For polypropylene (PP) granules intended for manufacturing Large-Volume Parenteral (LVP) containers, the tests for extractables and leachables (E&L) should be selected based on the material, manufacturing process, intended use, contact conditions, and applicable pharmacopoeial/regulatory requirements.
1. First establish the intended use
Determine
followings:
- PP grade and additives used
- Final container type (bottle,
bag, etc.)
- Aqueous/non-aqueous
formulation
- Contact duration
- Storage temperature and
sterilization method
- Whether the container is in
direct contact with the injectable product
- Maximum
surface-area-to-volume ratio
2. Extractables testing
Extractables
are substances that can be extracted from the PP under exaggerated
laboratory conditions.
A typical
extractables assessment may include:
|
Test category |
Typical parameters |
|
Organic
volatile compounds |
GC-MS |
|
Organic
semi-/non-volatile compounds |
GC-MS /
LC-MS |
|
Elemental
impurities |
ICP-MS
/ ICP-OES |
|
Inorganic
ions |
IC /
suitable elemental or ion analysis |
|
Non-volatile
residue |
Gravimetric |
|
Specific
additives/degradation products |
Targeted
HPLC/GC/LC-MS |
|
UV-absorbing
substances |
UV-Vis,
where applicable |
|
pH /
conductivity |
For
aqueous extracts, where relevant |
The exact
extraction solvents, temperatures and durations should be scientifically
justified according to the intended application.
3. Leachables testing
Leachables
are substances that actually migrate into the drug product during normal
storage/use.
For an
LVP container, the leachables program should generally be based on:
- Drug formulation composition
- Proposed shelf life
- Storage conditions
- Sterilization conditions
- Extractables profile
- Toxicological assessment of
identified extractables
- Expected patient exposure
Therefore, you
should not simply perform every possible E&L test on the PP granules.
The extractables study is normally used to establish the potential chemical
profile, followed by a risk-based
leachables study on the finished container/product system.
4. Important point: granules vs. finished container
If your
customer is asking specifically for PP granules, distinguish between:
PP raw
material qualification
→ Identification, physicochemical properties, additives, elemental impurities,
etc.
Extractables
study
→ Usually performed on the material/component under controlled extraction conditions.
Leachables
study
→ Preferably evaluated using the final PP container/closure manufactured
from the granules, because processing, molding, sterilization and the final
container geometry can affect migration.
5. Regulatory/pharmacopoeial framework
For
pharmaceutical packaging used with parenteral products, the assessment should
be checked against the applicable requirements, such as:
- USP <1663> – Assessment of
Extractables Associated with Pharmaceutical Packaging/Delivery Systems
- USP <1664> – Assessment of Drug
Product Leachables Associated with Pharmaceutical Packaging/Delivery
Systems
- USP <661> /
<661.1> / <661.2> – Plastic packaging systems and plastic
materials of construction, as applicable
- Ph. Eur. requirements for
plastic materials/containers, where applicable
- Applicable ICH Q3E
principles for extractables/leachables risk assessment, where applicable
- Relevant regulatory/customer
specifications for the particular LVP product.
USP <1031> – Biocompatibility of Pharmaceutical Packaging Systems and
Their Materials of Construction
USP <1031> provides guidance for the biocompatibility
evaluation of pharmaceutical packaging systems and their materials of
construction. It describes a risk-based approach for
assessing the potential biological effects of materials and substances that may
come into contact with pharmaceutical products.
For Polypropylene (PP) bottles used for Large-Volume Parenteral
(LVP) products, USP <1031> should be considered together with
the relevant USP chapters for plastic materials, extractables, leachables, and
biological reactivity.
Recommended Evaluation Approach for PP LVP Bottles
1. Material
Characterization
o
Identification and characterization of the PP
material
o
Evaluation of additives and processing aids
o
Assessment according to USP
<661.1>, where applicable
2. Extractables
Assessment
o
Evaluation of substances that may be extracted
from the PP material under exaggerated laboratory conditions
o
USP <1663> – Assessment of
Extractables Associated with Pharmaceutical Packaging/Delivery Systems
3. Leachables
Assessment
o
Evaluation of substances that may migrate from
the PP bottle into the actual LVP formulation during storage
o
USP <1664> – Assessment of Drug
Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems
4. Biological
Reactivity / Biocompatibility
o
USP <87> – Biological Reactivity
Tests, In Vitro
o
USP <88> – Biological Reactivity
Tests, In Vivo, where applicable and scientifically justified
o
The need for these tests should be determined
based on the material, intended use, route of administration, duration of contact,
and chemical characterization.
5. Toxicological
Assessment
o
Identified extractables and leachables should be
evaluated for their potential biological and toxicological risks.
o
The assessment should consider the
concentration, patient exposure, duration of exposure, and potential toxicity
of the identified substances.
Important Point
USP <1031> does not prescribe one
fixed set of biocompatibility tests for every PP LVP bottle. The
appropriate testing strategy should be established using a risk-based
approach, considering the formulation, container material,
manufacturing process, sterilization conditions, storage period, and potential
patient exposure.
A suitable overall evaluation pathway is:
Hi. I’m Writer of Researchsop.com. ’ ’ Please share these SOPs to all concern pharma people for their development. I like to fullfill the need of curious people. These things inspire me to make things looks better.
0 comments:
Post a Comment