AVCN2 GV.

Huỳnh Thanh Tùng

Session 3 ‐ Quality assurance and auditing

I. GOOD PHARMACEUTICAL INDUSTRY PRACTICE (GXP)

Quality choices

Right
dosage
Right Right
product expiry date

Right Right
appearance batch record

No
contamination

GxP is an abbreviation for good practice. The ‘x’ is used to indicate the many different areas of ‘good practice’ which
are required by international regulatory Authorities.

• Good Auditing practice (GAP) ‐ kiểm tra/ đánh giá

• Good Clinical practice (GCP) ‐ lâm sàng
• Good Documentation practice (GDP) ‐ tài liệu/ hồ sơ
• Good Laboratory practice (GLP) ‐ phòng thí nghiệm
• Good Manufacturing practice (GMP) ‐ sản xuất
• Good Research practice (GRP) ‐ nghiên cứu
• Good Safety practice (GSP) ‐ an toàn

What is GMP?
Good Manufacturing Practice (GMP) is a system for ensuring that products are consistently produced and controlled
according to quality standards.

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Exercise 1 Pg.29 ‐ General information on GMP
Reading Key points
Different quality assurance (đảm bảo chất lượng) processes are
required for each area of good practice.
Quality assurance (QA) includes:
 Quality control (kiểm soát chất lượng)
 Product sampling (lấy mẫu sản phẩm)
 Endpoint testing (thử nghiệm thời điểm cuối)
QA ensures Standard operating procedures(SOPs) are followed and
products meet high industry standards

Which answer is not correct?

Why is product sampling carried out?
A. To introduce product quality
B. To check product quality.
C. To make sure SOPs are followed.
D. To meet high industry standards.
Documentation (tài liệu/ hồ sơ) is important at every step involved
in drug manufacturing:
 Prevent product contamination (bị hỏng/ nhiễm bẩn)
 Enable traceability (truy xuất nguồn gốc)
 Allow full product recall (thu hồi sản phẩm)
Internal audit (đánh giá nội bộ): inspection (kiểm tra) and validation
(xác nhận) of operational methods, procedures, equipment to
ensure:
 Functionality (Chức năng)
 Accuracy (Độ chính xác)
 Validity (Tính hợp lệ)

Which answer is not correct?

Why do operational methods and procedures have to be validated?
A. To complete the quality assurance process.
B. To make sure products perform their intended function.
C. To complete the inspection process.
D. To isolate products of high quality.

Which aspect of drug manufacturing enables traceability?

A. Quality assurance
B. Quality control
C. Holistic approach
D. Documentation
A holistic approach (Cách tiếp cận toàn diện) looks at all
aspects of a pharmaceutical company together to make sure
that the entire process meets high industry standards.

Standard operating procedures (SOPs) are a set of written

instructions:
 to maintain performance and results.
 basis of good QA and QC system.

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Exercise 2 Pg.29
Traceability Endpoint testing
Holistic approach Product recall
Quality assurance Validation
Quality control Contaminated product
1. The documentation required for all research processes and development steps ensures the traceability of a drug.
2. A holistic approach considers laboratory and manufacturing processes and environments together and not
individually.
3. Quality assurance involves all manufacturing processes in GMP which make sure the goods produced are kept at
high standards.
4. Quality control involves interim and product sampling procedures, which are carried out to check product
quality.
5. At the end of every stage of a product’s manufacturing process, endpoint testing is done to maintain quality
standards.
6. Even a product that has been marketed for years might have to be taken off the market in a product recall if
serious adverse reactions occur.
7. Manufacturing processes and procedures must go through periodic validation to guarantee that they are still of
an acceptable standard.
8. Contaminated products are no longer pure and acceptable for sale or public use and, therefore, must be
returned to the manufacturer, or destroyed.

II. QUALITY ASSURANCE AUDITS

What is an internal audit?
An internal __________ involves inspection and validation of operational methods, procedures, equipment
to ensure functionality, accuracy and validity.
Internal audit process

Audit finding/ observation

The audit finding can be classified into 2 groups:
• Compliance
• Non‐compliance :
– Critical ( Nghiêm trọng)
– Major (Nặng)
– Minor (Nhẹ)

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Corrective Action/Preventive Action (CAPA)
• Part of Quality Management System (QMS)
• Systematic investigation of errors or deviations
• Preventive action (PA) – prevent occurrence of errors
• Corrective action (CA) – prevent recurrence of errors
Exercise 3 Pg.30
Key vocabulary Question
Interoffice Memorandum • Interoffice Memorandum ‐ Bản ghi nhớ nội bộ
Date: Monday
To: Philip Reuter, Laboratory Management • Laboratory Management ‐ Quản lý phòng thí nghiệm
From: Joseph Mason, Quality Assurance Internal Auditing • Quality Assurance Internal Auditing ‐ Phòng đánh giá nội bộ
Subject: Annual audit of SOPs for laboratory safety đảm bảo chất lượng
Cc: Richard Jacobs, Senior Quality Auditor; Gail Webber, • Auditor ‐ Đánh giá viên
Operations Auditor
Attachment: Audit checklist for laboratory systems and • Attachment ‐ Đính kèm
procedures (see p. 86)
What kind of internal audit has been scheduled?

How often does this type of audit have to be done?

This memo is to advise you that your department has • This memo is to advise you that ‐ Bản ghi nhớ này báo cho
been scheduled for a periodic audit of the laboratory ông/ bà biết rằng
safety systems and procedures. • Periodic audit ‐ Đánh giá định kỳ
The timetable for the various laboratory audits is as • Laboratory safety systems and procedures ‐ Hệ thống và
follows: quy trình an toàn phòng TN
Laboratory 1:Tuesday and Wednesday • Timetable ‐ Thời gian biểu
Laboratory 2:Wednesday and Thursday
Laboratory 3:Thursday and Friday When will the audit take place?

Please make sure that all the laboratory staff are advised • Please make sure Xin hãy đảm bảo rằng
and prepared in accordance with standard audit • Standard audit procedure ‐ Quy trình đánh giá chuẩn
procedure. Two members of our audit team (Richard • Audit checklist ‐ Danh sách đánh giá
Jacobs and Gail Webber) will begin this internal audit on
Tuesday, two weeks from tomorrow, using the latest What documentation is necessary for the audit?
company approved audit checklist (see attachment).

The completed checklist and original audit results will be • Safety procedures ‐ Quy trình an toàn
reviewed with you and the Research and Development • Correspondence ‐ Thư/ thư tín
Vice President. Our goal is to identify any areas requiring
corrective or preventive action before a summary report What is the objective of this audit?
of the status of these actions is issued. This is done to
assure compliance with industry standards, especially for
safety procedures.
Please confirm receipt of this memo and send us a copy of
all your correspondence with regard to this scheduled
audit.

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III. USEFUL PHRASES
Informing
INFORMING USEFUL PHRASES EXAMPLE
Reason for the memo. This memo is to advise you that... This memo is to advise you that your department has
Bản ghi nhớ này báo cho.. been scheduled for a periodic audit
Areas will be The ... will be reviewed... The completed checklist and original audit results will
audited/reviewed Cái... sẽ được xem xét... be reviewed with you and the Research and
Development Vice President
Objective of an action. Our goal is to... Our goal is to identify any areas requiring corrective or
Mục tiêu của chúng tôi là... preventive action before a summary report of the
status of these actions is issued.
Department involved. The... department is scheduled for... The production department is scheduled for an
Phòng.... được lên kế hoạch cho... internal audit next Monday.
Planned schedule The timetable is as follows:... The timetable for the various laboratory audits is as
Thời gian biểu như sau: ... follows:

What to prepare Please make sure that... Please make sure that all the laboratory staff are
Xin hãy đảm bảo rằng.. advised and prepared in accordance with standard
audit procedure
Ask for a copy of Please send us a copy of... Please send us a copy of all your correspondence with
something. Vui lòng gửi cho chúng tôi... regard to this scheduled audit.
Ask for verification Please confirm... Please confirm receipt of this memo.
Vui lòng xác nhận...

Complete Exercise 4 Pg.31

Match the tasks on the left with the phrases on the right.

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Exercise 5 Pg.32
Complete the memo to your own staff. Let them know about an upcoming audit. Use the Useful
Phrases

Exercise 7 Pg.33

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Asking questions during an audit
TALKING TO STAFF USEFUL PHRASES
Name What is your name?
Job/ position What is your job?
Supervisor name What is your supervisor’s name?
Supervisor job/ position What is your supervisor’s job?

ASKING ABOUT PROCESSES & USEFUL PHRASES

PROCEDURES
Training How have you been trained to perform this procedure?
Bạn được huấn luyện để thực hiện quy trình này như thế nào?
Time to complete a process How much time does it take to complete this part of the process?
Cần bao nhiêu thời gian để hoàn thành phần này của quy trình?
Special procedures that must What special procedures must be followed in a laboratory?
be followed Quy trình đặc biệt nào phải được tuân thủ trong phòng TN?
What special procedures must be followed for this process?
Quy trình đặc biệt nào phải được tuân thủ trong quá trình này?

ASKING ABOUT POSSIBLE USEFUL PHRASES

ACTIONS TAKEN
Actions How do you handle toxic waste in the lab?
Làm thế nào để xử lý chất thải độc hại trong phòng TN?
How do you handle the transportation of animals in the lab?
Làm thế nào để xử lý việc vận chuyển động vật trong phòng TN?
What would you do if you got a toxic substance on your lab coat?
Bạn sẽ làm gì nếu có một chất độc hại trên áo khoác TN của bạn?
What would you do if you noticed non‐compliance with safety procedures by a
colleague?
Bạn sẽ làm gì nếu bạn thấy một đồng nghiệp không tuân thủ các quy trình an
toàn?

Exercise 11 Pg.33
Match the areas of non-compliance found by the auditors with their observations

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Suggesting corrective action
NEUTRAL STRONG
1. I suggest (v)... 1. I strongly suggest (v)...
I suggest you put ‘No toxic waste’ on the bin. I strongly suggest that we try to prevent it in future.
2. My suggestion (n) ... 2. The only solution is ...
My suggestion is that we redo the equipment list. The only solution is to rethink the process.
3. My recommendation ... 3. I’m convinced ...
My recommendation is to talk to the lab workers. I’m convinced we must repeat the last tests.
4. It might be possible ... 4. It is absolutely essential
It might be possible to relocate the equipment. It is absolutely essential to learn the safety rules.

Exercise 12 Pg.36

Laboratory clothing and equipment

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Laboratory safety symbols

Exercise 13 Pg.36
Read excerpts from Berner Pharmaceuticals’ SOP on laboratory procedures. Then match them to warning signs a‐e.

IV. STANDARD OPERATING PROCEDURES

Useful phrases
REQUESTING INFORMATION USEFUL PHRASES
Describe Please describe the procedure for the... process.
Vui lòng mô tả các quy trình....
Clarify Would you please clarify how you... ?
...Vui lòng làm rõ làm thế nào....
Explain Could you explain the procedure for the documentation of... ?
Bạn có thể giải thích quy trình...

ASKING QUESTIONS USEFUL PHRASES

Guidelines What are the guidelines for... ?
Hướng dẫn cho ...là gì?
Frequency How often do you have to... ?
Bạn phải làm... bao lâu một lần?
Special procedures What special procedures do you follow for ... ?
Bạn làm theo quy trình đặc biệt nào...?
Action How would you ensure good hygiene in the laboratory?
Bạn đảm bảo vệ sinh trong phòng TN như thế nào?

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Formulating SOP guidelines
SOPs often use the following structure: Something + must be or should be + verb
1. Proper protective clothing and safety equipment must be worn at all times.
2. Proper safety procedures must be carried out by laboratory staff.
3. Toxic or hazardous materials must be disposed of properly.
Exercise 14 Pg.37
1. Perform all work with virus‐infected animals in the bio‐safety cabinet.
________________________________________________________________________________________
2. Use disinfectant on equipment following any experiments with laboratory animals.
________________________________________________________________________________________
3. Wipe up all chemical spills in the laboratory immediately.
________________________________________________________________________________________
4. Wear laboratory gowns or lab coats, latex gloves, and safety glasses at all times.
________________________________________________________________________________________
5. Cover small biological agent spills with a paper towel and treat them with bleach.
________________________________________________________________________________________
6. Document all laboratory work in accordance with GLP.
________________________________________________________________________________________

V. DRUG CONTAMINATION: LESSONS TO BE LEARNED?

A few years ago, a well‐known European pharmaceutical company was forced to ______(1) one of its drugs due to
claims of product contamination. The recall took place following reports from patients that their medication had a
strange odour. Several patients from a number of different countries made the complaint within a short period of
time. A few patients experienced nausea immediately after taking the medication. Unfortunately, the drug
manufacturer was unable to say just how many patients were taking this drug at the time. However, it estimated the
global figure at over 40,000 people.
Immediate investigations showed that samples of the tablets contained abnormally high levels of a harmful genotoxic
substance. The product __________(2)was traced back to its manufacturing plant. According to reports, it seems that
an unanticipated reaction between the drug's active ingredient and the chemicals used as part of the cleaning
processes at the site was the cause of the contamination.
The company claims that a cleaning error was the reason for the entire incident. This clearly underlines the danger of
underestimating the importance of the cleaning process in pharmaceutical manufacturing. ______ (3) of cleaning
processes is essential in this industry, because chemical or bacterial contamination of drug products can potentially
lead to severe public health risks. Regulatory bodies, such as the US Food and Drug Administration (FDA) and the
European Medicines Agency (EMEA), require validation of cleaning processes. In fact, if there is evidence that a
company is trying to save money by reducing their cleaning activities, these agencies take action.
In the above case, no other products manufactured by the pharmaceutical company were affected by the mistake and
the contamination error was quickly rectified. However, the recall left seriously ill patients without proper medicine.
The World Health Organization recommended that patients try to find a suitable alternative.
1. A. recall B. return C. refund D. rebate
2. A. complaint B. contamination C. purity D. performance
3. A. Validation B. Valid C. Value D. Valuable
4. Why was the company forced to recall one of its drug?
A. Product contamination caused by a genotoxic chemicals used as part of the packaging processes.
B. Product contamination caused by an unanticipated reaction between the drug's active ingredient and
the chemicals used as part of the cleaning processes.
C. Product contamination caused by an anticipated reaction between the drug's active ingredient and
the chemicals used as part of the cleaning processes.
D. Product contamination caused by an unanticipated reaction between the drug's inactive ingredient
and the chemicals used as part of the cleaning processes.

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5. A genotoxic substance is_____
A. a product contamination caused by the chemicals used as part of the cleaning processes.
B. a chemical that damages cellular DNA, resulting in mutations or cancer.
C. a chemical that repair cellular DNA, preventing mutations or cancer.
D. a substance that has toxic effects on the lungs.

6. An odour is ______
A. a distinctive unpleasant smell.
B. a chemical that damages cellular DNA, resulting in mutations or cancer.
C. a chemical that repair cellular DNA, preventing mutations or cancer.
D. a substance that has toxic effects on the lungs

VI. ANSWER KEY

VII. REVIEW QUESTIONS

Quizlet flash cards – Unit 3: https://goo.gl/QU4gq8
Quizlet test – unit 3 https://goo.gl/oET43R

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Study online at quizlet.com/_3t2jo1

1. Audit An internal __________ involves inspection and 21. non- If any __________ is observed during the audit,
validation of operational methods, compliance the department will be informed so they can
procedures, equipment to ensure take corrective action.
functionality, accuracy and validity.
22. Odour An __________ is a distinctive unpleasant smell.
2. Auditor A/An __________ inspects and verifies the safety
23. Overshoes __________ are shoe covers used to reduce foot
procedures in the lab.
borne contamination and help maintain a
3. CAPA __________ stands for Corrective sterile environment.
Action/Preventive Action. It is a part of the
24. Preventive __________ prevents occurrence of errors
overall Quality Management System (QMS)
action
required for GMP
25. Product Even a product that has been marketed for
4. Checklist To ensure that laboratory workers are asked
recall years might have to be taken off the market in
certain questions about safety procedures,
a __________ if serious adverse reactions occur.
auditors use a __________.
26. Product The reason for interim testing, or __________, is to
5. Contaminated __________ are no longer pure and acceptable
sampling check the quality of pharmaceutical products.
drugs for sale or public use and, therefore, must be
returned to the manufacturer, or destroyed. 27. Quality __________ involves all manufacturing processes
assurance in GMP which make sure the goods produced
6. Corrective __________ prevents recurrence of errors
are kept at high standards.
action
28. Quality __________ involves interim and product sampling
7. Endpoint At the end of every stage of a product's
control procedures, which are carried out to check
testing manufacturing process, __________ is done to
product quality.
maintain quality standards.
29. Quality __________ (QMS) is a formalized system that
8. Eye bath ___________ is a/an apparatus to wash the eyes
Management documents processes, procedures, and
after exposure to chemical contamination.
System responsibilities for achieving quality policies
9. Finding Any observation or _______ noted by the and objectives.
auditors is categorized as either major,
30. Safety __________ make sure that the health and well-
minor, or critical.
procedures being of laboratory workers are guaranteed.
10. Fire blanket A/an __________ is a safety device consists of a
31. Standard _________ are a set of written instructions to
sheet of a fire retardant material which is
operating maintain performance and results. They are
placed over a fire in order to extinguish it.
procedures the basis of good QA and QC system.
11. GAP __________ stands for Good Auditing Practice. (SOPs)
12. Gas mask A/an __________ is a device that you wear over 32. Traceability The documentation required for all research
your face in order to protect yourself from processes and development steps ensures
poisonous gases. the __________ of a drug.
13. GCP __________ stands for Good Clinical Practice. 33. up-to-date Scientists often read journals and go to
international conferences, because they need
14. GDP __________ stands for Good Documentation
to stay _________ in their scientific fields.
Practice
34. Validation Manufacturing processes and procedures
15. Genotoxic __________ is a chemical that damages cellular
must go through periodic __________ to
substance DNA, resulting in mutations or cancer.
guarantee that they are still of an acceptable
16. GLP __________ stands for Good Laboratory Practice. standard.
17. GMP __________ stands for Good Manufacturing
Practice.
18. GRP __________ stands for Good Research Practice
19. GSP __________ stands for Good Safety Practice
20. Holistic A __________ looks at all aspects of a
approach pharmaceutical company together to make
sure that the entire process meets high
industry standards.
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