In the international pharmaceuticals industry, Good Manufacturing Practice (GMP) compliance is a fundamental foundation for the safety, quality, and efficacy of drugs. With expanding supply chains and more complex global partnerships, knowledge of the quality compliance environments of leading Asian pharmaceutical markets is a prerequisite. China, Japan, and Korea are particularly noteworthy drug markets, not only due to the size of their markets and enhanced R&D capacities, but also because of the alignment of their GMP systems with global standards.

China: Bridging Domestic Standards with Global Expectations

China’s path to a modern GMP program began in 1998 – far behind the time when similar frameworks were introduced in America and Europe. The Chinese government has since again and again sought quality advancements. The fourth revision of the Chinese GMP law went into effect in March 2011, the most significant change in the country’s strategy. This edition, which has 14 chapters and over 300 articles, relocated the country’s regulatory focus from “quality by test” to “quality by design,” in keeping with ICH Q8 and Q9 guidelines.

Inspection framework

China’s entry into the International Council for Harmonisation (ICH) in 2017 was a turning point, as the nation demonstrated it was capable of bringing its drug regulation up to international standards. Still, regardless of improvement, questions remain whether Chinese GMP practices are always equal to those of the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA).

The NMPA conducts thorough inspections to ensure that drug manufacturers are compliant with GMP standards. These inspections are essential for maintaining drug quality, safety, and efficacy.

Facility and Equipment: Inspectors evaluate the manufacturing plant and equipment design, maintenance, and sanitation. The layout must be designed to prevent cross-contamination, and equipment should be calibrated and properly maintained to consistently yield high-quality drug products.

Documentation and Records: Detailed examination of manufacturing records, quality control records, and standard operating procedures is done to review compliance with GMP. Complete and accurate records are a requirement for traceability and accountability during the manufacturing process.

Quality Management Systems: The effectiveness of the manufacturer’s quality assurance and quality control systems is evaluated. This includes assessing personnel qualifications, training programs, and the implementation of quality risk management practices.

Product Testing: Inspectors verify that in-process and finished product testing procedures are in place and effectively implemented. This ensures that products meet established specifications before release.

Recent trend

In spite of continued geopolitical tensions, Western pharmaceutical firms are still highly dependent on China for active pharmaceutical ingredients (APIs), excipients, and finished drug products. For such collaborations to be successful, GMP compliance in China needs to improve to better meet the stringent standards of Western regulatory agencies.

A report published in 2023 by Frontiers in Public Health, a journal based in Switzerland, provided some insight into China’s pharmaceutical manufacturing industry’s vulnerabilities and strengths. The research identified that foreign-funded and private businesses in China have more stringent GMP requirements than state-owned domestic Chinese enterprises. The report also identified that privately financed companies are more likely to be in better GMP compliance compared to those funded by state-subsidized bank loans. A further important finding was that higher fixed asset firms – generally a proxy for more established facilities – are more likely to be compliant with GMPs.

While some Chinese drug makers are now Western GMP compliant and confidently supplying regulated markets, others are behind. Yet more and more major Western pharmaceutical companies are opting to in-license Chinese pharmaceuticals, particularly those manufacturers that build GMP credibility. International GMP compliance for Chinese pharma manufacturers not only means a regulatory requirement but also a strategic imperative to enter global markets.

Japan: A Model of Regulatory Precision and International Harmonization

Japan has historically been known for its conservative and well-established drug quality system. Regulated by the Pharmaceuticals and Medical Devices Agency (PMDA) within the Ministry of Health, Labour and Welfare (MHLW), Japan’s GMP system is one of the world’s strongest. Foreign producers must comply with Japan’s GMP standards in order to obtain and maintain marketing authorization in Japan.

Japan’s GMP system is founded upon the “Ministerial Ordinance on Standards for Manufacturing Control and Quality Control for Drugs and Quasi-drugs” (Ordinance No. 179 of 2004). The ordinance requires compliance not only in domestic facilities but also in foreign facilities that export drugs or drug components to Japan.

Inspection Framework

There are two types of inspections: application-based inspections and non-application-based (risk-based) inspections.

Application-Based Inspections are triggered by:

New Drug Applications (NDAs): An application for marketing authorization of a new drug is submitted
Partial Change Applications: amendments to manufacturing information that is already approved
Post-Approval Change Management Protocol (PACMP): PACMP permits pre-approved post-market changes, and inspections are for verification of proper implementation
Periodic Inspections: Required every five years after approval to ensure continued compliance.
Product Category-Based Inspections: A new system that was introduced in 2021, enabling manufacturers to obtain three-year GMP certificates for some product categories. The certificates can exempt plants from future routine checks

Non-Application-Based Inspections include:

Routine Risk-Based Inspections: Depending on the risk level of the product, past compliance issues, and process complexity
For-Cause Inspections: In response to product recalls, complaints, or adverse event findings.

Notably, there are exemptions. For instance, factories with existing valid product-category GMP certificates that have not had previous problems are exempt from a repeat inspection. Likewise, third-party testing labs can be exempted if a successful audit was conducted in the recent past, or verifiable GMP records can be produced.

Emphasis on International Harmonization

Japan’s emerging GMP regulations, such as PACMP and product-category inspection systems, show robust international convergence. Japan is lowering regulatory obstacles to compliant manufacturers by embracing Mutual Recognition Agreements (MRAs) and Memorandums of Understanding (MOUs) with other regulatory authorities.

The Japanese acceptance of foreign GMP certificates and documentation, when necessary, is a sign that Japan is attempting to balance rigorous monitoring with global efficiency. This is achieved by permitting manufacturers to bypass redundant inspections while Japan’s high standards of quality and safety are still maintained.

Korea: Rising Pharmaceutical Power with Progressive GMP Evolution

Today, Korea is the world’s 10th largest market for pharmaceuticals – a meteoric rise driven by support from the government and rising innovation by Korean drug companies. Korean drugmakers used to be famous solely for making generics. Today, they produce new chemical entities (NCEs) and biopharmaceuticals. Korea’s GMP system, in turn, has improved in terms of both size and depth.

The Korean Ministry of Food and Drug Safety (MFDS), formerly known as the Korean FDA, is responsible for implementing Korea’s GMP policies. The country initially published its GMP guidelines in 1994 and later repeatedly issued important updates:

2002: Mandatory introduction of GMP requirements for APIs
2008: Introduction of pre-approval GMP inspections as well as enhanced standards on validation, qualification, and testing of product quality
2014–2015: Issuance of ordinances to harmonize Korean GMP standards with the Pharmaceutical Inspection Co-operation Scheme (PIC/S)
2016: Korean membership in ICH, enabling greater regulatory harmonization

Inspection Framework

There are two types of inspections:

Pre-Approval Inspections: Conducted before an API or drug is marketed
Post-Approval Surveillance: Usually conducted every three years to ensure ongoing compliance.

Depending on prior inspection outcomes and the risk level, these audits are either conducted on-site or via paper-based reviews. However, for new manufacturing processes or complex products, on-site audits remain the norm.

MFDS inspectors review various documentation during audits, including:

Facility plans and schematics
Cleanroom zoning and manufacturing process documentation
Batch production and quality control reports
Deviation handling logs and validation data

Korea has also made efforts to enhance regulatory transparency. In 2020, the MFDS published three significant guidance documents:

GMP Improvement Guide for Medicinal Products
FAQ on Medicinal Products, Quasi-Drugs, and Cosmetics
User Manual on the Official Communication Channel for Review and Approval

These publications outline critical information to domestic and foreign manufacturers and help them navigate Korea’s evolving GMP landscape.

Conclusion: Towards Convergence and Global Confidence

Japan is the standard of vigorous regulation and international harmonization, and Korea is an example of rapid development and regulatory transparency. China, whose global pharmaceutical activity is greatly expanding, is increasingly turning to international alignment of GMP standards, even though differences persist.

To drug companies around the globe, it is crucial to get to know each of these systems in detail – not only for regulatory compliance, but for success within the market. With these three Asian giants continuing to streamline their GMP systems and increasingly expanding mutual recognition with international counterparts, the future holds great promise for more harmonized, streamlined, and quality-oriented drug manufacturing.

Written by: Ames Gross – President and Founder, Pacific Bridge Medical (PBM)

Mr. Gross founded PBM in 1988 and has helped hundreds of medical companies with regulatory and business development issues in Asia. He is recognized nationally and internationally as a leader in the Asian medical markets. Mr. Gross has a BA degree, Phi Beta Kappa, from the University of Pennsylvania and an MBA from Columbia University.