Animal & Veterinary
FDA PARTICIPATES IN ANIMAL DRUG WORKSHOP IN CHINA
by Michael Smedley, Geoffrey Wong, Lonnie Luther, Ph.D. (FDA/CVM Office of New Animal Drug Evaluation) and Michael Spangenberg (formerly FDA Office of Regulatory Affairs)
FDA Veterinarian Newsletter July/August 1999 Volume XIV, No IV
In April 1999, a FDA Center for Veterinary Medicine (CVM) and Office of Regulatory Affairs (ORA) delegation participated in an Animal Drug Current Good Manufacturing Practice (cGMP) Workshop in Suzhou, China. This workshop was coordinated by Dr. C.K. Hsu, President of Shared Enterprises, Devon, PA, and sponsored by the Chinese Ministry of Agriculture (MOA). Prior to the Workshop, the FDA delegation visited the MOA’s National Institute for Control of Veterinary Bioproducts & Pharmaceuticals, which conducts animal drug residue testing and drug product testing, in Beijing, China. This facility also houses the country's herbal standards. While in Beijing, the FDA delegation also met and held discussions with the Deputy Director General of the Bureau of Animal Production & Health, MOA, Madame Jin Lan Feng. She is the highest ranking veterinarian in China and oversees all government veterinarians in China. The delegation also held discussions with Dr. Zhongwu Feng, the Director of the Veterinary Drugs and Apparatus Administration Division. The MOA regulates drugs, biologics, and herbal medicines for animals. The main responsibility of the Veterinary Drugs and Apparatus Administration Division is to implement the regulations of the animal drug administration, and to advise and approve animal drug standards, approve new drugs, bioproducts, and feed additive products. The MOA has a close partnership with the Provincial and Municipality Bureaus. The objectives for the Animal Drug cGMP Workshop were to improve drug quality, to promote development of the animal drug industry, to benefit farmers, to improve local human health, and to promote future international trade. After meeting with the MOA representatives in Beijing, the FDA delegation participated in the "Conference on Current Good Manufacturing Practices for the Animal Health Industry" in Suzhou. Mr. Michael Smedley from CVM presented lectures entitled, "Overview of the Current Good Manufacturing Practices in the U.S." and "Center for Veterinary Medicine’s Approach to cGMPs and the Pre-Approval Compliance Program." Mr. Geoffery Wong presented lectures entitled, "Relationship Between Veterinary Drug Master Files and cGMPs" and "Quality of Animal Drug Products in Relation to U.S. Filing Requirements for Chemistry/Manufacturing Changes." Dr. Lonnie Luther presented a lecture entitled "Generic Animal Drug Approval Requirements." Mr. Michael Spangenberg (formerly of ORA) presented a lecture entitled "FDA cGMP Inspections" and he also conducted two mock cGMP inspections.
The animal drug cGMPs are currently being written in China. However, they are not currently being enforced. The Chinese government plans to implement cGMPs for all animal drug facilities within the next five years. Dr. Feng stated that in the future, every animal drug manufacturer should meet cGMPs or their license will be revoked. The conference attendees represented China's animal drug industry, Provincial and Municipality local governments, and National government. In addition to the conference presentations, Investigator Spangenberg organized and conducted two separate mock cGMP inspections for the approximately 100 conference attendees. The mock inspection technique employed was geared towards demonstrating to the conference attendees what acceptable cGMPs might look like, as opposed to finding objectionable conditions within the drug manufacturing operations of the two (2) volunteer firms. The first mock inspection covered finished animal health products: soluble powders and Type A premixes for medicated feeds. Six separate areas of the firm’s drug manufacturing operations were selected for cGMP show-and-tell/demonstration purposes, which included the firm’s microbiological testing laboratory, GC chemical testing laboratory, batch production control records, label storage, raw material inventory identification and control, bulk component raw material storage integrity, in-process product transfer system cleanability, cleaning validation issues, stability, reserve, and sampling issues. The second mock inspection covered active pharmaceutical ingredients for animal health products. Eight separate areas of the firm’s drug manufacturing operations were selected for cGMP demonstration purposes, which included: raw material inventory identification and control, label storage, high performance liquid chromatography chemical testing laboratory, production equipment identification, production in-process control equipment calibrated and traceable to national standards, process water system monitoring, and environmental control systems. Both mock inspections were well received by the conference attendees and generated numerous questions during follow-up question and answer sessions. After the workshop, the FDA delegation toured a fermentation bulk chemical plant, in Zhejiang, China which was run by the Chinese government. This facility produced a number of fermentation products. The delegation also met with representatives from the Shanghai Animal Husbandry Office and visited the Shanghai Municipal Control Institute of Veterinary Drug and Feedstuff, and the Shanghai Animal Husbandry & Veterinary Station. These laboratories conduct animal drug residue testing, drug product testing, and animal diagnostic testing.
On their final day in China, the FDA delegation visited the Shanghai JiaDing Breeding Stock Farm for swine and observed a poultry operation at a government owned farm and processing plant. The breeding farm was established in 1958, and breeding of the Meishan pig started in 1963. There are currently 1300 pigs on the farm. Only 180 are Meishan, with the others being cross breeds. Some breeds were imported to China from Lincoln, Nebraska, and the Meishan swine have been imported to the United States as well. The Meishan pig is very popular in China because of its large litter size and preferred taste to the local population. However, the Meishan pig is approximately 50 percent fat; therefore, it does not promote a healthy diet. One purpose of this breeding farm is to breed a pig with lower fat content, higher litter size, and of quality taste to the local population. The trip provided FDA a better understanding of China's animal drug industry. It also provided the opportunity to develop an excellent working relationship with the Chinese regulatory officials. Hopefully, it also provided the Chinese with a better understanding of FDA's cGMP regulations.
FDA HELPS INDUSTRY PREPARE FOR Y2K
As the millennium approaches, there is growing concern regarding the impact of Y2K issues on the identity, strength, quality, purity, and potency, as well as safety, efficacy, and availability of products regulated by FDA. The animal health and feed industries are not exempt from computer problems at the beginning of the year 2000. Since virtually every organization's systems are composed of various layers of hardware and software that can be compromised by the Y2K problem, all businesses are vulnerable to potential Y2K mishaps. Computer errors may cause the shut-down of vital systems in communication and transportation, in addition to critical infrastructure systems such as power, water, banking, and telecommunications networks. For CVM-regulated products, date coding problems may result in process failures, the production and distribution of adulterated and/or misbranded products, and even product shortages. The FDA recommends that regulated industries take preventive measures to ensure that they have a Y2K effort in place including:
- Completion of any renovation in sufficient time to ensure a period of monitoring and problem resolution prior to when Y2K problems are expected to occur.
- For mission critical systems, review by an independent contractor/auditor to verify the Y2K compliance status of the systems. (For computerized systems regulated by the FDA, assure all changes have been validated and are in compliance with applicable GMPs).
- Development of contingency plans to ensure business processes will continue unabated regardless of impact of Y2K.
FDA intends to raise the awareness of regulated industries to the potential Y2K problems during routine field inspection activities. It is impossible to predict the extent of the Y2K impact on CVM's customers, but steps have been taken to ensure that CVM's internal computer systems are Y2K-ready. The steps taken at CVM began with determination of the Y2K compliance status of our inventory of hardware, system software, and application software. Remedial actions have been taken for identified problems, such as upgrading the BIOS of affected desktop computers and LAN servers, applying software service patches, and upgrading to the Y2K compliant version of system software. Compliance strategy has also taken the form of installing newer, compliant versions of desktop operating systems and office automation software. Another strategy has involved the planned re-development of mission-critical database systems by conversion to applications for the LAN environment with the stipulation of Y2K compliance. In these cases, the database applications were subjected to and passed independent verification of Y2K compliance following a prescribed testing process. Finally, CVM is preparing business process continuity contingency plans for major activities in the event of unanticipated power outages from Y2K-related problems. The Center for Veterinary Medicine (CVM) has identified two major areas that may be vulnerable to potential Y2K computer problems. Those areas are: 1. Sole source suppliers of significant ingredients or finished products. 2. Supplies, especially bulk drug substances, from foreign sources. CVM has appointed a Y2K Working Group to identify possible problems and to develop a Y2K Rapid Response Plan. The Group has mapped out precautionary steps to assure adequate communication in the event of emergency conditions. Teams have been formed to handle both anticipated and unanticipated issues resulting from Y2K computer problems. In addition, the Center has established contacts with other units of FDA, other Federal agencies, State counterparts, industry trade associations, and consumer groups. To provide industries with information and guidance on Y2K issues, FDA has been alerting them in direct correspondence, speeches, public appearances, meetings, workshops, and guidance documents. In order to avert problems before they become public health or regulatory issues, FDA and CVM will continue to work with regulated industries to disseminate and exchange information related to Y2K issues. For more information regarding Y2K, visit the FDA Home Page. For specific Y2K concerns related to animal health, you may contact CVM at 301-594-1736.