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 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/

Fundamentals of Microbiology [Part 2]

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 1]   We Live Surrounded by Microorganisms Individual microorganisms are very small and cannot be seen with the naked eye, so we rarely are aware of their existence in daily life. However, unless in a highly controlled environment, microorganisms should be considered to exist everywhere around us. In the air, water, sea, soil, on office desks, on the surface of the skin and mucous membranes, and even in the deep sea, stratosphere, desert sand... Microorganisms exist in almost all conceivable environments.As in the recent news that a large number of microorganisms found in meters underground, microorganisms can exist in places where ordinary animals and plants cannot survive. It is said that there are 1030 bacteria living on Earth, far more than the number of stars in the entire universe, and their weight (in terms of carbon content) is equivalent to the total of all plants on Earth. (https://yusukeokazaki.weebly.com/basic_info.html) It is also said that there are more than 100 trillion microorganisms (mainly bacteria) in our bodies. This is far more than the number of cells (about 37 trillion) that make up the human body. (Source: Hygienic Microbiology Research Center website) Despite this surprising number, these microorganisms are not evenly distributed throughout the body. Microorganisms mainly exist on the body surface and in the digestive tract including the oral cavity. It is said that there are thousands to tens of thousands of microorganisms per 1 cm²...

https://cm-plus.co.jp/en/column/gmp/2026_0804/

Fundamentals of Microbiology [Part 1]

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.   Microorganisms: The Basics of Basics The Earth was born approximately 4.6 billion years ago, and primitive life is said to have appeared about 600 million years after the Earth's birth, that is, about 4 billion years ago. Early life was by no means complex; it is thought to have been single-celled organisms, i.e., microorganisms, that could withstand the severe environment of that time. There are various theories, but humans appeared on Earth several hundred-thousands of years ago. In other words, as living beings on Earth, microorganisms are the senior of humans. Today, the existence of invisible tiny organisms called microorganisms is well understood. It is also well known that they may cause diseases, spoil foods, or produce useful substances through a process called fermentation. Such phenomenon caused by microorganisms has been well known since ancient times. Diseases caused by microorganisms, i.e., infectious diseases, have existed since before the birth of humans, and our ancestors would have experienced battles against such infectious diseases. It is self-evident that food spoils if left unattended, and various processing technologies such as drying and salting have been developed to prevent this spoilage. Alcohol and vinegar are also produced by microbial fermentation, and it is said that they have been known for thousands of years. These have been empirically recognized and passed down, but human beings did not recognize the fact that these phenomena are caused by tiny lives, i.e. microorganisms, until mid-1800s. And microbiology...

https://cm-plus.co.jp/en/column/gmp/2026_0610/

[Indonesia] Seminar – Strategic Synergy Between Pharmaceutical Industry Strategy, Regulatory Compliance, and Engineering Excellence for Global Quality and Competitiveness

PT. CMPLUS Consulting Indonesia, will hold a Seminar in Semarang, Central Java with the theme “Strategic Synergy Between Pharmaceutical Industry Strategy, Regulatory Compliance, and Engineering Excellence for Global Quality and Competitiveness” on Thursday, February 12, 2026, at Amarta Ballroom, Grand Candi Hotel, Semarang, Central Java. There will be three (3) sessions and one (1) special session, namely: “Strategic Industry Trends & Local Compliance,” “Project Management for Renovation Project,” “Risk-Based Cleanroom Management & Contamination Control Strategy (CSS),” and “Sustainability: Carbon Neutral.”   Flyer & Agenda 　 　 Please download the brochure for more detailed information. > Download Event Outline Title Strategic Synergy Between Pharmaceutical Industry Strategy, Regulatory Compliance, and Engineering Excellence for Global Quality and Competitiveness Program ·Opening speech Dra. Rustyawati, Mkes, Apt (Mrs) Head of BBPOM Semarang ・Session 1 : Strategic Industry Trends Local Compliance (From Compliance to Competitive Advantage: Strategic Industry Trends and Local Regulatory Readiness) Matheus Kristianto (Mr.) GMP Advisor, PT. CMPlus Consulting Indonesia. ・Session 2: Project Management for Renovation Project Yasuyuki Suga (Mr.) CMPlus Japan ・Session 3: Risk-Based Cleanroom Management & Contamination Control Strategy (CSS) Under BPOM CPOB 2024-2025: From Compliance to Productivity Gains. Ariyono W. Ardi, Apt. MM (Mr.) Associate GMP Expert, PT. CMPlus Consulting Indonesia. ・Special Session: Carbon Neutral Yoshiyuki Inoue (Mr.) PT. CMPlus Consulting Indonesia. Date and Time Thursday, February 12, 2026, 8:30 AM – 2:00 PM Venue AMARTA Ballroom, Grand Candi Hotel, Semarang > Google Map Entry Fee Free Registration Link Registration Form , Deadline for registration is February 5  

https://cm-plus.co.jp/en/news/event/2026_0122/

CM Plus group to speak at ISPE Indonesia Annual Conference 2025

ISPE Indonesia Annual Conference is the annual conference held by ISPE Indonesia Affiliate. This year, it is scheduled on 21, 22 May, 2025, in Jakarta, Indonesia. CM Plus, with PT.CMPLUS CONSULTING INDONESIA, will sponsor as platinum sponsor and make presentation. More information will follow. Here are the details. Presentation Outline Track - Title Project Management of Renovation Projects Table of contents 1. Purpose of Renovation Work 2. Project Management of Renovation Work 3. How to design in order to make Renovation Work easily 4. How to deliver C&Q for Renovation Work 5. Short Introduction of CM Plus Group Presenters Yasuyuki Suga (Mr.) General Manager of CM Plus Corporation (Japan) Director of ISPE Japan Affiliate Leader of Engineering COP in ISPE Japan Affiliate Date and Time Wednesday 21th May, 2025 xx:xx – xx:xx Venue - Conference Outline Title ISPE Indonesia Annual Conference 2025 Date 21-22 May, 2025 Venue Aston Kartika Hotel & Conference Center, Jakarta, Indonesia

https://cm-plus.co.jp/en/news/event/2025_0417/

Pharmaceuticals and Medical Devices

Home/ Services/ Engineering, Project Management/ Sectors/ Pharmaceuticals and Medical Devices SectorsPharmaceuticals and Medical Devices CM Plus responds to clients’ needs with top-level expertise and technical capabilities in the construction of production facilities in the fields of pharmaceuticals, medical devices, and more. From sterile pharmaceuticals to active pharmaceutical ingredients, regenerative medicine, and medical devices, we have been meeting numerous needs since our founding, from the business planning stage to basic design, construction, and IQ/OQ phases.We flexibly respond to client situations, not only for new construction, but also for expansion, relocation, partial renovations, and technology transfer. Sector Details Our services range from pharmaceuticals (sterile pharmaceuticals, oral drugs, active pharmaceutical ingredients, vaccines, biopharmaceuticals, investigational drugs, and diagnostics) to medical devices, regenerative medicine, and cell therapy.We also provide a wide range of services from R&D facilities to clinical trials, pilot plants, and commercial production. Sterile Pharmaceuticals Oral Drugs Medium-Molecule API Large-Molecule (Biopharmaceutical) API Regenerative Medicine (Consultation Service) Features The pharmaceutical and medical device sectors deal with products that directly impact human health, thus requiring stricter quality control than other products. The characteristics of manufacturing facilities include: Compliance with GMP is required (PIC/S, cGMP, EU-GMP, and GMPs of various countries). Advanced environmental control (cleanliness management, temperature and humidity management, room pressure management, pharmaceutical water management, etc.) is necessary. Advanced hazard management (chemical hazards, biohazards), management of hazardous materials, and management of poisons/narcotics may be required. Since the production equipment and the building/architectural facilities need to function as a cohesive unit, complex integrations between them arise. Proper commissioning and qualification (C&Q) based on accurate risk analysis are required. Keys to Success How to Ensure the Success of Construction Projects in the Pharmaceutical and Medical Device Sectors: From the early planning stages, proceed while consciously including GMP compliance and validation at each step by confirming specifications accurately....

https://cm-plus.co.jp/en/service/engineering/field/pharma_medical-device/

Sterile Pharmaceutical Manufacturing Facility

Home/ Services/ Engineering, Project Management/ Sectors/ Pharmaceuticals and Medical Devices/ Sterile Pharmaceutical Manufacturing Facility Pharmaceuticals and Medical DevicesSterile Pharmaceutical Manufacturing Facility About Sterile Pharmaceuticals Sterile pharmaceuticals include injectable drugs administered by injection, dialysis agents administered through dialysis, and eye drops administered to the eye. Direct containers in contact with the drug have functions to maintain the quality of the drug and to ensure user convenience. These containers include ampoules, vials, cartridges, infusion bags, pre-filled syringes (PFS), blow-fill-seal (BFS), form-fill-seal (FFS), and plastic containers. Sterile pharmaceuticals are manufactured using either terminal sterilization methods or aseptic processing methods to ensure sterility. When handling various containers such as vials and syringes, the supply form of direct containers called NEST, where pre-washed and sterilized direct containers are set in dedicated cases, is sometimes used. In such cases, devices like filling machines are also dedicated to NEST, but they feature easy container switching. Filled products are packed in single or multiple layers of films or paper, labeled with legally mandated information (such as lot numbers, expiration dates, and GS1 barcodes), and maintain the quality of the product during transportation and prevent errors and ensure convenience during use. Example of a Sterile Pharmaceutical Manufacturing Process The following diagram illustrates the process flow of a vial product using the aseptic method as an example of a sterile pharmaceutical. Example of Process Flow Diagram:Vial Product Using Aseptic Method   Weighing of raw materials, preparation and processes from washing of containers filling/stoppering/sealing, these processes are conducted in a clean room controlled for appropriate particle count, temperature, and humidity to prevent microbial and foreign matter contamination. Particularly, the filling and stoppering processes are performed in grade A cleanliness environments, classified as critical areas. Vials are depyrogenized through a dry heat sterilization tunnel, while rubber stoppers are washed and sterilized using...

https://cm-plus.co.jp/en/service/engineering/field/pharma_medical-device/sterile_medicine/