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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5855_Библиотеки_им_академика_М_И_Перельмана.pdf
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- •About the Authors
- •Preface
- •Acknowledgements
- •Contents
- •1.1. Singapore as a British Colony
- •1.5.1. Levelling Up the Pharmaceutical Inspection System of Singapore
- •1.5.2. Advantages of PIC/S Membership to Singapore and Other Participating Authorities
- •1.6. Emergence of MNC Pharmaceutical Manufacturing Industry in Singapore
- •1.6.1. Why do MNC Pharmaceutical Manufacturers Set Up Facilities in Singapore?
- •2.2. Geographical Background of ASEAN vis-à-vis Asia and the Rest of the World
- •2.4. Formation of an ASEAN MRA Taskforce on GMP Inspection
- •2.5. Signing of ASEAN Sectoral MRA on GMP Inspection
- •2.6. Formation of ASEAN JSC on GMP Inspection and Establishing Register of ASEAN LIS
- •2.8. Assessment of FDA Philippines by ASEAN PoE
- •2.9. Register of ASEAN Listed Inspection Services (LIS)
- •3.1. Introduction: Urgency of Training ASEAN Inspectors
- •3.3. Collaboration with Korea Ministry of Food and Drug Safety (MFDS)
- •3.4. Collaboration with the Generics and Biosimilars Initiative (GaBI)
- •3.5. Pre-employment Training in Pharmacy and Pharmaceutical Science Schools
- •4.1. Introduction
- •4.2. Historical Context to WHO Reliance Initiative
- •4.3. The First NRAs to Achieve ML4 and WLA Status
- •4.5. Other International Reliance and Harmonization Initiatives
- •4.5.1. Access Consortium
- •4.5.2. Association of Southeast Asian Nations (ASEAN)
- •4.5.3. East African Community (EAC)
- •4.5.4. European Medicines Agency (EMA)
- •4.5.6. International Council for Harmonization (ICH)
- •4.5.6.1. Introduction
- •4.5.6.2. ICH Members and Observers
- •4.5.6.3. Future Direction
- •4.5.7.1. Introduction
- •4.5.7.2. Addressing Common Regulatory Issues
- •4.5.7.3. ICMRA Pilot Program for Collaborative Hybrid Inspection
- •4.5.8. International Pharmaceutical Regulators Program (IPRP)
- •4.5.9. Latin America
- •4.5.10. Pharmaceutical Inspection Co-operation Scheme (PIC/S)
- •4.5.10.1. Introduction
- •4.5.10.2. PIC/S Participating Authorities
- •4.5.11. WHO Collaborative Registration Procedure for Medical Products (CRP)
- •4.5.12.1. Introduction
- •4.5.12.3. WHO Inspection Report
- •4.5.13. ZaZiBoNa
- •4.6. Conclusion
- •5.1. Introduction to GMP
- •5.2. Overview of the PIC/S GMP Standard
- •5.3. How is an On-site GMP Inspection Conducted?
- •5.3.1. Why is the Warehouse Inspected?
- •5.3.3. Why are the Production Areas Inspected?
- •5.3.4. Why are the Packaging Areas Inspected?
- •5.3.5. Why are the QC Laboratories Inspected?
- •5.3.6. Why do GMP Inspectors Visit Other Miscellaneous Areas?
- •5.3.8. Why is there a Need to Conduct Documentation Audit/Review?
- •5.3.8.1. Assessing Product Quality Review
- •5.3.8.3. Assessing Self-Inspection Program
- •5.4. The 20 Annexes of PIC/S GMP Standard
- •5.5. PIC/S Inspection System: A Risk-based Approach
- •5.5.1. Whom can the GMP Inspector Interview?
- •5.5.2.1. Inspector’s Expectations of a Manufacturer
- •5.5.2.2. Manufacturer’s Expectations of an Inspector
- •5.6. Who Inspects the Inspectors?
- •6.1. Historical Development of Pharmaceutical Quality
- •6.2. What is a High-Quality Medicinal Product?
- •6.3. Purity of a Medicinal Product: Elimination of Impurities and Contaminants
- •6.3.1. What is a Contaminated Medicinal Product?
- •6.3.2. Why is There a Need to Control Impurities?
- •6.3.2.1. Types of Impurities from APIs
- •6.3.2.2. Types of Impurities from Container-Closure System
- •6.3.3. Control of Intrinsic Contaminants
- •6.3.4. Control of Extrinsic Contaminants
- •6.3.5. General Assessment of Cross-Contamination Risks
- •6.4. Stability and Shelf-Life Testing of a Medicinal Product
- •6.4.1. Why is Proper Storage, Distribution and Handling of a Medicinal Product Important?
- •6.6. Summary of High-Quality Medicinal Products
- •7.1. Introduction to Stability and Quality
- •7.3.1. Why is Proper Storage Important?
- •7.3.2. Why is Proper Transportation of a Medicinal Product Important?
- •7.3.3. Why is Proper Handling of a Medicinal Product during Use Important?
- •7.4.1. Number and Size of Batches
- •7.4.2. Testing Frequency
- •7.4.3. Storage Conditions
- •7.4.4. Test Methods
- •7.4.5. Container-Closure Systems
- •7.5. Stability Study Schedule and Report
- •7.6. Temperature Excursions and Product Stability
- •7.8. Cold Chain Products and Temperature Excursions
- •7.11. Conclusion
- •8.1. Christopher Columbus versus the Vikings
- •8.4. Pharmaceutical Data Integrity and ALCOA
- •8.5. Article(s) on Pharmaceutical Data Integrity
- •Introduction
- •Current trends
- •Reasons for Data Integrity violations (inadvertent and intentional)
- •Assuring and promoting Data Integrity via legislation and guidance documents
- •Legislation
- •Guidance documents
- •Proposed Solutions to Better Promote and Assure Data Integrity
- •Culture of integrity
- •Database management systems
- •Robust quality agreements
- •Collaboration between countries
- •Computerized systems validation
- •List of abbreviations
- •Conclusion
- •Authors
- •References
- •9.1. Pharmaceuticals versus Biopharmaceuticals
- •9.2. Transcription and Translation: Central Dogma of Genetics
- •9.3. Biotechnology-derived Medicinal Products: Microbial versus Mammalian Substrates
- •9.4. Manufacture of Biotechnology-derived Medicinal Products: Key Processes
- •Introduction
- •Manufacture of biopharmaceuticals — an overview
- •Procurement and testing of biological starting materials
- •Generation and characterization of cell banks/seed lots
- •Cell culturing
- •Challenges concerning manufacture of biopharmaceuticals
- •Extensive process and product understanding required
- •Inherent variability of host cells
- •Downstream processing remains a key bottleneck
- •Review of current GMP frameworks for biopharmaceuticals
- •Challenges in the regulation of biopharmaceuticals
- •Resource-intensive evaluation of biosimilarity
- •Growing number of data integrity lapses
- •Proposed solutions to challenges of biopharmaceuticals
- •Optimizing biopharmaceutical manufacturing with Industry 4.0
- •Enhancing data integrity with a culture of quality (quality culture)
- •Conclusion
- •List of abbreviations
- •Authors
- •References
- •10.1. Introduction
- •10.2. Advantages of Nanomedicines
- •10.3. Types of Nanomedicines
- •10.3.1. Nanocarrier Systems
- •10.3.2. Nanosuspensions
- •10.4. Future of Nanomedicines
- •10.5. GMP Requirements Governing Nanomedicines and Challenges
- •10.5.1. Lack of Trained Personnel to Operate Manufacturing Processes
- •10.5.2. Lack of Safety Protocol for Manufacturing Personnel
- •10.5.3. Challenges in Controlling for Nanoparticle Contamination
- •10.6. Conclusion
- •11. Novel and Traditional Vaccines
- •11.1. Historical Development and Evolution of Traditional and Novel Vaccines
- •11.2. Traditional Vaccines Versus Novel Vaccines
- •Introduction
- •Traditional vaccines
- •Novel vaccines
- •Vaccine manufacture
- •Vaccine storage, transport and distribution
- •Regulatory controls
- •Challenges, safety and quality issues and possible solutions
- •Conclusion
- •Authors
- •References
- •12.1. Cells and Tissues
- •12.2. Gene Therapy Products
- •12.3. Published Article on CTGTPs
- •Introduction
- •CTGTPs and their principles of action
- •Manufacturing of CTGTPs
- •Premises and equipment
- •Materials and processing
- •Starting material
- •Quality control
- •Cryopreservation
- •Human resource and accreditation
- •Potential solutions to the challenges encountered in manufacturing
- •Outsourcing
- •Technology
- •Control of CTGTPs
- •Current regulatory framework
- •Risk-based approach
- •Conclusion
- •Authors
- •References
- •13. Hand Sanitizers
- •13.1. What are Hand Sanitizers?
- •13.4. Published Article and Commentary on Hand Sanitizers
- •Introduction
- •The microbiology of bacteria, fungi and viruses
- •Antimicrobial compounds and their applications in hand sanitizers
- •FDA policy for testing of alcohol and USP limits for methanol
- •Common myths about hand sanitizers
- •A lack of regulatory framework
- •Proposed solutions
- •Tightening the regulatory framework
- •Training pharmacists on hand sanitizer vigilance
- •Public Education
- •Conclusion
- •Authors
- •References
- •14. Pharmaceutical Dosage Forms
- •14.1. Introduction
- •14.2. What Are Pharmaceutical Dosage Forms?
- •14.4.1. Routes of Administration
- •14.4.1.1. Oral Dosage Forms — Solids
- •14.4.1.2. Oral Dosage Forms — Liquids
- •14.4.1.3. Topical Dosage Forms
- •14.4.1.5. Inhaled Dosage Forms
- •14.4.1.6. Ophthalmic Dosage Forms
- •14.4.1.7. Nasal Dosage Forms
- •14.4.1.8. Otic Dosage Forms
- •14.4.1.9. Rectal Dosage Forms
- •14.4.1.10. Vaginal Dosage Forms
- •14.4.1.11. Transdermal Patch
- •14.4.2. Physical Forms
- •14.4.2.1. Solid Dosage Forms
- •14.4.2.2. Liquid Dosage Forms
- •14.4.2.3. Semi-solid Dosage Forms
- •14.4.2.4. Gaseous or Aerosol Dosage Forms
- •14.5. Manufacture and Important Characteristics of Common Pharmaceutical Dosage Forms
- •14.5.1. Tablets
- •14.5.2. Capsules
- •14.5.3. Solutions
- •14.5.4. Suspensions
- •14.5.5. Emulsions
- •14.5.6. Creams
- •14.5.7. Ointments
- •14.5.8. Metered Dose Inhalers
- •14.6. Overall Summary of the Manufacture of a Pharmaceutical Dosage Form
- •15.1. Introduction

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Manufacture and Supply, Science and Reg ulation Towards High-Qua lity Medicinal Products

Developing a Training and Continuous Training Program for ASEAN Inspectors
States were requested to review the training modules and curriculum proposed and to explore funding mechanisms. The ASEAN
JSC on GMP Inspection was also advised to consider making use
of ISPE regional conferences and seminars to publicize the ASEAN
harmonization initiative on GMP inspection, as well as to seek out
training opportunities via ISPE aliates in the Asia-Pacific region.
These included the Singapore, Japan, Indonesia, Thailand and Philippines ISPE Aliates.
Following this major collaborative TNA initiative, an invitation
was extended to the Chair of ASEAN JSC on GMP Inspection to
deliver a keynote presentation at the ISPE Singapore Conference
2012. Arising from this presentation, Pharmaceutical Engineer-
ing, the technical magazine of ISPE, published an article entitled
“A SE A N Harmonization on GMP Inspection and Training of
ASEAN Inspectors”, in its January/February 2013 issue. Essentially, this article provided a progress report on ASEAN harmonization on GMP inspection and its proposed training initiatives to
fulfil ASEAN Economic Community 2015. The publication of this
article by ISPE Pharmaceutical Engineering was very good publicity
for the harmonization eort by ASEAN as the magazine is widely
read globally by pharmaceutical manufacturing professionals,
consultants, academia and regulators. The following year, a similar presentation was also delivered at the ISPE Japan Conference
in Tokyo on 11 April 2013. This event was also very well attended
by more than 300 participants from the Japanese pharmaceutical
industry, the Japan Pharmaceutical and Medical Device Agency,
academia as well as editorial sta from Pharm Tech Japan — a leading
Japanese pharmaceutical journal. Pharm Tech Japan published a
paper entitled “Towards a Harmonized ASEAN GMP Inspection
73

74
Manufacture and Supply, Science and Reg ulation Towards High-Qua lity Medicinal Products
System using the PIC/S Framework as Benchmark” in its June
and July 2013 issues, in Japanese and English respectively. The
co-authors of this article were Mr. Bob Tribe from ISPE AsiaPacific, Prof. Chan Lai Wah from the National University of
Singapore (NUS) and Mr. Sia Chong Hock from the Singapore
HSA, who was concurrently the Chair of ASEAN JSC on GMP
Inspection. The Japanese version of the article was translated by a
bilingual Japanese sta from ISPE Japan Aliate.
ASEAN harmonization on GMP inspection and training of inspectors
Updates on ASEAN harmonization on pharmaceutical inspections
and the progress on the implementation of the ASEAN Sectoral

Developing a Training and Continuous Training Program for ASEAN Inspectors
MRA were also shared with participants at several other ISPE Conferences over the years. These conferences included the:
· ISPE Indonesia Conference held at the Holiday Inn Kemayoran,
Jakarta from 9 to 10 May 2017;
· ISPE Philippines Conference held at the Shangri-La Makati,
Manila from 25 to June 2018;
· ISPE Thailand Conference held at the Ambassador Hotel from
16 to 17 July 2018;
· ISPE Singapore Conference held at Suntec Convention Centre
from 30 to 31 August 2018 and;
· ISPE Asia-Pacific Conference held at Marina Mandarin Hotel
from 30 September to 1 October 2019.
75

76
Manufacture and Supply, Science and Reg ulation Towards High-Qua lity Medicinal Products
ISPE Singapore 2018 Conference: Suntec Convention Centre, 30–31 August 2018
From left to right: Moderator (Robert Tribe) from ISPE with regulatory panelists
from Thailand, Russia, Europe, Singapore and PIC/S — 30 August 2018
For all his unstinting eorts and dedicated contributions to Singapore, ASEAN and beyond, in the field of pharmaceutical inspection,
regulation and quality assurance of medicinal products, the ISPE
Singapore Aliate bestowed on the co-author (Sia Chong Hock) an
award in recognition for his “Lifetime Contribution to Pharmaceutical Regulatory Practices”. This award was presented to him on the
occasion of the 16th Anniversary Celebration of ISPE Singapore Aliate on 25 August 2016.

Developing a Training and Continuous Training Program for ASEAN Inspectors
77
Co-author (Sia Chong Hock) recognized for “lifetime contribution to pharmaceu-
tical regulatory services” by ISPE Singapore Aliate on 25 August 2016
3.3. Collaboration with Korea Ministry of Food and Drug Safety (MFDS)
The ASEAN JSC on GMP Inspection has to go beyond having just
five ASEAN Listed Inspection Services in its Register of ASEAN
Listed Inspection Services. The ultimate goal is to eventually have
10 ASEAN Listed Inspection Services in order to optimize and
reap all the benefits of the ASEAN Sectoral MRA on GMP Inspection. This would necessitate standardizing and harmonizing the
inspection framework for all ASEAN Member States, including the

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Manufacture and Supply, Science and Reg ulation Towards High-Qua lity Medicinal Products
Visit to Myung In Pharmaceutical, Korea — 18 October 2016
competency and skills of the ASEAN GMP inspectors. The training
and continual training of ASEAN inspectors is crucial in helping
the inspectors keep abreast with the latest developments in GMP
compliance and quality assurance of medicinal products. ASEAN
is fortunate to find suitable collaborators and partners in this mission. At an inaugural Korea-ASEAN GMP Conference held from
19 to 20 April 2015 in Seoul, the MFDS expressed strong interest
in advancing technical cooperation with ASEAN on GMP training.
A Concept Note on training of ASEAN Inspectors was submitted
by ASEAN JSC to Korea MFDS in November 2015. This led to the
invitation of Korea MFDS to the ASEAN JSC Meeting held in Siem
Reap, Cambodia from 17 to 18 May 2016. The Siem Reap meeting
resulted in a successful and breakthrough outcome, with both parties agreeing on a training framework guided by an ASEAN-ISPE
TNA (for inspectors) that was conducted in 2010. For practical
reasons and ease of implementation, Korea MFDS recommended

Developing a Training and Continuous Training Program for ASEAN Inspectors
that the training courses be conducted in South Korea. This arrangement was intended to facilitate seamlessly the conduct of classroom
lectures in South Korea, supplemented with experiential training
in the form of on-site visits to pharmaceutical manufacturers, also
located in South Korea. The language of training and instruction
would be in English. The ASEAN JSC on GMP Inspection agreed in
principle with the proposals from Korea MFDS. Following the May
2016 Siem Reap meeting, one event after another happened very
quickly. An ASEAN delegation of pharmaceutical GMP inspectors,
including Chair of ASEAN JSC on GMP Inspection, was invited to
participate in the 2016 Korea-ASEAN Pharmaceutical GMP Conference, held in Seoul from 18 to 20 October 2016. The agenda for
this conference included country presentations from South Korea
and ASEAN delegates and site visits to Myung In Pharmaceuticals
and other South Korean pharmaceutical manufacturing facilities,
as well as a taste of South Korean cuisines and an immersion into
South Korean culture — all very educational, interactive and highly
enriching for everyone. There was also high-profile media coverage,
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“Money Today Network”, 18 October 2016

80
Manufacture and Supply, Science and Reg ulation Towards High-Qua lity Medicinal Products
including prime-time television coverage of this 2016 Korea-ASEAN
Pharmaceutical GMP Conference by a South Korean broadcasting
company, namely, Money Today Network (see image on previous page).
To capture this landmark 2016 Korea-ASEAN GMP Conference,
a group photo of the ASEAN delegates, together with our South
Korean counterparts, was taken against the beautiful skyline of
Seoul.
Korea-ASEAN GMP conference 2016
Seoul, 18–20 October 2016
By September 2017, the first Korea-ASEAN Inspectors’ Training Course was conducted in the city of Osong, South Korea from
4 to 7 September by Korea MFDS in collaboration with the Korea
Pharmaceutical Manufacturers Association, now renamed as the

Developing a Training and Continuous Training Program for ASEAN Inspectors
Korea Pharmaceutical and Biopharmaceutical Manufacturers Association. This inaugural training course included both classroom
lectures as well as site visits to selected South Korean pharmaceutical manufacturing facilities. The second and third training courses
for ASEAN inspectors were conducted in 2018 and 2019 respectively.
Again, there were didactic classroom lectures together with experiential site visits to pharmaceutical manufacturing facilities such as
LG Chemicals and CJ Healthcare, a company with the catchy slogan
“Heal the World”, which sounded like a Michael Jackson hit song.
There were also visits to biopharmaceutical manufacturing facilities such as Samsung Biologics and Celltrion. These South Korean
pharmaceutical and biopharmaceutical manufacturers had state-ofthe-art facilities and manufacturing standards, comparable to other
world-class MNC pharmaceutical manufacturers.
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Site visit to Korean manufacturers
1st Korea-ASEAN Inspectors’ Training Course
Osong, Korea, 4-7 September 2017
Classroom lecture
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