STIKES Anwar Medika 1

2019
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ALUR PRODUKSI
PPIC PRODUKSI
FORMULASI

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FINISHED
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PENGEMASAN
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RAW MATERIAL PENIMBANGAN

PENCAMPURA
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GUDANG
QA KARANTINA
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TUBE

DUS
BOX

KEMAS PRODUK
SEKUNDER JADI
GUDANG PRODUK JADI
FLOW PROCESS SALEP
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 Outline
Brief introduction on Quality by Design(QbD)
Example approach to identify critical quality
attributes (CQA)
Example approach to identify critical material
attributes (CMA) and critical process
parameters (CPP)
Illustrative examples
Concluding remarks
2
 What is Quality by Design(QbD)?
 A systematic approach to development that begins with
predefined objectives and emphasizes product and process
understanding and process control, based on sound science and
quality risk management. (ICH Q8R2)
Systematic Approach
Predefinedobjectives  Define Quality Target Product Profile (QTPP)
 Identify Critical Quality Attributes (CQA)
Product and process  Identify critical material attributes (CMA*)and
understanding critical process parameters (CPP)
 Establish the functional relationships that
link CMA/CPPto CQA
Process control  Develop appropriate Control Strategy,including
justifications
Sound science  Science-driven development (scientific literature,
prior knowledge, DOEsetc.)
Quality risk  Risk-based development (ICH Q9) 3
*management
CMA definition will be given later.
What is a Quality Target ProductProfile
(QTPP)?
ICH Q8(R2) Definition: A prospective
summary of the quality characteristics of a
drug product that ideally will be achieved to
ensure the desired quality, taking into
account safety and efficacy.

TPP: labeled use, safety

and efficacy

QTPP: quality characteristics

to ensure safety and efficacyas
promised in the label 4
 Guidance for Industry
Q8, Q9, & Q10 Questions and Answers
The Quality Target Product Profile (QTPP) provides an
understanding of what will ensure the quality, safety, and
efficacy of a specific product for the patient

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QbD for ANDAs: An Example for IR Dosage Forms. April 2012. 6

http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplicat
ions/AbbreviatedNewDrugApplicationANDAGenerics/UCM304305.pdf
 Points to Consider
Guide for ICH Q8/Q9/Q10 Implementation
The Quality Target Product Profile (QTPP) describes the
design criteria for the product, and should therefore form
the basis for development of the CQAs, CPPs, and
control strategy.

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 Definitions
 Critical Quality Attributes (CQA)
– A physical, chemical, biological, or microbiological
property or characteristic that should be withinan
appropriate limit, range, or distribution to ensure
the desired product quality (ICHQ8)
 Critical Process Parameter (CPP)
– A process parameter whose variability has an impact on a CQAand therefore
should be monitored or controlled to ensure the process produces thedesired
quality. (ICH Q8)
 Critical Material Attribute (CMA)*
– A physical, chemical, biological or microbiological property or characteristic of
an input material that should be within an appropriate limit, range, or
distribution to ensure the desired quality of outputmaterial.

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*CMA is not defined in ICH guidance, but used here for discussion purposes
 Approach to Identify CQAs
1. Consider all DPquality attributes; physical attributes,
identification, assay, content uniformity, dissolution
and drug release, degradation products, residual
solvents, moisture, microbial limits, etc.
2. Identify a CQAbased on the severity of harm to a
patient (safety and efficacy) resulting from failure to
meet that quality attribute.
– Identified before taking intoaccount risk control
– Does not change as a result of risk management

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Q
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 Not a CQA

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CQA

QbD for ANDAs: An Example for IR Dosage Forms. April 2012.

 Definitions
 Critical Quality Attributes (CQA)
– A physical, chemical, biological, or microbiological property or characteristic
that should be within an appropriate limit, range, or distribution to ensure the
desired product quality (ICHQ8)
 Critical Process Parameter (CPP)
– A process parameter whose variability has an impact on a
CQAand therefore should be monitored or controlled to
ensure the process produces the desired quality. (ICHQ8)
 Critical Material Attribute (CMA)*
– A physical, chemical, biological or microbiological property
or characteristic of an input material that should be within
an appropriate limit, range, or distribution to ensure the
desired quality of output material.
*CMA is not defined in ICH guidance, but used here for discussion purposes
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Relationship between CMAs, CPPs andCQAs

CPPs

CMAs Pharmaceutical CQAs

Unit
Input Operation Output
Materials Materials or
Product

CQAs = f (CPP1, CPP2 , CPP3 …CMA1, CMA2, CMA3…)13

Linking Patient - Product - Process
Clinical Outcome
Patient (Safety & Efficacy)

CriticalQuality
Product Attributes
(CQA)

Formulation Critical Material Attributes

/Process (CMA)
Critical Process Parameters
(CPP) 14
Example Approach to Identify Material
Attributes and Process Parameters

Useful tools:
Risk assessment, prior knowledge, established science…..

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 Example Approach to Identify Material
Attributes and Process Parameters

Drug ProductCQAs: Intermediate CQAs: Process Variables:

Content Uniformity Blend Uniformity 1. Particle size distribution
2. Loading level
3. Number of revolutions

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 Identifying Potentially High Risk MAs or PPs

 Special considerations for unique DS/DPproperties

– e.g. RHcan be potentially high risk for a hygroscopic formulation

Yu et al, Understanding Pharmaceutical Quality by Design, The AAPS Journal, 2014 , 16(4) 771- 783 17
Example Approach to Determine Criticality
Once potentially high risk variables are identified:
 Identify levels or ranges of these potentially highrisk
attributes and/or parameters.
 Design and conduct experiments, using DOEwhen
appropriate.
 Analyze the experimental data to determine if a
material attribute or process parameter iscritical.
– If variability has an impact, then need to monitor and/or control
 Develop a control strategy.

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 Tugas Kelompok 5-7 orang ATAU
Sesuai kelompok praktikum
Buat Resume mengenai Proses Pembuatan Salep (Pilih Formula bebas)
1. Identifikasi CPP dan CQAnya
2. Terdapat Flow Process Pembuatannya (diagram)
3. Kenapa CPP dan CQA tersebut yang terpilih, jabarkan alasan ilmiahnya
4. Tentukan Kontrol Stategi agar CPP dan CQA terkendali (dalam bentuk table)
5. Tugas di emailkan ke fithrul.mubarok23@gmail.com dengan subject judul Resume, bentuk file PDF
6. Maksimal 10 halaman tidak termasuk cover
7. Bila telat 1 hari kurang point 10%, 2 hari 20% dst
8. Maksimal tanggal 31 Oktober 23.59 WIB

Clue
- Pahami proses pembuatan salep di Industri (tonton video di Youtube)
- Formula salep dapat dipilih di buku Handbook of Pharmaceutical Manufacturing
Formulations - Semisolid Products
- Buat resume yang ilustratif
 Tugas Kelompok 5-6 orang
Buat Resume mengenai Proses Pembuatan Salep (Pilih Formula bebas)
1. Terdapat Flow Process Pembuatannya (diagram)
2. Sebutkan bahan-bahan dari formula dan fungsinya (emulgator, chelating agent dll…) bentuk tabel
Kenapa urutan pembuatannya seperti itu
3. Parameter apa untuk Pemeriksaan Produk jadi pada salep ?apa fungsi pemeriksaannya? (bentuk
table)
4. Tugas di emailkan ke fithrul.mubarok23@gmail.com dengan subject judul Resume, bentuk file PDF
5. Maksimal tanggal ……..
6. Bila telat 1 hari kurang point 10%, 2 hari 20% dst

Clue
- Pahami proses pembuatan salep di Industri (tonton video di Youtube)
- Formula salep dapat dipilih di buku Handbook of Pharmaceutical Manufacturing
Formulations - Semisolid Products
- Buat resume yang ilustratif