Slide 1 of 19 D.K. Mubangizi, Dar Es Salaam Sept.

2007

Training Workshop for Evaluators
from National Medicines Regulatory
Authorities in East African
Community

Dar Es Salaam, Tanzania
Date: 10 to 14 September 2007
Evaluation of Quality and Interchangeability of
Medicinal Products
Slide 2 of 19 D.K. Mubangizi, Dar Es Salaam Sept. 2007

Evaluation of Quality and Interchangeability of
Medicinal Products
Finished Pharmaceutical Products
Manufacturing process and in-process controls
Process validation
Compliance with GMP
Presenter: Deus K. Mubangizi, pharmacist, MSc(Pharm.)
deuskm@yahoo.co.uk, dmubangizi@nda.or.ug
Chief Inspector of Drugs, National Drug Authority
WHO expert
Slide 3 of 19 D.K. Mubangizi, Dar Es Salaam Sept. 2007

Quality dossier / Section 3
Finished Pharmaceutical Product (FPP)
3.1. Manufacturing and marketing authorization
3.2. Pharmaceutical development
3.3. Formulation
3.4. Sites of manufacture
3.5. Manufacturing process
3.6. Manufacturing process controls of Critical steps and intermediates
3.7. Process validation and Evaluation
3.8. Specifications for excipients
3.9. Control of the FPP
3.10. Container/closure system (s) and other packaging
3.11. Stability testing
Slide 4 of 19 D.K. Mubangizi, Dar Es Salaam Sept. 2007

Quality dossier / Section 3
Finished Pharmaceutical Product (FPP)
3.12. Container labelling
3.13. Product information for health professionals
3.14. Patient information and package leaflet
3.15. Justification for any differences to the product in the country or
countries issuing the submitted WHO-type certificate(s)
Slide 5 of 19 D.K. Mubangizi, Dar Es Salaam Sept. 2007

3.4. Manufacturing sites
Name and street address of each facility where any aspect of
manufacture occurs including production, sterilisation,
packaging and quality control
Include any alternative manufacturers
Certificate issued by the Competent DRA according to WHO
Certification scheme for each site where a major step of
manufacturing is performed
Submit a valid GMP certificate (may not insist if inspected
by WHO)
Slide 6 of 19 D.K. Mubangizi, Dar Es Salaam Sept. 2007

3.5. Manufacturing Process
Flow chart with indication of each step showing where
materials enter the process. Indication of critical steps and
in-process controls
Description of manufacturing/packaging including
Scale
Equipment by type (e.g. tumble blender) & working capacity
Process parameters for steps, (e.g. time, temperature, pH)
Environmental conditions, e.g. relative humidity for hygroscopic
FPPs., area class for sterile FPPs
Slide 7 of 19 D.K. Mubangizi, Dar Es Salaam Sept. 2007

3.5. Manufacturing process (cont.)
Proposal for reprocessing justified with data.
Copy of master formula.
Batch manufacturing record real batch.
Sterile products sterilisation steps and/or aseptic
procedures.
Description of in-process tests including plan of sampling
and acceptance limits).
Data for 3 full scale batches to support achievement of
predetermined specifications.
Slide 8 of 19 D.K. Mubangizi, Dar Es Salaam Sept. 2007

3.6. Manufacturing Process Controls of
Critical steps and Intermediates

Identification of critical steps with test methods and justified
acceptance criteria
Information on quality of isolated intermediates, test
methods and justified acceptance criteria to control them
Slide 9 of 19 D.K. Mubangizi, Dar Es Salaam Sept. 2007

3.7. Process Validation and Evaluation

WHO validation definition
The documented act of proving that any procedure, process,
equipment, material, activity, or system actually leads to the
expected results.


Slide 10 of 19 D.K. Mubangizi, Dar Es Salaam Sept. 2007

3.7. Process Validation and Evaluation


What should be validated ?
Any aspect of operation, including significant changes to the
premises, facilities, equipment or processes, which may affect
the quality of the product, directly or indirectly, should be
qualified and validated
Slide 11 of 19 D.K. Mubangizi, Dar Es Salaam Sept. 2007

3.7. Process Validation and Evaluation

Purpose of validation
Process validation is intended to establish that the proposed
manufacturing process is a suitable one and yields
consistently a product of the desired quality.

i.e. that the process is suitable and under control
Slide 12 of 19 D.K. Mubangizi, Dar Es Salaam Sept. 2007

3.7. Process Validation and Evaluation
Validation mandatory for processes including a critical step
The aim is to show that critical steps are under control and lead
continuously to the desirable quality
Examples of critical steps (list non exhaustive)
mixing,
coating,
granulation,
emulsification,
non-standard sterilisation
Slide 13 of 19 D.K. Mubangizi, Dar Es Salaam Sept. 2007

3.7. Process Validation and Evaluation
3.7. Process Validation and Evaluation (details on first 3 production batches)
Batches
batch number
batch size
place and date of manufacture
batch number of API(s)
yield
batch purpose (validation, stability, clinical trial )
Process
equipment
process parameters
validation protocol.
Results
critical steps
in process control
finished product specification
Slide 14 of 19 D.K. Mubangizi, Dar Es Salaam Sept. 2007

3.7. Process Validation and Evaluation


Concurrent validation carried out during normal production
on the first 3 production batches
OR
For well-established processes
process data, in-process controls and quality controls on a
total of 10- 25 batches to present a statistically significant
picture
Slide 15 of 19 D.K. Mubangizi, Dar Es Salaam Sept. 2007

3.7. Process Validation and Evaluation
If validation data (on production scale batches) are not available
submit
validation protocol,
commitment that validation report will be submitted later
for evaluation,
commitment that data will be available in case of
inspection,
commitment that WHO will be informed of any significant
deviation.
Slide 16 of 19 D.K. Mubangizi, Dar Es Salaam Sept. 2007

3.7. Process Validation and Evaluation
Validation protocol should include
brief description of the process with summary of critical steps and parameters to be
followed during validation,
specifications of the FPP at release,
details of analytical procedures and limits,
sampling plan,
unifromity of dosage units essential for FDCs,
proposed timeframe
Validation report when submitted should include
results for each batch, certificates of analysis, batch production
records, report on usual findings, modifications, observations and
conclusions
Slide 17 of 19 D.K. Mubangizi, Dar Es Salaam Sept. 2007

THANK YOU