ANNEX 11改定版の考察

EU薬事規則はVolume 1からVolume 9まであります。
その中でVolume 4がGMPです。
このGMPには、付属資料がありAnnexと呼ばれています。
その第11章であるAnnex11は、コンピューター化システム（Computerised Systems）です。
現行のAnnex 11は「原則」「要員」「バリデーション」「システム」の4つの枠組みからできていますが、たったの2ページであり、概念的なもので具体性には乏しいようです。
Annex 11の改定版のドラフトが2008年2月にGMP/GDP InspectorsWorking Group（IWG）によって承認され、2008年4月にパブリックコメント（public consultation）募集用に発表されました。
改定版のドラフトは9ページあり、規制要件としては、限界まで具体的なものにしたと思われます。。
2008年10月31日までパブリックコメントを募集しています。
改定版はPrincipleと19の章からできています。
特に注目すべきは、第13章「Printouts」です。
「記録の印刷は、オリジナルの入力からデータに変更があったかどうかを示すものでなければならない。
複雑なシステムの場合、査察官がオンラインでシステムの電子記録（例えば、データベース、クロマトグラフィ、プロセスコントロール等）にアクセスし、調査できることが必要となるかもしれない。」とあります。
これは、規制当局は紙媒体よりも電子で査察を行うことを示唆しています。
米国ではPart11発効後に、Typewriter Excuseという言葉が生まれました。
Part11査察を受けた製薬企業の主張は以下のようなものでした。
「真の記録は紙の記録である。我々はコンピュータを単に記録を作成するために使っているに過ぎない。」
これに対してFDAは「プリントアウトを本質的に信頼することはできない、なぜならプリントアウトにはデータの再構築または生データから再現するために必要なメタデータ情報を含んでいないからである。」
等と主張しました。
つまり印刷物には、監査証跡等のメタデータの情報がなく、規制当局が紙媒体で査察を行った場合、その改ざんの有無が確認できないのです。
多くの場合、いわゆるハイブリットシステムを運用されていることと思います。ハイブリットシステムとは、電子で記録を作成し、紙媒体で署名することを言います。
この場合、紙媒体上で承認をしたからといって、電子記録を削除してはなりません。
なぜならば改ざんしたものを印刷し、承認したのち、証拠を消したと判断される可能性があるからです。
FDAは、印刷後に電子記録を削除したシステムに関してワーニングレターを発行したことがあります。
Annex 11は、こういった米国の規制当局と製薬企業の議論をよく研究し、改定案を作成したようです。
Annex 11の改定に伴い、PIC/Sの改定も必至と思われます。

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