dr. j. p. prasad scientist & head, blood products nib .... experiences of...dr. j. p. prasad...

National Institute of BiologicalsMinistry of Health & Family WelfareGovernment of India

Dr. J. P. Prasad

Scientist & Head, Blood Products

NIB, NOIDA

Email: [email protected]


PRESENTATION PLAN

• Global Market of Plasma Derived Products

• Indian Market

• Quality Control evaluation at NIB

National Institute of BiologicalsMinistry of Health & Family WelfareGovernment of India 3

The global plasma fractionation market is estimated to grow at a CAGR of 6.7% from 2016 to 2021 to reach USD 26.07 Billion by 2021.

The immunoglobulin segment accounted for the largest share of the market in 2015

Growing aging population, rising incidences of bleeding and immune disorders, and growing use of immunoglobulin and alpha-1-antitrypsin are expected to propel the growth of this market.

Global market for Plasma Derived products

Source: Markets & Markets: Global Forecast to 2021


The Worldwide Plasma Fraction Market

4

10%

46%

9%

4%2%

29%

Worldwide Plasma Fractions market by Product- $11.7 billion

Albumin IVIG Factor-VII Sp.IG factor-IX All others

The Marketing Research Bureau


0.01

1.64

3.44

5.74

0 1 2 3 4 5 6

Factor VIII per capita consumption

USA

INDIA

JAPAN

SWEDEN

0.1

23.6

29.3

57.5

0 5 10 15 20 25 30 35 40 45 50 55 60

IVIG grams/ thousand population

USA

INDIA

JAPAN

SWEDEN

1

281

367

534

0 50 100 150 200 250 300 350 400 450 500 550

Albumin Kgs./ million population

USA

INDIA

JAPAN

SWEDEN


Needs about 900,000 liters of plasma proteins per year

largely import dependent for plasma protein therapies and is depending on few domestic fractionation

plants for self-sufficiency in plasma medicines.

Has about 1 % self sufficiency Index by global

norms for Albumin and IVIG. Factor VIII is still worse (The

Source - PPTA-2014)


Indigenous Manufacturers licensed on Form-28E to manufacture for sale and distribution of Blood

Products

M/s. HemarusTherapeutics Ltd., Telengana

M/s. Reliance Life Sciences Pvt Ltd.

Navi Mumbai

M/s. Bharat Serums and

Vaccines Ltd., Mumbai

M/s. Intas Pharmaceuticals,

Ahmedabad

M/s. Virchow Biotech Pvt Ltd.,

Telengana


Source: ppta.org

Plasma Derived Products

are inherently complex

and variable, a vigilant

monitoring is required to

ensure the quality as well

as safety of such

products.


NIB OVERVIEW


CERTIFICATION

ISO 17025 : 2005 CERTIFICATION BY NABL

Initiation of ISO:9001, ISO:14001 & OSHAS 18001

MONOGRAPH DEVELOPMEN

T

PUBLICATION OF 23 MONOGRAPHS ON BIOLOGICALS IN INDIAN PHARMACOPOEIA

REFERENCE STANDARD

PREPARATION OF NATIONAL REFERENCE STANDARD FOR INSULIN

HIV, HBsAg & HCV PERFORMANCE PANEL

Red Blood Cell Panel (35)

COLLABORATION

*WHO- NIBSC, UK, INTERNATIONAL COLLABORATIVE STUDIES FOR PREPARTION OF INTERNATIONAL REF . STD- PEG G-CSF & HBsAg

*IIT- DELHI-CHEMOMETRIC ANALYSIS

*DBT-BIOTECHNOLOGY, ADVANCED BIOLOGICALS & BIOPHRAMACEUTICALS

*JAMIA HAMDARD-BIOINFORMATICS

SUCCESSFUL PARTICIPATION IN PROFICIENCY

TESTING PROGRAMME

*EDQM- FRANCE:a) HCV RNA NAT TESTING-100% with excellent remarkb) COAGULATION FACTOR VIII POTENCY ASSAY*NSRL AUSTRALIA: EQAS for HIV, HCV, HBV & SYPHILIS SEROLOGY

*CMC VELLORE: EQAS FOR ANALYTES GLUCOSE & HbA1c

ESTABLISHMENT OF IT- ENABLED

SYSTEM PROCESS

* e-PUBLISHING INCLUDING e-TENDERING* SAMPLE TRACKING* INVENTORY MODULE *e-OFFICE BEING ESTABLISHEDDEVELOPMENT OF

INDIGENOUS SOFTWARES

*HEMO-VIGIL-Haemovigilance *AKS SOFTWARE –Drug Survey*e-BLOOD BANKING-Blood Banks

MAJOR SCIENTIFIC ACHIEVEMENTS OF NIB

12


NIB SCIENTISTS DECLARED AS GOVERNMENT ANALYSTS

Name of NIB Scientist and Lab notified as CDL

Products

Dr. J. P. Prasad, Scientist Grade-II,Blood Product Lab

(i) Human Albumin; (ii) Human Normal Immunoglobulin (IV & IM); (iii) Human Coagulation Factor VIII; (iv) Human Coagulation Factor IX; (v) Plasma Protein Fraction; (vi) Fibrin Sealant Kit; (vii) Anti-Inhibitor Coagulation Complex.

Dr. Renu Jain, Scientist Grade-I,Recombinant Product Lab

(i) r- Insulin and Insulin analogues; (ii) r-Erythropoietin (EPO); (iii) r-Granulocyte Colony Stimulating Factor (G–CSF)

Dr. Reba Chhabra, Scientist Grade-I, Immunodiagnostic kit Lab

(i) Human Immunodeficiency Virus; (ii) Hepatitis B Surface Antigen;(iii) Hepatitis C Virus

Ms. Ajanta Sircar, Scientist Grade-III,Biochemical Kit Lab

(i) Glucose Test Strips;(ii) Fully automated analyser based glucose reagents

Dr. J. P. Prasad, Scientist Grade-II,& Ms. Kanchan Ahuja, Scientist Grade-III,Blood Grouping Reagent Lab

Blood Grouping reagents


Monograph : book of Standards and Specifications

Genesis of IP Blood Products Monographs

2014

IP 2016

Participatingas expertmemberfrom BPL forreview ofBloodProductsMonographsand GeneralChapter.

CONTRIBUTED IN REVIEW OF 7 MONOGRAPHS:

1. Human albumin,

2. Plasma Protein Fraction,

3. Human Normal Immunoglobulin for intravenous use,

4. Human Normal Immunoglobulin,

5. Dry Anti-Hemophilic Factor-VIII,

6. Coagulation Factor-IX and

7. Fibrin Sealant kit


Plasma Derived SamplesRegulatory Functions at NIB

1- Human Albumin

2- Human Plasma Protein Fraction

3- Human Normal Immunoglobulin (IV)

4- Human Normal Immunoglobulin (IM)5- Human Normal Immunoglobulin (IV) Bulk6- Human Normal Immunoglobulin (IM) Bulk7 Hepatitis B Immunoglobulin8 Rabies Immunoglobultin

9- Anti –D Immunoglobulin (IV) 10- Anti –D Immunoglobulin (IM11- Human Tetanus Immunoglobulin (IM)12- Human Tetanus Immunoglobulin (IM) Bulk

13- Human Coagulation Factor VIII plasma derived14- Human Coagulation Factor VIII recombinant

15- Human Coagulation Factor IX

16- Fibrin Sealant Kit

17- Anti-Inhibitor Coagulant complex

18- Anti-Thrombin III concentrate

19-Human Fibrinogen


Sample receipt SRRD Unit, coding of samples

Laboratory: sample entry, sample transfer

Laboratory testing

Test report compilation

Test report(s) verification

Test report approval

Report compilation

COA for decoding

Decoding by SRRD file

sent to the lab

Protocol scrutiny by the lab

Final COA

Approval by the DD(QC)

SRRD UNIT Report

dispatch

Turn Around Time- 45 DAYS

Referred by CDSCO/State Drug Offices/Port Offices

4

e –Mail to Referred body

& copy to Manufacturer

By Post to Referred body

& copy to Manufacturer

NIB Website

TESTING PROCESS : FLOW CHART

321

5

6

7

891011

13

12


Sl. No. Requirement Document submitted by the manufacturer/ importer

Comments

1 Batch release from country of origin

2 Plasma pool certificate from NCL/manufacturer

3 Summary information of the plasma pool:

A. Source of plasma

B. Period of collection of plasma

C: Certificate of plasma compliance tointernational standards

4 Name of three countries

5 Method of viral inactivation

6 Certificate of analysis with name ofpharmacopoeia complied

Scrutiny of protocol

NIB/BPL/PRO/DOC

File No :SRRD Code :Name of the Product :Lot / Batch No. :Manufacturing date :Expiry date :Category of the product as per the lot release procedure:

Signature:……………..


METHODS FOR TESTING OF VARIOUS PLASMA DERIVED PRODUCTS AS PER INDIAN PHARMACOPOEA

18

Iidentification

• DID

• SDS-PAGE

• Assay

Purity

• HPLC

• Protein composition

impurities

• Anti-A Anti-B

• Anti-D

• Haem

• PKA

• IgA

• ACA

Potency

• Factor VIII

• Factor IX

• Specific potency assay IgG

• Total protein content

Viral markers

• HIV 1& Ab

• Anti-HCV Ab

• HBsAg

General safety

• Sterility

• Pyrogen

• Abnormal toxicity

• BET

General Tests

• pH

• Osmolality

• Moisture content

Tests for limits

• Sodium

• Potassium

• Heparin

• Activated coagulation factors


0

100

200

300

400

500

600

700

2010-11 2011-12 2012-13 2013-14 2014-15 2015-16

179

208 219

534

593609

177205 217

520

564593

2 3 2 1429 16

No

. of

bat

che

s

Trends of Various Blood Products Tested at NIB in last 6 Years

No. of batches received and evaluated No. of batches found SQ No. of batches found NSQ


Indigenous & Imported samples(2015 To 2016)

313298

Indigenous ImporterNumber of batches received Number of imported

batches receivedNumber of indigenous

batches receivedTotal SQ NSQ Total SQ NSQ Total SQ NSQ

609 596 16 296 294 02 313 299 14

SQ – Standard Quality NSQ – Not of Standard Quality

4.4%Not of Standard

Quality


PERFORMANCE EVALUATIONIN INDIGENOUS AND IMPORTED BATCHES OF PLASMA DERIVED PRODUCTS

21

Parameters found

Out –of -specification

Human albumin

Total proteinsodium contentpre kallikrein activator

Immunoglobulin

Protein composition

Total protein

Factor VIII/IX

Potency assay


5.00%6.00%7.00%8.00%9.00%

10.00%11.00%12.00%13.00%14.00%15.00%16.00%17.00%18.00%19.00%20.00%21.00%22.00%23.00%

1

12

23

34

45

56

67

78

89

100

111

122

133

144

155

Samples

Range as per I.P. 19.00 % -21.00%

Range of In-house Control-19.54%-20.50%

No. of Samples

5.00%6.00%7.00%8.00%9.00%

10.00%11.00%12.00%13.00%14.00%15.00%16.00%17.00%18.00%19.00%20.00%21.00%22.00%23.00%24.00%25.00%

1 3 5 7 9 11131517192123252729

In-HouseControl

Samples

Range as per I.P. 19.00 % -21.00

Range of Protein Std.8% ± 0.2

No. of

No. of Samples %

PERFORMANCE EVALUATION HUMAN ALBUMIN-TOTAL PROTEIN CONTENT


Thanks

Trend analysis of HAS batches of an Indigenous manufacturer for sodium content tested at National institute of Biologicals showing systematic error.


Comparative Results of Immunoglobulin Sample –Protein composition with HPLC & SDS-PAGE

Sample showing OOS Result

Sample showing within Specification Result


• Claimed 20%

• Actual content lower than the limits in the Certificate of Analysis

• Withdrawn from the supply

Protein standard from established manufacturer /

supplier of certified standards

• Imported batches of Human albumin having OOS result for total protein

• Standard used by the manufacturer/ Control laboratory found of higher value

• Product not recommended for marketing in India

In –House Protein standard of International Control

Laboratory

• Ploy specific AHG: Minimum potency preparation

• Withdrawn from the marketInternational Reference

standard NIBSC, UK

NIB’s Role in assessing the suitability of Reference standards / Certified Reference Materials

The Following standards found not suitable for use in test/ analysis of batches:


Conclusion

• Overall, the global consumption of plasma derived medicinal products has gone up over the last 20 years .

• Use of plasma derived medicinal products may vary from country to country .

• The Quality of the plasma derived products must checked for it quality to protect public health.

• The reference standard/ material and critical reagents should be tested before use.

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dr. j. p. prasad scientist & head, blood products nib .... experiences of...dr. j. p. prasad...

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