Professional Documents
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Pharm-II)
The components or compositions Manufacturing (Process and equipment) of an immediate release dosage form
SUPAC guidance covers y Component and composition change y Manufacturing site change y Batch size change y Manufacturing process and equipment change
SUPAC industry perspective: It is based on interviews with 6 companies in the first half of 1997. Shorter waiting times for site transfers. More rapid implementaion of process and equipment changes.
y Production of fewer unmarketable stability batches y Reduced administration costs for documentation of
Level 1 changes
y Level 1 changes are those that are unlikely to have any
Examples
y deletion of color or flavor y excipient change with total additive effect of up to 5%
Percent excipient (w/w) of total formulation, less than or equal to the following percent ranges
5 3 1 0.5 0.25 1 1 0.1 1
Filler Disintegrants Starch Other Binder Lubricant Ca or Mg Stearates Other Glidant Talc Other Film Coat
SS (Semisolid) Chemistry Application/co same documentation mpendial release requirement* Stability One batch 1 st batch with testing with long term LT stability testing ( 1 LT) None none Dissolution Documentatio n In vivo None none Filling Annual report same documentation (all information including LT)
IR
MR (nrc) same
MR (rc) same
Same as SS
Same as SS
none
none
none same
none same
Examples:
y change in technical grade of excipient y excipient change with total additive effect of up to 10%
Excipient Filler Disintegrant Starch Other Binder Lubricant Calcium or magnesium stearate Other Glidant Talc Other Film Coat
6 2 1
0.5 2
2 0.2 2
SS
MR (nrc)
MR (rc)
In vivo
Release and Release and batch record executed batch record 1 batch with 3 same month accel and 1 batch LT* Yesdepends Yes- Compare on Permeability and solubility@ None none
release and release and executed batch executed batch record record same Same
Yes- compare
Yes- compare
none
Filing documentation
Non for nonnarrow therapeutic index (T.I.) AND Single dose for narrow T.I. Same as IR
Case A
HP, HS
Dissolution of 85 % in 15 min. in 900 ml 0f 0.1 N HCl. If drug product fails to meet the criteria then go for the Case B, C
Case B
LP, HS
Multi point dissolution profile according the compendial medium at 15, 30, 45, 60 and 120 min.
Case C
HP, LS
Dissolution profile comparison in water, 0.1 N HCl, pH 4.5, 6.5 and 7.5. adequate sampling at 15, 30, 45, 60 and 120 minute or until either 90 % of drug from the drug product is dissolved.
y Level 3 changes are those that are likely to have a significant impact on
y y Tests and filing documentation very depending on the following three factors:
y y y
y
y Examples y
y
y y y
y
any Q & Q excipient changes to a narrow Rx drug other drugs not meeting the dissolution criteria changes in excipient range of low solubility, low permeability drug addition or deletion of release controlling excipient(s)
Change in release controlling excipients >10%
SS
Release and Release and batch record executed batch record 1 batch with 3 Same and first months accel three batches 1 LT with LT Same as Level Not required 2 Bioequivalence Same needed PA (accel stab) Same AR (LT stab)
and
A. Manufacturing site Level I changes y Level I changes is defined as changes in manufacturing site
y within a single facility where the same equipment,
SOPs, environmental conditions and controls, and personnel common to both sites are used
manufacturing site
y within a contiguous campus, or between facilities in
adjacent city blocks, where same equipment, SOPs, environmental conditions and controls, and personnel common to both sites are used
IR Chemistry documentation
SS
MR Release; Notification of location of new site and updated executed batch record 1 batch w/3 months accel. 1 st LT* Extended and delayed None CBE (accel stab) AR (LT stab)
Same as IR Release; Notification of location of new site and updated batch record 1 LT 1 st LT
Stability testing
where the same equipment, SOPs, environmental conditions and controls are used
IR Chemistry documentation Stability testing SBI (significant body of 1 batch w/3 months information available) * acel. Upto 3 batch with LT NSBI (significant body Upto 3-3 months accel. of information is not Upto 3 LT* available) * Dissolution In vivo File
SS
MR Release; same
Same; 1 st three batch Same; 1 st three batch LT LT Three batch with months accel. Three batch with LT 3 Three batch with three months accel. 1 st three production batches with LT Extended and delayed Single bioequivalence PA (accel stab) AR (LT stab) dose
As per low permeability comparison and high solubility None none CBE (accel stab) AR (LT stab) Same as IR
y change to larger or smaller production batch y < 100,000 unit scale down not covered y scale up validation needed y may need inspection
pilot/biobatch where cGMPs, SOPs and controls, formulation and manufacturing procedures are the same.
IR Chemistry documentation Release; Notification of change and updated batch record 1 LT Release none AR (LT stab)
SS Release; Notification of change and updated batch record 1 st LT none none same
MR Release; Notification of change and executed batch record 1 st LT Release None Same
times the pilot / bio batch where cGMPs, equipment, SOPs and controls, formulation and manufacturing procedures are same.
IR Chemistry documentation Release; Notification of change and updated batch record 1-3 mos accel 1 LT One batch with 3 months accelerated stability study 1 LT As per low permeability, high solubility None CBE (accel stab) AR (LT stab)
MR Release; Notification of change and updated batch record Same 1 st LT Same Three batch with long term stability study Extended and delayed none same
Stability testing
SBD
Dissolution
comparision
In vivo File
none same
changes that may affect equipment changes that may affect the manufacturing process
A change to automated or mechanical equip. to move ingredients, a change to alternative equipment of same design and operating principle, a change to different capacity equipment.
IR Chemistry Release; Notification of change and updated batch record 1 LT Release None AR (LT stab)
SS Release; Notification of change and updated batch record 1 LT None none same
MR Release; Notification of change and updated batch record 1 LT Release None Same
IR Chemistry documentation
SS
MR
Release; Release; Release; Notification of Notification of Notification of change and change and change and updated batch updated batch updated record record executed batch record One batch with 3 Same 1 st LT months accelerated stability study 1 LT Yes (Case C) comparision None PA (accel stab) AR (LT stab) none CBE (accel stab) AR (LT stab) Same Three batch with long term stability study Extended delayed none and
ranges.
IR Chemistry Release documentation SS release MR Release; Notification of change and updated executed batch record Release None AR
Release None AR
None none AR
changes such as mixing times and operating speeds outside of application/validation ranges
IR Chemistry documentation
SS
MR same
Stability testing
Stability: SBD Stability: NSBD Dissolution File Yes (case B) CBE (accel stab) AR (LT stab)
1-3 mos accel * 1 st LT 3-3 mos accel @ comparision same Extended delayed) same and
used in the manufacture of the product, such as a change from wet granulation to direct compression of dry powder.
SS
MR Release; notification of change and updated executed batch record Three batch with 3 months accelerated stability study 1 st 3 LT @
Stability: SBD
One batch with months accel. 1 LT Upto 3-3 mos accel. Upto 3 LT * Yes (Case B) Study needed PA (accel stab) AR (LT stab)
y http://www.fda.gov/cder/guidance.htm