Released by FDA: 1/20/00.  Posted by FDA: 2/29/00

Mr. Teng Shao Yun 
Director 
Shanghai Shen Xing Pharmaceutical Factory 
201 Hu Yi Road 
Nanxiang, Shanghai 
China

Dear Mr. Teng:

This is regarding the inspections of your active pharmaceutical ingredient (API) manufacturing facilities in Shanghai, China on November 4-8, 1999 by FDA Investigators Robert C. Horan and Thaddeus Sze.  The inspection revealed numerous deviations from current good manufacturing practices (CGMP) in the manufacture of active pharmaceutical ingredients. T he deviations were listed on an FDA-483, List of Observations, issued to Mr. (confidential, deleted by FDA) at the close of the inspection.  These deviations cause the API product to be adulterated within the meaning of Section 501(a)(2)(B) of the U.S. Federal Food, Drug, and Cosmetic Act. Section 501(a)(2)(B) of the Act requires that all drugs be manufactured, processed, packed, and held according to current good manufacturing practice.  No distinction is made between active pharmaceutical ingredients and finished pharmaceuticals, and failure of either to comply with CGMP constitutes a failure to comply with the requirements of the Act.

Specific areas of concern include, but are not limited to the following:

1. Low levels of organic volatile impurities, which are not part of the reaction process, are found in the finished (confidential, deleted by FDA) API.  The source of these impurities has not been determined and therefore the amounts present in the API cannot be controlled.  Lack of controls over possible impurities includes, but is not limited to: 

1. Inadequate validation of the (confidential, deleted by FDA) processes 
2. Use of technical grade raw materials with inadequate purity specifications
3. OVI testing is not conducted on each batch of finished API

2. The stability testing program is deficient in that stability samples are not stored under controlled temperatures and the analytical method has not been demonstrated to be stability indicating by forced degradation studies.

3. Master production records were not signed and dated by the individuals responsible for their approval.

The above deficiencies are not to be considered as an all-inclusive list of the deficiencies at this facility.  FDA inspections are audits and are not intended to uncover all CGMP deviations that exist.  We recommend that you evaluate the facility on an overall basis for CGMP compliance.  Until the deficiencies noted during this inspection have been corrected, this office will recommend disapproval of any applications listing this facility as the supplier of the active pharmaceutical ingredients.

Please address your response to this letter to Compliance Officer John M Dietrick at the address provided above.  In your response, please include a timetable of when the corrections will be completed and attach supporting documents.  Any documents provided should be in English or accompanied by an English translation.

To schedule a reinspection after corrections have been completed, contact Rochelle Kimmel, Associate Director, Drug & Biologic Group, Division of Emergency and Investigational Operations (HFC-133), 5600 Fishers Lane, Rockville, Maryland 20857.  You may wish to contact that office at (301) 827-5663 or by FAX at (301) 443-6919.

Sincerely,

 

John M. Dietrick
Compliance Officer 
Foreign Inspection Team