{"id":6337,"date":"2026-08-03T11:00:54","date_gmt":"2026-08-03T02:00:54","guid":{"rendered":"https:\/\/cm-plus.co.jp\/en\/?post_type=column&p=6337"},"modified":"2026-08-15T17:08:57","modified_gmt":"2026-08-15T08:08:57","slug":"2026_0803","status":"publish","type":"column","link":"https:\/\/cm-plus.co.jp\/en\/column\/gmp\/2026_0803\/","title":{"rendered":"PMDA ORANGE LETTER_2026.06"},"content":{"rendered":"

ORANGE LETTER<\/strong><\/span><\/p>\n

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.<\/p>\n

CM Plus provides abridged English translations of the Orange Letters, for our clients’ reference.<\/p>\n

\n


\nObserved Regulatory Attention\/Notification of GMP Elements LETTER<\/span><\/p>\n

Author: <\/strong>PMDA
\nIssue: <\/strong>June 2026
\nTitle: <\/strong>Management of Expiration Date and Retest Period of API – Preventing Misunderstandings Regarding Retest
\nRelated GMP Ministerial Ordinance Clause:<\/strong> Article 3-2, etc.<\/p>\n

Cases<\/strong><\/p>\n

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.<\/p>\n

Background<\/strong><\/p>\n

\n

\u2666Regarding the storage of APIs, the GMP Ministerial Order requires management under appropriate conditions that do not give impact to quality.<\/p>\n

\u2666For 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).<\/p>\n<\/div>\n

Observations<\/strong><\/p>\n

\n

\u2666At 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.<\/p>\n

\u2666Specifically, with the intention of reducing raw material waste and ensuring a stable product supply, the related SOP stipulated: “In principle, APIs that have exceeded their expiration date cannot be used. However, based on data supporting stability, they may be used for limited batches.”<\/p>\n<\/div>\n

Problems and Risks<\/strong><\/p>\n

\n

\u2666Although the concepts regarding management and usability differ between APIs with specified expiration dates and those with specified retest periods, this manufacturing site established operational procedures at its own discretion that could allow for the use of APIs even after the expiration date.<\/p>\n

\u2666The manufacturing site did not correctly understand the definitions of expiration date and retest period. Under such conditions, there is a risk that products with insufficient quality assurance could be distributed, and discrepancies with approved matters could potentially violate Article 3-2 of the GMP Ministerial Order.<\/p>\n<\/div>\n

Subsequential Actions<\/strong><\/p>\n

\n

\u2666Considering the consistency with the approved matters, the sentences starting with “In principle…” and “However…” in the procedure were deleted. This clarified that APIs that have passed their expiration date cannot be used.<\/p>\n<\/div>\n

Check Points<\/strong><\/p>\n

\n

\u2666Can you explain the respective definitions of the expiration date and retest period, as well as the handling of APIs after the retest period has passed?<\/p>\n

\u2666For raw materials other than APIs, are you strictly complying with the approved matters and using them within the defined range based on data?<\/p>\n

\u2666Are you fully aware that operations lacking objective grounds or ambiguous expressions in procedures pose a risk of causing inconsistencies with approved matters?<\/p>\n<\/div>\n

Catchword
\nRetesting is not a means to use expired APIs!\u00a0<\/strong><\/p>\n

\n

\u2713 Both the expiration date and the retest period are “approved matters” set based on scientific evidence to ensure the quality of the API, and they cannot be changed at the discretion of the manufacturing site. Since misunderstandings like this case are still frequently observed both at domestic manufacturing sites and overseas ones in recent years, we request that the definitions of expiration dates and retest periods, as well as their differences, be reconfirmed and thoroughly disseminated within manufacturing sites.<\/p>\n

\u2713 Including manufacturing sites other than formulation plants, please re-check whether the descriptions in your procedures are consistent with regulatory terms and concepts and ensure that “provisos” or “exception rules” are not inadvertently permitting inappropriate operations as a result.<\/p>\n

Source: PMDA, “ORANGE Letter” (Issue: June 2026)\u00a0 \u00a0 https:\/\/www.pmda.go.jp\/files\/000281160.pdf<\/a><\/p>\n<\/div>\n

\n

About GMP Platform<\/strong> (<\/span>https:\/\/www.gmp-platform.com\/<\/a><\/span>)<\/span><\/p>\n

\n
\"\"<\/div>\n
GMP Platform is a free GMP-related information portal established in 2012 and operated by CM Plus Corporation. Built on CM Plus\u2019s founding principle of addressing quality-related issues in life science facilities, the site provides practical, expert-led information for life science manufacturing professionals. With more than 26,000 registered users, GMP Platform introduces the latest GMP-related regulations and trends in Japan, the United States, Europe, and other regions, along with translated and explanatory articles on guidelines, technical articles, seminars, e-learning programs, and books. It is widely used by professionals involved in GMP compliance, quality assurance, and the development of effective quality systems. Please use Google Translate or similar translation tools to read more articles originally published in Japanese.
\n*If you are using Google Chrome, right-click and select “Google Translate” on the article.<\/div>\n<\/div>\n","protected":false},"featured_media":6370,"template":"","columncat":[61],"columntag":[],"keywords":[11],"acf":[],"yoast_head":"\nPMDA ORANGE LETTER_2026.06\uff5cCM Plus<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/cm-plus.co.jp\/en\/column\/gmp\/2026_0803\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"PMDA ORANGE LETTER_2026.06\uff5cCM Plus\" \/>\n<meta property=\"og:description\" content=\"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. 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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, […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/cm-plus.co.jp\/en\/column\/gmp\/2026_0803\/\" \/>\n<meta property=\"og:site_name\" content=\"CM Plus\" \/>\n<meta property=\"article:modified_time\" content=\"2026-08-15T08:08:57+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/cm-plus.co.jp\/en\/wp-content\/uploads\/2024\/05\/ogp.png\" \/>\n\t<meta property=\"og:image:width\" content=\"928\" \/>\n\t<meta property=\"og:image:height\" content=\"485\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"4 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/cm-plus.co.jp\/en\/column\/gmp\/2026_0803\/\",\"url\":\"https:\/\/cm-plus.co.jp\/en\/column\/gmp\/2026_0803\/\",\"name\":\"PMDA ORANGE LETTER_2026.06 | CM Plus\",\"isPartOf\":{\"@id\":\"https:\/\/cm-plus.co.jp\/en\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\/\/cm-plus.co.jp\/en\/column\/gmp\/2026_0803\/#primaryimage\"},\"image\":{\"@id\":\"https:\/\/cm-plus.co.jp\/en\/column\/gmp\/2026_0803\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/cm-plus.co.jp\/en\/wp-content\/uploads\/2026\/08\/GMPP_cat_EN_other2.jpg\",\"datePublished\":\"2026-08-03T02:00:54+00:00\",\"dateModified\":\"2026-08-15T08:08:57+00:00\",\"breadcrumb\":{\"@id\":\"https:\/\/cm-plus.co.jp\/en\/column\/gmp\/2026_0803\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/cm-plus.co.jp\/en\/column\/gmp\/2026_0803\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\/\/cm-plus.co.jp\/en\/column\/gmp\/2026_0803\/#primaryimage\",\"url\":\"https:\/\/cm-plus.co.jp\/en\/wp-content\/uploads\/2026\/08\/GMPP_cat_EN_other2.jpg\",\"contentUrl\":\"https:\/\/cm-plus.co.jp\/en\/wp-content\/uploads\/2026\/08\/GMPP_cat_EN_other2.jpg\",\"width\":928,\"height\":485},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\/\/cm-plus.co.jp\/en\/column\/gmp\/2026_0803\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"\u30db\u30fc\u30e0\",\"item\":\"https:\/\/cm-plus.co.jp\/en\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Column\",\"item\":\"https:\/\/cm-plus.co.jp\/en\/column\/\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"PMDA ORANGE LETTER_2026.06\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\/\/cm-plus.co.jp\/en\/#website\",\"url\":\"https:\/\/cm-plus.co.jp\/en\/\",\"name\":\"CM Plus\",\"description\":\"Your Partner in Facility Construction, Quality Assurance, and GMP Education\/Training\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\/\/cm-plus.co.jp\/en\/?s={search_term_string}\"},\"query-input\":\"required name=search_term_string\"}],\"inLanguage\":\"en-US\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"PMDA ORANGE LETTER_2026.06\uff5cCM Plus","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/cm-plus.co.jp\/en\/column\/gmp\/2026_0803\/","og_locale":"en_US","og_type":"article","og_title":"PMDA ORANGE LETTER_2026.06\uff5cCM Plus","og_description":"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. 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