Transcript Diapositive 1

Manufacturing Process of
Drug Product:
Container closure system
Compatibility
Ratiya KUKHETPITAKWONG
27 April 2016
Container Closure System
คำจำกัดควำม (Definition)
Material of construction
อ้ำงถึงสำร (substances)
Packaging component
ส่วนของระบบปิ ดของภำชนะบรรจุ
Primary packaging component - ภำชนะบรรจุปฐมภู ม ิ
Secondary packaging component - ภำชนะบรรจุทุตย
ิ ภู ม ิ
Container closure system (Packaging system)
ระบบปิ ดของภำชนะบรรจุ
Package (Market package)
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Quiz
ภำชนะบรรจุทุตย
ิ ภู ม ิ
ภำชนะบรรจุปฐมภู ม ิ
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Containers
http://www.chinazfeng.com/Attachment/
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http://www.greatbearhealthcare.co.uk/
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คุณสมบัตข
ิ อง Packaging Component
A packaging system found acceptable for one drug
product is not automatically assumed to be appropriate
for another.
Information depend on
Dosage form
Route of administration
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Risk-base approach
Degree of
Concern
Associated with
the Route of
Administration
Likelihood of
Packaging Component-Dosage Form Interaction
High
Medium
Highest
Inhalation Aerosols &
Solutions; Injections &
Injectable suspensions
High
Ophthalmic Solutions &
Suspensions;
Transdermal Ointments
& Patches; Nasal
Aerosols & Sprays
Low
Topical Solutions
Suspensions; Topical &
Lingual Aerosols; Oral
Solutions & Suspensions
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Low
Sterile Powders &
Powders for Injection;
Inhalation Powders
Topical Powders; Oral
Powders
Oral Tablets & Oral
(Hard & Soft Gelatin)
Capsules
Information that should be submitted for any
drug product (1/2)
Description
Overall general descriptions of the container closure system, plus:
For each Packaging Component:
• Name, Product code, manufacturer, physical description
• Materials of construction (for each, name, manufacturer, product code)
• Description of any additional treatments or preparations
Suitability
Protection: (By each component and/or the container closure system, as appropriate)
• Light exposure
• Reactive gases (e.g., oxygen)
• Moisture permeation
• Solvent loss or leakage
• Microbial contamination (sterility/container integrity, increased bioburden, microbial limits)
• Filth
• Other
Safety: (for each material of construction, as appropriate)
• Chemical composition of all plastics, elastomers, adhesives, etc.
• Extractables, as appropriate for the material
• Other studies as appropriate
Compatibility: (for each component and/or the packaging system, as appropriate)
• Component/dosage form interaction
• May also be addressed in post-approval stability studies
Performance: (for the assembled packaging system)
• Functionality &/or drug delivery, as appropriate
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Information that should be submitted for any
drug product (2/2)
Quality control
For each packaging component received by the applicant:
• Applicant’s tests & acceptance criteria
• Dimensional (drawing) & performance criteria
• Method to monitor consistency in composition, as appropriate
For each packaging component provided by the supplier:
Stability
Guidance for industry Q1A(R2) Stability testing of new drug substances and products
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Potential effects of Packaging
component/dosage form interactions
Hemolytic effect
Pyrogenic effect
Potency of drug product or concentration of
antimicrobial preservatives
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ข้อควรพิจำรณำ
Suitability for intended use
Quality control of Packaging Components
Associated components
Packaging components which are typically intended to
deliver to dosage form to the patient but are not stored in
contact with the dosage form for its entire shelf life.
Secondary packaging components
Packaging components which are not intended to make
contact with the dosage form.
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Suitability for intended use (1/2)
Protection
Light exposure
Moisture permeation
Seal integrity or leak test
Compatibility
<661> Containers-Plastics
Polyethylene (PE) containers: HDPE, LDPE
Polypropylene (PP) containers:
PE terephthalate (PET) bottles and PET G containers
Physicochemical tests: IR, DSC, Heavy metals & nonvolatile residue, &
component used in contact with oral liquid
<381> Elastomeric closures for Injections
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Suitability for intended use (2/2)
Safety
<87> Biological reactivity test, in vitro
<88> Biological reactivity test, in vivo
Performance
<671> Containers-Performance testing
Moisture permeation
Light transmission
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Quality control of packaging components
Physical characteristics
Dimension criteria
Physical parameters critical to the consistent manufacture of
a packaging component
Performance characteristics
Chemical composition
New materials of packaging component may result in new
substances being extracted into the dosage form or a
change in the amount of known extractables.
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Compatibility
<1664> Assessment of Drug Product Leachables
Associated with Pharmaceutical Packaging Delivery
Systems.
Definition
Extractables - organic & inorganic chemical entities that can be released
from a pharmaceutical packaging/delivery system, packaging component, or
packaging material of construction under laboratory conditions. Extractables
themselves, or substances derived from extractables, have the potential to
leach into a drug product under normal conditions of storage and use.
Leachables – organic or inorganic chemical entities that migrate from a
packaging/delivery system, packaging component, or packaging material of
construction into an associated drug product under normal conditions of
storage and use or during accelerated drug product stability studies.
Leachables are typically a subset of extractables or are derived from
extractables
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Studies on Extractables and Leachables
Extractables studies - the overall laboratory processes
required in order to create extractables profile(s) of
particular pharmaceutical packaging/delivery systems,
packaging components, or materials of construction.
Extraction studies are also referred to as Controlled
Extraction Studies.
<1663> Assessment of Extractables Associated with
Pharmaceutical Packaging/Delivery Systems.
Leachables Studies - laboratory investigations into the
qualitative and quantitative nature of a particular leachables
profile(s) over the proposed shelf-life of a particular drug
product.
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Leachable study
่ วยสรรหำ packaging components & their materials of
เพือช่
construction
Leachable characterization (for high-risk dosage form)
Trend identification in leachables accumulation levels
Individual leachable evaluation
Qualification of the leachables on a safety basis
กำรหำควำมสัมพันธ ์ระหว่ำง Leachables-Extractables
กำรพิจำรณำ specification & acceptance criteria ของ leachables
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Decision tree for identification &
qualification Q3B(R2)
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Toxicological Evaluation
Safety Concern Threshold (SCT) – the threshold below
which a leachable would have a dose so low as to present
negligible safety concerns from carcinogenic and
noncarcinogenic toxic effects
Qualification Threshold (QT) – the threshold below which
a given non-carcinogenic leachable is not considered for
safety qualification unless the leachable presents
Analytical Evaluation Threshold (AET) – the threshold at
or above which a particular extractable &/or leachable
should be identified, quantified, & reported for potential
toxicological assessment
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่
ข้อควรพิจำรณำเพิมเติ
ม
Submission of Investigational New Drug (IND)
Submission on packaging of a drug product by another
firm
Contract packager
บริษท
ั ทีร่ ับจ้ำงบรรจุภณ
ั ฑ ์ผลิตภัณฑ ์ยำ ผู ร้ ับจ้ำงมีควำมร ับผิดชอบต่อ
คุณภำพของผลิตภัณฑ ์ระหว่ำงขนส่ง (Shipping) กำรเก็บร ักษำ
(Storage) และกำรบรรจุภณ
ั ฑ ์ (Packaging)
Repackager
่ อผลิ
้
บริษท
ั ทีซื
ตภัณฑ ์ยำจำกผู ผ
้ ลิตหรือผู กระจำยยำและทำกำรบรรจุ
่
่
่ ษท
ภณฑ ์ใหม่เพือขำยภำยใต้
กำรติดฉลำกทีแตกต่
ำงไปจำกผู ผ
้ ลิต ซึงบริ
ั ผู ้
้ องร ับผิดชอบต่อคุณภำพและควำมคงสภำพของผลิตภัณฑ ์ยำทีบรรจุ
่
ซือต้
้ั
ภัณฑ ์ใหม่นน
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Examples of the items that have been
submitted
Descriptive information:
General description of the component and the address of the manufacturing site
Description of the manufacturing process for a packaging component and operations performed after
manufacture, but prior to shipment (washing, coating, sterilization or depyrogenation)
Description of the acceptance, in-process, and release controls for materials of construction, the
manufacturing process, and the finished product (component or assembled component)
Characterization of the key properties
Information about suitability:
Protection provided by the component
Safety information on the materials of construction or the finished component
Compatibility of the materials of construction or the finished component with the specific dosage
form, the specific drug product, or equivalent materials
Information about quality control:
Dimensional (an engineering drawing) & performance criteria for the component
A description of the quality control measures used to maintain consistency in the physical and
chemical characteristics of packaging components
A summary of the quality assurance/quality control criteria when release of the component is based
on statistical process control
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เอกสำรอ้ำงอิง
Guidance for industry: Container closure systems for
packaging human drugs & biologics (May, 1999)
ICH Impurities in New Drug Products Q3B(R2) (June 2006)
PDA J Pharm Sci and Tech 2013, 67: 413-429.
USP
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Thank you for your attention
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