Program Profesi Apoteker

25 Agustus 2018
 Taufik Akbar
E: taufikakbar.90oz@gmail.com

Yogyakarta

First copy product

Memastikan produk yang
01 dikembangkan bioequiv-
alen
2011 2013 2018
Troubleshooting
02 Improvement produk ek-
sisting

FARMASI UAD PSPA UAD DEXA MEDICA

Scientific writing
R&D Formulation
03 Publikasi ilmiah: paper,
patent, seminar
 Why pharmacy?

Why industries?

Interested with R&D?

Farmasi UAD
 Singkatan
API : Active Pharmaceutical Ingredient
DMF : Drug Master File
SPC : Summary Product Characteristic
BE : Bioequivalence
USP : United States Pharmacopeia
NF : National Formulary
Ph. Eur/EP : European Pharmacopeia
BP : British Pharmacopeia
JP : Japanese Pharmacopeia
FI : Farmakope Indonesia
FDA : Food and Drug Association
BCS : Biopharmaceutical Class System
PENGEMBANGAN PRODUK
ICH Q8 (Pharmaceutical Development)
ICH Q9 (Risk Management)
ICH Q10 (Pharmaceutical Quality System)
 Pengembangan produk
Untuk merancang kualitas produk dan
proses produksinya agar secara konsisten
menghasilkan performance yang diinginkan

ICH Q8
Informasi dan pengetahuan yang
diperoleh memberikan pemahaman
Parameter kritis umumnya diiden-
ilmiah untuk mendukung pemben-
tifikasi melalui risk assessment
tukan design space, spesifikasi dan
kontrol proses
 Trial and error
ICH Q8

Target pengembangan

Quality after De-

sign
Pemahaman produk dan proses

Quality by De-
sign (QbD)

Pengendalian proses berdasar

pemahaman ilmiah
Kualitas produk didasarkan
pada hasil pengujian QC

Quality risk management

(Q9 & Q10)
Quality by Design
“Quality cannot be tested into product, it should be built
in, or by design.”
 Process validation
Traditional process validation
Quality can not be adequately assured
merely by in-process and finished-
product
- This shows that only sampled units
meets the desired quality
Each step of process must be con-
trolled to assure that the finished prod-
uct meets all quality attributes includ-
ing specification
- Control of the process affect every
unit in the batch, not just sampled
unit
Quality by Design
- It is a comprehensive, systemic,
knowledge and risk-based quality
methodology
Quality By Design is:
- “Understanding what factors have
an impact on variation in your
process and also on your product’s
performance; then establishing a
control plan to monitor and maintain
product quality”
Quality by Design Crucial for
product / process
development
 Step 1. Process design
Determine Quality Target Product
Profile (QTPP)

Identify Critical Quality Attributes

(CQA) of finished product
Investigate Critical Material At-
tributes (CMA) of API and excipient

Determining the appropriate

process and specifying the Critical
Process Parameters (CPP)
Establish relevant control strate-
gies
 Explanations
QTPP
CQA CMA CPP
 Defines  Subset of  Critical at-  Critical pa-
product QTPP tributes of rameters of
material that process that
 Target goals  Critical pa-
influence influence
rameters
product qual- product qual-
 Safety, effi-  Safety and ity ity
cacy, iden- efficacy
tity, purity,
potency

Control strategies
Is a control plan of a product obtained from comprehensive understanding regarding formula
and process
 QTPP
Dosage Form
Route of
administration
Strength CQA
Weight
Assay (efficacy)
Pharmacokinetics
Impurities (safety)
Appearance
Identity C.U. (efficacy)
Assay
Dissolution
Impurities (efficacy)
Content uniformity
Friability
Dissolution
Residual solvents
 Case study

Latar belakang Target produk

01 Produk PDE-4 Film Coated Tablet
0.5 mg akan dikembangkan
02 Generic pertama dari innovator

Profil stabilitas Complexity

03 Terdegradasi dengan pada kondisi
asam dan basa serta mudah
04 Homogenitas, study bioequivalen,
stabilitas
teroksidasi
 QTPP
QTPP Target Justification
Dosage form Film coated tablet Pharmaceutical equivalence require-
ments: same dosage form

Dosage design Immediate release tablet with film coating and without score Immediate release design needed to
meet label claims
Route of administration Oral Same as RLD
Dosage strength Each film coated tablet contains 500 mcg PDE-4 Pharmaceutical equivalence require-
ments: same strength
Pharmacokinetics The absolute bioavailability of PDE-4 following a 500 mcg oral Bioequivalent requirement compared
dose is approximately 80%. to RLD
Tmax PDE-4: approximately 1 hour (0.5 – 2 hours) in the
fasted state

Stability At least 24 months at room temperature Equivalent or better than RLD

 QTPP
QTPP Target Justification
Drug Physical attributes Must meet compendia or other Pharmaceutical equivalence requirements
product Identification applicable quality standards for oral
quality products
attributes Assay
(intermediate Uniformity of dosage unit
product)
Dissolution
Drug Physical attributes Must meet compendia or other Pharmaceutical equivalence requirements
product Identification applicable quality standards for oral
quality products
attributes Assay
(finished Uniformity of dosage unit
product)
Dissolution
Impurity
Microbial limit
Container closure system PVC/PVDC aluminum blister Needed to achieve the target shelf-life and
Box, 3 blister x 10 film coated tablet to ensure product integrity during shipping

Alternative methods of administration Not applicable None are listed in the SPC of RLD
CQA – Intermediate Product
CQA – Intermediate Product
CQA – Finished Product
CQA – Finished Product
CMA
CPP
Section Break
Questions?
 AGENDA

1 Preformulasi & trial formulasi

2 Strategi Bioequivalen

3 Patent

4 Discussions