Transfer of A Manufacturing Process: Case Study Solid Dosage Transfer Within Technical Operations
Transfer of A Manufacturing Process: Case Study Solid Dosage Transfer Within Technical Operations
Overview of Product
Product fitted into therapeutic area
Purchased from big pharma
Product:
Highly potent
Explosive
Traditional production
Project history/setup
Due diligence
1 day to technically review process
Statisical process control (SPC) to determine variation
Robustness of process
Clarification of scope
Bulk: Transferred CH to UK
Bulk: UK site produced small quantity of batches
Packaging outsourced to TPM
Other sites involved due to regulatory demands of
certain countries
Selection of TPM
Initial overview communication
Showing show stopper issues
No confidentiality agreement
Explosive, potent, volumes, major
process/analytical equipment, bulk volumes &
packaging forms & splits
Proof needed of EU GMP licence
TPMs selected
Knowledge from RUs people
Conferences
Web sites
Criteria used
Commitment to quality
Flexibility
Reputation
Scope of resources
(people, equipment,
facility)
Price
Honesty
Financial standing
Experiences
Spent 6 months finalising TPM
selection process
TPM pulled out from selection
process on last day
Serious GMP failure during selection
process
TPMs pulled out immediately giving
clear rationale of why
Project Team
Makeup
Cross functional
Inter company
Intra company
Multi cultural
Multi experienced (high
& low)
Communication
High visibility with Sending
& Recieiving Units
Web/phone meetings
gotomeeting.com
Risks
Regulatory approach PAT vs traditional approach
Traditional approach
Process improvements
Minimise for reduction in regulatory effort
Technical report to support all changes
Changes made where significant cost saving could be realised
Timeline of transfer
Build up of safety stock from SU
Process Understanding
Historical review
Used during due diligence
Basis for writing Process Validation
HIGH
Friability
LOW
Mean weight
LOW
MEDIUM
Strength (g)
b
c
c
Dissolution
Content
of
Uniformity
Assay
Degradation
substances
Conclusions
Perform the LOD test on the tablets during
compression or a soon after compression as possible.
Recommend that this parameter be kept as a in process
control but is discarded as a final product release
parameter
Process shows excellent control.
The dissolution methodology has two additional steps if
S1 fails, with S2 and then S3 (if S2 fails) tests
becoming active.
During the process validation
attention should be made to distribution of active and
the performance of the dissolution method. This should
be cited within the process validation protocol.
LOW to
MEDIUM
LOW
LOW
LOW
Risk
HIGH
LOW
Upper strength
Similar manufacturing process (2 part)
g API quantities
Historical review
Good degree of statisitcal control
Robust
Conclusion
Lower strength (x1 ag & x2 bg) = 3 batches
Upper strength (x1 cg & x2 dg) = 3 batches
WEIGHT_EUR_PH
Indivi d.
140
USL
135
130
O
O
O
O
O
ucl
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
cl
Target
O
O
lcl
125
LSL
120
SAMPLE_POINT:
Individ.:
USL: 139.5
cl: 129.8
LSL: 120.1
13
ucl: 133.43
lcl: 126.17
Target: 129.8
17
21
* Rule violation
Subgrp Size 5
RU similar to SU process
Validation Report
People issues
Language
Cultural
Experience
Technical
Communication
High turnover of people
Maintenance of product
Routine management of
TPM
Customer & TPM
All key functions
represented
QC, QA, Logistics,
TechOps, Srn Manager
Guest members
Regulatory, R&D
Meetings
Customer ~ monthly
Customer/TPM ~ yrly
(low)
Fixed agenda
Issues
Packaging
Yield ~ high # batch changes
Artwork ~ did not appreciate
complexity
Scope poorly defined for TPM
Marketing
Closer, better and flexible
understanding of their needs
Project Management
Late start to project
Transfer strategy
Well defined and good use of
SPC in understanding the
process being transferred
Project team
Well supported by
management
Team worked well
understanding each others
roles and expertise
Analytical methods
Significant amount of
variation associated to
methods
Timelines and effort needed
to perform testing
Excellent support from R&D
Maintenance
Selection of TPM
TPM honest, ethical &
trustworthy
References
Article or book
Title
Sampling- procedures and charts for
inspection by variables for percent
nonconforming
Control charts - General guide and
introduction
Control charts for arithmetic average
with warning limits
Reference and/or
Year
IS0 3951:1989 (E)
IS0 7870:1993(E)
ISO 7873:1993(E)
ISO 7966:1993(E)
IS0 8258:1991(E)
2000
1992
1982
1984
Author
International
Standard
International
Standard
International
Standard
International
Standard
International
Standard
Mal Owen and John
Morgan
Wheeler, D. J. and D.
S. Chambers
W. Edward
Western Electric
Thanks
QPharma: R&D, Logistics, Regulatory,
Marketing, QA & Technical groups (D, CH, DK)
RU & SU ~ Confidential
Contact details
ifo@qpharma.se
end