內部稽核經驗分享經驗分享經驗分享經驗分享

--品質系統維持--

吳怡萍吳怡萍吳怡萍吳怡萍 ypw_t@itri.org.tw

886-35912819

Div HCT/P Development BEL ITRI

Internal Audit is a Tool of

Quality Control

4 sides of the base of the Great

Pyramid Giza are

perpendicular to within 3.5 arc

seconds.

Arc second = 1/ 60*60*360

to ensure products or service are designed and produced to meet or exceed customer requirements.

W. Edwards Deming and Joseph Juran.

Total Quality Control is the most necessary

inspection control of all in cases where, despite statistical quality control techniques or quality improvements implemented, sales decrease.

For instance, all parameters for a pressure

vessel should include not only the material and

dimensions but operating, environmental, safety,

reliability and maintainability requirements.

CAPA focuses on the systematic

investigation of discrepancies (failures

and/or deviations) in an attempt to prevent

their recurrence.

Base of Internal Audit, Wikipedia

Due to practical constraints, an

audit seeks to provide only

reasonable assurance that the

statements are free from material

error. Hence, statistical sampling is

often adopted in audits.

♦ Authentic raw materials

♦ Sampling♦ Statistical interpretation

第2 章 品質計畫建立與維持

8節稽核稽核稽核稽核(一）本規範所規定之品質稽核，應每年至少執行一每年至少執行一每年至少執行一每年至少執行一

次次次次。必要時，並應執行特別稽核。稽核應依一定程序為之，以確保品質計畫之有效執行，辨認產品偏差之趨向及重複發生之問題。

(二）品質稽核人員須具備相關知識、訓練與經驗。被稽核事項之直接負責人員，不得自為稽核人員。

(三）稽核或再稽核之報告應妥為保存，交由機構管

理者審閱，並製作審閱紀錄。

人體細胞組織優良操作規範91.12.13 衛署醫字第0910078677 號公告

Compliance

Upgrading,

EndlesslyCorrective

measures

STD;

PreventionID

Target

Methodology

Selection

Communication

Education

Realization;

Plan carried

out

Root and Cause

Analysis

Result

Evaluation

5W 1H: What? Who? When? Where? Why? How?

FDA Register, Vol. 69, No. 226 68613, also discussed about AUDITAUDIT, 2004-11-24

(Comment 50) One comment requested more flexible language to replace the requirement for a comprehensive quality audit no less than once in 12 months. Another comment asserted that the requirement for an annual comprehensive audit is more stringent than the requirements applicable to blood component processing.

(Response) In response to these comments, we have revised proposed § 1271.160(d). Section 1271.160(c) now requires only that a quality audit of core CGTP activities be performed periodically for management review.

The new language provides establishments with a greater degree of flexibility in determining how and when to audit their quality programs. We also may issue future guidance making recommendations on what we would consider to be a periodic audit.

21 CFR Parts 16, 1270, and 1271 Current Good Tissue Practice for Human Cell, Tissue, and Cellular and Tissue- Based Product Establishments; Inspection and Enforcement; Final Rule

(Comment 51) Two comments asserted that internal audit findings should not be available to FDA representatives.

(Response) With respect to quality audits, while some firms choose to provide quality audits to FDA, FDA’s current practice is generally not to review or copy the actual quality audit reports during routine inspections and investigations except in certain limited circumstances (FDA Compliance Policy Guide 130.300). However, the firm should have a mechanism to demonstrate to the FDA representative that quality audits are being performed and that corrective actions are being implemented when problems are identified.

2009-01

What are core CGTP requirements? Core CGTP requirements (§ 1271.150(b)) are those requirements that directly

relate to preventing the introduction, transmission, or spread of communicable

disease by HCT/Ps. The core CGTP requirements include requirements for:

• facilities (§ 1271.190(a) and (b));

• environmental control (§ 1271.195(a)); • equipment (§ 1271.200(a));

• supplies and reagents (§1271.210(a) and (b)); • recovery (§ 1271.215);

• processing and process controls (§ 1271.220); • labeling controls (§ 1271.250(a) and (b));

• storage (§1271.260(a) through (d));

• receipt, predistribution shipment, and distribution of an HCT/P (§ 1271.265(a) through (d)); and

• donor eligibility determinations, donor screening, and donor testing (§§ 1271.50, 1271.75, 1271.80, and

1271.85).

Another Angle to look at Internal Audit

• A simulation process of Inspection

• A less stressful learning

• A creative and stimulating process of risk prevention and quality improvement in voluntary manner.

A proof of commitment in regulatory compliance

Heinrich (1959), a safety engineer in

America, used statistics in the 1920s to

construct the "accident pyramid". His

description of the relationship between

major, minor and no-injury accidents

was an attempt to show how important

the injury potential is in the process of

accident prevention.

During the 1960's, another U.S.

insurance industry specialist, Frank

Bird (1980), brought Heinrich's

theory up to date. He did this through

a survey of 1,700,000 accidents and

devised his "accident ratio" which,

although not identical to Heinrich's,

showed that the same pattern

applied.

1

29

300

1

10

30

600

Risk v.s. Damage

Causes of the Accidents/ Undesirable event

or Incompliance (發生意外事故原因發生意外事故原因發生意外事故原因發生意外事故原因)

一一一一、、、、不做不做不做不做（（（（紀律紀律紀律紀律））））1.不願改變過去不正確的工作習慣不願改變過去不正確的工作習慣不願改變過去不正確的工作習慣不願改變過去不正確的工作習慣(SOP)

2.便宜行事便宜行事便宜行事便宜行事3.減少費用減少費用減少費用減少費用

4.節省時間節省時間節省時間節省時間

二二二二、、、、不知不知不知不知（（（（教育教育教育教育、、、、訓練訓練訓練訓練））））1.未具該方面知識未具該方面知識未具該方面知識未具該方面知識----未告知未告知未告知未告知

2.不知如何做不知如何做不知如何做不知如何做----教導不完全教導不完全教導不完全教導不完全3.不知會產生何種危險不知會產生何種危險不知會產生何種危險不知會產生何種危險----說服力說服力說服力說服力不足不足不足不足

Risk Levels in Environments/ Processes

可選擇可選擇可選擇可選擇

無無無無 知知知知 冒冒冒冒 險險險險 風險風險風險風險(極高極高極高極高)

保保 保保險險 險險

殘留危險殘留危險殘留危險殘留危險

行為管理行為管理行為管理行為管理

可改善可改善可改善可改善

無法改善無法改善無法改善無法改善

認認認認 知知知知

不可控制

不可控制

不可控制

不可控制

可可 可可控控 控控

制制 制制

變更生產方式變更生產方式變更生產方式變更生產方式

安全裝置安全裝置安全裝置安全裝置

風險風險風險風險(中高中高中高中高)

風險風險風險風險(高高高高)不可選擇不可選擇不可選擇不可選擇

BEL QCMFinal report offered by BEL QCM2009-05-11

CMF QA吳DOH revisit 2009-04-16

BEL QCM吳

CMF QA吳 EMs陳CMF儀器設備稽查2009-04-10

BEL Quality committeeFY98 BEL儀器設備稽查規劃2009-03-09

CMF QA team2nd proposal for corrective action2009-03-09

CMF QA team1st proposal for corrective action2009-02-27

DOH inspectors 4+; entire CMF teamsDOH inspection2009-02-24

CMF吳,葉

A report generatedReply to the [suggestions] and more improvement initiated (SOP revising)

2009-01-19

BEL: 鄧Collective suggestions sent to CMF QA team 2009-01-16

CMF QA teamThe first infra improvement reported to auditors

2009-01-08

張,劉,鄧,謝,姚,黃Document review, SOP2009-01-08to 2009-01-12

Auditor: BEL QCM高,張,劉,鄭,鄧,張,謝,

姚,黃

Auditee: CMF施,吳,葉 (QA team)

Face to face meeting I on site visit to CMF

2008-12-05

Involved PersonnelWork Date

FY09 Compliance Upgrading Activity

BEL儀器設備稽查規劃：

預定稽查時間:4/1~4/30

稽查範圍:全所各研究室

稽查內容:

1.儀校系統之資訊更新(含儀校計畫).2.抽查現場儀器設備之校驗紀錄(對應儀校系統資訊),含未列系統帳之儀器設備.

3.cGMP/GMP/GTP/GLP/TAF-Lab驗證... (以下統一以GxP表示)等之≧100萬之儀器設備之IQ,OQ,PQ現況.

(安裝使用說明,操作說明,維護說明等資料建置現況)

稽查人員:高總監,Dr. 鄭, Ms.鄧

BEL儀器設備稽查規劃：

• 稽查方式:1.儀校系統全面稽查(全檢).2.自儀校系統抽樣10%後進行現場稽查(儀校計畫未完成者50%).3.自財管系統抽樣≧100萬之儀器設備之IQ,OQ,PQ現況,3.1 無GxP研究室->調查"安裝使用說明,操作說明,維護說明等"資料建置現況.3.2 有GxP研究室->稽查"安裝使用說明,操作說明,維護說明等"資料建置現況.

• 稽查紀錄與改善方式:1.儀校不符合院所規定者,開列"異常或不符合事項改善處理追蹤表".2.≧100萬之IQ,OQ,PQ現況不符合GxP要求者:2.1 無GxP研究室->提列建議事項.2.2 有GxP研究室->GxP使用之儀器設備,開列"異常或不符合事項改善處理追蹤表".

N

A

N

ANAV

V QA00

17

X

2009.02.1

8~23校正; 允收±1.5℃VVGTPL-06-

04-00

66267/04014200/低溫

培養箱

NA

NA

NAVV QA0016

X

2009.02.1

8~23校正; 允收±1.5℃VV同66267

66266/040

14100/低溫

培養箱

N

A

N

ANAV

V QA0019

X (現場無)

2009.07.0

2校正; 允收規格±1℃; ±5%RH

VVGTPL-06-

13-00

66173/040

13300/溫溼度紀錄器組

N

A

N

ANAVV

X (現場無)

2008.11.2

4校正VV Testo

521/526

GTPL-06-

24-00

74630/070

12100/攜帶

型壓力計

N

A

N

A.NAV?V

2008.11.2

7校正VX/OKGTPL-06-

22-00

69808/060

12200/細胞

計數機

設備置工廠, 只查閱文件V QA0025

V GTPL-

06-05-

01

2008.06.1

9委託Merck校正VX/OK

GTPL-06-

05-00

/06010000/空氣採樣器

N

A

N

A.NA.V

V QA00

02

X不需要

2006.03.0

2校正, 校正報告列印中V

V

Sanyo MPR-

414F

GTPL-06-

16-01

065291/04

009900/藥

品試劑低溫保存機組

VVVV

V 2003.12.4驗收報告V

2006.12.25

VVV56-NWI50

56-NWI70

061253/39

82100/流式細胞儀

PQ

OQ

IQ無有履歷

維護紀錄

使用紀錄

校驗後確認與驗收

無需

內校

外校

其他

無原廠手冊

SOP財編/儀器編號

整體稽核建議整體稽核建議整體稽核建議整體稽核建議：：：：

1. 3982100/流式細胞儀, 現場擺放兩份SOP, 建議只放置最新版本以免操作同仁混淆,該設備校正費用昂貴, 故訂定為免校,建議恢復校正

2. 部分儀器置於GTP工廠中, 不便進入, 改以文件審

3. 設備履歷資訊建設完善, 設備設置履歷卡

4. 工廠內不設計儀器標籤(避免標籤粉塵污染), SOP

不放置於工廠,避免紙張污染，但須明確標示使用狀態

1次/6月QA,1/4月維護,廠務1次/批批次清潔

1次/6月廠務,QC; 1/4月維護5次/週例行清潔

1次/年QA, 1/案生產,QC,QA,廠務不定期採購

1次/年QC, QA; 1/年QA,QC,生產,廠務,維護(內部)1次/年; (外

部)不定期人員訓練(內部/外部)

1次/年QA, 1/年QA,QC,生產，廠務1次/年文件修訂、複查

1次/年QC, QA; 1/年廠務,委託廠商1次/年機儀功能確認

1次/年QC, QA; 1/4月廠務, QA5次/週機儀監測

1次/6月QC, QA; 1/2月QC,廠務1/月環境監測

1次/3批QC, QA; 1/批QC,QA1次/批細胞產品出廠檢驗

1次/批QC, QA; 2/批QC2-3次/批細胞安全性監測

1次/批QA; 1次/批生產2-6週/批細胞製備操作

稽核稽核稽核稽核/週期週期週期週期(至少至少至少至少)

確認確認確認確認，，，，複核複核複核複核/

週期週期週期週期 (至少至少至少至少)參與人員參與人員參與人員參與人員

執行執行執行執行/週期週期週期週期(至少至少至少至少)

執行事項執行事項執行事項執行事項

品質記錄與維護程序書 CMF-14-00-00; 2009-03-09

Existing Check-up in CMF

SOP and Check List

Daily Walk Through and Periodic Checking

To survive, you need to put things in place ….

敬請指教敬請指教敬請指教敬請指教

Thank You for Your Attention

子路曰子路曰子路曰子路曰：：：：南山有竹南山有竹南山有竹南山有竹，，，，不揉自直不揉自直不揉自直不揉自直，，，，斬而用之斬而用之斬而用之斬而用之，，，，達於達於達於達於犀革犀革犀革犀革。。。。何學之為何學之為何學之為何學之為？？？？孔子曰孔子曰孔子曰孔子曰：：：：括而羽之括而羽之括而羽之括而羽之，，，，鏃而鏃而鏃而鏃而礪之礪之礪之礪之，，，，其入不益深乎其入不益深乎其入不益深乎其入不益深乎？？？？

節自節自節自節自「「「「孔子家語孔子家語孔子家語孔子家語」」」」子路見孔子子路見孔子子路見孔子子路見孔子