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Development of a Powerful

Screening System in China for

Detection of Counterfeits

Prof. Jin Shaohong

National Institute for the Control of

Pharmaceutical and Biological Products

(NICPBP) P.R. China

I , Scale of the problems in China

II, Characteristics and Functions of

Mobile Labs

III, Roles Played by Mobile Labs for

drug safety in Rural Areas of China

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Area: 9.6 millions km2

31 provinces 333 districts

2861 counties

Population: 1.3 billions (70% living in countryside)

I. Scale of the problems in China

A product that is deliberately and fraudulently

mislabelled with respect to source and/or

identity. Counterfeiting can apply to both generic

and branded products. Counterfeit products may

include: products with the correct ingredients,

with the wrong ingredients, without ingredients,

with incorrect quantities of active ingredients,

with fake packaging.

Definition of counterfeit drug

according to WHO

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Some cases of counterfeit and substandard

drugs found in China

1) Without Active Pharmaceutical Ingredient(API)

Amoxicilline

2) With wrong API (XingDuoKe Injection,

Inosine Injection)

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3) With incorrect quantities of active ingredients

In 1998 the results of a special program of the

quality surveillance of Norfloxacin Capsules showed

14% of tested samples contained less quantity than

its labeled.

In one ceased batch, there was only 3.4% of

Norfloxacin found .

Fake

Real

4) With correct ingredients but fake packaging

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Tetracycline Hydrochloride

Huangbo Capsules (Cortex Phellodendri)

(Berberine Hydrochloride)

5) Traditional Chinese Medicine (TCM )

adulterated with chemical drugs

5) Misusing toxic excipients Diethylene Glycol

(DEG) as Propylene Glycol in Armillarisin A

Injection -------- death of 11 patients in 2006

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II, Characteristics and Functions of

Mobile Labs

In order to combat the counterfeit and substandard

drugs distributed in rural areas of China, the National

Institute for the Control of Pharmaceutical and

Biological Products (NICPBP) in China developed a

mobile laboratory vehicle for drug screening tests

1, Equipments

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a,TLC system

b,Non-destructive instrument ---NIR

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c, Modified Vehicle

Ventilation Dual power supply

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2,Characteristics

Information system

Administrative Part

1, Manufacturer Information (about 200,000 entries)

Pharmaceutical Manufacturer’s Names, Addresses

Product Names, Licensed Numbers, Dosage forms,Strengths

2, Quality Information (up-to-date annually )

Unqualified or withdrawn Product Names, Batch Numbers ,

Manufacturer’s Names listed in National or Provincial “Drug

Quality Bulletin”

3, Database of Screening tests

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.Database of wet chemical methods

Records of Screening tests

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Information system Technical Part (SOP)

More than 800 drug preparations including anti-

malaria, anti-AIDs, anti-TB and other essential

drugs could be tested in mobile Lab.

1,Classical Screening Methods

Including

Chemical functional group reaction

TLC system for quick identification

Microscopic Pictures for Herb Medicine Identification

a. Manuals of SOP

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Chemical Reactions and TLC Identification

磷酸氯喹片

拼 音: Linsuan Lǜkuei Pian

英文名: Chloroquine Phosphate Tablets

1 参比物（对照品）

2样品

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Isoniazid Tablets【主要成分】异烟肼

【性状】本品为无色片。

【方法】

供试品溶液的制备：参照【取样方法参照表】取本品1/2片，研细，加乙醇50ml振摇使溶解，滤过，取滤液为供

试品溶液。

参比物溶液的制备：取异烟肼原料药适量，加乙醇制成1mg/ml的溶液，即得。

方法1、颜色反应鉴别

(1)取本品1/2片 (约相当于异烟肼50mg)，研细，加水5ml，使溶解，加氨制硝酸银试液2ml，有气泡生成且在试

管璧上生成银镜并伴有黑色沉淀（图1），则可做薄层鉴别进一步确证；若未发生上述反应，则为可疑样品。

操作方法：分别取供试品溶液及参比物溶液各2μl，分别点于同一块硅胶GF254薄层板（快检专用板）上，晾干

，将乙酸乙酯-无水乙醇-浓氨溶液(50∶5∶1)混合液【结核药－001】5～8ml倒入层析缸中，将完点样的薄层板放入，饱和5～10分钟，展开至前

沿离原点8cm，取出薄层板，待展开剂挥干（约2分钟），置紫外灯光254nm下检视（图2）。

结果判断：供试品应与参比物所显斑点颜色、位置相同，相对Rf值为1.0，则样品为正品；否则样品为可疑样品

。

1.参比物溶液

2.供试品溶液

英文名: Didanosine Capsules商品名: 惠妥滋 etc

主要成分：去羟肌苷

【性状】本品为肠溶胶囊剂，内容物为白色或类白色颗粒或粉末。

【方法】

供试品溶液的制备：参照【取样方法参照表】取本品1/2粒，加水15ml，超声提取10分钟，加乙醇35ml，摇

匀，滤方法1、颜色反应鉴别

(1)取本品1粒（相当于去羟肌苷0.1g），加水5ml，超声10分钟，过滤，取滤液2ml加硝酸银滴定液3～5滴，

参比物溶液的制备：取磺胺甲噁唑(SMZ)5mg，加乙醇至5ml，制成1mg/ml的参比溶液

方法2、薄层色谱鉴别

操作方法：分别取样品溶液和参比溶液各1μl，分别点于同一块硅胶GF254（快检专用板）板上，晾干，将氯

仿－甲醇（85∶15）【抗艾药－001】混合液5－8ml倒入层析缸中，再将点完样的薄层板放入，饱和8～10分钟，展开至前沿离原点8cm，取出晾

干（约2分钟），置紫外光灯254nm下观察（图2）。

结果判断:供试品所显主斑点为一个黑色斑点（图2），相对Rf值为0.24～0.50，否则为可疑样品。

1 参比物溶液

2 供试液

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Chinese Herb Medicine Identification

b. Screening test for detection of herb

medicines adulterated with Sidenafe

A. Acid solution，shake,filter

B. Oxidizing agent --- color fading

C. Trinitrophenol solution －－-

yellow precipitate ring

Characteristic：Rapid :few minutes

Low cost: 1 Dollar/Sample

Accuracy 99.2%（1083 Batches）

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Pills Sulfuric Acid Shaking Filtering

Filtrate Color fadingYellow precipitate

2, Modern Fast and Non-destructive Methods

Near Infra-Red (NIR) Spectrophotometer SOP

Data Bank of NIR Reference Spectra for Specified Drugs

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Establishing NIR Reference Spectra Database

（1）Qualitative Module

1. Spectra collection 2. Average spectra

calculation 3.Establishing qualitative

model

4, Unknown sample

determination

5. Retrieve the model6. Identification of

the tested sample

500060007000800090001000011000

Wavenumber cm-1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

Absorb

ance U

nits

500060007000800090001000011000

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

Absorb

ance

Units

Sample

Identified

as Material X

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1.Results from official methods 2. Spectra collection 3. Correlation between

NIR and official method

Report

Sample #081897-049

Component A 81.55%

Component B 5.38%

Component C 13.06%

4. Determination of

Unknown sample

5. Retrieve the quantitative

model6. Quantitative

estimation

Component A B C

Units % % %

spectrum1 71.30 7.03 21.67

spectrum2 79.30 3.06 17.64

spectrum3 78.40 8.34 13.26

spectrum4 84.03 4.32 11.65

… … … …

spectrum11 85.02 1.34 13.64

spectrum12 78.34 3.85 17.81

(2) Quantitative Module (Macrolide

antibiotics)

400 500 600 700 800 900 1000 1100 1200 1300 1400 1500 1600 1700 1800 1900 2000 2100 2200 2300 2400 2500

-0.0935

-0.0783

-0.0631

-0.0479

-0.0327

-0.0175

-0.0023

0.0129

0.0281

0.0433

0.0585

Vitamin C 500mg ProductsVitamin C 500mg Products

Wavelength

2n

d D

eriv

ati

ve

Vice Primer of China Ms.Wu Yi inspecting the NIR testing

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III.Roles Played by Mobile Labs for

drug safety in Rural Areas of China

China central government has allocated 70 million dollars for 400 mobile labs to combat counterfeit drugs and to protect the health of people living in rural areas of China

From April 2004 to Dec. 2005, initial trial has been conducted with 5 mobile labs in 5 different provinces of China. By the end of July 2006, 86 Mobile Labs had been equipped for 8 provinces

Very important roles have been played and some counterfeits and substandard drugs were detected

1,Mobile Labs Running in Rural

Areas of China-- in Hu Bei province

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Date Locations Number

of Places

Batches of

screening

tested

Batches of

sampled

Batches of

counterfeits

confirmed

April 8-12, 004 Anlu 8 74 0 0

27－29 April Xiannin 17 53 0 0

13－14, May Huangsh

e3 19 0 0

1-3 June Huang

gang9 79 5 5

8－17 ,July Huangmei 16 40 0 0

8－11 Dec. Xiangfan 3 23 10 9

1-4April ,2005 Xiangfan 20 114 10 9

18－21 May Yicang 16 87 11 6

3－5Nov. 2005 Tianmen 16 73 9 8

Total 108 562 45 37

Results of mobile lab running in Hubei province

Mobile Labs Running in Rural Areas

of China in An Hui Province

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Sampling in drug store

Labeled “Erythromycin Ethylsuccinate Tablets” Samples

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Working in mobile lab

Using NIR method in mobile lab

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Green line is real

Red line is fake

Retrieve the reference spectrum of defined drug

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NIR Report

NIR Report

NIR Report

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Performing chemical reaction in mobile lab

Only No. 4 and 8 are real, the rests are fake

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CounterfeitReal

Counterfeit labeled as legitimate “Erythromycin

Ethylsuccinate Tablets ”

The first 21 Mobile Labs were delivered to

Henan province in 2 March, 2006

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18 Mobile Labs were delivered to Hubei

province in 7 April, 2006

By the end of July 2006, a total of 85 Mobile Labs

were delivered to 8 provinces in China

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Achievements of 21 mobile labs running in

Henan province during the first three months

Types of

drugs

suspected

Screening

methods

employed

Batches of

suspicious

drugs sampled

Batches of

counterfeit and

substandard drugs

confirmed

Chemical and

TCM Drugs

Wet

chemical

methods

1164 983

Chemical

Drugs

NIR

methods

528 105

Total 1692 1088 (64.3%)

A total of 23,210 batches were inspected

Efficacy of 16 mobile labs running in Hubei province

in the first two months:

Total times of mobile labs dispatched: 202

Drug related units inspected:

(including drug stores, clinics) 587

Batches

Screened

6076

Batches of

suspicious drugs

sampled

718

Batches of counterfeit

and substandard drugs

confirmed

303

Total compliance rate

95.0%

Sampling rate

11.8%

Successful targeting rate

60%

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2. Mobile Labs have played very important roles

in detection of DEG in a special case

Using NIR Spectra

DEG

Propylene glycol

Propylene glycol

DEG

(Fist Derivative Curve)(Original NIR Spectra)

Armillarisin A Injection

DEG

Containing DEG Injection

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Name of Products DEG Content(% Spiked)

（GC method） （NIR method）

Armillarisin A Injection -10ml 31.0 30.8

Armillarisin A Injection -2ml 31.4 31.2

Betamethasone Sodium

Phosphate Injection *** 36.1 34.6

Betamethasone Sodium

Phosphate Injection ** * * 31.6 30.8

Puerarin Injection*** 42.4 49.1

Puerarin Injection **** 46.9 48.9

Nefopam Hydrochloride

Injection **** 7.3 7.0

Nefopam Hydrochloride

Injection ***** 6.1 7.3

Prospects of Mobile Labs

--- Powerful means to combat counterfeits

Continue to work in China

Willing to serve for international drug

procurements

Willing to help other countries for drug

quality surveillance

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