Chinese Pharmacopeia 2015 New Milestone of Excipients ...ipec-europe.org/UPLOADS/4_J_Zheng.pdf ·...

Chinese Pharmacopeia 2015New Milestone of Excipients Standards

in China

Jessica ZhengChair, Industry Liaison Committee, IPEC China

Regulatory Manager China, [email protected]

IPEC Europe Annual SeminarNice, Feb. 5, 2015

mailto:[email protected]

Content:

Chinese Pharmacopeia (ChP) regulatory position in China

Overview of ChP 2015

Features of Excipients standards in ChP 2015

ChP approach in harmonization and industry involvement

2

ChP Compliance is very important for excipient regulatory compliance in China!

ChP Regulatory Position in China

Drug Administrative Law (No.45, 2001)•Active ingredients, excipients used in drug manufacturing must meet the requirements for pharmaceutical application•Drug administrative law is under revision process, intend to further clarify the requirements of excipients

Administrative Regulation of Drug Registration (No. 28, 2007)•National drug standards are Chinese Pharmacopeia, drug registration standards and other drug standards issued by CFDA.•Drug registration standards should not be lower than monograph requirements in ChP.•The setting of test items and test methods in drug registration standards should meet the basic requirements of ChP.

Regulation of Strengthening Supervision on Excipients (2012)•For excipients already have national drug standards, must meet the requirements of national drug standards•CFDA organize ChP committee to formulate, revise and issue national excipients standards. To research and issue the recommended excipients standards.

3

ChP Regulatory Position in China

Chinese Pharmacopeia (2010)

• General notice No. 22: The drug substances and excipients used in preparations or dosage forms

should comply with the requirements stated in the individual monographs of this edition of

Pharmacopoeia.

CFDA notice about implement ChP 2010 (No.43, 2010)

• For any drug registration standard which not meet the ChP requirements, the drug manufacturer

should submit the supplementary application to change the drug registration standards.

ChP Compliance is very important for excipient regulatory compliance in China!

4

CFDA notice about renew registration of imported drug (No.18, 2009)

• Because of ChP or local pharmacopeia update, the registration standards of imported drug need to

update accordingly. The applicant need to submit the supplementary application separately before

the renew application.

Content:





5


Finalize*Manuscript

UnifyManuscript

PrintIssue

Implement

*: Draft and revision finalized by local drug institute and submitted to ChP committee

2015.72015.12014.122014.82014.72014.6

PublicComment

PublishChP 2015

PressProofread

Recent Time Schedule :

-10: data from ChP 2015 Compilation Situation, Wei Zhang, General Secretary of ChP Committee, 2014 Joint ChP-USP Science and

Standards Symposium6


The total No. of monographs in ChP 2015 is 5682, the growth reach 24.4%

The No. of monograph standards improvement is 2831

7


ChP main structure change: 3 volumes 4 volumes

Volume I: Traditional Chinese Medicine

Volume II: Chemical Medicine

Volume III: Biologics

Volume IV: General chapters (appendices),

Guidances and excipients monographs

8


New encoding system for general chaptersCoding Series Category

0100 Series General Chapter for Drug Formulation

0200 Series Other General Chapter

0300 Series General Identification Test

0400 Series Spectroscopic Methodology

0500 Series Chromatography

0600 Series Physical Constants Test Method

0700 Series Other test Method

0800 Series Limit Test

0900 Series Physical Properties Test method

1000 Series Molecular Biological Technique

1100 Series Biological Test Method

1200 Series Biological Activity Test Method

2000 Series Traditional Chinese Medicine Related Test Method

3000 Series Biological Product Related Test Method

8000 Series Reagents and Standard Substance

9000 Series Guidance

9


Pharmacopeia Supplement Edition

Three Pharmacopeia Supplement Editions for ChP 2010 have been issued by ChP

ChP will continue to issue supplement edition for ChP 2015

10

Content:





11

Features of Excipients Standards in ChP 2015

1. The number of excipients monographs increase significantly

The No. of excipients monographs in ChP 2015 will be around 271, new added 139, the growth will reach 105%

12


2. Increase the safety and functional requirements on excipients

Revise general chapter for excipients (0251)

Added classification description about chemical structure and drug dosage

form

Emphasize excipient GMP and GDP

Emphasize the sterility and microbial limit requirements on excipients for

injection and eye drops

Emphasize the label indicate “pharmaceutical excipient” and route of

administration

New draft guidance of research on functionality-related characteristics of pharmaceutical excipients (9701)

13


3. Excipient monographs for injection will be separately adopted

1 Propylene Glycol for Injection 丙二醇（供注射用）

2 Polysorbate 80 for Injection 聚山梨酯 80（供注射用）

3 Macrogol 300 for Injection 聚乙二醇300（供注射用）

4 Macrogol 400 for Injection 聚乙二醇400（供注射用）

5 Sodium Chloride for Injection 氯化钠（供注射用）

6 Soya Lecithin for injection 大豆磷脂（供注射用）

7 Egg yolk lecithin for Injection 蛋黄卵磷脂（供注射用）

8 Activated Charcoal for Injection 活性炭（供注射用）

9 Poly(lactide-co-glycolide)for Injection_5050 丙交酯乙交酯共聚物（5050）(供注射用)



12 Glycerol for Injection 甘油(供注射用)

13 SoybeanOil (For Injection) 大豆油(供注射用)

There are total 13 excipient

monographs for injection are

included in the up to date list

of excipients plan to adopted

by ChP 2015 (Sep. 2014). In

addition, there are 6

excipient monographs

included specification for

injection.

http://www.chp.org.cn/cms/business/

add-acc/accessory/000020.html

14

http://www.chp.org.cn/cms/business/add-acc/accessory/000020.html

Test Polysorbate 80 Polysorbate 80 for injection

Appearance Conform Conform

Specific gravity 1.06-1.09 1.06-1.09

25°C Viscosity 350-550mm2/s 350-450mm2/s

Acid value <=2.2 <=1

Saponification value 45-60 45-55

Hydroxyl value 65-80 65-80

Iodine value 18-24 18-24

Peroxide value <=10 <=3

Identification Conform Conform

pH value 5.0-8.0 5.0-7.5

UV absorbance:- at 225 nm- at 267 nm

NA<=1

<=0.1

Color Conform Conform

Ethylene glycol NA <=0.01%

Diethylene glycol NA <=0.01%

Triethylene glycol NA <=0.01%

Ethylene oxide <=1ppm <=1ppm

Dioxane <=10ppm <=10ppm

Freezing test Conform Conform

Water content <=3% <=0.5%

Ashes <=0.2% <=0.1%

Heavy metals <=10ppm <=10ppm

Arsenic <=2ppm <=2ppm

Composition of fatty acids

Myristic acid NA <=0.5%

Palmitic acid NA <=0.5%

Palmitoleic acid NA <=0.5%

Stearic acid NA <=0.5%

Oleic acid NA >=98%

Linoleic acid NA <=0.5%

Linolenic acid NA <=0.5%

Bacterial endotoxin NA <0.012EU

Asepsis NA Conform


Example: Polysorbate 80

15


Specific panel discussion of Polysorbate 80 for injection monograph was

held in Nov. 2014 by ChP committee, discussion group included people from

ChP, industry experts, Excipient makers and users. Representative of IPEC

China attended this discussion too.

Polysorbate 80 for injection monograph will be adopted by ChP 2015

separately, keep the specification of Oleic acid purity >=98%

For some specific drug formation needs, excipient user can define the

specific excipient standards needs based on usability and safety.

Propose CFDA to postpone the date of implement for excipients for

injection monographs, give industry enough time to verify in practices.

16


4. Atypical Active

In ChP 2010, there are some problems existing about atypical actives

monographs, such as inaccurate adoption, repeated adoption in API and

Excipient part, not consistent in test methods etc.

Possible situation in ChP 2015:

• Keep consistent test methods for same test item in atypical active

monograph adopted in API part and excipient part.

• Will still adopt atypical actives both in API part and excipient part.

• Keep necessary same standards for monograph in API part and excipient

part.

• Different supervision requirements on atypical actives used as API and

excipient

17

Content:





18

Page from International Harmonisation, Dr Samantha Atkinson , BP Commission, 2014 Joint ChP-USP Science and Standards Symposium

China signed MOU of Pharmacopeia harmonization, but not official member of PDG

Harmonization

19

ChP Update Process and Industry Involvement

ChP Committee

Drug Institutes

Other Drug Institutes

ChP Committee

CFDA

• Review revision and new draft monographs

• Publish on ChP website for public consultation

• Collect public comments• Evaluate, adopt or reject suggestions• Finalize and issue ChP 2015

• Implement ChP 2015

• Propose ChP 2015 excipients list (387)

• Clarify responsibility of each drug institute

2012.7.23

2015.7

3 months

• Collect and test samples• Test method verification• Propose revision and new draft

• Continue communication

• comply with current ChP monograph requirements

• IPEC China provide comments on proposed list

• Actively provide samples• Actively communication for

specifications and test methods

• Review the draft or revision• Submit official amending

suggestions to ChP directly or through IPEC China

20

ChP Feedbacks

ChP provided 2 batches official feedbacks for the ChP 2015 excipients public consultation. IPEC China coordinate the members comments submission.



21

37

48

2

22

39



22

Appreciate the comments from

Hannah Han (IPEC China)

Cloris Tian (IPEC China)

Colin Li (IPEC China)

Daniel Liu (IPEC China)

Nicol Fan (IPEC China)

Meredith Ge (IPEC China)

Chinese Pharmacopeia 2015 New Milestone of Excipients ...ipec-europe.org/UPLOADS/4_J_Zheng.pdf ·...

Documents

Transcript of Chinese Pharmacopeia 2015 New Milestone of Excipients ...ipec-europe.org/UPLOADS/4_J_Zheng.pdf ·...