Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5948_Библиотеки_им_академика_М_И_Перельмана
.pdf
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
1.
(a)
(b)
Health Canada I Health Products and Food Branch Inspectorate Validation Guidelines
for Pharmaceutical Dosage Forms (GUI – 0029) I December, 2009.
Note for Guidance on Process Validation – The Europe Agency fro Evaluation of
Medicinal Products; CPMP/QWP/848/96; EMEA/CVMP/598/99;
U.S. Food and Drug Administration, Manual of Standard Operating Procedures and
Policies, Communication, SOPP 8101.1, Version 1, Effectivity date February 11,
1999.
Federal Food, Drug and Cosmetic Act, Chapter III, Sections 301, 303, 304, as
amended by the FDA Modernization Act of 1997.
Federal Food, Drug and Cosmetic Act, Chapter V, Section 501 (a)(2)(B), as amended
by the FDA Modernization Act of 1997.
U.S. Food and Drug Administration, 21 CFR parts 210 & 211, Proposed Rule, Federal
Register, Friday May 3 1996 Docket No. 95N-0362.
U.S. Food and Drug Administration, 21 CFR parts 210 & 211, Proposed Rule, Federal
Register, Friday May 3, 1996 Docket No. 95N-0362, page 20113, proposed § 210.3
(b) (23).
U.S. Food and Drug Administration, 21 CFR parts 210 & 211, Proposed Rule, Federal
Register, Friday May 3, 1996 Docket No. 95N-0362, page 20115, proposed § 211.220
(c).
U.S. Food and Drug Administration, 21 CFR 601.12 (a), April 1, 2000.
Chaitanya kumar G, Rout RP, Ramtake S, Bhattachaiya S, Process Validation, The
Indian pharmacist, Aug 2005, 14-19.
Health Canada I Health Products and Food Branch Inspectorate Validation Guidelines
for Pharmaceutical Dosage Forms (GUI – 0029) I December, 2009.
Tetzlaff R. F, Sheppard R. E, LeBlanc A. J, The validation story, Perspectives on the
systemic GMP inspection approach and validation development. Pharm Tech March,
1993, 100– 116.
Zargar-Shoshtari K, Anderson W, Rice M (2015) Role of emergency ureteroscopy in
the management of ureteric stones: analysis of 394 cases. BJU Int 115:946–950.
Exercises
Multiple Choice Questions Carrying 01 Mark
Pharmaceutical process validation is the process which ensures
Enhancement of Cost of Quality of a product
Consistency in the Quality of a product
https://t.me/med1917
(c)
(d)
2.
(a)
(b)
(c)
(d)
3.
(a)
(b)
(c)
(d)
4.
(a)
(b)
(c)
(d)
5.
(a)
(b)
(c)
(d)
6.
(a)
(b)
(c)
(d)
7.
Increases the rejects
Increase the product recall
Quality of pharmaceutical product depends on
In-process testing of the product
Final testing of the product
Utilization of skilled personnel
Implementation of GMP
Quality of a product manufactured by a company depends on
Selection of quality components and materials
Appropriate product and process design,
Statistical control of the process through in-process and endproduct testing
All of the above
Conventionally the quality control procedures for finished product testing include
Establishment of specifications and performance characteristics,
Selection of appropriate method, equipment, and instrumentation to ensure that
testing of the product meets the specifications
All of the above
None of the above
Which of the following is not considered as a section of cGMP?
Marketing strategy
Equipment and building facilities
Production and process control
Packaging and labeling control
Validation activities should be performed by
Personnel who have necessary qualifications and experience in validation.
Personnel from same department
Management personnel only
Quality control personnel only
The validation master plan should be to the point and clear, unambiguous and should
contain
https://t.me/med1917
(a)
(b)
(c)
(d)
8.
(a)
(b)
(c)
(d)
9.
(a)
(b)
(c)
(d)
10.
(a)
(b)
(c)
(d)
11.
(a)
(b)
(c)
(d)
12.
(a)
(b)
(c)
Schedule of production
Schedule of Quality control test
Summary of facilities, systems, equipment and processes validated and to be
validated and calibrated
Schedule of sampling
The responsibilities of Metrology Personnel is to
Review and approve the calibration and/or service interval
Develop and control of metrology standard laboratory to support the ongoing
GMP processes at the premises
Review whether the performance of the calibration contractor can assure the
appropriate technical levels
Audit the calibration system to ensure the compliance with this document
Each item of the M & TE shall be assigned
A non-repetitive identification number
A repetitive identification number
An identification number
None of the above
The current Good Laboratory Practices is associated with
Humidity maintained in the production area
Precision of data
Sterilization temperature
Maintenance of equipments
Calibration Program are very much essential for
Packaging and labeling activities
Preventive Maintenance and Quality Assurance activities
Dispatch of finished products
Arrival of raw materials
The evaluation through installation qualification creates confidence that
The validation is performed for more than three times (three trials).
The operation is validated
The equipment is not accurately described
https://t.me/med1917
(d)
13.
(a)
(b)
(c)
(d)
14.
(a)
(b)
(b)
(d)
15.
(a)
(b)
(c)
(d)
16.
(a)
(b)
(c)
(d)
17.
(a)
(b)
(c)
(d)
18.
The equipment is properly installed meeting the specified guidelines set by the
manufacturer including the change in design at installation
The record pertaining to the SOPs for IQ does not cover which of the following?
Performance of the equipment
Set up of the equipment
Operation procedure of the equipment
Cleaning procedure of the equipment
The electronically interlocked barrier guards is provided for the
Avoiding chemical hazards
Protection from theft
Safety of the operator
None of the above
The purpose of testing equipment control function is to
See only whether the IQ records have been properly maintained or not
See whether the equipment contains any identification number
Verify whether the switches and push buttons are working properly as per the
manufacturer’s specifications
Verify whether validation of the equipment has been done properly
Which of the following is not mentioned in the validation Protocol Approval Sheet?
Steps taken for validation and acceptance criteria
The cost of the equipment purchased
Table of contents
Process flow chart
Which of the following parameters is not critically checked during validation of wet
granulation process for tablet preparation?
Mode of mixing of the ingredients
Mode and time of addition of the binder paste
Inlet/Outlet temperature and drying time during drying
Mixing time and speed during dry mixing
Which of following unit operations are primarily to be done to manufacture the
tablets?
https://t.me/med1917
(a)
(b)
(b)
(d)
19.
(a)
(b)
(b)
(d)
20.
(a)
(b)
(c)
(d)
1.
2.
3.
4.
5.
6.
7.
8.
Coating
Granulation
Drying
Compression
Which of the following points with respect to appearance of coated tablets should be
observed?
Color uniformity
Weight uniformity
Disintegration time
Thickness of the tablets
What is the full form of URS with respect to audit the risk management, governance,
training, climate change validation and verification energy audits and social
compliance audits?
United Republic of Sudan
Urban and Remote place of Switzerland
United Registrar of Systems
United Registrar of States
B. Short Questions Carrying 3-5 Marks
Define the term, validation as per USFDA. What are the important factors to be
considered as per FDA to assure the quality of a product?
Write down the steps are recommended by FDA for conventional the quality control
procedures for finished product testing and to materialize the pharmaceutical process
validation.
Write down the sections wise control and qualification documents to be recorded as
per cGMP guidelines.
What are advantages of validation of pharmaceutical manufacturing processes?
Why calibration of equipments and instruments used in pharmaceutical manufacturing
is done?
Differentiate between calibration and validation.
Why calibration of an instrument is done and how ICH guideline is involved in this
activity?
What are different types of validation? What are the importances of validation?
https://t.me/med1917
9.
10.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
What are the activities of URS?
10.What is meant by installation qualification of facility?
C. Long Questions Carrying 7-9 Marks
Briefly explain the scope of validation of processes involved in pharmaceutical
manufacturing.
Explain the terms, ‘Validation and Calibration Master Plan’. What are contents of a
typical Validation Master Plan?
What are the responsibilities of QA personnel, Metrology personnel and Instrument
users in a pharmaceutical manufacturing company?
What do you understand by ’the ICH guidelines for calibration of an instrument’ used
in pharmaceutical manufacturing industry?
Explain briefly the WHO guidelines for calibration of instruments and equipments
used in pharmaceutical manufacturing industry.
Point wise make a list of complete works to be done for validation with an assumption
that the work is being done from scratch.
What is meant by prospective validation? Prepare a list of equipments/facilities
including measuring, monitoring/recording equipment along with its calibration status.
Explain the term, ‘retrospect .0ive validation’. Write down some of the essential
elements for retrospective validation.
What are the purposes of URS inspection? Mention the salient features of technical
quality inspection by URS.
Explain briefly the pharmaceutical manufacturing process modeling.
Answers
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
b d d d a b c b a b b d a c c b a a b c
https://t.me/med1917
CHAPTER 4
cGMP & Industrial Management
Objectives and policies of current good manufacturing practices, layout of buildings,
services, equipment and their maintenance Production management: Production
organization, materials management, handling and transportation, inventory management
and control, production and planning control, Sales forecasting, budget and cost control,
industrial and personal relationship. Concept of Total Quality Management.
Introduction
In 1963 the first edition of GMP regulation was published in the United States. It was to be
followed for the manufacture, packaging, and storage of pharmaceutical products. In 1971 in
England the Inspectors of medicines of department of Health and Social Security compiled
and prepared the guide to GMP, in consultation with other related authorities. The guide was
also known as the Orange Guide because the color of its cover page was orange.
In 1978 the US FDA prepared the GMP regulations and circulated in the name of the United
States CFR Chapter 21. The content of the Orange Guide was restricted to the manufacture
of drug under the Medicines Act 1 . Principle wise both Orange Guide and GMP were
similar; but the Orange Guide was issued as an advisory whereas the GMP was introduced
as regulations. The first edition of the Orange book was of only 20 pages. In 1972 third
impression of this guide was reissued which contained extra 2 pages of appendix about
sterile medicinal products. The second edition of the guide was published in 1977. It
contained 52 pages and five appendices. In 1980, the series of guidance documents that have
a major effect on the interpretation of current GMP (cGMP) 2 was published by the US-FDA.
Third edition of the guide contained 110 pages and five appendices. It was published in the
year1983.
In 1983 the US congress approved the Federal Anti-tempering Act. According to the Act,
tampering of the packaged consumer products would be treated as a crime. In this year a
Guide to Inspection of Computerized Systems in Drug Processing was also published. In
1987, the guideline on General Principles of Process Validation was published. In March
1997, the US FDA issued 21 CFR Part 11 to deal with the use of electronic records and
signature and in 2000, the US FDA introduced a guidance document on the incorporation of
risk management into device development
3,4
. In 2007, the new edition of this Orange Guide
was published by the Medicines and Healthcare products Regulatory Agency (MHRA).
https://t.me/med1917
Objectives
The objective of Good Manufacturing Practices (GMPs) in pharmaceutical industry is to
record the production, distribution, and consumption of pharmaceutical products. The GMP
was introduced primarily to regulate manufacturing and packaging operations in the
pharmaceutical industry. To achieve permission from the competent authority (Drugs
Control Department) for marketing a product, it is necessary to have compliance with GMP.
Even the pharmaceutical industries of Western countries cannot sell their products in this
country without having the marketing authorization of this country. GMP compliance has
been almost accepted throughout the World. However, for implementation of GMP the
company has to upgrade the manufacturing as well as quality control facilities; hence, it
requires a major investment. As a result, small scale pharmaceutical industries face a
financial problem. The business in local markets also becomes a problem for these
companies.
Good Manufacturing Practice (GMP) facilitates assurance of Quality of pharmaceutical
product. The compliance with GMP ensures that the products being produced are
consistently assure the quality standards and suitable for their intended use. Thus, GMP can
reduce the risk of failure in pharmaceutical industry. There are two types of risk associated
with pharmaceutical products:
Cross-contamination, particularly with unexpected contaminants,
Mix-ups, particularly false labeling
Cross contamination refers to the contamination of a material at starting level, intermediate
stage, or after finish with another material at any stage. Usually, human beings working in
pharmaceutical industry, equipment, air, raw materials and water are the main sources of
cross contamination. Human beings work as the carrier for microbial contamination such as
staphylococcus species during manufacturing operations. The microbial species when
introduce into thee medicines the consequences may be life threatening and may cause
allergic reactions. All the contaminating microbes may not be susceptible to all
antimicrobials. Penicillin products should be
https://t.me/med1917
•
•
•
•
•
•
•
Fig. 4.1 Basic rules of GMP
produced and handled carefully and caution, because some people are sensitive to
penicillins. Since there is a possibility of cross contamination, penicillin products must be
produced under complete separate environment and area. Air carries many organic and
inorganic particles which contaminate the product and some degrade its quality. Water may
also contaminate a product, particularly when the pipe carries the water is not sanitized.
Many problems may occur due to contamination including study failure, premature death
and illness. Thus, to prevent these problems an effective risk management policy should be
implemented.
Therefore, the primary objectives of GMPs can be summarized as
5,6
:
To ensure that a drug or its product is being manufactured in a healthy and hygienic
condition,
To maintain the consistent quality of products,
To regulate the production, analysis, storage, and distribution of a product,
To ensure the maintenance of hygiene within the manufacturing premises,
To avoid cross contamination during any stage of handling of a drug product,
To ensure that only healthy personnel are involved in the manufacture of a drug
product,
There is no mix-up at any stage,
https://t.me/med1917
•
•
•
•
•
To ensure that proper environmental conditions including circulating air is being
maintained in a manufacturing premises,
To maintain all the records starting from incoming materials to outgoing products,
To ensure that the products are manufactured under strict and effective surveillance
and following the validated method of manufacture,
To reduce the product recall,
To reduce the cost of quality.
Policies of Current Good Manufacturing Practices
The purpose of this policy is to make sure that the compliance with current Good
Manufacturing Practice (GMP) regulations for food and drugs would ensure the in-built
quality of the products being manufactured and marketed. It is the responsibility of all
involved personnel at every level of the organization to act according to the policy and a risk
of violating this policy is to be detected. Departmental Managers are accountable for
compliance with this policy and the General Manager has final authority to take decision
regarding any GMP issue 7 .
As the drug handlers, we have a responsibility towards our customers to maintain high
standards of the drug safety. To ensure safety to the customers, high quality products are to
be produced and all the employees must follow all GMP’s listed below:
Personal Hygiene Requirements
Personal hygiene is very important. All personnel working in the production area are
expected to maintain a high degree of personal cleanliness. The following rules apply to all
of them:
Keep the finger-nails clean and neatly trimmed. Dirty nails are a popular place for
bacteria to hide and grow.
Nail polish is not permitted in the production area. The polish may flake off and
contaminate the product. Bacteria may also hide in cracks in the nail polish.
Every personnel must wear a protective hair net in the production area. There must be
no exposed or loose hair overhang from and under the hairnet. Hair carries many
microorganisms. (1 hair follicle can contain up to 50,000 microorganisms).
Men with mustaches or beards must cover them fully with a beard net.
All jewelry, including watches, must be removed when entering into the plant. Plain
wedding bands without stones or settings are allowed. This is not only to protect the
products being produced from contamination, but also to protect from injury and/or
the loss of a valuable possession. The skin-areas underneath the jewelry is normally
https://t.me/med1917
Соседние файлы в папке Библиотека им академика М.И. Перельмана