Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5335_Библиотеки_им_академика_М_И_Перельмана.pdf
12
Manufacture and Supply, Science and Reg ulation Towards High-Qua lity Medicinal Products
Clinical Practice and Good Laboratory Practice, were non-existent
until the Medicines Act and the Health Products Act were promulgated in 1975 and 2007, respectively. The 1975 Medicines Act of
Singapore was modeled closely after the 1968 Medicines Act of the
United Kingdom, whilst the 2007 Health Products Act was uniquely
Singapore.
1.3. The Government Production Laboratories
and Store (GPLS)
Winding the clock back to the 1960s and early 1970s, the pharmaceutical manufacturing sector of Singapore comprised mainly the
local generic medicines manufacturers such as Beacons Pharmaceuticals, Leung Kai Fook, Malaysia Chemist, Sunward Pharmaceutical
Evolution of Pharmaceutical Inspection in Singapore and Benchmarking to PIC/S
and the Drug Houses of Australia. These manufacturers co-existed
with the Government Production Laboratories and Store (GPLS).
During those days, there were no regulatory framework for the
inspection and licensing of domestic pharmaceutical manufacturers, including GPLS. In contrast, the US, UK and Australia had
already established their national regulatory frameworks for medicinal products, including their very own national GMP codes. Back
then, Singapore did not have a national GMP standard. Domestic
pharmaceutical manufacturers, including GPLS, were guided by the
nascent World Health Organization (WHO) GMP Guidelines for
Pharmaceutical Products which was published in 1969. During its
heyday, GPLS produced a wide range of medicinal products, including intravenous injections, eye drops and other sterile products.
The following photographs show some manufacturing activities at
GPLS in the 1970s, including the filling of pre-sterilized infusion
fluids into bottles, and visual inspection of post-sterilized infusion
fluids for particulate matters.
13
Filling pre-sterilized infusion fluids into bottles
14
Manufacture and Supply, Science and Reg ulation Towards High-Qua lity Medicinal Products
Inspection of post-sterilized infusion fluids
In addition to sterile infusion fluids and injectable products, other
non-sterile liquids, creams and ointments were also manufactured
and packed at GPLS. The photographs on the next page show the
filling of creams into tubes by a semi-automatic machine and a
small in-house Quality Control (QC) Laboratory where physical and
chemical tests were performed before the products were released to
the public hospitals and polyclinics for dispensing to patients.
All in all, more than 400 dierent types of medicinal products in
various pharmaceutical dosage forms and strengths were manufactured at GPLS during the prime of its existence. The attached photograph shows one of the warehouses filled to the brim with finished
products.
It was not until 1973 that Beecham Pharmaceuticals became
the first MNC to set up a pharmaceutical manufacturing facility
in Singapore (at Quality Road, Jurong) to produce semi-synthetic
Evolution of Pharmaceutical Inspection in Singapore and Benchmarking to PIC/S
Semi-automatic filling of creams into tubes
15
Small in-house QC laboratory
penicillin products. This was followed 16 years later (in 1989) with
the setting up of the second MNC pharmaceutical manufacturing
facility by Glaxo (at Pioneer Sector 1, Jurong), to produce ranitidine
active pharmaceutical ingredient (API). Today, many world-class
MNC companies have set up, or will be setting up, pharmaceutical
16
Manufacture and Supply, Science and Reg ulation Towards High-Qua lity Medicinal Products
Warehouse for finished products
and biopharmaceutical manufacturing facilities in Singapore, and
they include Schering-Plough, Novartis, GlaxoSmithKline (GSK),
Amgen, Abbott, Merck, Pfizer, Baxter Healthcare, Thermo-Fischer
Scientific, Moderna, BioNTech and AstraZeneca. The mid-1980s
was a recession period for Singapore. In 1987, the Singapore government took the decision to shut down GPLS, which by then had been
renamed as the Pharmaceutical Department (PD) of the Ministry
of Health. One of the reasons for the closure of the production laboratories was to stimulate the local pharmaceutical manufacturing
industry to grow and expand, whilst the Ministry of Health and PD
took on the role of pharmaceutical inspection, licensing and overall
regulatory oversight of the pharmaceutical trade and indust r y.
The premises vacated by GPLS in 1987 have since made way for the
Outram Community Hospital, which is part of the SingHealth Cluster. Two photographs herein show the contrasting premises of GPLS
in 1987 and the new façade in 2022.
Evolution of Pharmaceutical Inspection in Singapore and Benchmarking to PIC/S
Closure of Government Production Laboratories and Store (GPLS) in 1987
Co-author (Sia Chong Hock), seated 2nd row, 3rd from left
17
Government Production Laboratory and Store (GPLS) renamed Pharmaceutical
Department (PD) — 1987
18
Manufacture and Supply, Science and Reg ulation Towards High-Qua lity Medicinal Products
Outram Community Hospital (located at former GPLS site), present day
1.4. Establishment of Health Sciences Authority (HSA)
and Its Audit (Inspection) Units
Following the closure of GPLS, the licensing of pharmaceutical manufacturers and the registration of medicinal products commenced
in 1987 under the framework of the Medicines Act. For the inspection and licensing of pharmaceutical manufacturers, the WHO
GMP Guidelines for Pharmaceutical Products was initially adopted
as the national inspection standard for Singapore. Today, the Pharmaceutical Inspection Co-operation Scheme (PIC/S) Guide to GMP
for Medicinal Products is the legal GMP standard as Singapore is
now a member of PIC/S. In 1990 and 1996, manufacturers of contact
lens substances and cosmetic products, respectively, were subjected
Evolution of Pharmaceutical Inspection in Singapore and Benchmarking to PIC/S
to GMP inspection and licensing. Arising from this development, a
dedicated GMP Unit was established in 1997 within the Singapore
Ministry of Health to deal with the increasing types and number
of manufacturers, including manufacturers of Chinese Proprietary
Medicines (CPM) in 1999. The establishment of the GMP Unit was
also to deal with the increasing specialization in the field of GMP
inspection.
On 1 April 2001, the HSA was ocially established by the Singapore
Parliament as a statutory board under the Ministry of Health. Concurrently, the GMP Unit was also upgraded to become the Division
of Manufacturing and Quality Audit, with three dierent but complementary functional units, namely:
— GMP Audit Unit;
— GDP Audit Unit; and
— Certification Unit.
19
Singapore Health Sciences Authority (HSA)
20
Manufacture and Supply, Science and Reg ulation Towards High-Qua lity Medicinal Products
The principal functions of the GMP Audit Unit included the audit
and licensing of manufacturers of sterile and non-sterile medicinal
products, cosmetic products, contact lens substances and CPM. In
this regard, the main objective of the GMP Audit Unit is to help
ensure that licensed manufacturers consistently produce quality
medicinal products through compliance with GMP standards. On
the other hand, the principal functions of the GDP Audit Unit
included the audit and licensing of importers, wholesale dealers as
well as the retail, polyclinic and hospital pharmacies. In this regard,
the main objective of the GDP Audit Unit is to ensure that the quality of medicinal products manufactured continue to be maintained
or preserved down their supply chain through compliance with
GDP standard. The principal functions of the Certification Unit
included the granting of various certificates and licenses such as the
Certificate of a Pharmaceutical Product and Certificate of Licensing Status (under the WHO Certification Scheme), the GMP Certificate, as well as the Import and Export Licenses for Psychotropic
Substances and Narcotic Drugs. A key objective of the Certification
Unit is to ensure that all manufacturing and distribution activities
are restricted only to licensed, approved, authorized or certified
companies.
1.5. Accession of Singapore to Pharmaceutical
Inspection Co-operation Scheme (PIC/S)
In line with the national goal of Singapore to be a life sciences hub,
the GMP Audit Unit embarked on a quality journey to benchmark
itself against overseas centers of excellence in the field of GMP
inspection and licensing of pharmaceutical manufacturers. This
quality journey commenced in April 1997, well before the ocial
Evolution of Pharmaceutical Inspection in Singapore and Benchmarking to PIC/S
establishment of HSA (in 2001). In July 1997, the GMP Audit Unit
submitted a formal application to accede to PIC/S. Things moved
fast and furious from then onwards.
21
(From left) Mr. Sia Chong Hock, the late Mrs. Tan Shook Fong and Ibu Kustantinah
in Zeist, Netherlands, 1998.
In 1998, the Director of the National Pharmaceutical Administration (the late Mrs. Tan Shook Fong) and Head of the GMP Audit
Unit (Mr. Sia Chong Hock) were invited to attend a PIC/S Committee of Ocials Meeting in the Netherlands. This unforgettable
mission is forever etched in the mind of the co-author: “The meeting was held in a small town called Zeist, located in Utrecht province, which was quite a long distance from Amsterdam. Both my
Director and I (Sia Chong Hock) took a direct flight from Singapore