This document discusses the process validation of transdermal drug delivery systems. It begins by defining transdermal drug delivery systems as patches designed to deliver medication through the skin. It then lists some advantages and disadvantages of these systems. The document outlines the key elements that must be considered for transdermal validation, including planning, documentation, understanding processes, and communication. It describes the specific unit operations and materials used in transdermal system production like material receipt, mixing, coating, drying, laminating, and pouching. The document also discusses qualification of equipment and processes, assumptions that must be in place before validation, and the documentation required as part of the validation matrix, including the validation protocol.

1. PROCESS VALIDATION OF
TRANSDERMAL
Presented By :
Sarvesh Maurya
M Pharm
Pharmacology
L.H.Hiranandani,ulhasnagar.

2. Transdermal drug delivery system
 Transdermal drug delivery system,also known as
“patches” designed to deliver a therapeutically
effective amount of drug across a patient’s skin.
 Are designed to support the passage of drug
substances from the surface of the skin,through its
various layers,and into the systemic circulation.

3. Advantages –
o Provide improved systemic bioavailability of active ingredients
o No GI degradation
o Permit slow,timed release of the active
o Avoid the affect of bolus drug dose
o Provide for multiple daily doses with a single application
o Provide instantaneous identification of medication in emergency
Disadvantages –
o Limited skin permeability
o Restricted to potent drugs
o Cause irritation
o May be conductive to bacterial growth
o Adhesion time is typically limited
o Cannot use for large molecules (>500 Dalton)

4. Transdermal Validation Elements
Planning
Documentation
Time
Budget
Resources
Quality
Understanding
Communication

5. Unit Operation and Material/Composition
1. Material Ordering and Receipt-
 Firstly,material is ordered
 Material is received and placed in qurantine
 Intimation of the material to QC department
 After QC testing the material is approved or rejected and then released.
Path of raw material and components

6. 2. Dispencing process-
weighing of raw material is done
3. Mixing process-
components are then mixed
under controlled conditions
(eg.,time,agitation,temperature)
intermediate is sampled and then analysed
by a quality department.

7. 4. Coating,Drying,and Laminating Process
• Intermediate is pumped through
the slot die onto a release liner
through the oven of the coater.
• This coated liner is bonded to a
backing film.
• The laminate resulting from this
processing step is then sliced (slit)
lengthwise and cut into independent
rolls appropriate for the final system
size.

8. 5.Pouching process
The wound rolls of laminate are transferred to the pouching and die cutting
equipment. The pouching process involves taking these slits and overlapped
rolls,cutting them into individual system and then finally sandwiching them
between two layers of poly pouch material.

9. Transdermal System-Process
Qualification
 I.Q.-Review purchase order,design specification,equipment manual.
 O.Q.-Perform trial OQ to confirm ranges
 P.Q.-PQ trials to confirm performance of equipment.
Equipments
 Include equipment qualification
 Perform Factory acceptance testing(FAT)
 Equipment IQ/OQ activities and Performance
Qualification(PLC/Automated controls) process validation
Process
 Ranging studies
 Demonstration,PQ,Trials.

10. Process-specific validation for transdermals
 Process-specific validation such as
mixing,coating,pouching,shoud be performed prior to
formal transdermal process validations.
 During the mixing operation,the mix time and the mix
RPMs shoud be monitored.
 During the coating process,controlled condition and
coating weight shoud be monitored.thickness of the
casting solution layer should be controlled.
 During the pouching process,operator should perform
routine monitoring of heat seal temperature,and heat
seal pressure, and at the same time check the integrity
of the sealant layer.

11. Prevalidation assumptions for transdermals :-
 Sound development package in place
 Ranging studies completed and documented
 Facility qualification completed and documented
 Equipment qualification completed and documented
 Appropriate analytical methodology implemented and
validated
 Personnel training completed and documented
 Process trials and demonstrations executed and documented
 Change control in place and effective
 All supporting documentation (validation SOPs,demonstration
documentation,etc.) in place
 Appropriate operating procedures In place
 Document maintenance (number,filing,retrieval) in place.

12. Validation Documentation for the Matrix
Transdermal System
The Protocol :
A document stating how validation will be conducted, including
test parameters, product characteristics, manufacturing equipment,
and decision points on what constitutes acceptable test results.
Validation protocol accomplishes following-
 It details the item or items (subject) undergoing validation.
 Provide an objective and an overview of what is being done and
why.
 It will typically reveal how many successful batches must be
performed.
 It discusses equipment used to process the “subject”.
 It details critical process parameters,acceptance criteria,sample
points ,and the test methods to be used.

13. 1. Format : Basics
2. Cover Sheet
3. Table of Contents :
 Section I :
 Background/Methodology
 Objective
 Scope
 Responsibilities
 Background
 Process Description
 Critical process control parameter
 Validation Procedure and Methodology
 Documentation
 Execution
 Postexecution
 Validation sampling plan
 Acceptance criteria/rationale
 Labeling
 Conditions
 Method of analysis
 QualificationVerification

15.  section II
 Data Documentation
 SafetyAwareness
 Required Determinations
 Training
 Availability of SOPs
 Materials
 Sample Execution
 Results
 Conclusions

16. References :
1) R.A.Nash and A.H.Wachter Pharmaceutical
Process Validation ,Third edition,pg no.237-
287.
2) Agallo James,Carleton j. Fredric Validation of
Pharmaceutical Processes,Third Edition,pg
no.417-428.

17. Thank you