investigation on packaging material of counterfeit … · pemeriksaan fizikal ke atas sifat-sifat...

INVESTIGATION ON PACKAGING MATERIAL OF COUNTERFEIT

PANADOL® VARIANTS AND CREOBIC® CREAM BY NON-DESTRUCTIVE

TESTS

TUHFAH ZAHIDAH BINTI SHAMSUDDIN

A dissertation submitted in partial fulfilment of the

requirements for the award of the degree of

Master of Science (Forensic Science)

Faculty of Science

Universiti Teknologi Malaysia

2014

iii

Especially to my beloved Mother with endless gratitude and admiration

iv

ACKNOWLEDGEMENT

The writer wishes to acknowledge the supervisors; Assoc. Prof. Dr. Azli Bin

Sulaiman and Assoc. Prof. Dr. Wan Aizan Binti Wan Abdul Rahman for their

guidance and patience alongside the journey in establishing this dissertation.

To Assoc. Prof. Dr. Umi Kalthom Binti Ahmad and Dr. Naji Arafat Bin

Mahat for their endless encouragement. Ministry of Health (MOH) and

Pharmaceutical Enforcement Division, MOH for the trust and financial support.

Infinite appreciation to Malaysia Fire and Rescue Department of Johor, UTM

lecturers, staffs and friends whom have contributed to this achievement.

v

ABSTRACT

The World Health Organization (WHO) has defined counterfeit drugs as

those which are “deliberately mislabelled with respect to identity and/or source”.

Packaging materials are ubiquitous and manufacturers are able to obtain them from

multiples of supplier. That is the reason for the unfeasible confiscation. There are a

few methods used to detect counterfeit products through its packaging: visual

inspection (visible light) and other optical methods such as infrared and ultraviolet

analysis as well as pattern recognition. The objective of this study is to differentiate

the features on the packaging material found from the original and the counterfeit of

the same fast-moving pharmaceutical products. There are four different product

packaging investigated obtained through over-the-counter purchase, from the

complainant or seized by the authority. Firstly, examination is carried out on the

direct paperboard packaging by comparison; physical examination on the basic

properties (viz. dimension, thickness and prints), microscopic, optical character

recognition (OCR) and near infrared analysis. Then, further investigation on the

information printed and hologram serial number was done. Determination of the

originality of the products upon procurement was done through authenticating the

hologram. Microscopic examination on the printed paperboard exhibited consistent

printing effect for all of the counterfeit and the genuine ones. Results on OCR for

certain parts of the prints show constant difference between the original and

counterfeit. However, the IR results indicated that such differences may prove

inconsistent and hence unreliable to be used for comparison. In conclusion, the

counterfeit pharmaceutical packaging may be distinguished from the genuine ones

through physical examination of its basic properties, microscopic observation and

OCR.

vi

ABSTRAK

Pertubuhan Kesihatan Sedunia (WHO) telah mentakrifkan ubat palsu sebagai

“kesilapan pelabelan yang disengajakan berkenaan dengan identiti dan/atau sumber”.

Bahan pembungkusan boleh didapati secara meluas daripada sumber pembekal yang

banyak. Oleh sebab itu, rampasan terhadap bahan mentah pembungkusan untuk

ubatan palsu sukar dilakukan. Terdapat beberapa kaedah yang biasa digunakan untuk

mengesan produk palsu melalui pembungkusan: pemeriksaan visual dan kaedah

optik lain seperti analisis inframerah dan ultralembayung serta pengecaman corak.

Objektif kajian ini adalah untuk membezakan ciri-ciri bahan pembungkusan yang

terdapat pada produk tulen dan palsu daripada produk farmaseutikal tertentu.

Terdapat empat bahan pembungkusan produk yang berbeza diperolehi melalui

pembelian di kaunter, daripada pengadu atau disita oleh pihak berkuasa. Pemeriksaan

dijalankan terhadap bungkusan kotak luar dengan membuat perbandingan;

pemeriksaan fizikal ke atas sifat-sifat asas (dimensi, ketebalan dan cetakan),

pemeriksaan mikroskopik, pengecaman aksara optik (OCR) dan analisis inframerah.

Kemudian, siasatan lanjut mengenai maklumat yang tercetak dan nombor siri

hologram dilakukan. Penentuan awal ketulenan produk dilakukan semasa perolehan

melalui pengesahan hologram. Pemeriksaan sifat-sifat asas serta mikroskopik ke atas

kualiti percetakan boleh membezakan antara produk palsu dan tulen. Hasil analisa

OCR untuk bahagian-bahagian tertentu pada percetakan di luar kotak pembungkusan

menunjukkan perbezaan antara produk tulen dan palsu. Walau bagaimanapun,

analisis inframerah menunjukkan spektrum yang tidak dapat membezakan antara

produk palsu dan produk tulen. Kesimpulannya, bahan pembungkusan produk

farmaseutikal palsu dan tulen boleh dibezakan menggunakan sifat-sifat asas,

pemeriksaan mikroskopik dan OCR.

vii

TABLE OF CONTENT

CHAPTER TITLE PAGE

DECLARATION ii

DEDICATION iii

ACKNOWLEDGEMENT iv

ABSTRACT v

TABLE OF CONTENT vii

LIST OF TABLES x

LIST OF FIGURES xi

LIST OF ABBREVIATIONS xv

LIST OF APPENDICES xvi

CHAPTER 1 INTRODUCTION 1

1.1 Introduction 1

1.2 Research Background 1

1.3 Problem Statement 2

1.4 Research Objectives 3

1.5 Scope of the Research 3

1.6 Significance of Research 4

viii

CHAPTER 2 LITERATURE REVIEW 6

2.1 Background Study 6

2.2 Pharmaceutical Supply and Distribution 7

2.3 Regulatory Body, Laws and

Enforcement Division

8

2.4 Anti-counterfeiting Measures 9

2.5 Types of Counterfeiting 12

2.6 Packaging Material 13

2.7 Forensic Perspective 14

2.8 Paperboard Focussed 15

CHAPTER 3 METHODOLOGY 19

3.1 Introduction 19

3.2 Products Selection 19

3.3 Sampling Pattern and Procurement 21

3.4 Apparatus 22

3.5 Instrumentation 23

3.6 Procedure 23

3.6.1 Physical Evaluation 23

3.6.1.1 Special Feature(s)

Detection

23

3.6.1.2 Dimension and

Thickness

Measurement

23

3.6.2 Fourier Transform Infrared –

Attenuated Total Reflectance

(FTIR-ATR)

25

3.6.3 Microscope Observation on

Print Quality

25

ix

3.6.4 MeditagTM Serial Number

Investigation

26

3.6.5 Pattern Recognition 26

CHAPTER 4 RESULTS AND DISCUSSION 27

4.1 Introduction 27

4.2 Procurement and Distribution Pattern 27

4.3 Physical Evaluation 31

4.3.1 Special Feature(s) Detection 31

4.3.2 Dimension and Thickness

Measurement

34

4.4 Fourier Transform Infrared – Attenuated

Total Reflectance (FTIR-ATR)

36

4.5 Microscope Observation on Print

Quality

45

4.6 MeditagTM Serial Number Investigation 48

4.7 Pattern Recognition 50

4.8 Limitations 54

CHAPTER 5 CONCLUSIONS AND

RECOMMENDATIONS

55

5.1 Conclusions 55

5.2 Recommendations 57

REFERENCES 58

APPENDICES 62

x

LIST OF TABLES

NO. TITLE PAGE

4.1 Dimension and Thickness Measurement 35

4.2 Missing Hologram Reported from a Pharmaceutical

Company

50

4.3 Comparison text recognized in Panadol® Actifast

(Based on Figure 4.22)

52

4.4 Comparison text font in Panadol® Actifast

(Based on Figure 4.22)

53

xi

LIST OF FIGURES

NO. TITLE PAGE

2.1 Phases in implementing the registration scheme 11

2.2 Sheet-fed offset printing unit 16

2.3 Gravure printing 16

2.4 Flexographic printing 17

3.1 MeditagTM Decoder 20

3.2 MeditagTM Hologram; (a) Second Generation (b)

Third Generation

20

3.3 Second Generation Hologram Positive Identification;

(a) Before – KKM visible, (b) After – KKM invisible

21

3.4 Second Generation Hologram Negative Identification;

(a) Before – KKM visible, (b) After – KKM remain

visible

21

3.5 Reverse Tuck End with Tab used in Creobic® Cream 24

3.6 Straight Seal End used in Panadol® 24

3.7 Reverse Tuck End used in Panadol® Actifast and

Panadol® Extend

25

4.1 Counterfeit samples procured according to districts in

Johor

28

4.2 Genuine samples procured according to districts in

Johor

29

4.3 Counterfeit samples scattering pattern 29

4.4 Distribution of products procured according to

originality

32

4.5 Comparison of the shadow effect on each alphabet on

the brand name in PR (a) Counterfeit (b) Genuine

32

xii

4.6 Comparison of the bullet position and capitalization of

alphabet ‘I’ in the suitability statement in Panadol®

Actifast (a) Counterfeit (b) Genuine

33

4.7 Comparison of image sharpness of the human figure

on Panadol® Extend (a) Counterfeit (b) Genuine

33

4.8 Comparison of the existent of the mole/black colour

dot of the partial face on Creobic® Cream

(a) Counterfeit (b) Genuine

34

4.9 Comparison of common peaks from IR spectrum of

the coat surface of the paperboard packaging for

Panadol® (a) Counterfeit (b) Genuine

37


the inner side of the paperboard packaging for

Panadol® (a) Counterfeit (b) Genuine

38



Panadol® Actifast (a) Counterfeit (b) Genuine

39



Panadol® Actifast (a) Counterfeit (b) Genuine

40



Panadol® Extend (a) Counterfeit (b) Genuine

41



Panadol® Extend (a) Counterfeit (b) Genuine

42



Creobic® Cream (a) Counterfeit (b) Genuine

43



Creobic® Cream (a) Counterfeit (b) Genuine

44

xiii

4.17 Comparison of the print of the shadow effect from the

alphabet on the brand name of Panadol®;

Magnification 10 x 3.2 (a) Counterfeit (b) Genuine

45

4.18 Comparison of the print of the shadow effect from the

trademark of Panadol® Actifast; Magnification 10 x

3.2 (a) Counterfeit (b) Genuine

46

4.19 Comparison of the print of the caplet on Panadol®

Extend; Magnification 10 x 3.2 (a) Counterfeit (b)

Genuine

46

4.20 Comparison of the location of the mole/black colour

dot of the partial face on Creobic® Cream;

Magnification 10 x 3.2 (a) Counterfeit (b) Genuine

47

4.21 Genuine hologram serial number bought by

companies legitimately for their pharmaceutical

products found on counterfeit samples

49

4.22 OCR output for Panadol® Actifast (a) Genuine

(b) Counterfeit 1 (c) Counterfeit 2

50

xiv

LIST OF ABBREVIATIONS

API - Active pharmaceutical ingredient

CC - Creobic® Cream

cm - Centimeter

DCA - Drug Control Authority

DUNAS - Dasar Ubat Nasional

FTIR-ATR - Fourier Transform Infrared – Attenuated Total Reflectance

MOH - Ministry of Health

mm - Millimeter

MTDCC - Ministry of Domestic Trade, Co-operatives and Consumerism

nm - Nanometer

NPCB - National Control Pharmaceutical Bureau

OCR - Optical character recognition

OTC - Over-the-counter

PA - Panadol® Actifast

PCA - Principal Component Analysis

PE - Panadol® Extend

PED - Pharmaceutical Enforcement Division

ppi - Pixel per inch

PR - Panadol®

RFID - Radio frequency identification

SD Standard Deviation

TDM - Toxicity Drug Monitoring

USFDA United State Food and Drug Administration

WHO World Health Organization

xv

LIST OF APPENDICES

NO. TITLE PAGE

A Abstract: Oral presentation at 11th Indo Pacific

Association of Law, Medicine and Science

(INPALMS) Congress 2013

62

B1 IR spectrum coat surface of genuine Panadol®

(Example)

63

B2 IR spectrum inner side of genuine Panadol®

(Example)

64

B3 IR spectrum coat surface of counterfeit Panadol®

(Example)

65

B4 IR spectrum inner side of counterfeit Panadol®

(Example)

66

C1 IR spectrum coat surface of genuine Panadol®

Actifast (Example)

67

C2 IR spectrum inner side of genuine Panadol®

Actifast (Example)

68

C3 IR spectrum coat surface of counterfeit Panadol®

Actifast (Example)

69

C4 IR spectrum inner side of counterfeit Panadol®

Actifast (Example)

70

xvi

D1 IR spectrum coat surface of genuine Panadol®

Extend (Example)

71

D2 IR spectrum inner side of genuine Panadol® Extend

(Example)

72

D3 IR spectrum coat surface of counterfeit Panadol®

Extend (Example)

73

D4 IR spectrum inner side of counterfeit Panadol®

Extend (Example)

74

E1 IR spectrum coat surface of genuine Creobic®

Cream (Example)

75

E2 IR spectrum inner side of genuine Creobic® Cream

(Example)

76

E3 IR spectrum coat surface of counterfeit Creobic®

Cream (Example)

77

E4 IR spectrum inner side of counterfeit Creobic®

Cream (Example)

78

CHAPTER 1

INTRODUCTION

1.1 Introduction

Throughout the chapter, discussion will be from the investigation on the

information on the paperboard packaging such as the manufacturing date and

hologram serial number search using the Mediharta Sdn. Bhd. official web site,

observations using microscope, Fourier transform infrared – attenuated total

reflectance (FTIR-ATR) and optical character recognition (OCR). The findings of

the sampling pattern and procurement of the samples will also be discussed.

1.2 Research Background

In this study, focussed is on the paperboard packaging. There are several

analysis to be used on this material. Since the information pertaining to the medicine

is printed on the paperboard, there is also of importance to analyse this as a way to

recognize its authenticity. In Malaysia, a medicinal product will only be recognized

as registered when there are two (2) features; product registration number and

MeditagTM hologram. Thus, the hologram will also be investigated through its unique

serial number.

2

1.3 Problem Statement

Counterfeit medicine has flooded Malaysia market and has been an issue

among healthcare professionals. Public seem to have easy access to counterfeit

medicine rather than the authentic due to the vast availability and cheaper price.

Usage of counterfeit medicine will endanger lives due to the unknown ingredient in

the products.

Although the better way to ensure a fake drug is by direct analysis of the

active pharmaceutical ingredient (API), but this is not feasible due to short course

therapies and what only remains is the packaging material. Nevertheless, most

patients/customers will discard the packaging materials as thought to be unimportant

although it contain most of the information pertaining to the medication.

Furthermore, modus operandi of modern criminals’ separately ship packaging

materials of the fake and the raw materials for the pharmaceutical dosages makes it

even harder for the perpetrators to be caught.

Counterfeiting is also a form of intellectual property infringement. Even

though this is not of forensic significance but this may be the main reason if a jointly

effort to be applied in further studies.

The importance to precede such study is to prepare the authorities, stake

holders and public in differentiating fake medicinal products. For the authorities to

know that there are such analyses to be done on the packaging and possibly

determining its source; for the stakeholders to cooperate and challenge the current

situation on counterfeiting and for the public to be more careful in purchasing their

health care products to ensure its safety, efficacy and quality.

3

1.4 Research Objectives

The objectives of this study are:

i. To determine the features on the packaging material found in the original

and the counterfeit on the same fast-moving pharmaceutical products by

visual examination.

ii. To create a simple, reproducible, reliable and applicable method viz.

infrared analysis, microscopy observation and pattern recognition for

early detection of counterfeit in the department.

1.5 Scope of the Research

The samples for this study was procured in the state of Johor and only

accounts for the centre of each districts and regions. Samples consist of three (3)

Panadol® variant; namely Panadol®, Panadol® Actifast and Panadol® Extend as

well as one (1) topical antifungal, Creobic® Cream.

Analysis of the packaging material is via visual examination of the printed

side of the paperboard, microscope observation of the print quality, attenuated total

reflectance infrared analysis on the paperboard box and the coated surface as well as

optical character recognition of the printed side of the paperboard.

4

1.6 Significance of Research

The need to conduct this research is to point out the manifestation of

counterfeit pharmaceuticals in the market from a scientific point of view. Currently,

there is no study pertaining to the investigation of these counterfeit from the

packaging material use in Malaysia. Since there are countless of packaging materials

suppliers and manufacturers, a better framework must be implemented in the

packaging material procurement process to reduce the counterfeit products.

There is no provision under the laws enforced by Pharmacy Enforcement

Division to try cases pertaining to counterfeits. At present, the fake medicinal

products were prosecuted under different Acts and for offences not mentioning

counterfeiting; and the practice as stated below:

1. Section 13 Possession for sale of poison and sale of poison, Poisons Act 1952

which only can try cases where the content has been confirmed containing

poison as listed in the First Schedule, Poisons List.

2. Section 15 Adulteration, Sales of Drugs Act 1952 which needs to analyse the

ingredients and to be compared with the declared content and does not

provide any means to charge the counterfeiter.

3. Regulation 29 Directions, Control of Drugs and Cosmetics Regulation 1984

which states that the Director of Pharmaceutical Services may issue written

guidelines pertaining to labelling, storage including requirement of the

containers etc. The labelling includes the use of hologram at point of sale.

Unfortunately, according to Mediharta Sdn. Bhd., the maker for MeditagTM

hologram there has not been a case relating to the counterfeit holograms.

5

Recently, Pharmacy Enforcement Johor received information pertaining to

the supply of packaging material and enquires whether there are any way(s) to

determine the culprit of this counterfeiting activity. Since the core function of the

department is to investigate offences made under the act and forensic science may

contribute to finding the probable source, no doubt this study should be conducted.

58

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