江苏华兰药用新材料股份有限公司

1. Industrial Standard Questions

Standard of needling desquamation of butyl rubber stopper for frozen dry and powder injections?

Answer: ≤5particles

Insoluble particles on surface of butyl rubber stopper for transfusion?

Answer: ≤30 invisible particles with the diameter ≥10um

≤3 invisible particles with the diameter ≥25um

Standard for ash content of butyl rubber stopper for frozen dry and powder injections?

Answer: ≤50%

National standard for ash content of butyl rubber stopper for transfusion?

Answer: ≤45%

National standard for ash content of butyl rubber stopper for powder injections?

Answer: ≤45%

How long is guarantee period of Ceclor powder injections and curative drug for transfusion?

Answer: 2 years.

2. Short Answer Questions

Which factors affect clarity (turbidity) of Ceclor powder injections?

Answer: ① temperature; ② humidity; ③ storage period and environment (observation time); ④ formula of rubber stopper; ⑤ inversion; ⑥ silicone oil     

Which factors affect clarity of transfusion injections (especially curative transfusion injections)?

Answer: ① formula of rubber stopper; ② rinsing process of rubber stopper; ③ sterilization temperatures of liquid medicine; ④ storage periodand environment of drug; ⑤ filling conditions

3. Question-Response

Key factors affecting needling desquamation:

Structure of stainless steel needle head √;

Shape chamfer of needle head √;

Resin needle ×;

Size of needle head ×;

Formula of rubber stopper √;

Puncture 2 times and over at the same position √;

Temperature and environment to use drug (important) √;

Note: "√" is correct answer; while "×" is wrong;

Correct way:

Answer: ① use needle with side openings;

Adjust formula of rubber stopper;

Change puncture method to avoid needling twice at one place;

Temperature when using drug.

What rubber stopper can avoid turbidity of Ceclor powder injection out of limit?

Answer: compound film rubber stopper.

Which method can reduce particles on surface of rubber stopper?

Answer: ① cleaner, potcher and dryer can't adopt drum-type in order to reduce possibility of particles caused by friction between rubber stoppers as well as between rubber stopper and drum;

Adopt clean air and flow flow effect to evenly turn rubber stopper over to achieve perfect cleaning and potching effects;

Don't dewater and dismantle rubber stopper manually but semi-automatic or automatic dewatering and unloading method in order to reduce or avoid risks of cross contamination.

Dry with static processes such as microwave method in order to avoid particles caused by friction between rubber stoppers when drying.

When pharmaceutical enterprise opens carton and the first layer of plastic bag, reduce cross contamination, especially process environment control is important.

What may cause jumping-stopper resulted in applying stopper after high-speed repacking and filling of rubber stoppers for powder injections and transfusion?

Answer: interior diameter tolerance of glass bottle neck is a little bigger -- matching;

Interior diameter plane of bottle neck appears out-toe -- shape (stopper, bottle)

Structure of rubber stopper neck is unreasonable, diameter tolerance of rubber stopper is a little bigger, degree of silicification.

Better solutions:

Control interior diameter tolerance of bottle neck;

Try straight interior diameter plane or in-toe;

Add anti-jumping rib on diameter plane of rubber stopper;

The most effective way is to make neck place of rubber stopper as horn in reverse (solved by Lanling).

In case any medical dispute caused by needling desquamation, what explanation is good to deal with such dispute?

Answer: ① explain reasons for needling desquamation, e.g. needle, temperature, etc., so national standard hasn't made any qualitative regulation for needling desquamation but quantitative ones only;

Explain nertianon reactivity of needling desquamation itself will not react with drug liquid, which has no effect to human bodies;

Ultimate filter is mounted to avoid infusion apparatus go into human bodies. Bring infusion apparatus filter sample to demonstrate on field for nurses and patients.

Do you think the higher gel content the better rubber stopper?

Answer: design for formula of rubber stopper is a complex process integrated with chemical, physical and biological properties. Dosages of multiple accelerators, activators and fillers are at certain rates except the main material -- halogenated butyl rubber to satisfy requirements for production process and use of rubber stopper. In general, rubber stopper with higher gel content is softer and lack of due stiffness, which is bad for filling machine production, especially rubber stopper for frozen dry powder preparations for injection may take stopper out when dehumidify with half stopper.

 

General requirements for disposable rubber stopper:

In addition to standard requirements, it shall also satisfy:

Min biological load;

Clean (rinsed by water for injection);