A comparison between CSV Guideline / regulations in Japan, India and China

CSV guideline in Japan

Although GxP regulations and rules are established on a regional and national basis, on the other hand, regulations and guidelines for CSV are mostly issued by regulatory authorities.

In Japan, “Guideline for proper management of computerized systems in pharmaceutical and quasi-drug manufacturers” was issued by the Ministry of Health, Labour and Welfare in 2010, and started enforcement on April 1, 2012.

By then, the “Guideline for Proper Management of Computer-Used Pharmaceuticals Manufacturing Plants” was published in 1992, but it was abolished in 2005. The current guideline was a revised version of the guideline in 1992, and have been aligned to be consistent with global standards such as GAMP5 and other guidelines like EU Annex 11 and US 21 CFR Part 11. After soliciting public comments, the official version was published reflecting the contents.

About the guideline:
Scope – Systems that carry out the works of the GQP Ministerial Ordinance and the GMP Ministerial Ordinance.
Categorization – based on the same concept as GAMP5, and proposes a mechanism for categorizing software and verifying simple software easily and complex software intricately.

Requirements – major 3 are as follows:

• Establishment of own “Computerized System Management Rules”
• Implementation of each computerized system in accordance with own “Computerized System Management Rules”
• Maintaining and recording of each computerized system operations and changes

CSV regulation in India

Historical background:
Schedule M (Good Manufacturing Practices and Requirements of Premises, Plant and Equipment for Pharmaceuticals Products) is a part of Drug and Cosmetic act 1940. The quality objectives can be achieved by GMP and hence they were implemented as “Schedule M” in 1988. The Schedule M has again been amended in a major way by drugs and cosmetics act (8th amendment) rule, 2001.
CDSCO (Central Drugs Standard Control Organization), Department of Health and Family Welfare had issued a draft notification in October 2018 seeking to revise and upgrade Schedule M.

About the Guideline:
It is GMP for pharmaceuticals that should be followed by pharmaceutical manufacturing units in India. It is a part of Quality Assurance which ensures that the products are consistently manufactured and controlled to the quality standards appropriate to their intended use.
At present, while majority of small and medium drug manufacturers in India comply with Schedule M, only around 20% of the firms meet WHO-GMP norms, leading to dual standards of quality.

Requirements of Schedule M:

• Wherever documentation is handled by electronic data processing methods, authorized persons shall enter modify data in the computer. There shall be record of changed and deletions. Access shall be restricted by “passwords” or other means and the result of entry of critical data shall be independently checked.
• Batch records electronically stored shall be protected by a suitable back-up. During the period of retention, all relevant data shall be readily available.
• Computerized systems should be validated.

CSV regulation in China

To summarize the evolve process of computerized system related regulations in China, NMPA has issued the “GMP Annex-Computerized System” in May 2015, which describes detailed requirements for the construction, validation, maintenance and use of computerized systems in scope of pharmaceutical manufacturers. In 2017, the “Good Non-clinical laboratory Practice” added sections of computerized system validation and electronic data during revision. The “Management for Drug Records and Data (Trial)” has been issued in December 2020 which contains further requirements for the creation, use, and maintenance of electronic data as well as computerized systems.

Meanwhile, like “Good Clinical Practice of Pharmaceutical Products” and “Good Vigilance Practice of Pharmaceutical Products “, these important regulations have involved general requirements for information system validation and management at the time of being issued.
In China, most CSV projects adopt GAMP5 approach (Guideline from ISPE, not a regulation) to address regulations and manage the lifecycle of a computerized system, which usually includes four phases:

• Concept Phase (preliminary business analysis, preliminary risk assessment, supplier selection, supplier audit, etc.);
• Project Phase (System construction, Demo and validation);
• Operation and Maintenance phase;
• Decommission (when a new system replaces the old, or when the business is obsoleted, here comes the decommissioning phase)

According to regulations, changes in the system lifecycle should be managed by corresponding change procedures. During operation and maintenance, it is mandatory to monitor the performance status of the system and define a good way to collect system incidents and solve the problems. During any upgrade or decommissioning, it must guarantee that the all system data can be accessed and traced within the specified retention period.

Conclusions

The following table is a brief summary of this article:

Their quality measurement is based on GAMP. GAMP stands for Good Automated Manufacturing Practice. GAMP guidance aims to achieve computerized systems that are fit for intended use and meet current regulatory requirements, by building upon existing industry good practice in an efficient and effective manner. GAMP5 is in reference to a guidance document entitled [GAMP5: A Risk-Based Approach to Compliant GxP Computerized Systems], which was published by the International Society for Pharmaceutical Engineering (ISPE) based on input from pharmaceutical industry professionals.

Although the strategies defined in the document are not regulations, but guidelines, the framework outlined in it provides a comprehensive approach to computerized system validation that is generally accepted within the pharmaceutical industry. Moreover, the risk-based approach advocated is in line with the application of the European EMA and US FDA regulations governing computerized system validation, EU GMP Annex 11 and 21 CFR Part 11 to ensure world-class quality, efficacy and safety for drugs.