1.

Manage batch disposition and implement integrated batch release

The authorized/Qualified Person is a named person, authorized for batch release

a. ensures that the batch and its manufacture comply with the provisions of the marketing
authorisation
b. ensures that manufacture has been carried out in accordance with GMP
c. confirms that the released product meets the required quality
d. ensures that any deviations, planned changes or Out of Specification (OOS) results in
production or quality control have been investigated and authorized by the persons
responsible in accordance with a defined system
e. ensures that any changes requiring variation, marketing or manufacturing authorization
have been notified and, when applicable, authorized by the relevant authority
f. ensures that all necessary checks and tests have been performed and approved
g. ensures that all necessary production and quality control documentation has been
completed and endorsed by the staff authorized to do so
h. considers the results of the executed batch production record and the laboratory
control record

Executed Batch Record Review

An executed batch (production) record review determines compliance of drug product production
records with all established and approved written procedures. It is valid for the entire manufacturing
workflow up to the packaging of the product.
In the context of an executed batch record review, at least the following points are checked:
1. the confirmation by the responsible person for production, that the batch has been
manufactured according to the requirements in the master batch record
2. plausibility, completeness and traceability of all data;
3. GMP-compliance of the manufacturing documentation (e.g. completeness of all signatures of
persons involved); -
4. conformance with the limits on In-Process Controls, process monitoring (e.g. yields, critical
process parameters) and, when applicable, environmental monitoring (e.g. particle and
microbiology monitoring);
5. comprehensive explanation of special occurrences (such as plant disturbances, the presence of
OOS results, deviations, procedural or technical changes);
6. the compliance of raw materials, starting materials, intermediates and packaging materials with
their specification, if not done previously to release by the Quality Unit;
 7. that all raw materials, starting materials, intermediates, bulk products and packaging materials
are released, if not done previously to release by the Quality Unit;
8. checks the Certificate of Conformance for the intermediates used or evaluates the respective
batch records;
9. confirmation of the cleanliness and released status of the equipment/apparatus used;

3. Manage deviation

SOP Deviation FLOW OF DEVIATION CAPA Tracking.xlsx

Management.pdf MANAGEMENT WITHIN COMMERCIAL OPERATIONS.pdf

4. Manage return products

Produk Kembalian karena Salah Kirim atau Salah Administrasi

 Periksa dokumen terkait dan buat Tanda Terima.

 Letakkan produk ke atas palet dan masukkan ke rak area Karantina.
 Berikan penandaan pada produk kembalian tersebut menurut Protap Penandaan, No ...........
 Beritahukan ke Bagian Pengawasan Mutu dengan mengirimkan kopi No ..........
 Bagian Pengawasan Mutu mengambil sampel dan melakukan pemeriksaan serta memberikan
rekomendasi terhadap status produk kembalian sebagai berikut:  dapat digunakan kembali;
dikemas ulang; atau  dimusnahkan.
 Bagian Pemastian Mutu memberikan keputusan akhir.
 Bagian Gudang atas dasar Butir (keputusan Pemastian Mutu) melakukan salah satu hal sebagai
berikut :  memasukkan produk kembalian ke stok gudang; atau  menyerahkan ke Bagian
Produksi untuk dilakukan pengemasan ulang; atau  memindahkan produk kembalian tersebut
ke Area DITOLAK dan memberikan penandaan status sesuai Protap Penandaan No ........; atau 
bersama Bagian Pengawasan Mutu dan Bagian Pemastian Mutu melakukan pemusnahan sesuai
Protap Pemusnahan Produk Jadi No .....

Produk Kembalian karena Kadaluwarsa

Periksa dokumen terkait dan buat Tanda Terima.
 Tempatkan produk di atas palet, beri label DITOLAK dan masukkan ke Area DITOLAK.
 bersama Bagian Pengawasan Mutu dan Bagian Pemastian Mutu melakukan pemusnahan sesuai
Protap Pemusnahan Produk Jadi No .....

Produk Kembalian oleh Sebab Lain

 Tempatkan produk ke atas palet, masukkan ke area karantina.
 Berikan laporan kepada Bagian Pemasaran.
 Beritahukan ke Bagian Pemastian Mutu.
 Kembalikan ke stok sesuai keputusan Bagian Pemastian Mutu.
Produk Kembalian karena Penarikan Kembali
 Periksa dokumen terkait dan buat Tanda Terima.
 Tempatkan produk di atas palet, beri label DITOLAK dan masukkan ke Area DITOLAK.
 Lakukan pencatatan dan rekonsiliasi sesuai Protap Penarikan Kembali Produk Jadi No ...... dan
laporkan ke Kepala Bagian Pemastian Mutu.
 Buat laporan kepada Kepala Bagian Pemastian Mutu, Kepala Bagian Pemasaran dan Kepala
Bagian Keuangan untuk hasil Penarikan Kembali : Formulir Rekonsiliasi.
 Bersama Bagian Pengawasan Mutu dan Bagian Pemastian Mutu lakukan pemusnahan sesuai
Protap Pemusnahan Produk Jadi No .....
 Terbitkan Berita Acara Pemusnahan Produk.

5. Manage product recall

SOP_Product
Recall.pdf

6. Manage Product Quality Review (PQR)

Regular periodic or rolling quality reviews of all authorized medicinal products, should be conducted
with the objective of verifying the consistency of the existing process, the appropriateness of current
specifications for finished product, to highlight any trends and to identify product and process
improvements.
should include at least:
a. A review of starting materials including packaging materials used in the product, especially those
from new sources;
b. A review of critical in-process controls and finished product results;
c. A review of all batches that failed to meet established specification(s) and their investigation;
d. A review of all significant deviations or non-conformances, their related investigations, and the
effectiveness of resultant corrective and preventive actions taken;
e. A review of all changes carried out to the processes or analytical methods;
f. A review of Marketing Authorisation variations submitted, granted or refused
g. A review of the results of the stability monitoring programs and any adverse trends;
h. A review of all quality-related returns, complaints and recalls and the investigations performed
at the time;
i. A review of adequacy of any other previous product process or equipment corrective actions;
j. For new Marketing Authorisations and variations to Marketing Authorisations, a review of post-
marketing commitments;
k. The qualification status of relevant equipment and utilities, e.g. HVAC, water, compressed gases,
etc;
l. A review of any contractual arrangements as defined in Chapter 7 to ensure that they are up to
date.
The manufacturer and, where different, Marketing Authorisation holder should evaluate the results of
the review and an assessment made as to whether corrective and preventive action or any revalidation
should be undertaken, under the Pharmaceutical Quality System. There should be management
procedures for the ongoing management and review of these actions and the effectiveness of these
procedures verified during self-inspection.

7. Manage Quality Risk Management (QRM) activities at the site

Risk assessment is a systematic approach for identification and evaluation of any potential risk for an
event, system, process or product. Identified potential risks are analyzed for their relative severity using
risk analysis tool and with scientific based assessment.
Area of applicability:
- Product design + development including transfer of manufacturing processes
- Regulatory Compliance + Management of changes
- Facility Design Reviews
- Deviations and product complaint, counterfeit, Issue Management, Recalls
- Qualification + Validation activities
- Auditing and Inspection

Risk Assessment.doc Attachment 2_Risk Attachment 1_Risk

Ranking.docx Assessment Report.docx

8. Manage gap assessment of QA activities and deployment of Takeda Global QMS related with QA
 Pembuatan
Dokumen ver.02.doc

9. As QA Validation, support QA validation review and guidance for validation

Validation Master Plan

VMP is an overview document that captures all necessary qualification and validation processes
and activities for an organizational unit (production unit, control laboratory, building, etc) or a
complex project.
Contents of VMP as follows :
Tasks of the unit as well as the organizational structure of all validation / qualification activities
or the project.
Building and/or installation plan, if applicable including personnel and material flow (generally as
a drawing), use of recycled products and/or solvent, interfaces with other systems and/or projects
and the cleanliness class concept.
Products to be manufactured / tested
List of the functional representation in the qualification / validation team and description of
responsibilities.
List of governing documents that define the requirements for qualification / validation and
change control.
List of all technical installation and determination of the need for qualification
All technical system are listed and the need for qualification is stated including the results of the
determination of the GMP-relevance of computerized systems.
Usually, the technical systems are divided into the following categories :
 Bangunan dan fasilitas ( Premises / facilities)
 Sarana penunjang (Utility systems)
 Peralatan teknis atau mesin (Techical equipment)
list consists of information :
 Tehnical installation name
 Asset number (if available)
 System number of document
 Assessment of GMP relevant
 Calibration requirement for system contain measuring devices to be calibrated
 Date of the initial qualification
  Date of last qualification
 due dates for regular re-qualification
 The procedures ensuring the maintenance of the qualified status

Identification of all processes, analytical methods and cleaning procedures are listed and
determination of the need for validation
Usually, list of these are divided into the following categories :
 operational processes
 Analytical method as well as IPC, stability testing, analytical methods for the verifica-
tion of cleaning process.
 Cleaning, disinfection and sterilization process

Daftar berisi informasi tentang (list consists of information ) :

 Item / product / system name
 Product number or item, if any.
 System number of document
 Assessment of GMP relevant
 date of last qualification
 due dates for regular re-qualification)
Special decisions (e.g. cleaning validation lead product, validation matrix approach or
validation transfer) are comprehensively documented and justified.
Identification of all computerized systems and determination of the need for qualification and
validation)
Usually, list of all computerized systems divided into the following categories :
 Computer equipment
 Computerized system
 Computer controlled processes

list consists of information :

 identification number
 document system number
 The assessment of electronic record/ electronic signature
 date of initial qualification / validation
 date of last qualification / validation
 due date of regular re-qualification/ validation

Schedule for qualification and validation activities

Layout
Each site defines the requirements for the format / layout of the VMP as well as of associated
documents, based on valid local qualification / validation protocol / report follow template
attached in Validation Master Plan (VMP).

01.01.50-03 VMP.rtf

a). Process Validation

Validasi Proses : Tindakan pembuktian yang didokumentasikan bahwa proses yang dilakukan dalam
batas parameter yang ditetapkan dapat bekerja secara efektif dan memberi hasil yang dapat terulang
untuk menghasilkan produk jadi yang memenuhi spesifikasi dan atribut mutu yang ditetapkan
sebelumnya.
Validasi Prospektif : Validasi yang dilakukan sebelum pelaksanaan produksi rutin dari produk yang akan
dipasarkan.
Validasi Retrospektif : Validasi dari suatu proses untuk suatu produk yang telah dipasarkan berdasarkan
akumulasi data produksi, pengujian dan pengendalian bets.
Validasi Konkuren : Validasi yang dilakukan pada saat pembuatan rutin produk untuk dijual.

Critical Parameter / Points in Process Validation :

  Waktu proses (mis : pencampuran, granulasi, pengeringan, penyalutan, pelarutan,
waktu simpan)
 Suhu proses (mis : mixing, pelarutan, filtrasi, pengeringan, penyalutan).
 Kecepatan proses (mis : kecepatan pencampuran, kecepatan pencetakan, kecepatan
penyemprotan, penyaringan, pemanasan, pendinginan).
 Tekanan (process pressure)
 pH
 Conductivity
 Yields
 Microbial load
Semua pengawasan dalam proses untuk produk harus dievaluasi, misalnya :
Solid Granulation Moisture, particle size, solvent residues
Mixing Blend uniformity
Compression Weight, hardness, thickness, content uniformity, dissolution/ disin-
tegration, appearance.
Coating Dissolution/ disintegration, appearance, weight variation
Semi Solid Mixing Uniformity, homogeinity, particle size and distribution, viscosity
Liquid Mixing Uniformity, foreign particles, dissolution of ingredients

PV 01.03.02-07.doc

Risk analysis Refagan PVP Refagan VR Refagan 10th

ed 10.xls 10th.doc Ed.doc

Risk analysis attach 3 VP Incidal ed12.doc VR Incidal ed12.doc

Incidal ed 12.xls

Risk analysis attach 3 VP Mycospor ed VR Mycospor ed

Mycospor Cream Hf ed 3.xls 03.doc 03.doc

b). Cleaning Validation

Ray Collyer_Cleaning
Validation principles.pdf
 Chemical Cleaning Chemical Cleaning Chemical CV
Validation Matrix 2013.xlsx
Validation Matrix 2013 (To be
Status.xls
Printed).xlsx

c). Qualification

Kualifikasi Instalasi
Teknis.doc

Risk IQ Worksheet Killian OQ Worksheet Killian QP 05.02.16-08.doc QR 05.02.16-08.doc

Analysis_05.02.16-08.xls TX.doc TX.doc

d. Computerized System validation

Attach. 16A List of List of CSV for VMP

CSV status (GMP Relevant).xlsx
2012 (QA-QC).xlsx

CLEANLINESS CLASS :
 SOP Cleanliness Lampiran SOP Lampiran SOP
Class.pdf Cleanliness Class.pdf Cleanliness Class 2.pdf

QUALITY MANUAL :
Quality Manual provides an overview of the Quality Management System in country
The Quality Manual serves as the policy base for the Compliance Management System (CMS) that apply
to the facilities, products and cGMP activities.
1. Company’s strategic mission and values
2. Organizational structure
3. Management responsibility
4. Quality Management Review
5. Compliance Management system
 Reporting KPIs
 Quality Risk Management
 CAPA
 Quality Management Review
 Change Management
 Quality of Conformance

Site Master File :

Contents :
1. General Information (GMP License, Factory address and Head Office, Product dosage
form produced at the site, authority audit that already passed, etc)
2. Quality policy :
- Responsibility of the QA function
- Quality Management system
- Management of suppliers and contractors
- Quality Risk Management
- Product Quality Review
3. Personnel : Number of employees engaged in the QMS, Organization Chart of the site
Management)
4. Premises and equipment
5. Documentation
6. Production : type of product, process validation
7. Quality Control
8. Distribution, complaints, product defect and recalls
9. Self inspection

SOP Site Master SMF-Sunthi Sepuri 1

File.doc Mei 2014.pdf
GMP Training

06.01.08-07_GMP GSOP 192-3_GMP

Training.doc Training.pdf

Quality Management Review

SOP_Quality
Management Review.doc

Change Management

01.01.12-09_Change attachment
control.doc 3_01.01.12-09.xls

1. Deputy of Head of Quality in releasing product to market

2. Prepare regulatory documentation package for submission to local FDA (BPOM)
3. To lead and manage the site validation activities and assure that validations comply
with the company procedure and local cGMP regulations (Manufacturing and Packaging
process validation, Chemical and Microbiological cleaning validations, and Computer-
ized System validation)
4. To lead and manage the qualification of building, utilities, machineries and laboratory
instruments and assure that qualifications comply with the company and local cGMP
regulations
5. Perform GMP trainings and ensure the completion of the training metrics of all depart-
ment.
6. Perform packaging material development management and ensure the packaging ma-
terials used for the packaging process comply as per registration approved by local
FDA and fulfill stability requirement.
7. Perform in process control at manufacturing and packaging lines to assure the manu-
facturing and packaging process are performed according to the validated procedures
written in master batch records.
8. Manage retained sample handling
9. To lead the documentation system management at the site
10. Coordinate change management system at the site and assure its process is performed
in compliance with the company procedure and local cGMP regulation.
11. Perform GMP Self-Inspection program and to follow up the CAPAs/gaps to be closed
appropriately as per committed time line, as well to manage the qualification of the
inspectors.
12. Perform regulatory compliance management checking program to ensure all process
and products manufactured at the site comply with the company regulation and local
cGMP regulation.
13. Perform Product Quality Review activities and to monitor the CAPAs/gaps to be closed
appropriately as per committed time line
14. Perform supplier management and audits and to monitor the CAPAs/gaps to be closed
appropriately as per committed time line
15. Review completed manufacturing and packaging batch record and to assure its com-
pliance prior to releasing process by the head of quality.
16. Perform product technical complaint handling, lead the investigation and provide re-
sponse letter for the complainant. Provide the trending monthly.
17. Perform deviation management system, lead the investigation and following up the
CAPAs.
18. Perform Quality Management Review quarterly
19. Perform GMP audits to the third-parties (contract manufacturers, suppliers and dis-
tributors) and to assure that the CAPAs/gaps are closed appropriately and in timely
manner
20. Set up and maintain the Quality Assurance Agreements with Contract Manufacturers
and distributors.