GMP WATCH NEWS – A Veteran’s Perspective［3］

Paradigm Shifts in Pharmaceutical Quality Systems A Historical Review and Future Perspectives [Part 3] From QC to the Pharmaceutical Quality System (PQS) When GMP was first introduced in 1963, the “testing” conducted by the QC department played a central role. However, as GMP evolved, there was a dramatic increase in complex tasks beyond testing, such as document control, change control, and deviation management. Consequently, the FDA revised CGMP in 1978, significantly strengthening the authority of the QC department. It clarified the department’s independence from the manufacturing department and its final authority over release decisions, effectively mandating that the QC department also assume the current role of Quality Assurance (QA). Furthermore, in 1987, the ISO 9000 Series (Quality Management Systems) was established, clearly defining the term “Quality Assurance (QA)” and spreading it worldwide. This marked the point at which QC, responsible for testing, and QA, responsible for ensuring the integrity of the entire system, became clearly distinguished. In 2008, ICH Q10 introduced the concept of a “Pharmaceutical Quality System (PQS),” which includes management responsibility. QA was redefined not merely as an on-site monitor, but as a department responsible for quality assurance at the management level. By the way, the term “Quality Unit (QU)” was first used in ICH Q7, “Guideline on Good Manufacturing Practice for Pharmaceutical Active Substances,” published in 2000, where a QU was defined as an organization responsible for both QC and QA. Furthermore, in the FDA guidance document “Quality System Approach” published in 2006, the traditional regulatory term “Quality Control Unit” was replaced with “Quality Unit.” Due to the historical evolution of GMP, department names vary widely: some companies have QA functions within their “QC units,” while others have “QA units” that also perform testing; in smaller factories, a single department may handle everything. Therefore, we have decided...

https://cm-plus.co.jp/en/column/gmp/2026_1023/

Fundamentals of Microbiology [Part 6]

What Are Bacteria 2-1 Bacteria are representative of microorganisms, and the term is widely known, but only few people may explain them clearly. Living organisms are made of cells. Note) Cells are roughly divided into two types. Simply put, they can be called "lower organisms" and "higher organisms", but they are prokaryotic cells without a cell nucleus and eukaryotic cells with intracellular structures such as a cell nucleus or mitochondria. Bacteria are representative of these lower prokaryotic cells. Incidentally, eukaryotic cells are cells of animals, plants, fungi, etc., and are considered higher organisms than prokaryotic cells. Note) All living organisms from microorganisms such as bacteria to humans have cells as their basic unit. However, viruses do not have a cellular structure. This is also a point of debate as to whether viruses are living organisms or not. Bacterial cells are surrounded by a tough cell wall like an eggshell, and there is a cell membrane inside. Bacteria are "single-celled organisms" where each individual consists of one cell and reproduces by binary fission. The size of one cell is about 0.2 to several micrometers (1 μm = 1/1000 mm), and individual cells cannot be seen with the naked eye. Note) Note) Recently, there have been reports that "giant white filamentous bacteria up to 2 cm in size have been discovered", but this is an exception. Generally, the size of bacteria is at most several micrometers, so they cannot be seen with the naked eye. Currently, bacteria are classified based on the base sequence of the 16S rRNA gene. However, historically, they were classified by their morphology and simple biochemical properties. Therefore, the shape and properties of bacteria are still important guidelines for understanding bacteria even today. Bacteria are morphologically divided into cocci, bacilli, and spirilla. Cocci include Staphylococcus or Streptococcus, which...

https://cm-plus.co.jp/en/column/gmp/2026_1019/

GMP WATCH NEWS – A Veteran’s Perspective［2］

Paradigm Shifts in Pharmaceutical Quality Systems A Historical Review and Future Perspectives [Part 2] Implementation of Process Validation The concept of validation has its roots in the space technology developed during the U.S. Apollo program (1960s). Launch rockets are single-use. The concept of sampling inspection—where one might say, “Let’s test-launch it; since it worked, we’ll launch it again”—simply does not apply. Therefore, NASA rigorously applied the principles of reliability engineering—the idea that “if the design and manufacturing processes are flawless, the final product must also be flawless”—and established the prototype for the concept of validation. FDA officials wondered, “Why isn’t the same level of precision in quality assurance found in the rocket industry being applied to the pharmaceutical industry, where human lives are at stake?” and introduced the NASA-derived approach of “building quality into the process” into the world of GMP. It can be said that validation is a technology “adapted from the pharmaceutical world to the quality assurance techniques cultivated in NASA’s Apollo program—an environment where failure was not an option.” Understanding this background should help explain why validation places such a strong emphasis on “documentation” and “advance planning.” The definition of process validation issued in 1987 was “the establishment of evidence that provides a high degree of assurance that a process can consistently produce products that meet specified standards and quality characteristics.” But what does “consistently produce” actually mean? Since the definition provided only a conceptual framework without specifying concrete methods for validating pharmaceutical manufacturing processes, it caused considerable confusion among regulatory authorities and pharmaceutical companies worldwide. The FDA must have been quite troubled by this as well; in 1993, the FDA specifically presented “the successful production of three consecutive batches at actual production scale” as a requirement for completing validation. This became widely recognized within the industry,...

https://cm-plus.co.jp/en/column/gmp/2026_0928/

[Vietnam] CM Plus Group to speak at GMP/EU-GMP WORKSHOP 2026

The ISPE Singapore – VNPCA GMP Workshop is an annual event organized by the ISPE Singapore Affiliate in collaboration with VNPCA, bringing together professionals from the pharmaceutical and life sciences industries to exchange knowledge, insights, and best practices in GMP. This year’s workshop will be held on November 5–6, 2026, in Ho Chi Minh City, Vietnam. CM Plus is pleased to participate as a sponsor and contribute to the workshop with a presentation, sharing our expertise and insights in the pharmaceutical industry. Please see the presentation and workshop details below. Presentation Outline Title  Current C&Q Approach and Introduction to E-Document & GMP Research Systems Key Topics Current C&Q approach in compliance with WHO GMP and PIC/S GMP Annex 15 Contamination Control Strategy (CCS), including microbiological contamination control Speakers Mr. Tahara Shigehiro – Senior GMP Consultant, CM Plus Corporation, Japan Ms. Bui Thi Hong Loan – GMP & Validation Assistant, CM Plus Vietnam Co., Ltd. Date & Time  November 5, 2026 | 10:45–11:15 Venue  Mai House Saigon Hotel 157 Nam Ky Khoi Nghia, Xuan Hoa Ward, Ho Chi Minh City, Vietnam WORKSHOP DETAILS Event Name  ISPE SINGAPORE & VNPCA GMP/EU-GMP WORKSHOP 2026 From Compliance to Proactive Quality Management Program details Date  November 5–6, 2026 Location  Mai House Saigon Hotel 157 Nam Ky Khoi Nghia, Xuan Hoa Ward, Ho Chi Minh City, Vietnam  

https://cm-plus.co.jp/en/news/event/2026_0914/

GMP WATCH NEWS – A Veteran’s Perspective

Paradigm Shifts in Pharmaceutical Quality Systems A Historical Review and Future Perspectives [Part 1] Introduction It has been nearly half a century since I first became involved in pharmaceutical GMP. During that time, GMP has evolved significantly, and unfamiliar GMP-related technical terms—such as “validation” and “qualification”—have been introduced. As GMP has evolved, I feel that the meanings and usage of these terms have shifted subtly. I wrote this article to clarify the meanings of these confusing terms by sharing stories from my own experience with GMP. I hope this helps readers understand that “GMP is not a law, but a science for ensuring quality.” The Birth of GMP I’m sure many of you have felt frightened after seeing news reports of mobile batteries suddenly catching fire inside carry-on luggage on planes or trains. While factors such as the product being subjected to a strong impact could be causes of the fire, I understand that in many cases, the user is not at fault. According to news reports, there is no doubt that changes in manufacturing processes resulting from intense price competition are a contributing factor to these accidents. I am shocked—and even angered—by the fact that companies, which should be responsible for product quality, do not know where the parts were made or how the products were assembled, and by their lack of a proper response. However, even in the Japanese pharmaceutical industry several decades ago, efforts to improve processes with the aim of reducing costs and enhancing quality were encouraged. While process yield and productivity did indeed improve, these changes were not managed in accordance with established rules. As a result, situations arose where it was unclear when, by whom, or how changes had been made. Although manufacturing instructions did exist, they were not updated every time a change...

https://cm-plus.co.jp/en/column/gmp/2026_0825/

PMDA ORANGE LETTER_2026.07

ORANGE LETTER To encourage voluntary quality improvements at pharmaceutical manufacturing sites, Japanese regulatory agency PMDA has been publishing anonymized, highly useful findings from its inspections based on Japanese GMP Ministerial Order. These are published in a format known as the "ORANGE Letter" since 2022. CM Plus provides abridged English translations of the Orange Letters, for our clients' reference. Observed Regulatory Attention/Notification of GMP Elements LETTER Author: PMDA Issue: July 2026 Title: Airflow Visualization Testing (Smoke Testing) in Aseptic Areas Related GMP Ministerial Ordinance Clause: Article 24-3 Cases Defects in product contamination prevention control were observed. In a smoke test conducted in an aseptic area, the site failed to detect the product contamination risk suggested by the test results, and there were omissions in some of the evaluations. Background ♦Regarding the production control of sterile pharmaceuticals, the GMP Ministerial Order stipulates that necessary measures be taken to prevent contamination of starting materials, packaging/labeling materials, and products from contamination, etc. by microorganisms, etc.. ♦PIC/S GMP Guidelines Annex 1 specifies that airflow pattern under all actual operational conditions should be evaluated to confirm that contamination risks from personnel, equipment, etc., are adequately controlled. Observations ♦Upon reviewing the video of a smoke test conducted in the aseptic area of a freeze-dried product line, it was observed that air coming into contact with the operator who is transferring the product to the freeze dryer was flowing into the openings of partially stoppered vials. However, the potential risk of this airflow on product sterility had not been evaluated. Furthermore, smoke tests for certain processes had not been conducted. ♦When reviewing the results of environmental monitoring for the aseptic area of the production line, microorganisms suspected to be derived from operators were found. This suggested the possibility that contamination prevention measures in the aseptic area were not...

https://cm-plus.co.jp/en/column/gmp/2026_0814/

PMDA ORANGE LETTER_2026.06

ORANGE LETTER To encourage voluntary quality improvements at pharmaceutical manufacturing sites, Japanese regulatory agency PMDA has been publishing anonymized, highly useful findings from its inspections based on Japanese GMP Ministerial Order. These are published in a format known as the "ORANGE Letter" since 2022. CM Plus provides abridged English translations of the Orange Letters, for our clients' reference. Observed Regulatory Attention/Notification of GMP Elements LETTER Author: PMDA Issue: June 2026 Title: Management of Expiration Date and Retest Period of API - Preventing Misunderstandings Regarding Retest Related GMP Ministerial Ordinance Clause: Article 3-2, etc. Cases Due to insufficient understanding of the definitions of the expiration date and the retest period APIs, established procedures allowed for the use of APIs even after their expiration date by repeatedly conducting retests on the APIs intended for manufacturing. Background ♦Regarding the storage of APIs, the GMP Ministerial Order requires management under appropriate conditions that do not give impact to quality. ♦For APIs with an "expiration date" specified in the approval document, they can only be used during this valid period and never can be used after their expiration date. On the other hand, for APIs with a specified "retest period", they can be used during the retest period, and even after the retest period has passed, they can be used if they pass a retest immediately prior to use (Refer to GMP Case Studies 1) GMP 21-4). Observations ♦At the manufacturing site, tablets were manufactured using an API with an expiration date specified in the approval document. However, the procedure is specified in a way that allows for the use of API after the expiration date by conducting a retest. ♦Specifically, with the intention of reducing raw material waste and ensuring a stable product supply, the related SOP stipulated: "In principle, APIs that have exceeded...

https://cm-plus.co.jp/en/column/gmp/2026_0803/

Fundamentals of Microbiology [Part 5]

History of Microbiology 2-2 After Pasteur's negation of the theory of spontaneous generation in the mid-19th century, many studies were conducted on the relationship between diseases and microorganisms, deepening the understanding of what we now call infectious diseases. Heinrich Hermann Robert Koch of Germany discovered anthrax bacteria, tuberculosis bacteria, and cholera bacteria. He also established a pure isolation method for bacteria that was not possible before. Koch's postulates, the basic guidelines proposed by Koch to prove the pathogen of an infectious disease, are still used today to prove the causal relationship in infectious diseases. Koch’s Postulates (Quoted from Wikipedia) 1.  The microorganism must be found in abundance in all organisms suffering from the disease but should not be found in healthy organisms. 2.  The microorganism must be isolated from a diseased organism and grown in pure culture. 3.  The cultured microorganism should cause disease when introduced into a healthy, susceptible organism. 4.  The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent. Reference （Koch, Robert. Zur Unterusuchung von pathogenen Organismen. 1881. Mittheilungen aus dem Kaiserlichen Gesundheitsante, Vol.1. 1-48） During this period, Japanese microbiologists also achieved many results. Shibasaburo Kitasato (pure culture of tetanus bacteria in 1889, development of serum therapy in 1890) and his student Kiyoshi Shiga (discovery of dysentery bacteria in 1897) are widely known as prominent microbiologists. Later, at the end of the 19th century, Dmitri Iosifovich Ivanovsky of Russia discovered viruses, revealing the existence of pathogens smaller than bacteria. Entering the 20th century, Alexander Fleming of the United Kingdom discovered penicillin in 1928, and Selman Abraham Waksman of the United States discovered streptomycin in 1946, marking the beginning of the antibiotic era. Subsequently, new antibiotics were discovered one after another, and thanks to the treatment...

https://cm-plus.co.jp/en/column/gmp/2026_0929/

Fundamentals of Microbiology [Part 4]

This article is an updated 2026 version of the popular 50-part Japanese series “Microorganisms, Too Embarrassed to Ask Others About!” (いまさら人には聞けない！微生物のお話), previously published on GMP Platform*. Over the next several installments, I will explore a wide range of topics related to microorganisms, from the fundamentals to more in-depth insights that are not widely known even among professionals in the field. Previously... -  Fundamentals of Microbiology [Part 3]   History of Microbiology 2-1 Microorganisms existed long before the appearance of humans, as well as many ancient organisms we know such as dinosaurs and trilobites on Earth. Some dinosaur fossils show clear traces of having suffered from infectious diseases. Our ancestors, primitive humans, would have also known phenomena caused by microorganisms such as disease and spoilage through experience. Alcohol is said to have been known since thousands of years BCE. However, at that time, since individual microorganisms were invisible to the naked eye, they could not be recognized that these were due to the activities of living organisms like humans. It is said that Antonie van Leeuwenhoek of the Netherlands was the first to observe individual microorganisms as separate living beings. In 1674, he observed lake water and dental plaque using a hand-made microscope and is said to have observed and recorded microorganisms for the first time in history. The magnification of the microscope he used at that time is said to be about 260 times, and this magnification is a bit harsh for observing bacteria. He may have had better eyesight than most people.   Figure-1 3d illustration of Leeuwenhoek's Microscope With the invention of the microscope, it became known that there are small "things" invisible to the human eye in nature. But at that time, it was only that rare things could be seen, and it was not recognized that...

https://cm-plus.co.jp/en/column/gmp/2026_0907/

Fundamentals of Microbiology [Part 3]

This article is an updated 2026 version of the popular 50-part Japanese series “Microorganisms, Too Embarrassed to Ask Others About!” (いまさら人には聞けない！微生物のお話), previously published on GMP Platform*. Over the next several installments, I will explore a wide range of topics related to microorganisms, from the fundamentals to more in-depth insights that are not widely known even among professionals in the field. Previously... -  Fundamentals of Microbiology [Part 2]   Properties of Microorganisms Microorganisms play an extremely important role in decomposing substances in the Earth's environment. If microorganisms did not exist and substance decomposition did not occur, we should be able to see fresh dinosaur corpses. In addition, microorganisms can not only decompose things but also produce other substances. Thanks to this, we can enjoy delicious wine and cheese. On the other hand, some microorganisms are pathogenic. Pathogenic microorganisms (pathogens) infect various animals and plants including humans and cause diseases. This is an infectious disease. And it is also microorganisms that produce antibiotics often used as therapeutic agents for bacterial infections. In this way, microorganisms have both positive and negative aspects for us humans. While we can live a prosperous life by making good use of the properties of microorganisms, we may also suffer great damage from the harm caused by microorganisms. We often hear the question "Are microorganisms our enemies or friends?" But as can be seen from the above examples, it is impossible to unilaterally argue whether they are enemies or friends. However, in the world of medical devices and pharmaceuticals, microorganisms are basically "enemies". Of course, there are many pharmaceutical active ingredients produced using microbial fermentation, so they may be considered friends. But even in that case, microorganisms other than the target bacterial species should not exist and are enemies. Author Tatsuo Furuya Senior Consultant, GMP Platform, CM Plus...

https://cm-plus.co.jp/en/column/gmp/2026_0818/