The document discusses Current Good Manufacturing Practices (CGMP) regulations enforced by the FDA to ensure drug products' identity, strength, quality, and purity. It outlines the history, objectives, requirements for facilities, personnel, equipment, and packaging, as well as the FDA's recall system to protect public health against defective products. The content also covers the classification of over-the-counter (OTC) drugs, safety regulations, and tamper-resistant packaging guidelines.

1. Presented By :Salma Rashid Shaikh
1st Year M.Pharm
Department Of Pharmaceutical Quality
Assurance

2. Current Good Manufacturing Practices
• Objective of CGMP
• CGMP facility requirements:
• Laws governing preparation and distribution of existing
product:
• A) CGMP
• B) OTC Human drug
• C) The FDA Recall System
• D)Temper Resistant Packaging
Content

3. CGMP refers to the Current Good Manufacturing
Practice regulations enforced by the FDA.
Adherence to the CGMP regulations assures the identity, strength, quality,
and purity of drug products by requiring that manufacturers of
medications adequately control manufacturing operations.
CGMP refers to the Current Good Manufacturing Practice regulations
enforced by the FDA.
CGMPs provide for systems that assure proper design, monitoring, and
control of manufacturing processes and facilities.
CGMP Definition

4. • cGMP regulation assures the Identity, Strength, Quality, and purity of the drug
product.
• The quality of product depends on the starting
material,production,building,equipment and personnel involved.
• In the manufacturing of product to ensure overall control and monitoring.
• Ensure the consumer receives product of specified quality.
• To detect and investigate product quality deviation
• To Obatained appropriate quality raw material
• Maintaining reliable testing laboratories.
• To prevent instances of Contamination, Mix-ups failure and error.
Objective of CGMP

5. 1902-Development of the biological control act
1906-Development of the pure food and drug Act
1937-Sulfanilamide Elixir incident
1938-fedral food, Drug and Cosmetic Act
1941-initiation of GMP
1944-Development of public Health service Act
1962- Kefauver-Harris Drug Amendments released (It introduced a requirement for drug manufacturers to provide
proof of the effectiveness and safety of their drugs before approval, required drug advertising to disclose accurate
information about side effects, and stopped cheap generic drugs being marketed as expensive drugs under new trade
names as new "breakthrough" medications)
CGMP Regulation

6. 1963-Establishment of GMPs for drug
1975 - camps for Blood and Components Final Rule
1976 - Medical Device Amendments
1978 - camps for Drugs and Medical Devices
1979 - GLPs Final Rule
1980 - Infant Formula Act is passed Sulfathiazole tablets contaminated with phenobarbital
1941 - 300 people died/injured FDA to enforce and revise manufacturing and quality control
requirements
1941 - GMP is born Thalidomide tragedy Thousands of children born with birth defects due to
adverse drug reactions of morning sickness pill taken by mothers Strengthen FDA’s regulations
regarding experimentation on humans and proposed new way how drugs are approved and regulated
“Proof of efficacy” law.

7. The approval process for new and generic drug marketing applications includes a review of the
manufacturer's compliance with the CGMPs.
FDA assessors and investigators determine whether the firm has the necessary facilities, equipment, and
ability to manufacture the drug it intends to market.
Code of Federal regulation(CFR) : FDA's portion of the CFR is in Title 21, which interprets the Federal food
,drug and cosmetic act and related statutes, including the Public Health Service Act.
 Code Of Federal Regulation(CFR)
21 CFR Part 210 Current Good Manufacturing Practice in Manufacturing Processing, packing, or
Holding of Drugs and Raw Material.
21 CFR Part 211 Current Good Manufacturing Practice for Finished Pharmaceuticals.
21 CFR Part 314 For FDA approval to market a new drug.
21 CFR Part 212 Current Good Manufacturing Practice for Positron Emission Tomography Drugs.
21 CFR Part 600 Biological Products: General.

8. Part-211 subdivided into following subparts:
1. Subpart A : General provision
2. Subpart B : organization and personnel
3. Subpart C : Building and facilities
4. Subpart D : Equipment's
5. Subpart E : Control of components and drug product containers
and closures
6. Subpart F : Production and process Control
7. Subpart G : Packaging and Labelling control
8. Subpart H : Holding and distribution
9. Subpart I : Laboratory Control
10.Subpart J : Records and Reports
11.Subpart K :Returned and salvaged drug product

9. Personnel
Sanitation
Premises
Equipment SOP’s
Batch
Manufacturing
Records
Self Inspection And
Audit
Master Formula
Records
General
considerations Raw Materials
Warehousing Area
Labels And Other
Printed Materials.
Components of CGMP

10.  GENERAL CONSIDERATIONS
a) Compliance with GMP
b) Consistent uniform batches
c) Location And surroundings
d) Water system e) Disposal Of Waste
 PERSONNEL
• Qualified Personnel:
a)Experienced
b)Sufficient Number
c) Written job description
d)Trained
• Health
a) Diseases. (communicable or non communicable).
b) Open Lesions.
C) Skin diseases.
d) Allergic conditions.

11.  PREMISES:
POINTS TO BE CONSIDERED.
1) Location 2) Design and Construction 4) Location Geography, climate and economic factors
Neighbours
Premises must be located to minimize risks of cross-contamination, e.g. not located next to a malting
factory with high airborne levels of yeast Pollution/effluent control.
• Building :it is evident that building used for manufacture,processing,packaging,labelling or
Holding of drug product should be clean and kept in an orderly manner.
Space provision must be made and gives certain general instruction on space utilization ,as for
following
1)The appropriate place of equipment and material to minimize the risk of mix-ups between different
drugs and all that is required to prepare a product(should also provide for the minimizing of cross
contamination).
2)The receipt, storage ,and holding of all substances for a pharmaceutical product before release for
use.

12. The law also specifies the Lighting,Ventilation and screening requird to control the environment of the
facility,together with other steps to asure that certain areas shall be protected from microbial contamination or dust
or be maintained at special humidity and room Temp. condition.
 Minimize contamination of product.
 Endeavour to minimize microbial contamination from one area to another regardless of the dosage form being
prepared.
 Provide storage condition that will maintain raw material and finished product in a stable form.
 Other general provision are as mentioned
 Suitable water must be available, continuously under pressure from a system free of defects,so that any water
used not been contaminated
 Locker facilities Must be provided for the employees such that they can prepare themselves for duties in their
work place.
 There must be a safe and sanitary procedure for the disposed of sewage ,trash and other Material.
 When needed suitable housing shall be provided for the care of any laboratory animals needed.

13.  Design
Minimize risks of errors Permit effective cleaning Permit effective maintenance Avoid cross-
contamination, build-up of dirt and dust Maximum protection against entry of insects, birds and animals
Separate facilities for other products such as some antibiotics, hormones, cytotoxic substances.
Maximum protection against entry of insects, birds and animals. Finishing floors, walls, and Ceilings
should be smooth, impervious, hard-wearing, easy to clean
Specific Areas
1) Production areas
2) Quality control areas
3) Weighing areas
4) Storage areas
5) Ancillary areas
Hygiene Eating, Drinking, Smoking Should not be allowed in the Production area.
 Plumbing
Potable water shall be supplied under continuous positive pressure in a plumbing system. Potable water
shall meet the standards prescribed in the Environmental Protection Agency's Primary Drinking Water
Regulations .
Drains shall be of adequate size and, where connected directly to a sewer, shall be provided with an air
break to prevent back siphonage.

14.  Washing and toilet facilities.
Adequate washing facilities shall be provided, including hot and cold
water, soap or detergent, air driers or single-service towels, and clean
toilet facilities easily accessible to working areas.
 Sanitation
There shall be written procedures for use of suitable rodenticides,
insecticides, fungicides, fumigating agents, and cleaning and
sanitizing agents.
 Maintenance
Any building used in the manufacture, processing, packing, or holding
of a drug product shall be maintained in a good state of repair

15.  Raw material:
Inventory should be maintained for Raw materials to be used at any
stage of manufacturing:
• Records should be maintain as per Schedule U.
• Should be purchased from approved sources.
• Must be checked by QC department on receipt
• Should be labeled
 Self Audit & Inspection
Regular independent inspection is necessary to evaluate the manufacturer’s
compliance with GMP in all aspects of manufacturing Procedure for self
inspection shall be documented indicating
a)Evaluation
b)Conclusion
c)Recommendations for Corrective action There should be a BMR ( Batch
Manufacturing Record) and MFR (Master Formula Record)

16.  EQUIPMENTS
Equipment shall be located, designed, constructed, adapted and maintained to suit the operation to be
carried out. Should be made of non reactive material, such as High grade of steel Equipment should be
a) Calibrated.
b) Checked.
c) Labelled.
d) Sterilized.
e) Accompanied with SOP.
Equipment used for the manufacture ,processing,packaging,labelling,holding,testing,or control of drugs
shall be maintained in a clean and orderly manner and shall be of suitable type,size,construction and
location to facilitate cleaning maintainance and operation for intended purpose.
The equipment should be:
1) So constructed that all surfaces that come into contact with a drug product shall not be
reactive,additive or absorptive.
2) So constructed and installed to facilitate adjustment,disassemble,cleaningand maintenance to assure
the reliability of control procedure,uniformity of production and exclusion from the drugs of contaminants
from previous and current operation
3) So constructed that any substances required for operation of the equipment such as lubricant,or
coolant,do not contact drug product.

17.  Packaging & Labeling Control
1. Materials examination and usage criteria.
 Records shall be maintained for each different labeling and packaging material indicating receipt,
examination or testing, and whether accepted or rejected.
 Labels and other labeling materials for each different drug product, strength, dosage form, or quantity
of contents shall be stored separately with suitable identification.
 Use of visual inspection to conduct a 100-percent examination for correct labeling during or after
completion of finishing operations.
2. Labeling issuance.
 Strict control shall be exercised over labeling issued for use in drug product labeling operations.
 Labeling materials issued for a batch shall be carefully examined for identity and conformity to the
labeling specified in the master or batch production records.
3. Packaging and labeling operations.
Prevention of mix-ups and cross-contamination by physical or spatial separation from operations on
other drug products
Examination of packaging and labeling materials for suitability and correctness before packaging
operations, and documentation of such examination in the batch production record.

18.  WAREHOUSING AREA (WAREHOUSE)
Warehousing area should be designed and adapted to
ensure good storage conditions.
Should be clean, dry and maintained with acceptable
temperature limits.
Should have appropriate house-keeping and rodents,
pests and vermin control. Separate sampling area for
active raw material and excipients.
Every Material stored should be labeled properly.
Fire Prevention.

19. OTC definition: OTC Drugs Are Defined As Drugs That Are Safe And Effective For Use By The General
Public Without Seeking Treatment By A Health Professional. Fda's Review Of OTC Drugs Is Primarily Handled By Cder's
Office Of Nonprescription Drugs.
In The Code Of Federal Regulations,title 21,part 330 Outlines The General Information For The Regulations Covering Otc
Human Drug Products That Are Generally Recognized As Safe And Effective And Not Misbranded.
Product Must Be Manufactured In Compliance With CGMP..
Materials That Are Under The Otc Classification Must Be Reviewed By The Appropriate Fda Division To Evaluate Elements
Concerning Labelling,quantities Of Active Ingredient,animal Safety Data,human Safety Data,and Other Elements That Would
Support The Marketing Of The Appropriate Products.
The Categories That Have Been Designated In The Otc Area Are Antacids,laxatives,antidiarrheal,emetics,anti
Emetics,antiperspirants,sunburn,treatments Product,dandruff Products,oral Hygiene Products,hematinics,sedative,and Other
Sleeping Aids,contraceptive Products,dentifrices And Dental Products,cold Remedies,ophthalmic Productsand Miscellaneous.
Over the counter(OTC) Human drug

20. Part 331-”antacid Products Of Over The Counter Human Use”.
In The Monograph ,Such Items Are Addressed As Active Ingredients, Test And Procedures, And
Labeling.
Very Specific Information Is Given On How Materials Are Categorized And What Tests Are Used For
Their Evaluations.
A Manufacturer Of These Particular Type Of Products Would Have To Comply With All Points As
Stated In The Regulations.
Depending On The Monograph, appropriate Warning Labels Are Necessary To Ensure Safety For The
Consuming Public.
This Might Include,”avoid Alcoholic Beverages While Taking This Product”, “Do Not Take This
Product If You Are Taking Sedatives Or Tranquilizers Without First Consulting Your Doctor,”and So
Forth.

21. The FDA Recall System
Overview
A recall is a method of removing or correcting products that are in violation of laws administered by the Food and
Drug Administration (FDA). Recall is a voluntary action that takes place because manufacturers and distributors carry
out their responsibility to protect the public health and well-being from products that present a risk of injury or gross
deception or are otherwise defective. 21 CFR 7 provides guidance so that responsible firms may conduct an effective
recall.
Medical device recalls are usually conducted voluntarily by the manufacturer under 21 CFR 7. In rare instances, where
the manufacturer or importer fails to voluntarily recall a device that is a risk to health, FDA may issue a recall order to
the manufacturer under 21 CFR 810,Medical Device Recall Authority.
21 CFR 810 describes the procedures the FDA will follow in exercising its medical device recall authority under
section 518(e) of the Federal Food, Drug, and Cosmetic Act (Act).
Under 21 CFR 806,Medical Device Correction and Removals, manufacturers and importers are required to make a
report to FDA of any correction or removal of a medical device(s) if the correction or removal was initiated to
reduce a risk to health posed by the device or to remedy a violation of the Act caused by the device which may
present a risk to health.

22. Definitions
Correction means repair, modification, adjustment, relabeling, destruction, or inspection (including
patient monitoring) of a product without its physical removal to some other location.
Market withdrawal means a firm's removal or correction of a distributed product which involves a
minor violation that would not be subject to legal action by the FDA or which involves no violation, e.g.,
normal stock rotation practices, routine equipment adjustments and repairs, etc.
Recall means a firm's removal or correction of a marketed product that the FDA considers to be in
violation of the laws it administers and against which the agency would initiate legal action, e.g.,
seizure. Recall does not include a market withdrawal or a stock recovery.
Recall strategy means a planned course of action to be taken in conducting a specific recall, which
addresses the depth of recall, need for public warnings, and extent of effectiveness checks for the recall.
Recalling firm means the firm that initiates a recall or, in the case of a Food and Drug
Administration-requested recall, the firm that has primary responsibility for the manufacture and
marketing of the product to be recalled.
Removal means the physical removal of a device from its point of use to some other location for
repair, modification, adjustment, relabeling, destruction, or inspection.

23. Risk to health means (1) A reasonable probability that use of, or exposure to, the product will cause
serious adverse health consequences or death; or
(2) That use of, or exposure to, the product may cause temporary or medically reversible adverse
health consequences, or an outcome where the probability of serious adverse health consequences is
remote.
Routine servicing means any regularly scheduled maintenance of a device, including the
replacement of parts at the end of their normal life expectancy, e.g., calibration, replacement of
batteries, and responses to normal wear and tear.
Repairs of an unexpected nature, replacement of parts earlier than their normal life expectancy, or
identical repairs or replacements of multiple units of a device are not routine servicing.
Stock recovery means the correction or removal of a device that has not been marketed or that has
not left the direct control of the manufacturer, i.e., the device is located on the premises owned, or
under the control of, the manufacturer, and no portion of the lot, model, code, or other relevant unit
involved in the corrective or removal action has been released for sale or use.

24. Classification
Recalls are classified
into a numerical
designation (I, II, or III)
by the FDA to indicate
the relative degree of
health hazard presented
by the product being
recalled.
Class I - a situation in
which there is a
reasonable probability
that the use of, or
exposure to, a violative
product will cause
serious adverse health
consequences or death.
Class II - a situation in
which use of, or
exposure to, a violative
product may cause
temporary or medically
reversible adverse health
consequences or where
the probability of
serious adverse health
consequences is remote.
Class III - a situation in
which use of, or
exposure to, a violative
product is not likely to
cause adverse health
consequences.

25. On November 5, 1982, regulations were issued in the federal register Concerning the use of tamper resistant packaging
for otc drugs, which included certain human drugs,Cosmetic Products , contact lens solution and solid dosage form.
This was due to the unfortunate poisoning that took place in chicago beginning. on September 30, 1982, and that was
followed by in tempering a the ensuring weeks involving tempering with Tylenol after distribution retail settings. A
temper-resistant package is defined as “one having an indicator or barrier to entry, which it breached or missing
reasonably be expected to provide visible evidence to consumers that tempering has occured“.
Because of the tragedy of 1982, this evidence an OTC products was very important to tablets, capsules, certain liquids
and other Substances that would be detrimental to the public it tempered with.
unfortunately it did not stop and during 1985 further tempering and cases occurred.
Packages considered to be tamper resistant are defined as follows:
 Film wrappers
 Blister or strip packs
 Bubble packs
 Shrinks seal and bands
 Foil,paper or plastic pouches
 Bottle seal
 Tape seal breakable caps
 Sealed tube
 Sealed carton
Tamper-resistant packaging

26. References:
1. Walter lund,the pharmaceutical CODEX, principle and practice of pharmaceutics, twelth edition, CBS
publishers, first indian reprint 2009,page no.371
2. S. Iyer, guidelines on compound quality of pharmaceutical products, published by D.K publication, first
edition, January 2003,page no.81-88
3. Manohar A.Potdar, cGMP current good manufacturing practices for pharmaceuticals, published by
pharmamed press, first edition 2012, page no.339,360,372
4. .P Sharma,how to practice Gmps,A plan for total quality control, VANDANA publication, second
edition,1995,page no.108,144,150,164
5. Angel S. arambulo,Quality control in the pharmaceutical industry,volume-3,universal book
corporation,page no.15,56.
6. https://www.fda.gov/drugs/pharmaceutical-quality-resources/facts-about-current-good-
manufacturing-practices-cgmps.
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399016/
8. Gilbert S.Banker,modern pharmaceutics,fourth edition,revised and expanded,page no.637-642.