【最近のウォーニングレター】ASTROM通信 263号

今日から新年度が始まりましたが、いかがお過ごしでしょうか？

今回も、アメリカ食品医薬品局（FDA)が、アメリカ国外ではなく国内の製薬会社向けに出したウォーニングレター３件を取り上げ、FDAがどのような点を問題視して指摘したかを確認していきたいと思います。
是非最後までお読みいただければ幸いです。

最近のウォーニングレターの概要　　

注：文中のXXはウォーニングレターでマスキングされている文言及び具体的な社名・品名等です。

■CMS 641099■

2022年1月25日～2月9日のペンシルバニア州の製造所の査察でみつかった医薬品製造の重大なCGMP違反について発した2023年1月19日付ウォーニングレターには、下記の指摘事項があげられています。

●指摘１

貴社は医薬品の各ロットについて、リリース前に、各有効成分の同一性と濃度を含む製品の最終規格への一致について試験の判断を怠った。また、医薬品の各ロットについて、必要に応じて、好ましくない微生物を含まないことを試験することを怠った。(21 CFR 211.165(a),(b))
＜指摘１詳細＞
セクション704(a)(4)に基づく記録及びその他の情報の提供に関する我々の要求に対する貴社の回答は、貴社はOTCの手指の消毒薬の受託充填者であり、リリース前に最終製品のテストをしなかったと述べた。
具体的には、アメリカでの販売用に製造された手指の各消毒薬に関する分析試験及び微生物試験の最終製品の規格と試験方法を提出してほしいという我々の要求に対し、貴社は、これは“顧客により実施された”、“我々はボトルに充填しただけである”と回答した。
製品のオーナーと契約製造施設は、どちらも、原材料、医薬品の製造に使用される材料、最終製品のリスク管理と安全性の確認を含む品質保証のために、医薬品の製造の監督と管理の実施を含むCGMPの責任がある。
同一性、濃度、純度を含む完全なリリース試験は、医薬品をリリースして販売する前に実施されなければならない。適切な試験を実施しなければ、リリース前に貴社の医薬品が適切な規格を遵守していると保証するための科学的な根拠がない。
この文書への回答の中で、以下の情報を提供せよ：

  • バッチの処遇を判断する前に貴社の医薬品の各ロットを分析するために使用されている試験方法を含む、化学及び微生物試験の規格のリスト
    • この文書の日付時点で使用期限内にあるアメリカに出荷された医薬品の全てのロットの品質を判断するために保管サンプルの全ての化学及び微生物試験の実施をするためのアクションプランとタイムライン
    • 各ロットの保管サンプルの試験から得られた全ての結果のサマリ
      それらの試験で、医薬品が標準の品質を満たしていないことが明らかになった場合、顧客への通知や製品の回収等の迅速な是正処置を実施せよ。

●指摘２

貴社は、医薬品の各成分の同一性を検証するために少なくとも1つの試験を実施することを怠った。(21 CFR 211.84(d)(1))
＜指摘２詳細＞
貴社が提出した記録と情報は、貴社は医薬品の製造に使用される入荷した成分の適切な同一性試験を実施したことを示さなかった。具体的には、貴社は、原材料の各ロットの成分の同一性試験は“該当なし”で、エタノールまたはイソプロピルアルコールとメタノールの試験は、“各顧客により実施”で、手指の消毒剤に使用されるエタノールまたはイソプロピルアルコールの効能(分析)の検査は“該当なし”と回答した。
貴社は、エタノールを含む複数の医薬品を製造する。メタノールで汚染されたエタノールの使用は、世界中の人々のさまざまな致命的な中毒事件をもたらしてきた。
FDAのガイダンス文書Policy for Testing of Alcohol(Ethanol) and Isopropyl Alcohol for Methanol, Including During the Public Health Emergency(COVID-19)
を見よ。
この文書への回答の中で、以下の情報を提供せよ：

  • 成分の各ロットの、同一性、濃度、品質、純度に関する全ての規格への一致をどのように試験するつもりかの説明
    濃度、品質、純度に関する各成分のロットの試験をする代わりに、貴社の供給者の分析証明書(COA)から得た結果を受け入れるつもりなら、初期のバリデーションと定期的な再バリデーションを通じて供給者の試験結果の信頼性をいかに確実に確証するかを明記せよ。さらに、入荷した成分の各ロットについて、少なくとも１つの特定の同一性試験を常に実施することを約束せよ。

●指摘３

貴社が製造する医薬品が、それが持つとうたわれている、または、表示されている同一性、濃度、品質、純度を持つことを保証するために設計された製造と工程管理に関する文書化された手順を確立することを怠った。(21 CFR 211.100(a))
＜指摘３参照＞
貴社が提出した情報は、貴社の製造工程は再現可能で均一な特性と品質の製品を生産するために制御されていることを示していなかった。例えば、我々は貴社に製造された手指の消毒薬の完了した最新のロットの製造記録のコピーを提供するよう依頼した。貴社は回答の中で製造記録は“顧客によって保持されている”と述べた。
この文書への回答の中で、以下の情報を提供せよ：

  • 文書化手順が不十分な場所を特定するために、貴社の製造と品管の作業を通して使用される文書システムの完全なアセスメント
    貴社が、貴社の作業を通じて、帰属可能で判読可能、完全で原本性があり正確で同時性のある記録を保持していることを保証するために、貴社の文書化手順を包括的に改善する詳細なCAPAの計画を含めよ。
  • 貴社により販売されたの手指の消毒薬の全てのロットのリストと貴社が販売した全ての材料の完全な突き合わせ

●請負業者としての責任

医薬品は、CGMPを遵守して製造されなければならない。FDAは、多数の医薬品製造業者が製造設備、試験機関、包装業者、ラベル貼付業者などの独立した請負業者を使用していることを認識している。FDAは請負業者を製造業者の延長とみなす。
貴社には、製品のオーナーとの契約に関わらず、受託製造所として、貴社が製造する医薬品の品質に責任がある。貴社には、医薬品の安全性、同一性、濃度、品質、純度を保証するために、医薬品がFD&C Act 501(a)(2)(B)に従って製造されていることを保証することが求められている。
FDAのガイダンス文書Contract Manufacturing Arrangements for Drugs : Quality Agreements
を見よ。

●結論

この文書で挙げた違反は、貴社の製造所に存在する違反の包括的なリストではない。貴社には、全ての違反を調査し、原因を判断し、再発やその他の違反の発生を防止する責任がある。
全ての違反を速やかに是正せよ。この問題に迅速かつ適切に対応しない場合、通知なしで、これらに限定されないが、差し押さえや差し止め命令を含む規制または法的措置につながる可能性がある。未解決の違反は、他の連邦政府当局との契約を阻むかもしれない。
違反への対応の不履行は、FDAの輸出証明書の発行の差し控えにつながる可能性がある。全ての違反が完全に対応され、我々が貴社のCGMPの遵守を確認するまで、FDAは貴社の製造業者としての新薬の申請やリストの補完の承認を保留するだろう。また、我々は、貴社が全ての違反に対する是正処置を完了したことを確認するために再査察を行うかもしれない。

出典：https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/b-j-group-641099-01192023

～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～

■CMS 642082■

2022年7月26日～8月10日のマサチューセッツ州の製造所の査察でみつかった医薬品製造の重大なCGMP違反について発した2023年1月20日付ウォーニングレターには、下記の指摘事項があげられています。

●指摘１

貴社は、適切な品質部門と、品質管理部門に適用する単なる書面ではなく完全に順守される責任や手順を制定することを怠った。。(21 CFR 211.22(a),(d))
＜指摘１詳細＞
貴社は貴社のホメオパシー医薬品の製造を監督する責任と権限を持った品質部門(QU)を制定することを怠った。
貴社は、高品質の作業の管理を含む文書化した手順を持っていないと述べた。例えば、貴社は製造前に、サンプリング、検査、試験を記録して実施することを保証するための文書化された手順を持っていなかった。さらに貴社は、供給者の適格性評価に関するプログラムを制定することを怠り、貴社のホメオパシー医薬品がリリースや顧客への出荷の前に試験されることを保証するのを怠った。
品質部門の責任は、これに限定されないが、入荷した原材料、中間品、製品の合格・不合格を判断すること、製造作業中に管理が行われ完了されていること、製造記録はレビュされ説明のつかない不一致は調査されていることを含む。
これら及びその他の基本的は品質管理の責任は、貴社の医薬品の製造の効果的で適切な監督を実施するために不可欠である。
貴社の品質システムは不適切である。CGMPの規制要件である21 CFR Parts 210,211に従うための品質システムとリスクマネジメントアプローチを実装する助けとして、
FDAのガイダンス文書Quality Systems Approach to Pharmaceutical CGMP Regulations
を見よ。

●指摘２

貴社は、同一性、濃度、品質、純度に影響しないよう、温度、湿度、光の適切な状態のもとで医薬品を保管することを怠った。(21 CFR 211.142(b))
＜指摘２詳細＞
貴社は医薬品の適切な保管や倉庫保管をすることを怠った。例えば、供給者のバルクの分析証明書(COA)には、医薬品は、熱、日光、湿気に敏感であると書かれていたが、貴社は、温度、湿度を含む医薬品の保管条件をモニタすることを怠った。また貴社は、医薬品、容器、蓋の保管条件が不適切であることを認めた。医薬品の保持は、同一性、濃度、品質、純度に影響をしない適切な条件の下で実施されなければならない。

●指摘３

貴社は、医薬品の各ロットについて、製造、加工、包装、保持の重要なそれぞれの段階の完了の文書化を含む、製造記録を準備することを怠った。(21 CFR 211.188(b))
＜指摘３詳細＞
貴社は貴社の製造作業を記録したロットの製造記録を持っていなかった。貴社は、ロットの記録もロット番号もなかったと述べた。ロットの記録は、貴社の医薬品が適切に製造され、加工され、包装され、保持されていたことを保証するための重要な情報を収集するために必要である。

●医薬品の製造停止

2022年11月3日、FDAは貴社と電話会議を実施した。我々は、現在アメリカ市場にある医薬品の全てのロットを取り除き、更なる出荷を停止することを検討することを勧めた。
2022年11月5日、貴社はウエブサイトで、医薬品の販売を停止すると約束し、全ての医薬品の製造と販売を停止し、全ての医薬品の自主的回収を検討していると連絡した。
2022年11月21日、貴社は全ての医薬品の自主的回収を全国に発表した。
我々は、貴社が全ての医薬品の製造と販売を停止すると約束したと認識している。
この文書への回答の中で、貴社がこの製造所または他の製造所で、今後医薬品の製造を再開するつもりかどうかを発表せよ。FD&C Actで規制された製造を再開する計画があるなら、貴社が製造作業を再開する前に連絡せよ。CGMPの活動を再開するつもりなら、貴社には、貴社が継続的にCGMPを遵守できることを保証するために、全ての欠陥とシステム上の不具合を解決する責任がある。さらに我々が貴社で発見した違反の性質に基づき、貴社はCGMPの要件を満たすように貴社を支援するために、21 CFR 211.34に記載されている適格性のあるコンサルタントを雇うべきである。貴社がFDAと共に貴社のコンプライアンス状態の解決を達成しようとする前に、適格なコンサルタントが貴社のCGMP遵守に関し貴社の6つのシステム（品質システム、設備及び装置のシステム、原材料システム、製造システム、包装及びラベル貼付システム、試験管理システム）の全ての作業の包括的な監査を実施し、貴社の是正処置・予防処置の完了と効果も評価すべきである。

●所有者の責任

医薬品は、CGMPに従って製造されなければならない。FDAは、多数の医薬品製造業者が製造設備、試験機関、包装業者、ラベル貼付業者などの独立した請負業者を使用していることを認識している。FDAは請負業者を製造業者の延長とみなす。
貴社には、契約施設との契約に関わらず、貴社の医薬品の品質に責任がある。貴社には、医薬品の安全性、同一性、濃度、品質、純度を保証するために、医薬品がFD&C Act 501(a)(2)(B)に従って製造されていることを保証することが求められている。
FDAのガイダンス文書Contract Manufacturing Arrangements for Drugs : Quality Agreements
を見よ。

●施設登録と医薬品リスト登録違反

FD&C Act 510(j)(1)、21 U.S.C.360(j)(1)、21 CFR 207.41、21 CFR 207.49(a)(5)のもとで、アメリカの商用販売のために製造、調製、増殖、調合、または加工される全ての医薬品は、FDAのリストに登録されていないといけない。XX社は製造及び販売時点でFDAのリストに登録されていないといけないが、XX社自身の名前で販売していた。医薬品の適切なリスト登録の不履行は、FD&C Actの301(p)、21 U.S.C.331(p)のもとで禁止されていて、FD&C Act 502(o)、21 U.S.C.352(o)のもとで不正商標表示とされるだろう。
不正商標表示のされた医薬品の州際通商のための導入または配送はFD&C Act 301(a)、21 U.S.C.331(a)のもとで禁止されている。

●結論

この文書で挙げた違反は、貴社の製造所に存在する違反の包括的なリストではない。貴社には、全ての違反を調査し、原因を判断し、再発やその他の違反の発生を防止する責任がある。
全ての違反を速やかに是正せよ。この問題に迅速かつ適切に対応しない場合、通知なしで、これらに限定されないが、差し押さえや差し止め命令を含む規制または法的措置につながる可能性がある。未解決の違反は、他の連邦政府当局との契約を阻むかもしれない。
違反への対応の不履行は、FDAの輸出証明書の発行の差し控えにつながる可能性がある。
全ての違反が完全に対応され、我々が貴社のCGMPの遵守を確認するまで、FDAは貴社の製造業者としての新薬の申請やリストの補完の承認を保留するだろう。また、我々は、貴社が全ての違反に対する是正処置を完了したことを確認するために再査察を行うかもしれない。

出典：https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/atlantic-management-resources-ltd-dba-claire-ellen-products-642082-01202023

～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～～

■CMS 642374■

2022年8月1日～8月5日のテネシー州の製造所の査察でみつかった医薬品製造の重大なCGMP違反について発した2023年2月15日付ウォーニングレターには、下記の指摘事項があげられています。

●指摘１

貴社は、製品の各ロットについて、求められる通り好ましくない微生物が含まれていないことを、必要に応じて試験室で試験することを怠った。(21 CFR 211.165(b))
＜指摘１詳細＞
貴社は貴社のOTC医薬品を出荷のためにリリースする前に適切な試験することを怠った。例えば、貴社の手指の消毒薬や抗菌ハンドソープ医薬品のバッチレコードは微生物試験の要件を含んでいるが、貴社は微生物の属性について各ロットを試験することを怠った。代りに貴社は分析のためにサードパーティの試験機関にXXを送ることだけ行ったと我々査察官に語った。貴社は、査察官からのリクエストやサンプル試験の頻度の科学的根拠を求められた際、参照用の一般生菌数試験に含まれていた物に関する文書を提出しなかった。
この文書への回答の中で、以下の情報を提供せよ：

  • バッチの処遇を判断する前に医薬品の各ロットを分析するために使用されている試験方法を含む化学及び微生物の規格のリスト
  • この文書の日付時点で使用期限内にあるアメリカに出荷された医薬品の全てのロットの品質を判断するするために保管サンプルの全ての化学試験及び微生物試験を実施するためのアクションプランとタイムライン
  • 各ロットの保管サンプルの試験から得られた全ての試験のサマリ
    それらの試験で、医薬品の品質が標準を満たしていないことが明らかになった場合、顧客への通知や製品の回収等の迅速な是正処置をとれ。

●指摘２

そのロットが既に出荷されているかどうかに関わらず、ロットやその成分が満たすべき規格との説明のつかない不一致や不具合を徹底的に調査することを怠った。(21 CFR 211.192)
＜指摘２詳細＞
貴社は、抗菌ハンドソープ医薬品のいくつかの安定性のチェック中に規格外(OOS)の分析結果を調査することを怠った。例えば、抗菌ハンドソープ医薬品の中のクロロキシレノールの分析試験は、安定性のチェック時点で0.31％のXXを含んでいるという結果を示した。この製品に関する貴社の規格は、XX％であった。貴社はOOSの結果の調査の実施を怠った。
貴社は使用期限の切れた原材料の隔離や不合格にすることを怠り、最終製品に使用するのを防ぐことを怠った。2022年6月28日、貴社は、販売のためにリリースされた手指の消毒泡を製造するために、2021年6月17日に使用期限のきれた原材料の塩化ベンザルコニウム(BZK)を使用した。
我々は、貴社の回答で、貴社が使用期限の過ぎたBZKの隔離と、手指の消毒泡の回収を行ったと認識している。
貴社の調査のための品質システムは不十分で、安全で有効な製品の一貫した製造を保証していない。
不具合、規格外、傾向外、その他の予期しない結果の取り扱いと、貴社の調査の文書の更なる情報については、
FDAのガイダンス文書Investigating Out-of-Specification(OOS) Test Results for Pharmaceutical Production
を見よ。
この文書への回答の中で、以下の情報を提供せよ：

  • 査察の最初の日から3年内でこの文書の日付時点で使用期限内の現在アメリカ市場にあるアメリカ向け製品の全てのOOS(工程内試験及びリリース/安定性試験を含む)の結果の回顧的で独立したレビュと、各OOSに関する以下のことを含む分析の結果を要約したレポート
    • OOSの結果に関する科学的正当性とエビデンスが、決定的または非決定的に、原因となる試験のエラーを示しているかどうかの判断
    • 試験の根本原因を最終的に確認する調査について、論理的根拠を提供し、改善のために同じまたは類似の原因に対して脆弱な他の全ての試験方法が特定されていることを保証せよ。
    • 回顧的レビュによって、試験が決定的な根本原因でないか、根本原因が特定されていない全てのOOSの結果について、徹底的な製造のレビュ(例：ロットの製造記録、製造ステップの適格性、装置/施設の適合性、原材料のばらつき、工程能力、逸脱の履歴、苦情の履歴、ロットの不具合の履歴)を含めよ。各調査について、潜在的な製造の根本原因のサマリと、製造作業の改善についての情報を提出せよ。
  • 貴社のOOSの結果の調査システムに関する包括的なレビュと改善の計画
    是正処置・予防処置(CAPA)は、これに限定されないが、以下のことに対処すべきである：
    • 試験の調査に関する品質部門(QU)の監督
    • 試験管理の良くない傾向の確認
    • 試験のばらつきの原因の解決
    • 試験の原因が決定的であると判断されなかった場合はいつでも、潜在的な製造の原因の徹底的な調査の開始
    • 各調査の適切な範囲の決定と、そのCAPA
    • これら及びその他の改善されたOOSの調査の手順の改訂
  • 逸脱、食い違い、苦情、OOSの結果、不具合を調査するための貴社のシステム全体の包括的で独立したアセスメント
    このシステムを改善するための詳細なアクションプランを提出せよ。貴社のアクションプランには、これに限定されないが、調査能力、調査範囲の決定、根本原因の評価、CAPAの有効性、QUの監督、文書化された手順の大幅な改善を含むべきである。調査の全ての段階が適切に実施されることをいかに保証するかを検討せよ。

●指摘３

貴社の品質管理部門は、医薬品がCGMPを遵守して製造され、同一性、濃度、品質、純度に関して制定された規格を満たすことを保証するための責任を果たすことを怠った。(21 CFR 211.22)
＜指摘３＞
貴社のQUは貴社の医薬品の製造に関する適切な監督を規定しなかった。例えば、貴社のQUは以下のことを保証することを怠った：

  • 調査の取り扱い、製品の隔離、苦情の取り扱い、変更管理、安定性の不具合を記述した適切な手順(21 CFR 211.22(d))
  • 同一性、純度、濃度、その他の適切な品質の属性に関する入荷した成分の適切な試験
    (21 CFR 211.84(d)(1)、211.84(d)(2))
  • 適切で継続的な安定性プログラムの制定(211 CFR 211.166(a))

貴社の品質システムは不十分である。CGMPの規制要件21 CFR part210,211を満たすための品質システムとリスクマネジメントアプローチの実装の助けとして、FDAのガイダンス文書Quality Systems Approach to Pharmaceutical CGMP Regulations
を見よ。
この文書への回答の中で、貴社のQUが効果的に機能するための権限とリソースを与えられていることを保証するための包括的なアセスメントと改善計画を提出せよ。アセスメントは、これに限定されないが、以下のことを含めるべきである：

  • 貴社で使用される手順が安定していて適切であるかどうかの判断
  • 適切な手順の遵守を評価するための貴社の作業全体のQUの監督に関する規定
  • QUがロットの処遇を判断する前の、各ロットと関連する情報の完全で最終的なレビュ
  • 全ての製品の同一性、濃度、品質、純度を保証するための、調査の監督及び承認とその他の全てのQUの職務の遂行

●指摘４

貴社が製造した医薬品が、それが持つとうたっている、または、表示されている同一性、濃度、品質、純度を持っていることを保証するために設計した製造と工程制御に関する文書化された手順を制定することを怠った。(21 CFR 211.100(a))
＜指摘４＞
貴社は手指の消毒薬と抗菌ハンドソープ医薬品の製造に使用される製造工程と水システムを適切にバリデートすることを怠った。例えば、貴社のバッチレコードは、抗菌ハンドソープの濃度が低い場合、必要に応じてXXを加えるような、バリデートされていない工程内の調整を含んでいた。貴社は、均一な特性と品質の医薬品を一貫して製造するために、貴社の製造工程が管理されていることを証明しなかった。さらに、貴社は水システムをバリデートしておらず、手順を保持せず、調査者による依頼に基づいて規格を提出しなかった。
貴社は、安定した製造作業と一貫した医薬品の品質を保証するための工程のモニタリングに関する継続的なプログラムが欠けている。
FDAがプロセスバリデーションの適切な要素としてみなす一般的な原則とアプローチについて、
FDAのガイダンス文書Process Validation : General Principles and Practices
を見よ。
この文書への回答の中で、以下の情報を提供せよ：

  • 製品のライフサイクルを通じて、関連する手順と共に、管理状態を保証するための貴社のバリデーションプログラムの詳細なサマリ
  • 貴社が販売する各医薬品に関し適切な工程性能の適格性評価を実施するためのタイムライン
  • 貴社の工程性能のプロトコルと、装置及び施設の適格性評価に関する文書化された手順を含めよ
  • 継続的な管理状態を保証するための、ロット間及びロット内のばらつきの厳格なモニタリングを含む、貴社の各製造工程の設計、バリデーション、維持、管理、モニタリングに関する詳細なプログラム
    貴社の装置及び施設の適格性評価に関する貴社のプログラムも含めよ。
  • 貴社で製造される医薬品の各ロットで使用するのに許容できることを保証するための水の定期的な微生物試験を規定する水システムのモニタリングの手順
  • 貴社の水システムXXに使用される、総菌数と好ましくない微生物に関する現在のアクション/アラート限界
    貴社の水システムの総菌数の限度が、貴社で製造される各製品の使用目的の観点で適切に厳格であることを保証せよ。
  • 修正された水システムが、アメリカ薬局方(USP)収載のXX水の規格や適切な微生物の限度を満たす水を一貫して製造することを保証する継続的な管理、メンテナンス、モニタリングに関する貴社プログラムを管理する手順

●未承認新薬と不正商標表示の違反

省略

●CGMPコンサルタントの推奨

我々が貴社で発見した違反の性質に基づき、アメリカ市場向けの医薬品の製造を再開するつもりなら、貴社は、CGMPの要件を満たす助けをする21 CFR 211.34に記載されている適格性のあるコンサルタントを雇うべきである。貴社がFDAと共に貴社のコンプライアンス状態の解決を達成しようとする前に、適格なコンサルタントが貴社のCGMP遵守に関し貴社の全ての作業の包括的な監査を実施し、CAPAの完了と効果も評価すべきである。
貴社のコンサルタントの使用は、CGMPを順守するための貴社の義務を軽減するものではない。
貴社の経営陣には、継続的なCGMP順守を保証するために、全ての不備とシステムの欠陥を解決する責任が残る。

●結論

この文書で挙げた違反は、貴社の製造所に存在する違反の包括的なリストではない。貴社には、全ての違反を調査し、原因を判断し、再発やその他の違反の発生を防止する責任がある。
全ての違反を速やかに是正せよ。この問題に迅速かつ適切に対応しない場合、通知なしで、これらに限定されないが、差し押さえや差し止め命令を含む規制または法的措置につながる可能性がある。未解決の違反は、他の連邦政府当局との契約を阻むかもしれない。
違反への対応の不履行は、FDAの輸出証明書の発行の差し控えにつながる可能性がある。全ての違反に完全に対応され、我々が貴社のCGMPの遵守を確認するまで、FDAは貴社の製造業者としての新薬の申請やリストの補完の承認を保留するだろう。また、我々は、貴社が全ての違反に対する是正処置を完了したことを確認するために再査察を行うかもしれない。

出典：https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/midlab-incorporated-642374-02152023

まとめ

いかがでしたでしょうか。

1件目と2件目のウォーニングレターには、外部委託製造の管理に関する指摘が含まれていました。
1件目は受託側、2件目は委託側でしたが、どちらの立場であっても、また契約がどうなっていても、医薬品の品質に責任を負わなければならないとされています。
皆様の外部委託先の管理はいかがでしょうか。
製薬会社様の話を伺っていると、管理が不十分と感じることがよくあります。
医薬品医療機器総合機構(PMDA)が発行した2022年9月版オレンジレター【外部委託する際の委託管理の徹底について】でも、外部委託先の管理を徹底するように求めています。
オレンジレター：https://www.pmda.go.jp/files/000248233.pdf
この機会に、委託先の管理の定期的な適格性評価が行えているかを再確認してみるのもよいのではないでしょうか。

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