ANA 2 LEC-Packaging Material Quality Control and Stability Studies

plays a fundamental role in safeguarding the therapeutic properties of drug products due to external factors that might cause physical or chemical damage to the medical product. It is broadly classified into three main categories

PHARMACEUTICAL PACKAGING

Packaging?: direct contact to the medical product

Primary Packaging

holds the primary packaging and typically serves as promotional, branding and additional protective properties.

Secondary Packaging

used for transport and bulk handling

Tertiary Packaging

SIGNIFICANCE OF PACKAGING MATERIALS?

• Ensures stability - both chemically and physically

• Maintains sterility, specially on sterile products and products w/o preservatives

• Provides tamper evidence

• Facilitates easy identification and use by the patient or healthcare provider.

_______, which is the regulatory authority for pharmaceuticals in the Philippines, sets forth specific standards and specifications that ensure the safety, efficacy, and quality of pharmaceutical products, including packaging materials.

Philippine Food and Drug Administration (FDA)

• These standards are primarily derived from global guidelines (such as those from the FDA, EMA, and ICH) but are also tailored to meet local regulatory requirements. Key areas of focus include the following:

1. General Guidelines for Packaging Materials

   a. More on contamination (protected from contamination)

2. FDA Circulars and Guidelines

3. Specific Standards for Packaging Materials (ex: Glass, Plastic, others)

4. Packaging Labelling Standards

5. Stability and Shelf Life Testing and Corresponding Validation

MAJOR PROBLEMS WITH CONTAINERS: interaction of container towards drug

LEACHING

MAJOR PROBLEMS WITH CONTAINERS: interaction of drug toward the container

SORPTION

GENERAL TYPES OF CONTAINER: Protects against extraneous solids and liquids and loss of drug under ordinary conditions

Well-closed container

GENERAL TYPES OF CONTAINER: well-closed container but may prevent, efflorescence delinquency or evaporations

Tight-container

GENERAL TYPES OF CONTAINER: impervious to air or any other gases

Hermetic container

GENERAL TYPES OF CONTAINER: prevents photochemical deterioration

Light-resistant container

GLASS PACKAGING MATERIAL description: Highly-resistant, borosilicate glass

TYPE I

GLASS PACKAGING MATERIAL description: Treated soda-lime, glass

TYPE II

GLASS PACKAGING MATERIAL description: Soda-lime glass

TYPE III

GLASS PACKAGING MATERIAL description: General purpose

TYPE IV/NP

GLASS PACKAGING MATERIAL characteristics:

Used by all products. Used by parenteral products

Contains silicon dioxide treated with sulfur dioxide to increase resistance and boric oxide.

TYPE I

GLASS PACKAGING MATERIAL characteristics:

Contains Silicon dioxide + sulfur dioxide (inner surface)

TYPE II

GLASS PACKAGING MATERIAL characteristics: Silicon dioxide only

TYPE III

GLASS PACKAGING MATERIAL characteristics: Low resistance glass

TYPE IV

QC Test for glass that Asses leaching property

TEST FOR HYDROLYTIC RESISTANCE

OLD USP TESTS for glass

POWDERED GLASS TEST, WATER ATTACK TEST,SURFACE GLASS TEST

OLD USP TEST: I and III

POWDERED GLASS TEST

OLD USP TEST: II

WATER ATTACK TEST

OLD USP TEST: I and III

SURFACE GLASS TEST

OLD USP TEST: Crushed glass is titrated with sulfuric acid

POWDERED GLASS TEST

OLD USP TEST: Intact glass is titrated with sulfuric acid

WATER ATTACK TEST

OLD USP TEST: Intact glass is titrated with Hydrochloric acid

SURFACE GLASS TEST

NEW USP TEST: Diff. type 1 glass, from type II and III

GLASS GRAINS TEST and SURFACE ETCHING TEST

NEW USP TEST: Diff. type I and II glass, from type III

SURFACE GLASS TEST

NEW USP TEST: Indicates the amount of the alkali content of the glass

GLASS GRAINS TEST

NEW USP TEST: Provides information on the inner surface durability of the glass container

SURFACE GLASS TEST

NEW USP TEST: Provides information on the inner surface of durability of the base glass

SURFACE ETCHING TEST

QC Test for glass that

Plastic Packaging Material: Food and beverages; Thermoplastic

I / Polyethylene terephthalate (PET)

Plastic Packaging Material: Aka rigid and durable plastics;Thermoset

II / High-density polyethylene

Plastic Packaging Material: Blister packaging, Medical supplies; Thermoplastic

III/ Polyvinyl chloride (PVC)

Plastic Packaging Material: Aka flexible plastics; Squeeze bottles; Thermoplastic

IV/ Low density Polyethylene (LDPE)

Plastic Packaging Material: Aka Plastics that are capable to withstand heating; Thermoplastic

V/ Propylene (PP)

Plastic Packaging Material: General Purpose; Thermoplastic

VI/ Polystyrene

BIOLOGICAL REACTIVITY IN VIVO: Parenteral Containers

System Injection Test and Intracutaneous Test

BIOLOGICAL REACTIVITY IN VIVO: Albino rabbit

Intracutaneous test and Eye irritation test

BIOLOGICAL REACTIVITY IN VIVO:Ophthalmic containers, medical devices and Albino Rabbit

Eye irritation Test

BIOLOGICAL REACTIVITY IN VIVO: Material in direct contact with tissues and Rabbit

Implantation Test

BIOLOGICAL REACTIVITY IN VITRO examples

Agar Diffusion Test,Direct Contact Test,Elution Test

BIOLOGICAL REACTIVITY IN VITRO test that has:
sample: Elastomeric Material

Test organism: Mammalian fibroblast cells or tissues

Agar Diffusion Test

BIOLOGICAL REACTIVITY IN VITRO Positive control:

Polyurethane film containing zinc diethyldithiocarbamate (ZDEC) or zinc dibutyldithiocarbamate (ZDBC)

Stability Studies: capacity of drug to remain within specification over time

STABILITY

Stability Studies: prevented by reduction/elimination of water from preparation

HYDROLYSIS

Stability Studies: prevented by antioxidants

OXIDATION

Stability Studies: prevented by using light-resistant containers

PHOTOLYSIS

defined as the period of time during a product remains within specification. It is estimated using the Arrhenius equation

SHELF LIFE

time or date prior to which a product is expected to remain stable and after which it must not be used.

EXPIRATION DATE

Expiration date = ???

Expiration date = Mfg date + shelf-life

EXPIRATION DATE ERROR (2)

• ALPHA RISK ,TYPE I ERROR, FALSE NEGATIVE

• BETA RISK, TYPE II ERROR, FALSE POSITIVE

Type of EXPIRATION DATE ERROR: Risk of rejecting a true null hypothesis (correct result)

ALPHA RISK ,TYPE I ERROR, FALSE NEGATIVE

Type of EXPIRATION DATE ERROR: An inspection/test may indicate that a product or process is defective when it is actually acceptable

ALPHA RISK ,TYPE I ERROR, FALSE NEGATIVE

Type of EXPIRATION DATE ERROR: Harms the company

ALPHA RISK ,TYPE I ERROR, FALSE NEGATIVE

Type of EXPIRATION DATE ERROR:

Ex: Expiration date was set too early

ALPHA RISK ,TYPE I ERROR, FALSE NEGATIVE

Type of EXPIRATION DATE ERROR: Accepting a false null hypothesis (bad result)

BETA RISK, TYPE II ERROR, FALSE POSITIVE

Type of EXPIRATION DATE ERROR: An inspection/ test may indicate that a product or process is acceptable when it is actually defective

BETA RISK, TYPE II ERROR, FALSE POSITIVE

Type of EXPIRATION DATE ERROR: Harms the patient (unacceptable risk)

BETA RISK, TYPE II ERROR, FALSE POSITIVE

Type of EXPIRATION DATE ERROR: It can be reduced by increasing sample size or improving the accuracy of the measurement tool

BETA RISK, TYPE II ERROR, FALSE POSITIVE

Type of EXPIRATION DATE ERROR:

Example: Expiration date was set too late

BETA RISK, TYPE II ERROR, FALSE POSITIVE

CLIMATIC ZONES:

• TEMP. IN CELCIUS: 21+-2

• RELATIVE HUMIDITY (%): 45+-5%

Temperate (I)

CLIMATIC ZONES:

• TEMP. IN CELCIUS: 25+-2

• RELATIVE HUMIDITY (%): 60+-5%

Subtropical/Mediterranean (III)

CLIMATIC ZONES:

• TEMP. IN CELCIUS: 30+-2

• RELATIVE HUMIDITY (%): 35+-5%

Hot and dry (III)

CLIMATIC ZONES:

• TEMP. IN CELCIUS: 30+-2

• RELATIVE HUMIDITY (%): 65+-5%

Hot and humid (IVa)

CLIMATIC ZONES:

• TEMP. IN CELCIUS: 30+-2

• RELATIVE HUMIDITY (%): 75+-5%

Preferred in the Philippines

Hot and very humid (IVb)

TYPES OF STABILITY STUDIES:

• Conduct under normal conditions

• Follow zero-order kinetics

• Testing period: 0, 3, 9, 6, 12, 18, 24, 36 months

LONG-TERM / REAL TIME STUDIES

TYPES OF STABILITY STUDIES:

• Designed to increase rate of chemical degradation by using exaggerated storage conditions

• Follows first-order kinetics

• Testing period: 0,3, 6 months

SHORT-TERM/ACCELERATED STUDIES

TYPES OF STABILITY STUDIES/type of container:

storage condition: 30 deg. Celsius/ 75% RH

Products in primary containers permeable to water vapor

TYPES OF STABILITY STUDIES/type of container:

storage condition: Same temp; RH not specified

Products in primary containers impermeable to water vapor

TYPES OF STABILITY STUDIES:

Storage condition: 25 deg. C / 60% RH

Min. Time Period:12

Testing Frequency: 0, 3,6, 9, 12

LONG TERM (REAL TIME)

TYPES OF STABILITY STUDIES:

Storage condition:30 deg. C / 60% RH

Min. Time Period: 6 months

Testing Frequency: 0, 3, 6

INTERMEDIATE

TYPES OF STABILITY STUDIES:

Storage condition: 40 deg.C / 75% RH

Min. Time Period: 6 months

Testing Frequency: 0, 3, 6

ACCELERATED

TYPES OF STABILITY STUDIES:

Storage condition: 60 deg. C /75% RH

Min. Time Period: 1 month

Testing Frequency: None; Simulates pilot testing

STRESS