and purity and still differ in how the peptide folds.
- Method
- Vibrational circular dichroism (VCD)
Manufacturing discipline and control
Does the vial stay in specification?
11Cake appearanceStructure and integrity of the lyophilised cake.
Cake structure, collapse, shrinkage and cracking are recorded with photographs before reconstitution.
- Method
- Visual inspection
12ColorColor of the cake and the reconstituted solution.
Color is assessed before and after reconstitution against reference standards.
- Method
- Visual comparison against color standards
- Reference
- USP <631>
13Clarity and degree of opalescenceClarity of the reconstituted solution.
The reconstituted solution is compared with reference suspensions to grade clarity and opalescence.
- Method
- Visual comparison against reference suspensions
- Reference
- Ph. Eur. 2.2.1
14Reconstitution timeTime to complete dissolution.
The time to full dissolution with the labelled diluent and volume is recorded for each vial tested.
- Method
- Timed reconstitution with the labelled diluent
15pHpH of the reconstituted product at a stated concentration.
pH is measured on the reconstituted product at a stated concentration.
- Method
- Potentiometric
- Reference
- USP <791>
16OsmolalityOsmolality of the reconstituted product.
Osmolality is measured on the reconstituted product at a stated concentration.
- Method
- Freezing point depression
- Reference
- USP <785>
17Fill weightNet fill per vial and consistency across the lot.
Net fill weight is determined for each vial tested and reported with the spread across the lot.
- Method
- Gravimetric
18Extractable volumeDeliverable volume after reconstitution.
The volume that can be withdrawn from the reconstituted vial is measured against the labelled volume.
- Method
- Volumetric withdrawal
- Reference
- USP <697>
19Water contentResidual moisture by weight.
Residual moisture in a lyophilised cake drives degradation. Water content is reported as a percentage by weight.
- Method
- Karl Fischer titration
- Reference
- USP <921>
Submit samples for Comprehensive Release
The online submission generates an itemised invoice and a shipping packet.