Quality Management System at Pharmaceutical Industry
Quality Management System at Pharmaceutical Industry
rakhmat.yuwono@id.etanabiotech.com
+62 08121874839
Term
Learning Matrix
70 : 20 : 10 Model
“Our Discussion”
…recent story in pharmaceutical industries
and some stories before ...
GVP GCP
GMP - Good
Practices GRP - Good
Manufacturing
Regulatory Practices
Practices
GDP GRP
DRUG
COMPLY TO
MARKETING DO NOT PLACE
AUTHORISATION PATIENTS AT
OR CLINICAL RISK
TRIAL
AUTHORIZATION
Inadequate
▪ Safety
▪ Quality
▪ Efficacy
Philosophy – Responsibility
▪ Moving from :
✔ Testing Final Product to Building into Product
✔ QC to QA
✔ Quality by Test to Quality by Design
▪ Beyond Compliance and moving to Quality
Culture
▪ Utilize modern science throughout product
lifecycle
▪ Quality Risk Management is a key enabler
throughout product lifecycle
Trend in Quality
Which is CORRECT ?
a. GMP is part of Quality Assurance
b. Quality Assurance is part of the GMP
What is Quality Management ?
▪ Suatu konsep luas yang mencakup semua aspek baik secara
individual maupun secara kolektif, yang akan memengaruhi
mutu produk. Manajemen Mutu adalah totalitas semua
pengaturan yang dibuat, dengan tujuan untuk memastikan
bahwa obat memiliki mutu yang sesuai tujuan penggunaan.
Oleh karena itu Manajemen Mutu mencakup juga CPOB -
CPOB, 2018
▪ A wide-ranging concept, which covers all matters, which
individually or collectively influence the quality of a product. It is
the sum total of the organised arrangements made with the
objective of ensuring that medicinal products are of the quality
required for their intended use. Quality Management therefore
incorporates Good Manufacturing Practice – PIC/S, 2022
What is Quality Management ?
▪ CPOB adalah bagian dari Manajemen Mutu yang memastikan
obat dibuat dan dikendalikan secara konsisten untuk
mencapai standar mutu yang sesuai dengan tujuan
penggunaan dan persyaratan Izin Edar, Persetujuan Uji Klinik
atau spesifikasi produk. CPOB mencakup Produksi dan
Pengawasan Mutu- CPOB, 2018
Unsur Dasar Manajemen Mutu
▪ Suatu infrastruktur atau sistem mutu Industri Farmasi
yang tepat mencakup struktur organisasi, prosedur,
proses dan sumber daya; dan
▪ Tindakan sistematis yang diperlukan untuk
mendapatkan kepastian dengan tingkat
kepercayaan yang tinggi, sehingga produk (atau jasa
pelayanan) yang dihasilkan akan selalu memenuhi
persyaratan yang telah ditetapkan. Keseluruhan tindakan
tersebut disebut Pemastian Mutu..
Unsur Dasar Manajemen Mutu
Infrastruktur / Tindakan
Sistem Mutu Sistematis
• Struktur • Kepastian
Organisasi • Tingkat
• Prosedur Kepercayaan
• Proses Tinggi
• Sumber Daya • Produk Selalu
Memenuhi
Persyaratan
What is GMP ?
▪ CPOB adalah bagian dari Manajemen Mutu yang memastikan
obat dibuat dan dikendalikan secara konsisten untuk
mencapai standar mutu yang sesuai dengan tujuan
penggunaan dan persyaratan Izin Edar, Persetujuan Uji Klinik
atau spesifikasi produk. CPOB mencakup Produksi dan
Pengawasan Mutu- CPOB, 2018
What is Quality Control ?
▪ Pengawasan Mutu adalah bagian dari CPOB yang mencakup
pengambilan sampel, spesifikasi dan pengujian, serta
mencakup organisasi, dokumentasi dan prosedur pelulusan
yang memastikan bahwa pengujian yang diperlukan dan
relevan telah dilakukan. Bahan tidak boleh diluluskan untuk
digunakan dan produk tidak boleh diluluskan untuk dijual atau
didistribusi sampai mutunya dinilai memuaskan - CPOB, 2018
Quality Management, Good Manufacturing
Practice and Quality Risk Management
…konsep dasar
Manajemen
Mutu, Cara
Pembuatan
Obat yang Baik
(CPOB), dan
Manajemen
Risiko Mutu
adalah saling
terkait...
Quality System – what should ensure ?
▪ Realisasi produk diperoleh dengan mendesain,
merencanakan, mengimplementasikan, memelihara Quality Manual
dan memperbaiki sistem secara berkesinambungan
sehingga secara konsisten menghasilkan produk dengan
atribut mutu yang tepat Technology
Transfer
▪ Product and process knowledge is managed throughout
all lifecycle stages
▪ Products are designed and developed in a way that takes Document
Management
account of the requirements of GMP, GLP and GCP
▪ Production and control operations are clearly specified
in a written form and GMP requirements are adopted. Production
Quality System – what should ensure ?
▪ Arrangements are made for the manufacture, supply and use of
the correct starting and packaging materials, the selection and
monitoring of suppliers and for verifying that each delivery is the
correct material from the approved supply chain
Third Party
Management Quality Control
/Supplier
Qualification
Quality System – what should ensure ?
▪ Products are not sold or supplied before the Batch Record
authorized persons have certified that each Review &
Product
production batch has been produced and controlled Release
in accordance with the requirements of the
marketing authorization and any other regulations Storage &
Distribution
relevant to the production, control and release of
pharmaceutical products.
▪ Satisfactory arrangements exist to ensure, as far as Production
possible, that the pharmaceutical products are
stored, distributed and subsequently handled so
that quality is maintained throughout their shelf-
life Quality Control
Quality System – what should ensure ?
▪ Regular reviews of the quality of pharmaceutical products are
conducted with the objective of verifying the consistency of the
process and identifying where there is a need for improvement;
▪ There is a system for QRM;
Product Quality
Review Quality Risk Management
Quality System – what should ensure ?
▪ Deviations, suspected product defects and other problems are
reported, investigated and recorded. An appropriate level of root
cause analysis is applied during such investigations. The most
likely root cause(s) should be identified and appropriate corrective
actions and/or preventive actions (CAPAs) should be identified
and taken. The effectiveness of CAPAs should be monitored.
Handling of
CAPA
Deviation
Quality Management System
Batch Record
Management Validation,
Quality Review &
Commitment/ Quality Manual Qualification &
Organization Product
Quality Policy Calibration
Release
Producy Document
Handling of Storage &
Product Recall Complaint & Management
Deviation Distribution
Return
Third Party
Banguna dan Management
Personnel Peralatan Production
Saranan /Supplier
Qualification
Internal/Extern
Quality Control CAPA Change Control Stability Study
al Audit
Management
Risk Continuous
Review (incl.
Identification Monitoring
Stakeholders)
Patient Product
Product Regulatory
Safety &
Quality Compliance Avaiability
Efficacy
KNOWLEDGE SHARING
QUALITY RISK MANAGEMENT
MANAJEMEN RISIKO MUTU
Why Important & Critical
▪ Manufacturing and use of a drug product involve some
degree of risk.
▪ Effective Quality Risk Management (QRM) ensure the high
quality of the drug product
✔ Proactive means to identify and control potential
quality issues
✔ improve the decision making if a quality problem
arises.
✔ facilitate better and more informed decisions
▪ Provide regulators with greater assurance of a company’s
ability to deal with potential risks and might affect the
extent and level of direct regulatory oversight
Why Important & Critical
▪ Improves decision making
▪ Identifies what gives most benefit to the patient
▪ Is scientific & data-driven
▪ Reduces subjectivity
▪ Ranks risk - allows prioritization
▪ Better use of resources
▪ Means of building in Quality
▪ Gives a company the ability to maintain compliance and
identifying product issues that could be harmful to
patients.
▪ Improves transparency - inside organisation and builds
trust with competent authorities
▪ Enables regulatory flexibility 45 | Q-Risk
Management | April
Learning Matrix
Risk Assessment
Risk Control
Risk Review
Risk Communication
Risk Assessment - Process
▪ Risk Identification is a
systematic use of information
to identify hazards referring to
the risk question or problem
description.
▪ Information : historical data,
theoretical analysis, informed
opinions, and the concerns of
stakeholders.
▪ Addresses the “What might go
wrong?” question, identifying
the possible consequences.
▪ Provides the basis for further
steps in the quality risk
management process.
52 | Q-Risk
Management | April
Risk Analysis
53 | Q-Risk
Management | April
Risk Evaluation
54 | Q-Risk
Management | April
Risk Evaluation - Output
▪ The output :
✔ quantitative estimate of
risk with a numerical
probability range of risk
✔ qualitative description
using qualitative
descriptors, such as
“high”, “medium”, or
“low”
55 | Q-Risk
Management | April
Risk Control - General
58 | Q-Risk
Management | April
Be Aware …
Is it a RISK ?
YES (if we know that)….
SUPPORTING SLIDES
KNOWLEDGE SHARING
DATA INTEGRITY
IMPORTANT & CRITICALITY
Why Important – Background ?
▪ Regulatory agencies have cited deficiencies in GMP data
integrity and data management for at least the past 15
years.
▪ It appears that the industry as a whole has made
limited progress in self identifying and remediating
these deficiencies.
▪ Regulators continue to identify the same set of
shortcomings including, but not limited to:
✔ shared passwords,
✔ lack of enabled audit trails,
✔ failure to review electronic data,
✔ failure to review and investigate all failed testing
results and failure to contemporaneously record
information.
Tianjin Zhongan Pharmaceutical
Tianjin Zhongan Pharmaceutical Co., Ltd.
“Failure to adequately complete and follow written procedures for
cleaning equipment and its release for use in API manufacture, and
to maintain adequate records of major equipment usage”
…failed to ensure that employees adequately cleaned after use. Your
equipment cleaning standard operating procedures require that
employees visually inspect equipment after the cleaning process. Our
inspection found in the manufacturing workshop for with various
levels of contamination and foreign objects inside, including what
looked like the remains of a pen in one of the (b)(4). Your employees
had labeled this equipment as clean. These are used for the
manufacture of multiple APIs.
… production system did not maintain equipment logs or other
documents that adequately record manufacturing operations
performed on individual pieces of equipment.
We note that your production operation supervisors and Quality Unit
(QU) failed to detect and correct these deficient cleaning practices
Sun Pharmaceutical Industries Limited
Sun Pharmaceutical Industries Limited
…missing the fundamental raw data and information necessary to
document your analyses. These analyses lack the following critical data:
• identification of the samples tested, including name and source, batch
number or other distinctive code, and date of the sample
• the complete record of all raw data generated during each test,
including graphs and electronic files from laboratory instrumentation
• test method used
• sample preparation as prescribed by the method, preparation and
testing of standards, reagents and standard solutions
• records of all calculations performed in connection with the test
• test results
• the signature of the person who performed each test and the date(s)
the tests were performed, and the date and signature of a second
person showing that the original records have been reviewed for
accuracy, completeness, and compliance with prescribed acceptance
criteria
Sun Pharmaceutical Industries Limited
…frequently performs “unofficial testing” of samples, disregards the
results, and reports results from additional tests. For example, during
stability testing, your firm tested a batch sample six times and
subsequently deleted this data.
Our investigators found your practice of performing initial “trial” sample
high performance liquid chromatography (HPLC) analyses prior to
acquiring the “official” analyses. The “trial” sample results were
subsequently discarded. Senior QC Officer confirmed that QC laboratory
employees had frequently practiced the use of “trial” injections at your
facility. Significantly, in addition to the example above, our inspection
found 5,301 deleted chromatograms on a computer used to operate two
HLPC instruments in your QC laboratory. Many of these files were “trial”
injections of batches
…similar unacceptable data handling practices were observed in your
laboratory’s conduct of gas chromatography (GC) analyses. The FDA
investigators reviewed what appear to be data from “unofficial” injections
for GC analyses for recovered raw material batch #(b)(4)…therefore, it
appears that out-of-specification data for batch #(b)(4) was considered to
be “unofficial,” while passing data were reported as the "official" results
Why Important ?
Why Important ?
Why Important ?
Why Important ?
Breaches of Data Integrity (BDI)
Data Integrity – Why fraud or breach ?
Data Integrity – Why fraud or breach ?
Data Integrity –Basic Principles
Data Integrity –Basic Principles
What is being challenged by Agency ?
Data Integrity –Basic Principles