Excipient GMP in China Manufacturer’s...
12
Excipient GMP in China Manufacturer’s Perspective Meredith Ge Chair, IPEC China Product Regulatory, Ashland (China) Email：[email protected] IPEC China ‐ Registered in Hongkong in 2008 ‐ 22 members (3 newly joined in 2013) 2
Transcript of Excipient GMP in China Manufacturer’s...
Excipient GMP in China Manufacturer’s Perspective
Meredith Ge
Chair, IPEC China
Product Regulatory, Ashland (China)
Email：[email protected]
IPEC China ‐ Registered in Hongkong in 2008‐ 22 members (3 newly joined in 2013)
2
IPEC China
3
Member increase in 2012/2013.
Excipientsmanufacturer
Most are chemical manufacturers.
Only a small portion of products are for pharmaceutical market. Most products will provide for other markets, such as food, personal care and other industrial application.
Only small number of companies will specifically produce pharmaceutical excipients.
4
1. Excipient GMP in China
2. Differences between China excipient GMP and IPEC‐PQG GMP
3. Suggestions
Clean area Validation Material balance
Shelf life/retest intervalExcipient used in sterile drugsRisk based approach
Regulatory requirementProblems and challenges
Content
5
1. Excipient GMP in China
Drug Administrative Law (2001)
Active ingredient, excipients used in drug manufacturing must meet requirement for pharmaceutical application.
Regulatory requirement
6
1. Excipient GMP in China
SFDA Good Manufacturing Practice for Pharmaceutical Excipients (2006)
Not mandatory in the past. Implement as reference.Pending questions: Become mandatory in future? To be updated or not? Does it apply to excipient manufacturers out of China but export excipients to China?
Regulatory requirement
7
Note: SFDA reorganized and changed name to CFDA (China Food and Drug Administration) in end March, 2013.
1. Excipient GMP in China
GB 50473‐2008 China National Standard for Pharmaceutical Industry Clean Facility Design Guideline
Clean facility definition: Facilities with air cleanness requirement for manufacturing of drug dosage forms, APIs, Bio‐products, radioactive drugs, pharmaceutical excipients, directly contacted packaging materials.
Regulatory requirement
8
1. Excipient GMP in China
SFDA Regulation of Strengthening Supervision on Excipients (Aug 1, 2012 publish. Feb 1, 2013 effective)
Drug manufacturers must strengthen the audit on excipients suppliers.
Excipient manufacturers need strictly implement Excipients GMP.
SFDA press conference in Aug, 2012. Official of SFDA drug registration department mentioned SFDA expect mandatory implementation of excipient GMP. Will focus on inspection but not certification conducted by SFDA.
Regulatory requirement
9
Problems and challenges
Different implementation in different provinces or districts due to non‐mandatory GMP in the past.
Put drugs/APIs GMP requirement on excipient.
Some China excipient GMP requirements are inconsistent with excipient GMP which is already widely accepted in other countries, for example IPEC PQG GMP.
CFDA expectation for mandatory implementation.
1. Excipient GMP in China
10
Questions
What GMP regulation/guidance should be followed in China?
Will the current China excipient GMP (2006) be updated?
What differences between China excipient GMP and IPEC PQG GMP?
Does China excipient GMP apply to excipient manufacturers out of China but export excipients to China?
1. Excipient GMP in China
11
2. Differences between China excipient GMP and IPEC‐PQG GMP
Clean area
Shelf life/retest interval
Validation
Excipient used in sterile drugs
Material balance
Risk based approach12
2. Differences between China Excipient GMP and IPEC‐PQG GMP
China Excipient GMP IPEC‐PQG GMP
Clean control, Clean area
‐ Need decide clean control requirement for facilities according to the application and characteristics of excipient.
‐ Need set up clean procedure for facility, equipments, utilities according to requirements for manufacturing and air cleaning control.
‐ Only allow people for manufacturing practice and approved people access to clean area.
‐ GB 50473‐2008 National Standard for Pharmaceutical Industry Clean Facility Design Guideline. The definition of clean facility include excipient facility.
No specific requirement for clean area
‐ Packaging area should be controlled, but didn’t limit how to do it.
‐ It’s up to the manufacturer to decide how to take effective control measurement to ensure product quality and avoid cross‐contamination.
13
China Excipient GMP IPEC‐PQG GMP
Shelf life
Products will not be allowed to use after shelf life even the products are still within specification. Unnecessary waste!
Retest interval, Re‐evaluation interval, or Expiry interval, Expiry date
Many excipients are very stable, without shelf life or expiry date. Product can be used after retest date if it’s still within spec.
Many China customer inquiries about the difference of shelf life and retest interval.
2. Differences between China Excipient GMP and IPEC‐PQG GMP
14
China Drug GMP (2010) (Ministry of Health, No. 79)
Recognize retest interval for excipients.
• Excipients need with suitable labeling indicated with shelf life or retest interval.
• Excipients can only be used after released by quality department and within shelf life or retest interval.
• Excipients need be stored according to shelf life or retest interval. If found situation may impact the quality during storage, need retest.
• Definition of retest interval: After a period of time during excipients storage, the date decided by companies for retest to ensure the products are still suitable for intended use.
2. Differences between China Excipient GMP and IPEC‐PQG GMP
IPEC China appeal to also reflect this in excipient GMP and other regulations regarding to excipients. 15
China Excipient GMP IPEC‐PQG GMP
More specific requirements for validation
•Need establish validation plan. Validation report need be reviewed and approved.•Plant building, facility and equipment DQ/IQ/OQ/PQ.• Specific requirements for process validation and cleaning validation.
Full validation typically performed in pharmaceutical industry may not always be carried out by excipient manufacturer.
• Each process step should be controlled to the extent necessary to ensure meet specifications.• Demonstrate the consistent operation of each manufacturing process.
2. Differences between China Excipient GMP and IPEC‐PQG GMP
16
China Excipient GMP IPEC‐PQG GMP
More specific requirement for non‐sterile excipient used in sterile drugs.
• If non‐sterile excipient is used in sterile drugs, need monitor process water used in final separation and refinery steps, need control total micros and endotoxin.
Consideration should be given to the end use of the excipient, particularly when excipient is direct component of sterile drug or one that is claimed to be pyrogen‐free.
2. Differences between China Excipient GMP and IPEC‐PQG GMP
17
China Excipient GMP IPEC‐PQG GMP
Material balance check for every batch.
May not easy to do exact calculation for excipient with continuous process.
• The material balance inspection should be made on every batch of products.
Theoretical mass balance for batch production.
•For batch production a theoretical mass balance may also be established with appropriate limits.
2. Differences between China Excipient GMP and IPEC‐PQG GMP
18
China Excipient GMP
IPEC‐PQG GMP
Not include risk assessment or risk based approach
Below aspects are similar with IPEC GMP:• GMP starting point • All intermediate might not require testing
Risk based approach. To be updated with risk assessment requirement.
•Judgment based on risk analysis and a thorough knowledge of the process is required to determine from which processing step GMP should be implemented. This is usually well before the final finishing operation and for example, may be identified using methods such as HACCP, FMEA or a detailed process flow diagram.
2. Differences between China Excipient GMP and IPEC‐PQG GMP
19
China Excipient GMP IPEC‐PQG GMP
Not include Consider risk of allergens, GMO for purchased materials
2. Differences between China Excipient GMP and IPEC‐PQG GMP
20
3. Suggestions
(1) Appeal to revise China excipient GMP regulation.
(2) Keep consistent with IPEC PQG GMP which is already widely recognized in other countries.
No mandatory requirement for “clean area”.
Accept “retest interval” for excipient.
Allow manufacturers to take effective measures for GMP compliance based on risk assessment.
21
3. Suggestions
(3) Seek public comments and provide transition period before formal implementation.
(4) Consider other related IPEC guidelines:GDP, Significant change, Qualification, Quality agreement, Stability
(5) Importance of supplier audit and third party audit.
22
The end
Thank you!
