Drug Selection 1

-
-
-
-
-

-
-

-
- ()
-

Drug Selection 2

.. (PL Law)

Drug Selection 3


Drug Selection 4

3 (Quality) (Safety)
(Efficacy)
1. (Quality)


2. (Safety)

3. (Efficacy)

3

Drug Selection 5


(original drug) (generic drug)
(bioequivalence)

Drug Selection 6



1./ -

2.

3.
4.

5.

6.

7.-

8.

Drug Selection 7

(Quality)

Drug Selection 8


United States Pharmacopeia (USP)
British Pharmacopoeia (BP)
Japanese Pharmacopoeia (JP)
European Pharmacopoeia (Ph. Eur.)
International Pharmacopoeia (Ph. Int.)
(release specification)
(shelf life specification)

Drug Selection 9

(Finished Product Specification; FPS)

Drug Selection 10

(Product name)
(Appearance)
(Test Name)
(Requirement, Acceptance criteria)
(Test method, Reference)
(Shelf-life)

Drug Selection 11

(Certificate of Analysis; COA)




(Finished Product Specification; FPS)

(dissolution) (related
substances)

Drug Selection 12

/ (Product Name)
(Batch number)
(MFG date)
(EXP date)
(Test names)
(Acceptance criteria)
(Test results)
(Analysis date)
(Name and signature of analyst)
(Name and signature of approver)
(Manufacturer's Contact Details)

Drug Selection 13


Drug Selection 14


Drug Selection 15

(bulk product)
(drug product)
(drug substance)



BP
USP

Drug Selection 16

(acceptance criteria)

Drug Selection 17

To pass
Passes

Drug Selection 18

ISO/IEC 17025 : 2005

ISO/IEC 17025 : 2005 /


3

Drug Selection 19

(Description)


(Identification)

(Assay) 95.0 - 105.0
(USP) 97.5 102.5 (BP, Ph. Eur.)
(Impurities)

Drug Selection 20

(Physicochemical properties) (Refractive index)
(Melting point) - (pH)

(Particle size)


(Polymorphic forms)


(Water content)

(Inorganic impurities)

(Microbial limits)

Drug Selection 21

(Description)


(Identification)
(Assay) 90.0 -
110.0
(USP) 95.0 - 105.0
(BP, Ph. Eur.)
(Impurity)

Drug Selection 22





-
(dry syrup)
-

Drug Selection 23
 ()
-


(uniformity of delivered dose)

Drug Selection 24
 ()
-

-

-

Drug Selection 25
 ()

Drug Selection 26

(Identification)

(IR)
(UV) (chromophore)

(Justification for specification)

Drug Selection 27

3

(organic impurities)

(inorganic impurities)

(residual solvents)

Drug Selection 28

3
Qualification Threshold
qualification threshold

Identification Threshold
identification threshold
Reporting Threshold
reporting threshold

1% 2
( 0.05%, 0.15%) 1% 1 ( 1.0%)

Drug Selection 29


Impurity 1 qualification threshold

Impurity 2, 3, 4 identification threshold qualification threshold

Other impurities reporting threshold

Drug Selection 30


Drug Selection 31


Drug Selection 32


2 (weight variation; WV)
(content uniformity; CU)
1. (weight variation)

2. (content uniformity uniformity of content)

Drug Selection 33
 ()
(content
uniformity)
(weight variation)
W1
W2 ( , )
W3
W4 25
25

Drug Selection 34


Drug Selection 35



130 mg
10
130 mg 234 mg
7.5
324 mg
5

Drug Selection 36


(average weight) (range)
130 10

Drug Selection 37



(controlled or modified release)

Drug Selection 38



Apparatus 1
dissolution medium
Apparatus 2
Apparatus 3
micro-particle
Apparatus 4 dissolution medium

Apparatus 5 dissolution medium

Apparatus 6
Apparatus 7
osmotic

Drug Selection 39

(Disintegration)

(Dissolution)

Drug Selection 40

(disintegration) ( )

(dissolution)

Drug Selection 41





(immediate release)

250 1.2-6.8 37
15 80% 1.2, 4.0 6.8

Drug Selection 42


Drug Selection 43
 (Good Manufacturing Practice; GMP)
(Good Manufacturing Practice; GMP)




GMP


2


(WHO GMP)


Pharmaceutical Inspection Cooperation Scheme (PIC/S)

Drug Selection 44
 (Certificate of Pharmaceutical Product; CPP)
(Certificate of Pharmaceutical Product; CPP)
(Good Manufacturing Practice; GMP)





(GMP) 24

Drug Selection 45


Drug Selection 46


(Glasses)
,
,
(Plastics)
,
, ,

(Metals)
,
,

Drug Selection 47


(protection)


(compatibility)

(absorption) (adsorption)
-

(safety)

(performance)

Drug Selection 48


Drug Selection 49

(protection)

(compatibility)

(safety)

(performance/drug delivery)

Drug Selection 50

USP

T tight containers

W well-closed containers

LR light-resistant containers

Drug Selection 51


High-density polyethylene (HDPE)
/

Drug Selection 52




2
(accelerated testing)
-

(real time testing)

(stability specification)
(shelf life specification)


5

Drug Selection 53


, , , -
,

,

Drug Selection 54

(Temperature)
(oxidation) (reduction) (hydrolysis)
- (pH)
4-8
(Moisture) (water content)

(Light)
(Pharmaceutical dosage forms)

(Concentration)
(Drug incompatibility)

(Oxygen)

Drug Selection 55

(WHO)


I 21 45%
II 25 60%
III 30 35%
IVA 30 65%
IVB 30 75%

Drug Selection 56

(IVB)
30 75%
2
3

Drug Selection 57

(real time stability)
30 75%

(accelerated) (stress)
40 75%

: (stress)

Drug Selection 58



12 3
6 12 5
5 ( 0, 3, 6, 9, 12, 18, 24, 36, 48, 60)

6 3
()
3
2 3

Drug Selection 59



(Tablets) , , , , , ,
,
(Hard gelatin capsules) (), , , ,
, ,
(Soft gelatin capsules) , , , ,
, , , -,
(Oral solutions) (, ), , ,
, , -, ,
(Oral suspensions) , , , ,
, -, , , ,

(Emulsions) , , , ,
, -, , ,

Drug Selection 60
 ()
(Oral Powders for Reconstitution)
, , , , ,


(Metered-dose inhalers and nasal aerosols) , , ,
, , , , ,
,

Drug Selection 61
 ()
(Nasal sprays) , , , , ,
, , -,
(Topical preparations) , , ,
(Ophthalmic and otic preparations) ,

(Suppositories) , , , , ,
,

Drug Selection 62
 ()
(Small volume parenterals) , , , ,
(), , , -,
/
(Large volume parenterals) , , , ,
(), , , -, ,
/
(Transdermal patches) , (in
vitro)

Drug Selection 63





(Bracketing design)
(Matrixing design)

Drug Selection 64
 (Bracketing Design)
Bracketing design /

3
3

Drug Selection 65
 (Matrixing Design)
Matrixing design


0, 3, 6, 9, 12, 18, 24 36
One-Half Reduction One-Third
Reduction

Drug Selection 66

Bracketing design Matrixing design

Drug Selection 67



25 60%

Drug Selection 68

(In-use stability study)
(multiple dose container)

(dry syrup) 2-8 7
2

Drug Selection 69




(Cold Chain System)

Drug Selection 70
 Vaccine Vial Monitor (VVM)



Vaccine Vial Monitor (VVM)

Vaccine Vial Monitor

Drug Selection 71
 (Safety)

Drug Selection 72


Drug Selection 73
 Look-alike Drug Appearance

Drug Selection 74
 Look-alike Packaging

Drug Selection 75
 Drug Name Confusion

Drug Selection 76
 Drug Name Confusion

Drug Selection 77
 Drug Name Confusion

Drug Selection 78
 Drug Name Confusion

Drug Selection 79

(Primacy packaging)

Drug Selection 80

(Secondary packaging)

Drug Selection 81


Drug Selection 82


Drug Selection 83


Drug Selection 84
 (Efficacy)

Drug Selection 85

(original drugs)
(clinical study)
4
1 (Phase I) 20-80

2 (Phase II) 100-300

3 (Phase III) 1,000-3,000

4 (Phase IV)

Drug Selection 86
 (Bioequivalence)
(bioequivalence)


(bioequivalence)





(bioequivalence)

Drug Selection 87



1.
GMP
GCP

GLP ISO/IEC 17025
2.



3.

4.
Cmax, AUC0-1, AUC0-, Tmax
90% CI 80-125%
5.

Drug Selection 88





(BCS I)

Drug Selection 89

biopharmaceutics classification system (BCS)
4
1 :
2 :

3 :
4 :

Drug Selection 90

(locally applied, locally acting products)
(bioequivalence)

(comparative in vitro studies)
(comparative pharmacodynamic studies)
(comparative clinical studies)

Drug Selection 91
 (Therapeutic equivalence)
Therapeutic equivalence

Drug Selection 92

Therapeutic equivalence 5
Safe and effective
Clinical trial
Pharmaceutical equivalent


Bioequivalence

Adequate labeled
Current GMP

Drug Selection 93
 Approved Drug Products with Therapeutic Equivalence Evaluations (Orange book)
Orange book (US FDA)
(therapeutic
equivalence)
orange book US FDA
US FDA
US FDA Therapeutic Equivalence Code (TEC)
A AA, AB, AN, AO, AP, AT AB
in vivo in vitro A
US FDA B
US FDA therapeutic equivalence

Drug Selection 94
 Orange book
Orange book

Drug Selection 95



?

Drug Selection 96



Inspection of Certificate of Analysis

Sampling and Analysis /

Efficacy and Safety Evaluation
Drug Use Evaluation (DUE)

Adverse Drug Reaction (ADR)
Medication Error (ME)

Drug Occurrence

Drug Recalls

Drug Selection 97
 (Green book)

(List of Quality Pharmaceutical
Products and Manufacturers; Green book)
(Quality Assurance Of Medicine Under Universal Health Coverage Program)
3

Drug Selection 98

()
7 ( )

http://www.tumdee.org/alert/
p g

Drug Selection 99
 UHOSNET (University Hospital Network)
(Generic Name)
(Essential Drugs)



(UHOSNET)

http://www.si.mahidol.ac.th/uhosnet-pharmacy

Drug Selection 100

 . (Safety Alert)
(.)

Drug Selection 101

Drug Selection 102
Drug Selection 103