C-3 cGMP

7/31/2019 C-3 cGMP

1/100

Chapter 3

cGMP and cGCP

7/31/2019 C-3 cGMP

2/100

Organization and Personnel

Responsibilities of quality control unit

Personnel qualifications

Personnel responsibilities

Consultants

7/31/2019 C-3 cGMP

3/100

Building and Facilities

Design and Construction features

Lighting

Ventilation, air filtration, air heating and cooling

Plumbing

Sewage and refuse

Washing and toilet facilities

Sanitation

Maintenance

7/31/2019 C-3 cGMP

4/100

Equipment

Equipment design, size, and location

Equipment construction

Equipment cleaning and maintenance

Automatic, mechanical, and electronic

equipment

Filters

7/31/2019 C-3 cGMP

5/100

Control of Components and Drug

Product Containers and Closures

General requirements

Receipt and storage of untested components, drug productcontainers, and closures

Testing and approval or rejection of components, drug

product containers, and closuresUse of approved components, drug product containers, andclosures

Retesting of approved components, drug product containers,and closures

Rejected components, drug product containers, andclosures

Drug product containers and closures

7/31/2019 C-3 cGMP

6/100

Production and Process Control

Written procedures;

deviations

Charge-in of

components

Sampling and testing of

in-process materials

and drug products

Calculation of yield

Equipment identification

Processing

Time limitations onproduction

Control of microbial

contamination

7/31/2019 C-3 cGMP

7/100

Packaging and Labeling Control

Materials examination and usage criteria

Labeling issuance

Packaging and labeling operations

Tamper-resistant packaging requirements for over-

the counter human drug products

Drug product inspection

Distribution procedures

7/31/2019 C-3 cGMP

8/100

Laboratory Controls


Testing and release for distribution

Stability testing

Special testing requirements

Reserve samples

Laboratory animals

Penicillin contamination

7/31/2019 C-3 cGMP

9/100

Holding and Distribution

Warehousing procedures

Distribution procedures

7/31/2019 C-3 cGMP

10/100

RecordsandReports


Equipment cleaning and use log

Component, drug product container, closures,

and labeling recordsMaster production and control records

Batch production and control records

Production record reviewLaboratory records

Distribution records

Complaint files

7/31/2019 C-3 cGMP

11/100

Returned and Salvaged Drug Products

Returned drug products

Drug product salvaging

7/31/2019 C-3 cGMP

12/100

cGMP Manufacturing Regulation Standard for the:BUILDINGS

@ Must be planned for easy cleaning, maintenance and freedom from

congestion and traffic

@ Adequate space for proper operation of manufacturing, processing,

packaging, control and storage of products and their components

@ Adequate locker facilities and hot and cold washing facilities, cleantoilet

@ Adequate supply of potable water, drains should be of adequate size,

equipped with traps to prevent backsiphonage

@ Suitable housing and space for the care of all laboratory animals

@ Safe and sanitary disposal of sewage, trash, and other refuse within

and from the buildings and immediate premises

7/31/2019 C-3 cGMP

13/100

EQUIPMENTEquipment used for the manufacturer, processing, packaging,

holding, testing, or control of drugs and cosmetics should be

maintained in a clean and an orderly manner

@ Its surface should not be reactive, additive or absorptive as to

alter the properties of the or cosmetics

@ It should prevent any substance required for its operations,

such as lubricants or coolants, to come in contact with the

product

@ It should facilitate adjustment, disassembly, cleaning and

maintenance as necessary to assure uniformity of production

@ It should be of suitable type, size and accuracy of any intended,

measuring, mixing, weighing, or other processing or storage

operation.

@ Each piece of equipment should have its own logbook and

identification number

7/31/2019 C-3 cGMP

14/100

Entries in the equipment logbook must cover:

1. Date when equipment was used

2. Name of product where equipment was used

3. Date when it was cleaned

4. Person responsible for cleaning

5. Date when equipment was validated

6. Result of validation

7/31/2019 C-3 cGMP

15/100

PERSONNEL

@ proper education, training and experience to

execute technological assignments

@ should have periodic health checks, free from

communicable disease and open lesions on theexposed surface of the body

@ good personal hygiene, wear clean outer garments.

@ no personnel should store personal belongings,

eat, food, drink beverages, or use tobacco in any butprescribed areas.

7/31/2019 C-3 cGMP

16/100

7/31/2019 C-3 cGMP

17/100

PACKAGING AND LABELING

@ to prevent mix-ups between drugs

during the filling, packaging, and

labeling operations

@ to assure that correct labels and

labeling are employed for the drug

@ to identify the finished product with a lotor control number

7/31/2019 C-3 cGMP

18/100

LABORATORY CONTROLS

@ appropriate specifications, standards,

and test procedures (identity, weight

variations,disintegration, homogeneity)

@ conform to appropriate standards of

identity, strength, quality and purity

7/31/2019 C-3 cGMP

19/100

Records and Reports

Name and strength of

the product

Dosage forms

Quantitative amounts ofcomponents and

dosage units

Complete

manufacturing and

control procedures

Special notations

Equipment used

Calibration of

instruments Distribution records

Dated and employee-

identified record

Specifications

7/31/2019 C-3 cGMP

20/100

EXPIRATION DATING

@ to ensure that drug product meets

applicable standards of identity,

strength quality, and purity at time of

use

@ it must bear an expiration date

determined by appropriatestability testing.

7/31/2019 C-3 cGMP

21/100

TAMPER EVIDENT PACKAGING

@ define as one having one or moreindicators or barriers to entry

which, if breach or missing, canreasonably be expected to provide

visible evidence to consumers that

tampering has occurred.

7/31/2019 C-3 cGMP

22/100

RETURNED and SALVAGED DRUG PRODUCTS

@ returned drug (from wholesalers) must beidentified by lot number and product qualitydetermined through appropriate testing.

@ drug products that meet specifications maybe salvaged or processed.

@ records for all returned products must bemaintained and must include the date and

reasons for return, quantity and lot number,

procedures employed for holding, testing, andreprocessing the product; and productdisposition.

7/31/2019 C-3 cGMP

23/100

Examples Of Packaging Tamper Resistant

Types of Package Tamper Protection

1. Film Wrappers Film wrapped and sealed around product

and/or product containers; film must be cutor torn to remove product

2. Blister/Strip Packs Individually sealed dosage units; removalrequires tearing or breaking individual

compartment

3. Bubble Packs Product and container sealed in plastic,

usually mounted on/in display card; plasticmust be cut or broken open to remove

product

4. Shrink Seals/Bands Bands or wrappers which are shrunk by heator drying to conform to cap and containers

must be torn to open

5. Foil, Paper, Plastic, Sealed individual packets; must be torn toPouches reach product

6. Bottle Seals Paper or foil sealed to mouth of a containerunder cap; must be torn or broken to reach

product

7/31/2019 C-3 cGMP

24/100

Examples Of Packaging Tamper Resistant

Types of Package Tamper Protection

7. Tape Seals Paper or foil sealed over carton flap or bottlecap; must be torn or broken to reach product

8. Breakable CapsPlastic or metal tearaway caps over container;must be broken to remove

9. Sealed Tubes Seal over mouth of tube; must be punctured toreach product

10. Sealed cartons Carton flaps are sealed; carton cannot beopened without damage

11. Aerosol Containers Tamper-resistant by design

7/31/2019 C-3 cGMP

25/100

INFORMATION AND TECHNOLOGY

@ can enhance pharmaceutical process development,

production efficiencies, product quality, and

regulatory compliance

@ used extensively in plant operations such as productionscheduling, in process manufacturing, quality control, and

packaging and labeling

@ robotic devices increasingly are being employed to replace

manual operations in production lines, analytical sampling,

and packaging. ( sampling and analysis, tablet contentuniformity, and dissolution testing)

7/31/2019 C-3 cGMP

26/100

Active Pharmaceutical Ingredients andPharmaceutical Excipients

1. Specifications and analytical methods for all reactive and non

reactive components used in synthesis

2. Critical chemical reaction steps

3. Handling of chemical intermediates

4. Effect of scale-up of chemical batches on the field

5. Quality of the water systems

6. Solvent handling and recovery systems

7. Analytical methods to detect impurities or chemical residuesand the limits

8. Stability studies of the bulk chemical

7/31/2019 C-3 cGMP

27/100

CURRENT GOOD COMPOUNDING PRACTICES

A number of reasons have been presented for the increase in preparing

patient-specific medications, including the following:

1. Many patients need drug dosage or strengths that are not commerciallyavailable.

2. Many patients need dosage forms, such as suppositories, oral liquids,

or topicals that are not commercially available.

3. Many patients are allergic to excipients in commercially available

product.

4. Childrens medications must be prepared as liquids, flavored to

enhance compliance, and prepared in alternative dosage forms,

such as lozenges, gumdrops, and lollipops.

5. Some medications are not very stable and require preparation and

dispensing every few days; they are not suitable to bemanufactured products

6. Many products are reported in the literature but are not manufactured

yet, so pharmacist can compound them for their physicians and

patients use.

7/31/2019 C-3 cGMP

28/100

7. Many physicians desire to try products in innovative ways, and

pharmacists can work with them to solve medication

problems.

8. Most products are not available for veterinary patients and

must be compounded.9. Home health care and the treatment of an increasing number of

patients at home has resulted in many community pharmacies and

home health care pharmacies preparing sterile products for

home use; formerly, most sterile products were in the

hospital.

10. Hospice care has resulted in new approaches to pain

management and higher concentrations and

combinations of drugs that are now used

CURRENT GOOD COMPOUNDINGPRACTICES

7/31/2019 C-3 cGMP

29/100

Pharmacopeia-National Formulary

Pharmacy Compounding, includes the following discussions:

1. Compounding environment

2. Stability of compounded preparations

3. Ingredient selection and calculations

4. Checklist for acceptable strength, quality and purity

5. Compounded preparations

6. Compounding process

7. Compounding records and documents8. Quality control

9. Patient counseling

7/31/2019 C-3 cGMP

30/100

The cGMP Regulations Establish

Standards for the Manufacturing Facilities and Equipment

Personnel

Components or Raw Materials

Production and Control Records and Procedures

Product Containers

Packaging and Labeling

Laboratory Controls

Distribution Records

Product Stability

Expiry Dating

Complain for all pharmaceutical productsmanufacturer

7/31/2019 C-3 cGMP

31/100

OBJECTIVES OF cGMP

SAFE

PURE

EFFECTIVE

7/31/2019 C-3 cGMP

32/100

NON COMPLIANCE TO cGMP

1. Quality variation and worse

2. Contamination

3. Mix ups

4. Errors

7/31/2019 C-3 cGMP

33/100

3 TYPES OF CONTAMINATION

Particulate

Cross Contamination

Microbial Contamination

7/31/2019 C-3 cGMP

34/100

CONTAINERS

According to USP, a container is that which holds the

article and is or may be in direct contact with the

article.

Immediate container is that which is in direct contact with the

article at all times.

The closure is part of the container.

The container must not interact physically or chemically with the drugso as to alter its strength, quality, or purity beyond the official

requirement.

Sterile hermetic containers are generally used to holdpreparations intended for injection or parenteral

administration

Depending on the intended use and type of

7/31/2019 C-3 cGMP

35/100

Depending on the intended use and type ofcontainer, among the qualities tested are thefollowing:

1. Physicochemical properties

2. Light-transmission for glass or plastic

3. Drug compatibility

4. Leaching and/or migration

5. Vapor transmission for plastic

6. Moisture barrier

7. Toxicity for plastic

8. Valve, actuator, metered dose particle size, spray characteristics, leaks

for aerosols

9. Sterility and permeation for parenteral containers

10. Drug stability for all packaging

7/31/2019 C-3 cGMP

36/100

CLASSIFICATION OF CONTAINERS

Well Closed containers protect thecontents from extraneous solids and from

loss of the drug under ordinary conditions of

handling, shipment, storage and distribution

7/31/2019 C-3 cGMP

37/100


Tight Containers protect the contentsfrom contamination by extraneous liquids,

solids or vapors from loss of the drug, from

efflourescence, hygroscopic or evaporation inhandling, shipment, storage, and distribution.

Tight containers can be reclosed after being

opened

7/31/2019 C-3 cGMP

38/100


Hermetic Container protect from air,gas under ordinary conditions of handling,

shipment, storage, and distribution. This

container is used for injection or parenteraladministration

FOUR CATEGORIES AND TYPE ACCORDING

7/31/2019 C-3 cGMP

39/100

FOUR CATEGORIES AND TYPE ACCORDINGTO ITS RESISTANT TO WATER (GLASS)

Type 1 - Highly resistant, Borosilicate glass

Type 2 - Treated Soda lime glass

Type 3 - Soda lime glassType 4 - General purpose Soda lime glass

7/31/2019 C-3 cGMP

40/100

ADVANTAGES OF PLASTIC OVER GLASSCONTAINERS

1. Lightness of weight and resistant to impact and

lower transportation costs and losses due to

container damage

2. Versatility in container design and consumeracceptance afforded by plastics

3. The interest and convenience in utilization low and

medium density polyethylene in the formation of

squeeze bottles

7/31/2019 C-3 cGMP

41/100

PROBLEMS OF USING PLASTIC ASCONTAINER/PACKAGING

1. Permeability of the containers to atmospheric

gases and to moisture vapor.

2. Leaching of the constituents of the container to

the internal contents

3. Sorption of drugs from the contents to the

container

4. Transmission of light through the container

5. Alteration of the container upon storage

7/31/2019 C-3 cGMP

42/100

TERMS

Permeability - The process of solution and diffusion penetrateinitially dissolving on the plastic material on one side and

diffusion on the other side.

Leaching - Term used to described the release or movement of

components of a container into the contents.SORPTION - Term used to indicate the binding of molecules to

polymer materials. It may be adsorption or absorption.

Tamper resistant or Tamper evident - is define as one havingindicators or barriers to entry which, if breached or missing,

can reasonably be expected to provide evidence to consumers

that tampering has occurred.

TYPE I II d III i t d d f t l d t TYPE NP i

7/31/2019 C-3 cGMP

43/100

TYPE I, II, and III are intended for parenteral products. TYPE NP isintended for other products.Each type is tested according to its resistance to waterattack. The degree of attack is determined by the amount of alkali releasedfrom the glass in specified test conditions.

Leaching of alkali from the glass into a pharmaceutical solution or

preparation could alter the pH and thus the stability of theproduct.TYPE I is the most resistant glass of the four categories

The termplastic does not apply to a single type of material but ratherto a vast number of materials, each developed to have desired features.

Example: the addition of methyl groups to every carbon atom in polymer

chains of polyethylene will give polypropylene, a material that can beautoclaved, where as polyethylene cannot.

If a chlorine atom is added to every other carbon in the polyethylene

polymer, Polyvinyl chloride (PVC) is produced. It has a good clarity, making itparticularly useful in the blister packaging of tablet and capsules. It has a significant

drawback for packaging medical devices (syringes): it is unsuitable for gamma

sterilization.Examples of NEWER plastics: polyethylene terephthalate (PET),

amorphous polyethylene terephthalate glycol (APET), and polyethylene

terephthalate glycol (PETG). Both APET and PETG have excellent transparency

and luster and can be sterilized with gamma radiation.

7/31/2019 C-3 cGMP

44/100

The Permeability of a plastic is a function of severalfactors:

1. nature of polymer itself;

2. the amounts and types of plasticizers, fillers,

lubricants, pigments and other additives;

3. pressure and temperature.

4. Generally, increases in temperature, pressure and

use of additives tend to increase thepermeability of plastic. Glass containers are less

permeable than plastic

7/31/2019 C-3 cGMP

45/100

Compounds leached from plasticcontainers are the polymer additives,

such as the plasticizers, stabilizers, orantioxidants. May be influenced by

temperature, excessive agitation of the

filled container.

7/31/2019 C-3 cGMP

46/100

Sorption occurs through chemical or physical meansdue to the chemical structure of the solute molecules

and the physical and chemical properties of the

polymer.

Sorption may occur with the active pharmacologicagents or pharmaceutical excipients. The

sorption of pharmaceutical excipients such ascolorants,preservatives, or stabilizers would

likewise alter the quality of product.

7/31/2019 C-3 cGMP

47/100

Deformations, softening, hardening, andother physical changes in plastic containerscan be caused by the action of the

containers contents or external factors,including changes in temperature and thephysical stress placed upon the containerin handling and shipping.

7/31/2019 C-3 cGMP

48/100

Child-resistant container

- is defined as one that is significantly

difficult for children under 5 years of

age to open or to obtain a harmful

amount of its contents within areasonable time and that is not difficult

fornormaladults to use properly

7/31/2019 C-3 cGMP

49/100

The 4 Basic designs commonly used are:

1. Align arrows

2. Squeeze and turn

3. Press down and turn

4. Latch top

7/31/2019 C-3 cGMP

50/100

Compliance Packaging

Factors associated with non compliance

1. Misunderstanding the dosingschedule

2. Confusion because the patient is takingmultiple medications

3. Forgetfulness

4. Feeling of well-being leading topremature discontinuance ofmedication

7/31/2019 C-3 cGMP

51/100

ContainersPhysical Evaluation

Shape

Volume

Finish

Opening Diameter

Height

Print

Cleanliness Stress crack resistance

Weight

Thickness

Color

Clarity Leak

Torque

Peeling of paint

Light transmision

7/31/2019 C-3 cGMP

52/100

The physico-chemical tests for containers

Identification

Infra-red properties

Thermal analysis

Moisture

Extractable substance

Non-volatile residue

Water vapor

permeation/transmission

Resistance to water

attack

7/31/2019 C-3 cGMP

53/100

Containers and Closure

Containers and closure depends on the

geometry of two

A. The material used in their construction

B. The composition of the cap liner and thetightness with which the cap has been

applied

Closures should fit the tread of the container

It should sit on a container without tilting, produce no leaks

Should not rotate continuously, be reasonably tight and

look elegant

7/31/2019 C-3 cGMP

54/100

LABELS

Product name/strength

Control code

Expiration date

Rx symbol Registration number

Incorrect

Glueing

Alignment

Torn/soiled

Freedom fromdust/smears

Missing

7/31/2019 C-3 cGMP

55/100

PACKAGE INSERTS

Incorrect

Missing

Freedom from dirt/smears

Torn/soiled

Poorly folded or inserted

7/31/2019 C-3 cGMP

56/100

ACCESSORIES

Missing

Mislocated

Freedom from dust and smears

Defective

7/31/2019 C-3 cGMP

57/100

PRINTING: Control Code/Expiration Date

Incorrect

Missing

Illegible

Smeared by legible

Mislocation

Printing skips

Misaligned

7/31/2019 C-3 cGMP

58/100

PRODUCT UNITS

Incorrect packaging

Empty package

Incomplete package

content

Incorrect count per unit

Incorrect count per

display unit

Contamination withforeign material

Wrong size

Improper assembly of

printed materials

Improper position of

liquid containers

Soiled packaging

component

Incorrect count per

packer/shipper

Ragged cuts

7/31/2019 C-3 cGMP

59/100

PACKAGING

Packaging according to USP andNF, a container is the device that

holds a drug and is or may be,

in direct contact with the drug.

7/31/2019 C-3 cGMP

60/100

Packaging Materials

Paper, foil, plastics or cellophane, foil to

foil, glass, cartons, wrapping papers,

shipping cases, cap liners, labels,

printed inserts, jars, and bottles

Light resistant container must met thestandard 290 to 450nm wavelength

light transmission.

7/31/2019 C-3 cGMP

61/100

Hermetic Container May Be:

1. Single Dose Container - intended as asingle dose and which once opened cannot

be resealed to assure sterility is maintained.

2. Multiple Dose Container - container whichpermits withdrawal of successive

portions of the contents without changing the

strength or enlarging the quality or purity

of the remaining portion.

7/31/2019 C-3 cGMP

62/100

Dosage Forms as Tablets, Capsules, Oral liquidsmay be Package in:

1. Single Unit Container - is one that isdesigned to hold a quantity of drugintended for administration as single

dose promptly after container is opened.2. Multiple Unit Container - contains

more than a single unit or dose of

medication. A single package is termedas UNIT DOSE.

7/31/2019 C-3 cGMP

63/100

Packaging

Consider the following points

1. The units may have to run on a high-speed line

2. They may involve a complicated assembly3. The package may be functional

4. The package must be completelycompatible with the product

5. The package must be protect the productand assure its stability

6. The package must ship well

7/31/2019 C-3 cGMP

64/100

PACKAGE INSERTS

Name of the drug

Formulation

Description of the

product

Pharmacology

Indications

Contraindication

Precautions

Adverse reaction

Dosage and mode ofadministration

Warnings

Information for the

patient Availability

Storage Conditions

Manufacturer and

distributor The date of the latest

revision of the packageinsert must be printed

7/31/2019 C-3 cGMP

65/100

Packaging control- Reasons

To assure that only those product that havemet the standards and specificationsestablished in the master formula recordsshall be distributed to the market

To prevent mix-ups and errors

To assure that correct labels and labelingmaterials are employed for the product

To assure that the finished product is properlyidentified with a control code that permitsconstruction of the history of the product

7/31/2019 C-3 cGMP

66/100

Mix-ups and Errors: Prevention

Prior to use, facilities are cleared out ofpackage finished products and packagingmaterials of the previous run

Products which are similar in appearance,containers or labeling are not processedsimultaneously on adjacent or nearby linesunless these operations are separated byphysical barrier

Proper reconciliation is done after thepackaging operation is completed

7/31/2019 C-3 cGMP

67/100

Important Points to be considered

7/31/2019 C-3 cGMP

68/100


in packaging: CONTAINERS

Freedom from cracks, chips

Freedom from dents, distortions

Contamination with foreign matter

Leakage

Fill/weight/volume


7/31/2019 C-3 cGMP

69/100


in packaging: STRIPS/POUCHES Product name/strength

Control code

Expiration date

Rx symbol

Leakers in vacuum

Weak seal

Empty or wrong count

Torn of pouch

Freedom from dust or

smears

Correct cutting

Powder in pouches and

seals

Perforations of tear

notches non-functional

Fill/weight/volume


7/31/2019 C-3 cGMP

70/100


in packaging: CLOSURES

Sealing tightness

Freedom from dust/smears

Crimping

Correct design/color

LABELING REQUIREMENTS

7/31/2019 C-3 cGMP

71/100

PRESCRIPTION DRUGS

1. Rx Symbol

@ All drugs which require the Rx of a

Physician,Dentist or Veterinarian shall bear an Rx

symbol

@ The symbol shall prominently placed on theprincipal display panel of the label

@ The symbol shall be of contrasting color to the

background on which it appears, with no particular

color required and shall not be less than 50% of theshorter dimension of the rectangular label

LABELING REQUIREMENTS

7/31/2019 C-3 cGMP

72/100

@ For products individually packed in foil or similarwrapper, the symbol shall appear on the foil and the outer

container from which they are removed for dispensing.

@ In case of ampules or other container, if too small,

unable to accommodate a label; the symbol shall appearon the outer container from which they are removed for

dispensing or use.

@ Rx requirement - Caution: Food, Drug and

Cosmetic Law prohibits dispensing withoutprescription

PRESCRIPTION DRUGS

1. Rx Symbol

2. Name of the Drug Product

7/31/2019 C-3 cGMP

73/100

The name of the product may either be given in the following nomenclature,

which should include the (1)pharmaceutical form, (2) mode of administration and(3) potency

A. Brand name - shall refer to the assigned name to theproduct

Example: X Tablet 325 mg

B. Generic name - shall refer to the common names ofscientifically recognized active ingredients

Examples: Acetaminophen Tablet 500 mg

Chloramphenicol Palmitate Suspension

125 mg/5mL

7/31/2019 C-3 cGMP

74/100

C. The brand name or generic of the product mustappear on the principal display panel of the

label

D. For products requiring reconstitution or dilutionprior to administration, the final form of the productfor administration shall be the pharmaceutical formto be used.

Example: Erythromycin Ethyl SuccinateGranules, For Suspension or For Syrup

7/31/2019 C-3 cGMP

75/100

3 Pharmacologic Category

7/31/2019 C-3 cGMP

76/100

Pharmacologic category states

the therapeutic action of the drug

The category should be printed on

the principal display panel of the

inner and outer label

3. Pharmacologic Category

4 F l ti

7/31/2019 C-3 cGMP

77/100

Formulation refers to the list and amount of activemedicinal ingredients per dosage unit expressed in the

metric system

@ amount of active ingredient must be stated

@ multiple components shall be enumerated

in the order of decreasing

pharmacologic activity

@ use of non proprietary name (INN) ispreferred whenever available

4. Formulation

7/31/2019 C-3 cGMP

78/100

@ electrolytes for replacement therapy must be

expressed in milliequivalence

@ the salt forms of vitamins/minerals must be statedExample: Vitamin D (Cholecalciferol)

Ferrous Sulfate (equivalent to elemental Iron)

@ in active ingredients of ophthalmic, otological drip,

injection, intravenous fluids, ointments, creams,vaginal and uterine tablets must be stated on the

label

@ the coloring agent- tartrazine should be indicated

with precaution since it causes allergic reaction to

some individuals

7/31/2019 C-3 cGMP

79/100

7/31/2019 C-3 cGMP

80/100

6. Dosage and Mode of Administration

Dosage - shall refer to the amount of intake ofthe drug at a given frequency interval,

condition and time of administration.

Mode of Administration - shall refer to thesite and manner the drug is to introduced into

the body.

7. Warnings, Contraindications and

7/31/2019 C-3 cGMP

81/100

7. Warnings, Contraindications andPrecautions

Warning - information about occurrence of seriouspotential hazards and side effects associated with the use

of the drug and the limitation of its use

Contraindications - the condition wherein the drug may

cause harm to the patientPrecautions - Instruction and special care to avoidundesired effects and to assure the safe and effective use

of the product

NOTE: Warnings, Contraindications and Precautions specificallyrequired must be stated on the label

P k I

7/31/2019 C-3 cGMP

82/100

8. Package Inserts

@ Contains information applying only tothe product and its active

substances@ All Rx drug product shall have

package insert

9 S f R f

7/31/2019 C-3 cGMP

83/100

9. Statement of Reference

@ when the space is limited on the label

the statementSee Package Insert is

necessary as notification for additionalinformation regarding the usage of the

drug.

10. Name and Addresses of the

7/31/2019 C-3 cGMP

84/100

@ must appear as one phrase on the

principal display panel of the

inner and the outer label

10. Name and Addresses of themanufacturer/importer/distributor/license/repacker

11 L t N b

7/31/2019 C-3 cGMP

85/100

11. Lot Number

Means any distinctive combination of letters ornumber, or both by which the complete history

of the product, control, packaging and distribution of

a batch or lot of a drug is determined

@ Lot Number is required to appear on bothinner and outer label of the product

@ Lot number must be printed on the tin foil orevery two pieces of the dosage form

12 E i ti D t

7/31/2019 C-3 cGMP

86/100

12. Expiration Date

It is the period beyond which a pharmaceutic specialtyis not expected to have retained its pharmacologicattributes to guarantee its safety, strength, quality andpurity, provided the prescribed storage conditions have

been maintained@ Shall expressed in terms of the month and year.

Last day of the month is assumed as theintended expiration date

@ for reconstitution - must stated suitable beyond-use-date and storage condition

13 Registration Number

7/31/2019 C-3 cGMP

87/100

13. Registration Number

Is the number assigned to the

pharmaceutical specialty upon

submission for registration.

14 N t C t t

7/31/2019 C-3 cGMP

88/100

14. Net Content

Is the total amount/quantity of the

dosage form in a certain container

expressed in metric system and mustdeclared in the inner and outer label

of the product.

15 St C diti

7/31/2019 C-3 cGMP

89/100

15. Storage Condition

Is the prevailing specified temperature,

humidity and other environmental factors

within which a range will optimal stability

based on experimental evidence of the

product

@ shall be printed on the inner and outer

label of the product

OTC LABELING

7/31/2019 C-3 cGMP

90/100

OTC LABELING

As noted, OTC package labeling must also include appropriatewarning statements

Examples:

The use of laxatives

WARNING:

Do not use when abdominal pain, nausea, orvomiting is present. Frequent or prolonged use of thispreparation may result in dependence on laxatives

OTC Cough Remedies

WARNING:

A persistent cough may be a sign of a serious condition. Ifcough persists for more than 1 week, tends to recur, or isaccompanied by a fever, rash, or persistent headache, consult adoctor.

LABELING

7/31/2019 C-3 cGMP

91/100

LABELING

According to regulations, drug labelingincludes not only the label placed onthe immediate container and

packaging but also the packageinserts, company literature,advertising and promotional

materials.

INFORMATIONS AFFIXED TO THE CONTAINER

7/31/2019 C-3 cGMP

92/100

INFORMATIONS AFFIXED TO THE CONTAINEROF LEGEND DRUGS

1. Nonproprietary name of the drug present and trademark

2. Name and address of manufacturer or distribution

3. Quantity, statement of the amount of each drug present per unit ofweight, volume, or dosage units

4. Pharmaceutical type of dosage form constituting the product

5. Net amount of drug product contained in the package in units of weight volume

6. The Legend - Caution

7. Usual dose

8. A label reference and see accompanying insert

9. Special Storage Instruction

10. FDA Registration Number

11. Manufacturers control number identifying the batch of lot number of drug

12. An expiry Date

13. For controlled drug- Warning - Habit Forming

14. Rx Symbol

Rx Label: When filling a Rx, information on the label

are the following:

7/31/2019 C-3 cGMP

93/100

are the following:

1. The name and address of the pharmacy

2. The serial number of the prescription

3. The date of the Rx or the date of filling and refilling

4. The name of the prescriber

5. The name of the patient

6. Directions for use, including precautions if any, as

indicated on the Rx

In addition to the above, state laws may require additional

7/31/2019 C-3 cGMP

94/100

information

7. The address of the patient

8. The initials or name of the dispensing

pharmacist

9. The telephone number of the pharmacy

10. The drug name, strength and manufacturers lot

or control number

11. The expiration date of the drug

12. The name of the manufacturer or distributor

Labeling

7/31/2019 C-3 cGMP

95/100

The word POISON and Vignette representing a skull and cross inprominent big letters should be printed on red labels.

For Both Rx and OTC Drugs

1. The products intended for external use, the statement FOR EXTERNAL USEONLY printed in red color shall appear on the inner and outer label ofthe container.

2. The warning statement should appear on the inner and outer label of theproduct.

3. All information required to appear on the label must be:

a. Clearly and prominently displayed

b. The information should be readable with normal vision withoutstraining

c. The color contrast, the position and spacing of the information

are to be taken into consideration in complying with

these requirements.

OTC Labeling: Patient-Oriented information is

included in the labeling including the following:

7/31/2019 C-3 cGMP

96/100

included in the labeling, including the following:

1. Product name and statement of identity, e.g. liquid antacid,

listing of active ingredients and net quantity of contents.

2. Statements of all conditions, purpose or uses for which the

drug is intended or commonly used.

3. Directions for used - quantity of dose

4. Dosage instructions - frequency of administration

5. Warnings - maximum duration of administration or application,

anticipated side effects

6. Cautionary statements - storage in a safe place out of the

reach of children

OTC Labeling: Patient-Oriented information isincluded in the labeling including the following:

7/31/2019 C-3 cGMP

97/100

included in the labeling, including the following:

7. Drug Interaction precautions

8. Route of administration or application

9. Preparation for use - shaking, dilution,adjustment of temperature

10. Declaration of presence of the dye Yellow No. 5(hypersensitive) and alcohol

11. If the medication is to be taken internally, thelabel must contain the statement: As withany drug, if you are pregnant or nursing ababy, seek the advice of a health professional

before using the product

Labeling of Drugs in Small Containers

When the inner label of a drug is too small to accommodate all the

7/31/2019 C-3 cGMP

98/100

When the inner label of a drug is too small to accommodate all the

information required, it should contain at least the following:

1. The proper name of the drug

2. The category of the drug

3. The potency of the drug

4. The net content of the drug

5. The route of administration

6. The name and address of manufacturer/distributor of the drug

7. The lot number of the drug

8. The expiration date of the drug

9. The registration number of the drug

NOTE: The labeling requirements of drug generally apply to all

container sizes. However, some containers are too small to carry all theinformation required by the Food and Drug Regulation

Terms generally used in such labeling defined by official

7/31/2019 C-3 cGMP

99/100

g y g y

compedias

1. Cold any temperature not exceeding 8 C. A refrigerator is acold place/maintained thermostatically between 20 C to

80 C. A freezer is -100 C to -200 C.

2. Cool - any temperature between 80 C to 150 C. A

refrigerator maybe also used.3. Room Temperature - temperature between 150 C to 300 C.

Official room temperature is 250 C.

4. Warm - temperature between 300 C to 400 C.

5. Excessive Heat - any temperature above 400 C

6. Protect from freezing/Keep away from freezing

7/31/2019 C-3 cGMP

100/100

C-3 cGMP

Documents

Transcript of C-3 cGMP