Skip to main content

Lyophilization


Defects-
a) Freezing stage-
1. Puffing - Top part of cake separate from lower part, sometimes rising to the shoulder of vial.
This typically happens as a result of incomplete freezing prior to pulling a chamber vacuum for primary drying phase.
It is important to allow adequate time for freezing (and temperature conditioning) before pulling chamber vacuum.
b) Primary drying stage-
1. Meltback - Usually occurs as a result of eutectic melting of crystalline components of the formulation (eg- Glycine or mannitol).
The frozen part of the plug melts and dissolves the dry portion of the plug, leaving (at its worst) a concentrated solution in the bottom of the vial.
The problem is avoided by staying below Tg (and so below eutectic temperature of crystalline components).
A similar product appearance will result if vacuum is lost before primary drying is complete, or if secondary drying is begun prematurely.
2. Collapse - Product affected by collapse is not just aesthetically unacceptable, there may also be impact on any protein active, with conformational changes affecting stability.
Tc is usually slightly higher than the Tg.
If the self temperature is too high during primary drying, the rate of ice sublimation will exceed the rate at which the sublimed ice can penetrate the dried layer of the plug above it.
The result will be an increase in product temperature above what is usually referred to as the 'collapse temperature' Tc, resulting in loss of structure of the plug or collapse.
3. Skin formation and meltback - Sometimes impermeable skin forms on the top of the product (this is usually formulation problem rather than a lyophilization cycle problem).
If temperature within the plug rises too high it will melt beneath the skin.
Labels:

Comments

Post a Comment

Popular posts from this blog

Change Management System

US Market (Supplement): Post approval drug manufacturing supplement for NDAs/ ANDA submitted to FDA for Major or Moderate manufacturing change. Major change - If a manufacturing change is considered to be major, an applicant must submit and receive FDA approval of a prior-approval supplement (PAS) before the drug product made with the change is distributed. Moderate change- If a manufacturing change is considered to be moderate, an applicant must submit a supplement at least 30 days before the drug product is distributed (a CBE-30 supplement) or, in some cases, submit a supplement at the time of distribution (a CBE-0 supplement).  “CBE” means “changes-being-effected”. Post manufacturing supplement - 1. CBE 0 (Change being effected before 00 days): 2. CBE 30 (Change being effected before 30 days): 3. PAS (Prior approval supplement): EUROPE Market (Variation): A variation to the terms of a marketing authorization is an amendment to the contents of the docume...
Post a Comment
Read more

NVPC

NVPC Online NVPC: Make= Beckman; Model= Met one 6015P; Capacity= 1CFM SOFTWARE= EnVigil Critical alarm: Critical alarms are those alarms when generated indicate excursion which may impact the product quality. Alarm generated in location where the NVPC probe is in close proximity to the product/ sterile container closure/ product contact path. Location for critical alarms includes grade A location - Filling station, Bunging station, Bunging Hopper station, Portable cart, IOS station, AGV station, Near lyophilizer door open, between lyophilizers (near Lyo) and Lyo LAF (rigid barrier transfer conveyor). Critical alarms include the following- 1.     Particle count excursion beyond the acceptance criteria at a particular location. 2.     Sensor Failure, Counter Flow Failure, ERROR or SKIPPED message. Ensure and verify the status of counter flow to meet the below set limit- Target Counter flow – 1.0 CFM. Minimum counter flow: ...
Post a Comment
Read more

Air velocity measurement and correlation to smoke study

Air velocity measurement As part of risk assessment this evaluation should also consider the selection of locations for the critical control points for monitoring air velocity as well as viable and non-viable particles. 1. Problem Statement- Where should airflow velocity measurements be taken with respect to a filling line or other aseptic processing areas? Recommendation Airflow velocity measurements should be taken at locations where meaningful and reproducible results can be obtained. This is typically at a distance of 6 inches from the filter face . Rationale for Recommendation The primary reason for airflow velocity measurements in unidirectional airflow areas (e.g., areas where product, product contact packaging components, and product contact surfaces are exposed) is to assure there is adequate airflow to protect the materials from external airborne contamination . Accurate measurements can be taken and changes over time detected when airflow velocities are e...
Post a Comment
Read more