Pharmaceutical

Scale-Up
 Product Quality Lifecycle Implementation (PQLI®)

CQAs= Critical Quality Attributes

PQSE= Pharmaceutical Quality System Elements
• Technology Transfer & Scale-up as a Part of
Pharmaceutical Quality Systems

ICH Q10
“The goal of technology transfer activities is to
transfer product and process knowledge between
development and manufacturing, and within or
between manufacturing sites to achieve product
realisation. This knowledge forms the basis for
the manufacturing process, control strategy,
process validation approach and ongoing
continual improvement.”
• Technology transfer adalah suatu proses
pengawasan dan penerapan/instalasi suatu
produk baru atau proses pada manufacturing
facility.

• Tujuannya/Alasan ?

• Apa yang ditransfer?

• Contoh ?
– Industri global yang punya cabang ?
– Perbaikan/peningkatan fasilitas produksi ?
– Contract manufacturing ?
 FORMULASI

• TAHAP PRE FORMULASI

• TAHAP FORMULASI SKALA LAB.
• TAHAP PENGUJIAN STABILITAS
• TAHAP FORMULASI SKALA TRIAL
PRODUCT
• TAHAP SKALA PRODUKSI (TRIAL SKALA
PRODUKSI/TRIAL UP)
• MASTER FORMULA
 TAHAP PREFORMULASI

• SURVEY TERHADAP PRODUK SEJENIS

• STUDY PUSTAKA TENTANG SIFAT FIS-KIM Z A, SEDIAAN,

FORMULA, SERTA METODE PRODUKSI

• INFORMASI SUPPLIER BAHAN BAKU

• INFO SIFAT FISIKA-KIMIA BAHAN BAKU DARI SUPPLIER

(BANDINGKAN)
 TAHAP FORMULASI SKALA LABORATORIUM

 Dibuat beberapa formula dari hasil rancangan

penelitian/study pustaka
 Formula dibuat skala lab. Kira-kira 5-10 kg bahan tiap
batch, sebanyak 3 batch.
 Untuk sediaan cair kira-kira 500 ml
 Analisa hasil apakah memenuhi parameter yang
ditetapkan
 Hasil baik jika tiap batch yang dibuat memenuhi
parameter yang ditetapkan
 Dipilih formula yang terbaik
 TAHAP PENGUJIAN STABILITAS

Formula terpilih (beberapa formula) akan dilakukan uji

stabilitas fisik-kimia, apabila hasil baik (tidak terjadi
ketidakstabilan secara fisika dan kimia, maka akan dilanjutkan
trial produksi
• Langkah awal pengembangan produk adalah
pengembangan oleh departemen R & D dan
kemudian diproduksi dalam skala industri

• Apakah produk yang dikembangkan oleh

departemen R & D dapat langsung diproduksi
Permasalahan ?

Large scale (in production).

Small scale (in laboratories or pilot plants)

Scale-Up Can Be Complex
 Tahap Formulasi Skala Trial Product
 Formula yang terbaik skala laboratorium, dilakukan trial
dalam skala yang lebih besar dg ukuran batch masing-
masing minimal sepersepuluh batch skala produksi

 Hasil dikatakan baik jika batch yang dibuat memenuhi

parameter yang ditetapkan
 Tahap Skala Produksi
(trial skala produksi/trial up)

 Bila hasil trial product baik, maka dilakukan peningkatan

kapasitas menjadi 3 batch
 Hasil dikatakan baik jika ke 3 batch memenuhi
parameter yang ditetapkan
 Pada tahap ini dilakukan validasi proses dan uji stabilitas
produk yang dihasilkan
 Butuh waktu lama
 SCALE UP
• Scale up is generally defined as process of increasing the batch
size.
• Scale up of process can also be viewed a procedure for applying
the same process to different output volumes

• Scale-up: The act of using results obtained from laboratory

studies for designing a prototype and a pilot plant
process;construction a pilot plant and using pilot plant data
for designing and constructing a full scale plant or modifying
an existing plant

• Ada dua perbedaan kecil antara 2 definisi tsb. : batch size

enlargement does not always translate into a size increase of
processing volume
• Contoh :
1. in mixing applications, scale up is indeed
concerned with increasing the linear
dimensions from laboratory to the plant size.

2. on other hand, processes exist (e.g.

tableting) for which “ scale up” simple means
enlarging the output by increasing the speed.
3. In biotechnologi : an increase of the scale is couterproductive dan
scale-down is required to improve the quality or quantity of the
product

 In moving from R&D to production scale, it is sametimes

essential to have an intermediate batch scale. This is achieved at
the so-called pilot scale, which is defined as the manufacturing
of drug product by a procedure fully representative of and
simulating that used for full manufacturing scale

 Once you understand what makes these processes similar, you

can eliminate many scale up problems
 Objective
• Examination of the formula to determine it’s ability to
with stand Batch-scale and process modification.

• Evaluation and Validation for process and equipments

• To identify the critical features of the process.

• Guidelines for production and process controls.

• To provide master manufacturing formula with

instructions for manufacturing procedure.

• To avoid the scale-up problems

 Why conduct Pilot Plant Studies?
• A pilot plant allows investigation of a product and
process on an intermediate scale before large
amounts of money are committed to full-scale
production

• It is usually not possible to predict the effects of a

many-fold increase in scale

• It is not possible to design a large scale

processing plant from laboratory data alone with
any degree of success