GMP,GLP,USFDA, etc

1. REQUIREMENTS OF GMP, cGMP,
GLP, USFDA, AND ISO 9000
SERIES.
PRESENTED BY-
ABHISHEK SRIVASTAVA
M PHARM 2nd SEM
Email: abhishekshrivastav662@gmail.com
Department of Pharmaceutical Sciences Dr. HariSingh Gour University Sagar M.P 470003

2. CONTENTS
GMP
• INTRODUCTION
• REQUIREMENTS OF GMP,cGMP
GLP
,USFD
A,WHO
• INTRODUCTION
• REQUIREMENTS OF GLP ,USFDA & WHO GUIDELINES
ISO
• INTRODUCTION
• ISO 9000 SERIES

3. INTRODUCTION
 WHAT IS GMP?
 GMP stands for Good Manufacturing Practices
 GMP is that part of Quality Assurance which ensures that products are
consistently produced and controlled to the quality standard
appropriate to their intended use and as required by the marketing
authorization.
 "GMP" - A set of principles and procedures which, when followed by
manufacturers for therapeutic goods, helps ensure that the products
manufactured will have the required quality.
 GMP covers all aspects of “manufacture” including collection,
transportation, processing, storage, quality control and delivery of the
finished product.

4.  Good Manufacturing Practices (GMPs) are regulations that describe the
methods, equipment, facilities, and controls required for producing:
 Human and veterinary products
 Medical devices
 Processed food etc.
 GMP protects the consumer from purchasing a product, which is not effective
or even dangerous.
 GMP regulations address issues including record keeping, personnel
qualifications, sanitation, cleanliness, equipment verification, process
validation, and complaint handling.
 In short GMP makes the difference between nearly right and exactly right.

5. OBJECTIVES OF GMP
 To produce products conforming to the predetermined specifications
 To produce products of consistent quality
 To minimize contamination eg:- microbial contamination.
 To eliminate error.
 Government requirement.
 Ensure quality product.
 Reduce rejects, recalls.
 Satisfied customers.
 Company image and reputation.

6. cGMP
 cGMP stands for Current Good Manufacturing Practices.
 Manufacturers who follow cGMPs must employ technologies and systems
which are up to date that also comply with GMP regulations.
 This flexibility allows companies to use modern technologies and innovative
approaches to achieve higher quality through continual improvement.
 Current good manufacturing practices are defined by the FDA as systems to
assure proper design, monitoring, and control over manufacturing processes and
facilities in pharma and other FDA-regulated industries. These systems are
designed to help organizations assure drug products are the correct identity,
strength, purity, and quality.
 cGMP the "c" stands for "current," reminding manufacturers that they must
employ technologies and systems which are up-to-date to comply with the
regulation.

7.  Why are CGMPs so important?
 A consumer usually cannot detect (through smell, touch, or sight) that a drug
product is safe or if it will work.
 While cGMPs require testing, testing alone is not adequate to ensure quality.
 In most instances testing is done on a small sample of a batch (for example,
a drug manufacturer may test 100 tablets from a batch that contains 2
million tablets), so that most of the batch can be used for patients rather than
destroyed by testing. Therefore, it is important that drugs are manufactured
under conditions and practices required by the cGMP regulations to assure
that quality is built into the design and manufacturing process at every step.
 Facilities that are in good condition, equipment that is properly maintained
and calibrated, employees who are qualified and fully trained, and processes
that are reliable and reproducible, are a few examples of how CGMP
requirements help to assure the safety and efficacy of drug products.

8. REQUIREMENTS OF GMPAND cGMP
 1. GENERAL REQUIREMENTS
1.1. Location and surroundings
The factory buildings for mfg. of drugs shall be so situated or shall have such
measures as: -
 To avoid risk of contamination from external environment.
1.2. Building and premises
 The building should be designed in such a way that permits mfg.
operations in hygienic conditions.
 Compatible with other mfg. operations.
 Adequately provided with working space.
 To avoid risk of mix-ups.
 To avoid contamination.

9.  1.3. Water system
 There shall be validated system for treatment of water to render it potable.
 Potable water should be used to perform all the operations except cleaning
and washing. The storage tanks shall be cleaned periodically and records
maintained by the licensee.
 1.4. Disposal of waste
 The disposal of sewage and effluents shall be in conformity with the
requirements of Environment Pollution Control Board.
 All bio-medical waste shall be destroyed as per the provisions of Bio-
Medical Waste Rules, 1996.
 Record shall be maintained.
 Provision shall be made for proper storage of waste materials.

10.  2. Warehousing area
 Adequate areas for proper warehousing of various categories of materials
and products.
 Designed and adapted to ensure good storage conditions.
 Quarantine area shall be clearly demarcated and restricted to authorized
persons.
 Separate sampling area for active raw materials and excipients.
 3. Production area
 Designed to allow the production preferably in uni-flow and with logical
sequence of operations.
 Separate mfg. facilities shall be provided for the mfg. of contamination
causing and potent products such as;
 β-lactam, sex hormones and cyto-toxic substance.
 Service lines shall be Well designed and constructed, shall be identified by
colours. Direction of flow shall be marked.

11.  4. Ancillary areas
 Rest and refreshment rooms shall be separate from other areas. Facility for
changing, storing clothes and for washing and toilet purpose shall be easily
accessible and adequate.
 Areas for housing animals shall be isolated and maintained as prescribed in
rule 150- C (3) of D & C Rules, 1945.
 5. Quality control area
 Quality control laboratories shall be independent of the production areas.
 separate areas shall be provided each for physico-chemical, biological,
micribiological or radio –isotope analysis.
 Adequate space shall be provided to avoid mix-ups and cross
contamination.The design of the laboratory shall take into account the
suitability of construction materials and ventilation.

12.  6. Personnel
 The manufacture and testing shall be conducted under direct supervision of
qualified technical staff.
 Personnel for QA & QC shall be qualified and experienced. No. of personnel
employed shall be adequate and in direct proportion to the workload.
 Personnel in production and QC lab. shall receive training appropriate to the
duties & responsibility assigned to them.
 7.Sanitation in manufacturing premises
 Manufacturing premises shall be Cleaned and maintained according to
validated cleaning procedures.
 Manufacturing areas shall not be use as storage or thoroughfare.
 A Routine sanitation program shall be drawn up and observed. Area shall be
Well lightened production area particularly where visual on line controls
carried out.

13.  8. Raw materials
 The licensee Keep an inventory of all raw materials to be used at any stage
of production of drugs and maintain records as per Schedule U.
 All materials shall store under appropriate storage condition & follow ‘first
in/first expiry’–‘first out’ rule.
 Raw material from each batch checked for quality & appropriately labels
the storage area.
 There shall be adequate separate area for materials “under test”,
“approved”, and “rejected” with arrangement and equipment.It allow dry,
clean and orderly placement of stored materials and products, wherever
necessary ,under controlled temp.and humidity.
 Only raw materials which have been released by the quality control
department and which are within their shelf- life shall be used . It shall be
ensured that all the containers of raw materials are placed on the raised
platforms/racks and not placed directly on the floor.

14.  9. Equipments
 Equipment shall be located, designed, constructed, adapted and maintained
to suit the operations to be carried out. The layout and design of the
equipment shall aim to minimize the risk of errors and permit effective
cleaning and maintenance in order to avoid cross- contamination, build –up
of dust or dirt and in general any adverse effect on the quality of product.
 Balance and other measuring equipment of an appropriate range, accuracy
and precision shall be available in the raw material stores, production and in
process control operation and these shall be calibrated and checked on a
scheduled basis in accordance with SOP and record maintained.
 To avoid accidental contamination, wherever possible, nontoxic / edible
grade lubricant shall be used and the equipment shall be maintained in a
way that lubricants don”t contaminate the products being produced.
 Defective equipment shall be removed from production and quality control
areas or appropriately labeled.

15.  10. Documentation and records
 It is the essential part of the Quality assurance system. as such , shall be
related to all aspect of GMP.
 Its aim is to define the specification for all materials, method of mfg. and
control, to ensure that all personnel concerned with manufacture know the
information necessary to decide whether or not to release a batch of a drug
for sale and to provide an audit trail that shall permit investigation of the
history of any suspected defective batch.
 Documents shall be approved, signed and dated by appropriate and
authorized persons.
 Document designed, prepared, reviewed and controlled, wherever
applicable, shall comply with these rules.
 The records shall be made or completed at the time of each operation in
such a way that all significant activities concerning the mfg. of
pharmaceutical product are traceable.

16.  11. Self-inspection and Quality audit
 It may be useful to constitute a self-inspection team supplemented with a
quality audit procedure for assessment of all or part of a system with the
specific purpose of improving it.
 Ensures that a company‟s operations remain compliant with GMP.
 Assists in ensuring continuous quality improvement.
 Should cover all aspects of production and quality control which are
designed to detect shortcomings in the implementation of GMP.
 Must recommend corrective action if shortcomings are observed and set a
timetable for corrective action to be completed.
 Special occasions may demand additional self-inspections. For example
 Recalls, Repeated rejections ,GMP inspections announced by the National
Drug Regulatory Authority.

17.  Quality Audit
 A quality audit consists of examination and assessment of all or part of a
quality system with the specific purpose of improving it. A quality audit is
usually conducted by outside or independent specialist or a team designed
by a management for this purpose. Such audits may also be conducted to
suppliers and contractors.
 12.Quality Control System
 Quality control shall be concerned with sampling, specification, testing,
documentation, and release procedures.
 It is not confined to laboratory operations but shall be involved in all
decisions concerning the quality of the product.
 The department as a whole shall have other duties such as to establish,
evaluate, validate and implement all Quality control procedure and
methods.

18.  All the batches released after certification of QC department. The area of
the quality control laboratory may be divided into chemical, instrumentation
,microbiological and biological testing.
 Adequate area having the required storage conditions shall be provided for
keeping references samples. The quality control department shall evaluate,
maintain and storage reference samples.
 All instruments shall be calibrated and testing procedures validated before
these are adopted for routine testing. Periodical calibration of instrument
and validation of procedures shall be carried out.
 Pharmacopoeias, reference standard, reference spectra, other references
materials and technical books, as required , shall be available in the quality
control laboratory of the licensee.

19.  13.Master formula records: -
 Related to –
 All mfg. procedures for each product.
 Batch size to be manufactured.
 Includes:-
Name of product with reference code.
Patent & proprietary name with generic name.
Description of dosage form.
Name, quantity & reference no. Of all starting material.
Detailed SOP with the time taken for each step.
Requirements for storage conditions of the products, containers, labeling
Packaging detail and specimen labels.

20.  14.Packaging records:-
 There shall be Authorized packaging instructions for each product, pack
size and type that includes; Name of product with other description,
volume of product in final container.
Complete list of all the packaging materials with quantities size & type.
Description of packaging operations.
 15.Product Recalls: -
 A prompt and effective recall system of defective products shall be
devised for timely information of all concerned stockists, wholesalers,
suppliers, up to the retail level within the shortest period.
 The distribution records shall be readily made available to the persons
designated fore recalls.
 The effectiveness of the arrangements for recalls shall be evaluated
from time to time. The recalled products shall be stored separately in a
secured segregated area pending final decision on them.

21. GLP(GOOD LABORATORIES
PRACTICES)
 GLP is an FDA Regulation
 GLP is a formal regulation that was created by the FDA(United
States Food and Drug Administration)in 1978.
 GLP embodies a set of principles that provides a framework within
which laboratory studies are planned performed ,monitored, and
achieved and reported.

22. WHY WAS GLP CREATED?
In the early 70's FDA became aware of
cases of poor laboratory practice all over
the United States.
They discovered a lot fraudulent
activities and a lot of poor lab practices.
Examples of some of these poor lab
practices found were-
1. Equipment not been calibrated to
standard form, therefore giving wrong
measurements.
2. Incorrect/inaccurate accounts of the
actual lab study.
3. Inadequate test systems.

23. PURPOSE OF GLPs:
GLP is to certify that every step of the
analysis is valid or Not.
• Assure the quality & integrity of data
submitted to FDA in support of the
safety of regulated products.
• GLPs have heavy emphasis on data
recording, record & specimen retention.

24. GOOD LABORATORY PRACTICES
PRINCIPLES
 1. Test Facility Organization and Personnel
 2. Quality Assurance Programme (QAP).
 3. Facilities.
 4.Apparatus, Material and Reagents.
 5. Test systems.
 6. Test and Reference Substances.
 7. Standard Operating Procedures (SOP).
 8. Performance of The Study.
 9.Reporting of Study Results.
 10. Storage and Retention of Records and materials.

25. 1.TEST FACILITY ORGANIZATION AND
PERSONNEL
 Personnel Responsibilities
 Should have the knowledge of the GLP
principles.
 Access to the study plan and appropriate SOP’s.
 Comply with the instructions of the SOP’s.
 Record raw data.
 Study personnel are responsible for the quality of
their data.
 Exercise health precautions to minimize risk
 Ensure the integrity of the study.

26. 2.QUALITY ASSURANCE PROGRAMME
(Responsibilities of the QA Personnel)
 Access to the updated study plans and SOPs
 Documented verification of the compliance study plan to the GLP
principles.
 Inspection to determine compliance of the study with GLP
principles.
 Three types of inspection.
 Study Based inspection
 Facility based inspections
 Inspection of the final reports for accurate and full description.
 Report the inspection results to the management
 Statements

27. 3.FACILITIES
 Suitable size ,construction and location
 Adequate degree of separation of the different activities.
 Isolation of test system and individual project from biological
hazards.
 Suitable rooms for the diagnosis treatment and control of disease .
 Storage Rooms .

28. 4.APPARATUS MATERIALS AND
REAGENT
 Apparatus of appropriate design and
adequate capacity.
 Documented Inspection, cleaning,
maintenance and calibration of apparatus.
 Apparatus and materials not to interfere with
the test systems.
 Chemicals, reagent and solutions should be
labeled to indicate identity, expiry and
specific storage instructions.

29. 5.TEST SYSTEM
 Physical and chemical test systems.
 Biological test systems.
 Records of source, date of arrival, and
arrival conditions of test systems.
 Proper identification of test systems in their
container or when removed.
 Cleaning and sanitization of containers.
 Pest control agents to be documented.

30. 6. TEST AND REFERENCE ITEMS
 Receipt, handling, sampling and storage
 Characterization.
 Known stability of test and reference items.
 Stability of the test item in its
vehicle(container).
 Experiments to determine stability in tank
mixers used in the field studies.
 Samples for analytical purposes for each
batch

31. 7.STANDARD OPERATING
PROCEDURES (SOP)
 Written procedures for a laboratories
program.
 They define how to carry out protocol
activities.
 Most often written in a chronological listing
of action steps.
 They are written to explain how the
procedures are suppose to work

32. 8. PERFORMANCE OF THE STUDY
 Prepare the Study plan.
 Content of the study plan.
 Identification of the study,
 Records.
 Dates.
 Reference to test methods.
 Information concerning the sponsor
and facility.
 Conduct of the study.

33. 9. REPORTING OF STUDY RESULTS
 Information on sponsor and test facility
 Experimental starting and completion dates.
 A Quality Assurance Program Statement.
 Description of materials and test methods.
 Results.
 Storage (samples, reference items, raw data,
final reports) etc.

34. 10. STORAGE AND RETENTION OF
RECORDS AND MATERIALS
 The study plan, raw data, samples.
 - Inspection data and master schedules.
 - SOPs.
 Maintenance and calibration.
 If any study material is disposed of before
expiry the reason to be justified and
documented.
 Index of materials retained.

35. CONCLUSION
 Gives better image of company as a Quality producer in Global
market
 Provide hot tips on analysis of data as well as measure uncertainty
and perfect record keeping & guideline for doing testing and
measurement in detail.
 Finally GLP Provide guidelines and better control for maintenance
of instruments, environment control ,preservation of test records etc.

36. USFDA
 The Food and Drug Administration (FDA or USFDA) is an agency of
the United States Department of Health and Human Services, one of
the United States federal executive departments.
 The FDA is responsible for protecting and promoting public health
through the regulation and supervision of food safety, tobacco
products, dietary supplements, prescription and over-the-counter
pharmaceutical drugs (medications), vaccines, biopharmaceuticals,
blood transfusions, medical devices, electromagnetic radiation emitting
devices (ERED), veterinary products, and cosmetics.
 The FDA also enforces other laws, notably Section 361 of the Public
Health Service Act and associated regulations, many of which are not
directly related to food or drugs.

37. OBJECTIVES OF FDA
 The FDA is responsible for protecting the public health by assuring
the safety, efficacy, and security of human and veterinary drugs,
biological products, medical devices, our nation’s food supply,
cosmetics, and products that emit radiation.
 The FDA is also responsible for advancing the public health by
helping to speed innovations that make medicines and foods more
effective, safer, and more affordable; and helping the public get the
accurate, science-based information they need to use medicines and
foods to improve their health.
 To participate with representatives of other countries to reduce the
burden of regulation, coordinate regulatory requirements, and
achieve appropriate equivalent arrangements.

38. WHAT FDA REGULATES
 FDA is the federal agency responsible for ensuring that foods are
safe, wholesome and sanitary; human and veterinary drugs,
biological products, and medical devices are safe and effective;
cosmetics are safe; and electronic products that emit radiation are
safe.
 FDA also ensures that these products are honestly, accurately and
informatively represented to the public.
WHAT FDA NOT REGULATES
 Advertising - except for prescription drugs, medical devices, and
tobacco products.
 Alcohol beverages .
 Consumer Products - paint, child-resistant packages, baby toys, and
household appliances (except for those that give off radiation).

39.  Drugs of Abuse - heroin and marijuana
 Health Insurance
 Meat and Poultry - except for game meats, such as venison, ostrich, an
snake.

40. ISO (INTERNATIONAL ORGANIZATION
FOR STANDARIZATION )
 The International Organization for Standardization is an independent,
non-governmental organization, whose membership consists of different
national standards bodies.
 As of 2022, there are 167 members representing ISO in their country,
with each country having only one member.
 The organization develops and publishes international standards in all
technical and nontechnical fields other than electrical and electronic
engineering, which are the responsibility of the International
Electrotechnical Commission.
 As of April 2022, the ISO has developed over 24,261 standards,
covering everything from manufactured products and technology to
food safety, agriculture, and healthcare.

41. ISO 9000
 ISO (International Organization for Standardization) has published
22027 International Standards (As on 5th Feb, 2018).
 ISO 9000 is one among the most popular standards of ISO.
 ISO 9000 is -A series of Quality Management System (QMS)
standards,
 Provide guidance and tools for companies and organizations,
 To ensure that their products and services consistently meet
customer’s requirements,
 For Consistent improvement in quality.

42.  ISO 9000-FAMILY OF STANDARDS
 ISO 9000 is a series of quality management system standards which
includes the following:
 ISO 9000:2015 - This specifies the fundamentals and vocabulary used in
all these ISO 9000 standards.
 ISO 9001:2015 - This is the Requirement standard that provides directions
on how to achieve quality requirements,
 Meet the significant regulatory requirements,
 Improve satisfaction for all stakeholders (customers, shareholders etc)
 Have a method of identifying and implementing the improvements.

43. ISO 9000:2015 principles of Quality
Management
 The ISO 9000:2015 and ISO 9001:2015 standards are based on seven
quality management principles that senior management can apply to
promote organizational improvement.


44.  ISO 9001:2015 specifies requirements for a quality management system
when an organization:
 a) needs to demonstrate its ability to consistently provide products and
services that meet customer and applicable statutory and regulatory
requirements, and
 b) Aims to enhance customer satisfaction through the effective application
of the system, including processes for improvement of the system and the
assurance of conformity to customer and applicable statutory and
regulatory requirements.
 All the requirements of ISO 9001:2015 are generic and are intended to be
applicable to any organization, regardless of its type or size, or the
products and services it provides.

45. REFERENCES
 1)Lachman, Leon, Herbert A. Lieberman, And Joseph L. Kanig “The
Theory And Practice Of Industrial Pharmacy” Philadelphia: Lea &
Febiger, 1976, Page No 804 .
 2)Good Laboratory Practice. By European Chemical Industry Ecology
And Toxicology Centre (Ecetoc), Monograph No. 1,brussels October
1979.
 3)Good Laboratory Practice. By G.E. Paget, Mtp Press Limited, Lancaster
1979.
 4)Dr. B.S. Kuchekar, Mr. A.M. Khadatare, FORENSIC PHARMACY 7th
Edition August 2007 Published By- NIRALI PRAKASHAN ,PP-17.8 To
17.11, 17.25 To 17.28
 5)Sachin C. Itkar, PHARMACEUTICAL MANAGEMENT 3rd Edition
May 2007 Published By- NIRALI PRAKASHAN ,PP-18.1 To 18.4 ,
18.21 To 18.24

46. THANKYOU
ANY QUESTION?