Concept of GMP & cGMP - PowerPoint Presentation

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Concept of GMP & cGMP

Dr. M.P.

Gowrav

Assistant Professor

JSS College of Pharmacy

S.S. Nagar, Mysuru-570015

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Contents

Introduction

Definition

Why GMPEvolution of GMPPrinciples of GMPWHO GMPUSFDA cGMPEuropean Medicines agency GMPPICsIndian GMPCFRHistory of CFRCFR Title 21References

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Students should be able toUnderstand the concept of GMP &

cGMP

Understand WHO GMP, EMA GMP & US

cGMPKnow the history of CFR & Parts of CFR3Learning outcomes

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DEFINITION: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.

Good Manufacturing Practices (GMPs) are regulations that describe the methods, equipment, facilities, and controls required for producing:

Human

and veterinary productsMedical devicesProcessed food4Introduction

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Usually see “cGMP” – where c = current, to emphasize that the expectations are dynamic. It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product.

These regulations, which have the force of law, require that manufacturers, processors, and packagers of drugs, medical devices, some food, and blood take protective steps to ensure that their products are safe,

pure and effective.

Require a quality approach to manufacturing, enabling companies to minimize or eliminate instances of contamination, mix-ups and errors. 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.5Introduction

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Final testing of the product cannot ensure the Quality efficiency and safety.Final testing may always not detect contamination, error, etc.

Conformance

to the predetermined specification.

To minimize contamination eg:- microbial contamination.To eliminate error.To produce product of consistent quality.Government requirement. Ensure quality product. Reduce rejects, recalls. Satisfied customers. Company image and reputation. 6Why GMP?

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1963: - first GMP publication –USA1971: -first revision1978: - Major revision

Current

regulation of GMP appear in part 210 (title 21) of code of federal regulations published by USFDA

7EVOLUTION OF GMP

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Unexpected contamination of products, causing damage to health or even death.Incorrect labels on containers, which could mean that patients receive the wrong medicine.Insufficient

or too much active ingredient, resulting in ineffective treatment or adverse effects.

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MAIN RISKS WITHOUT GMP

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Design and construct the facilities and equipments properlyFollow written procedures and Instructions

Document

work

Validate workMonitor facilities and equipmentWrite step by step operating procedures and work on instructionsDesign ,develop and demonstrate job competenceProtect against contaminationControl components and product related processesConduct planned and periodic audits9PRINCIPLES OF GMP

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WHO GMP requirements, norms and standards are useful for acceptance of product applications through the prequalification process for participation in global procurement programmesThese serve as reference guidance for national medicines regulatory authorities to enforce

Most NMRAs from developing countries follow the WHO GMP guidelines

WHO guidelines on GMP are contained in:

TRS 986Annex 3 TRS 822 (Biological products)Annex 4 TRS 937 (Validation & QA)Annex 5 TRS 961 (non-sterile products)Annex 6 (Sterile [pharmaceutical products- under revision to consolidate EU, PIC/S & WHO)Appendix 7, Annex 3 TRS 932 (validation of sterile products) Annex 7 TRS 908 (risk analysis application of Hazard analysis and critical control point)Annex 7 TRS 961 (transfer of technology)10WHO Good Manufacturing Practices

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cGMP refers to the Current Good Manufacturing Practices that are enforced by the US FDAThe US FDA governs

cGMP

through Code of Federal Regulations (CFR: title 21 (parts 1-1499)

CFRs have a legal binding force under Title 21 which interprets the Federal Food, Drug and Cosmetics Act and related statutes, including Public Health Service ActThe regulations enable a common understanding of the regulatory process by describing the requirements to be followed by drug manufacturers, applicants, and FDA21 CFR Part 314 - For FDA approval to market a new drug21 CFR Part 210 - Current Good Manufacturing Practice in Manufacturing Processing, packing, or Holding of Drugs21 CFR Part 211 - Current Good Manufacturing Practice for Finished Pharmaceuticals21 CFR Part 212 - Current Good Manufacturing Practice for Positron Emission Tomography Drugs21 CFR Part 600 - Biological Products11US Food and Drug Administration cGMP

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European medicines Agency (EMA) co-ordinates GMP and has a pivotal role in harmonization of GMP activities within European Union (EU)GMP mandate in EMA is enforced through regulations, directives and guides (provided under

Eudralex

)

Currently, regulation No. 1252/2014 (APIs) and directives 2003/94/EC (human medicines) and 91/412/EEC (veterinary medicines) applyRegulations have binding legal force in every Member State and enter into force on a defined date while directives lay down outcomes that must be achieved; therefore, each member state may have independent interpretation when transposing into national lawsEMA is only responsible for products authorized through the centralized procedure while Competent national authorities are responsible for products authorized at national level12European Medicines Agency GMP

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The Pharmaceutical Inspection Co-operation Scheme (PIC/S) is a non-binding, informal co-operative arrangement between Regulatory Authorities in the field of Good Manufacturing Practice (GMP) of medicinal products for human or veterinary useIt is open to any Authority having a comparable GMP inspection system

Currently has 52 active members, including US FDA, Health Canada's Regulatory Operations and Enforcement Branch, the South African Health Products Regulatory Authority, and several regulatory agencies of countries in Europe, Asia, the Middle East and the Americas

The PIC/S GMPs are equivalent to the EU GMP guidelines in terms of GMP requirements.

13Pharmaceutical Inspection Co-operation Scheme (PIC/S)

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Indian GMP regulations are underpinned by the Drugs and Cosmetics Act, 1940 under Rules 1945 (Schedule M)These are to be interpreted with many other conditions laid down under various rulesSchedule M covers all aspects of production from the raw materials, premises and equipment to the training and personnel

hygiene.

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Indian GMP

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What is CFR ?The Code of Federal Regulations (CFR) is the codification of the general and permanent rules and regulations (sometimes called administrative law) published in the Federal Register by the executive departments and agencies of the federal

government

of the United States

.The CFR is divided into 50 titles that represent broad areassubject to federal regulation.15CODE OF FEDERAL REGULATIONS (CFR)

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Each title is further divided into chapters, subchapters, parts, and sections.A regulation is cited by title, part, and section, e.g. 14

CFR 121.313

(Title 14, Part 121, Section 313

).The soft-cover volumes of the CFR are issued each year :Titles 1 – 16 are updated as of January 1Titles 17 – 27 are updated as of April 1Titles 29 – 41 are updated as of July 1Titles 42 – 50 are updated as of October 116CODE OF FEDERAL REGULATIONS (CFR)

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The online CFR is a joint project authorized by the publisher, the National Archives and Records Administration's (NARA) Office of the Federal Register (OFR), and the

Government Publishing

Office (GPO) to provide the public with

enhanced access to Government information.17CODE OF FEDERAL REGULATIONS (CFR)

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Franklin D. Roosevelt – 32nd President of the US.1935 - Instrumental in passing the Federal Register Act – empowered the National

Archives of

the US to form an Administrative Committee

– publish the Federal Register.The Federal Register Act - amended in 1937 to provide a “codification” of all regulations every five years – known as Code of Federal Regulations.18HISTORY OF CFR

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The first edition of the CFR was published in 1938 and included all finalized regulations that were published in the Federal Register from March 14, 1936 to June 1, 1938 Beginning in 1963 for some titles and for all titles in 1967, the Office of the Federal Register began publishing yearly revisions.

Beginning

in 1972 - published revisions were conducted in staggered quarters

.19HISTORY OF CFR

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Title 21 of the CFR is reserved for rules of the Food and Drug Administration.Governs food and drugs within the United States

for the

FDA, DEA, and the ONDCP.

In all, 21 CFR consists of 1499 parts.It is divided into three chapters:Chapter I — Food and Drug AdministrationChapter II — Drug Enforcement AdministrationChapter III — Office of National Drug Control Policy20CFR TITLE 21

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Most of the Chapter I regulations are based on the Federal Food, Drug, and Cosmetic Act.Notable sections:

– 11 Electronic records and electronic signature related.

– 50 Protection of human subjects in clinical trials.

– 54 Financial Disclosure by Clinical Investigators.– 56 Institutional Review Boards that oversee clinical trials.– 58 Good Laboratory Practices (GLP) for nonclinical studies.21CHAPTER I

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The 100 series are regulations pertaining to food.The 200 and 300 series are regulations pertaining to pharmaceuticals

The

500 series are regulations for animal

feeds and animal medications.The 600 series covers biological products.The 700 series includes the limited regulations on cosmetics.The 800 series are for medical devices.22CHAPTER I

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The 900 series covers mammography quality requirements enforced by CDRH.The 1000 series covers radiation-emitting device

The

1100 series includes updated rules with regards

to tobacco products.The 1200 series consists of rules primarily based in laws other than the Food, Drug, and Cosmetic Act:– Requirements for pasteurization of milk.– Sanitation on interstate conveyances.23

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Notable sections:– 1308 — Schedules of controlled substances1308.03(a) — Administrative Controlled Substances

Code Number

1308.11

— List of Schedule I drugs1308.12 — List of Schedule II drugs1308.13 — List of Schedule III drugs1308.14 — List of Schedule IV drugs1308.15 — List of Schedule V drugs24CHAPTER II

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The list of SCHEDULED DRUGS, as a part of the Controlled Substances Act, falls under the drug policy of the United States government. The following findings are required

for drugs

to be placed in the aforementioned schedules:

– The drug or other substance has a high potential for abuse.– The drug or other substance has no currently accepted medical use in treatment in the United States.– There is a lack of accepted safety for use of the drug or other substance under medical supervision.Administrative Controlled Substances Code Number (ACSCN)25

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There are a number of electronic sources for accessing CFR. For instance - FDsys.gov and the now GovInfo

, the

official online

document repository for the U.S. Government Publishing Office, is fully browsable, searchable, navigable by citation.GPO also maintains an up-to-date “Electronic Code of Federal Regulations (e-CFR)” service which presents CFR sections in their current form with any recent amendments from the Federal Register already incorporated. The e-CFR service is updated daily and also allows you to separately view appendices and supplements.26CFR in Modern Times

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TABLE OF CONTENTS –– CFR titles are broken down by chapter, subchapter, and part

.

– Immediately preceding each part is a table of contents

for the individual regulations contained within that part .TABLE OF CFR TITLES AND CHAPTERS –– Redesignation tables to help trace new location of parts and sections of A regulationLIST OF CFR SECTIONS AFFECTED IN THE VOLUME –– List of CFR Sect ions Affected in Each Volume indicates the Type of Change that was made.27Research Tools in CFR

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The Federal Register and the Code of Federal Regulations replaced the existing system of dual set of regulations and legislations that were in place. Although not perfect, the Federal Register and the CFR appear to have met their original purpose of providing the public with a comprehensive publication vehicle for all the regulations issued by Federal agencies and the President.

The

CFR provided a codified form of the regulations, based on title, chapters and subjects, that streamlined the process of finding the required regulations and laws for the pharmaceutical industry and the public in general, thereby making these guidelines easily accessible

28Key Points (Summary)

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References

FDA: Current Good manufacturing Practices (

cGMP

regulations) (accessed: https://www.fda.gov/drugs/pharmaceutical-quality-resources/current-good-manufacturing-practice-cgmp-regulations) EMA: Good manufacturing Practice (accessed: https://www.ema.europa.eu/en/human-regulatory/research-development/compliance/good-manufacturing-practice#legal-framework-and-guidance-sectionMcgee Pharma International (Nov. 2016): EU and US GMP/GDP: Similarities and Differences WHO (2014): Good manufacturing practices for pharmaceutical products: main principles In: WHO Expert Committee on Specifications for Pharmaceutical Preparations. Forty-eighth report. Geneva, World Health Organization (WHO Technical Report Series, No. 986), Annex 2. Uma Vasireddy (2015) 4th International Summit on GMP, GCP and Quality control: Comparison of guidelines of Indian GMP with WHO GMP (accessed: https://gmp-gcp-qualitycontrol.pharmaceuticalconferences.com/abstract/2015/comparison-of-guid elines-of-indian-gmp-with-who-gmp) India GMP: Schedule M (Part 1): Good manufacturing practices and requirements of premises, plant and equipment for pharmaceutical products.

http

://

www.llsdc.org/fr-cfr-research-guide

Panama

Refining Co. v. Ryan, 293 U.S. 388 (1935). Available

from: https

://supreme.justia.com/cases/federal/us/293/388/case.html

Griswold

, E.N. Government in ignorance of the law; a plea for

better publication

of executive legislation. 48

Harv

. L. Rev. 198-215 (1934

). Available from: https

://public.resource.org/48HarvLRev198.pdf

CFR

- Code of Federal Regulations Title 21. Available from

:https

://

www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm (Accessed

on 13th

July 2020)

https

://

en.wikipedia.org/wiki/Title_21_of_the_Code_of_Federal_Regulations

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Thank

You

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