Best Practices Injectable Packaging Lines

Manish Bhatkar

Hyderabad

11th Nov. 2016

Best Practice
A best practice is a method or technique that has been
generally accepted as superior to any alternatives
because it produces results that are superior to those
achieved by other means or because it has become a
standard way of doing things, e.g., a standard way of
complying with legal or ethical requirements.
Best practices are used to maintain quality as an
alternative to mandatory legislated standards and can
be based on self-assessment or benchmarking. Best
practice is a feature of accredited management
standards such as ISO 9000 and ISO 14001.
Reference: https://en.wikipedia.org/wiki/Best_practice

Injections USP <1>

Parenteral articles are preparations intended for injection through the
skin or other external boundary tissue, rather than through the
alimentary canal, so that the active substances they contain are
administered, using gravity or force, directly into a blood vessel,
organ, tissue, or lesion.
Parenteral articles are prepared scrupulously by methods designed to
ensure that they meet Pharmacopeial requirements for sterility,
pyrogens, particulate matter, and other contaminants, and, where
appropriate, contain inhibitors of the growth of microorganisms. An
Injection is a preparation intended for parenteral administration and/
or for constituting or diluting a parenteral article prior to
administration.

Injections Market Trends & Drivers

Industry Focus Shift (Oncology, Biologics)

Novel Drug Delivery Systems (Gaining Prominence)

$312 Bn. (2014) $363 Bn. (2017)

Packaging Best Practices Trends & Drivers

Quality Expectations WLs, Import Alerts/ Bans

Regulatory Requirements (Dose Count, Needlestick Legislation)

Regulatory Scrutiny Approval Delays

Cost Pressure Margins (Standard, Simple & Robust Pkg. Solution)

Drug Requirements Complexity (Simple & Safe Administration)

Self-Injection Technology Patient Focused Care

Supply Chain Need for Risk Mitigation

Packaging Best Practices Basis

Packaging Best Practices Basis

Injectable Packaging Process

Checks
Incoming
Material

Washing
&
Cleaning

Sterilization

Formulation

Filling
&
Sealing

Visual
Inspection

Packaging

Labeling

Checks
Finished
Product

Best Practices Selection of PPMs

BASIC REQUIREMENTS
q

Protection

Stability test conditions

q

Compatibility

Regulatory

Legislation
E.g. EC Packaging and
Packaging Waste Directive

Commercial
Image
Market requirements/trends
Dosing/patient compliance
Security/tamper evidence
Manufacturing
Economics COG
Corporate
Global Quality Policies

Best Practices Selection of PPMs

How the product will be used?

Single-Dose Container (Vials, Ampoules & PFS)

Multiple-Dose Container (Vials)
Single-Patient-Use Container (Cartridges & Pens for
Injection)

Selection of the Appropriate Package Type Terms and Recommendations for Labeling Injectable Medical Products Packaged in Multiple-Dose, Single-Dose, and Single-PatientUse Containers for Human Use - Draft Guidance for Industry, Oct. 2015

Best Practices Selection of PPMs

How the PPMs will be sterilized?
Saturated Pure Steam
Gamma Irradiation
The sterilization process transfers a significant quantity of
energy (heat or radiation) into the elastomer material that
can initiate a variety of chemical reactions. These reactions
have the potential to change;

The quantity of compounds present in the closures and/

or create new compounds, thus changing the
extractable/leachable profile of the closure,
Cross-linking reactions results in increasing the tensile
strength, hardness, modulus, and compression set, while
elongation is reduced.
Sheds particles and yellowing on radiation.

Best Practices Selection of PPMs

How the PPMs will be sterilized?

Review Article - Reducing the Risk of Contamination of Sterile Parenteral Products via Ready-to-Use Closure Components by Wayne Curry, Samuel Conway, Clara Goodfield, Kimberly Miller, Ronald L. Mueller,
and Eugene Polini. AAPS PharmSciTech, Vol. 11, No. 4, December 2010.

Best Practices Selection of PPMs

Appropriate for the intended use (ideal fit between
CC to ensure sterility throughout the product shelflife)?
CPPs: (1) Use of appropriate materials, (2) Matching
dimensional fit, and (3) Validated assembly parameters
CQAs: System fit
Basis: (1) Dimensional checks, (2) Visual verification, (3)
CCIT for presence of leak, leak rate & integrity over
shelf-life
Establishes: (1) CC specifications, (2) Routine operating
parameters, and (3) CCI over the product shelf-life

Best Practices Selection of PPMs

Product & CCS Compatibility
CPPs: (1) Use of appropriate materials, (2) Quality
audits, (3) TA, (4) Trending of incoming CC items test
results, and (5) Change control, (6) Management
Reviews
CQAs: Physico-chemical characteristics of the product
Basis: (1) USP 1660 inner surface durability, (2)
Product stability over shelf-life
Establishes: (1) CC specifications, (2) Routine QC test,
and (3) CC & product compatibility over the product
shelf-life

Best Practices Selection of PPMs

A Case

Problem: Stoppers popped-up post stoppering on of the

vials.
When: MF to support introduction of new vial (15mL, 20mm
neck size, molded glass vial) to be combined with an
existing elastomeric stopper (Chlorobutyl, 20mm, single leg
Lyo. Stopper).
Root cause: (a) short neck of the molded vial in comparison
to the same capacity tubular vial, and (b) single leg of the
Lyo. elastomeric stopper
Same elastomeric stopper successfully used on 10mL, 20mm
neck size tubular glass vials. Due to, comparatively short
neck size of the 15mL molded glass vial the elastomeric
stopper could not expand uniformly inside the vial neck.

Packaging Best Practices Trends & Drivers

Quality Expectations Visible Particulate Matter

Regulatory Requirements

Regulatory Scrutiny Approval Delays

Cost Pressure Margins (Cost of Components Processing Capex & Opex)

Drug Requirements Complexity (Custom Component Preparation Equipment)

Self-Injection Technology Patient Focused Care

Supply Chain Need for Risk Mitigation

Best Practices Washing & Sterilization of PPMs

Purpose: Reduction of Bio-burden, Pyro-burden and
Particulate Matter
CPPs: (1) Use of Appropriate Cleaning Agents Final Rinse
with WFI, (2) Quality of Cleaning Agents, (3) Trending of
Incoming CC items for Bio-burden, Pyro-burden, Particulate
Matter Extent and Characteristics, and (4) Change Control,
(5) Management Reviews
CQAs: Validated In-process Control Limits
Basis: Washing/ Cleaning Process Validation
Establishes: (1) Washing Process Controls, (2) Routine Inprocess Checks, and (3) Process Capability Index

Best Practices Washing & Sterilization of PPMs

Purpose: Sterilization @ Desired SAL
CPPs: (1) Use of appropriate Sterilizing Agent
Saturated Pure Steam, Dry Heat, Irradiation, (2)
Quality Monitoring of Sterilization Agents, (3) Change
control, and (4) Management Reviews
CQAs: Sterilization Cycle Capability to achieve the
desired/ validated Sterility Assurance Level SLR
Basis: (1) Comparison of Each Cycle Chart with
Standard Validation Cycle Chart, and (2) Comparison
of Sterilization Cycle Lethality F0
Establishes: (1) The Sterilization Cycle Specification,
and (2) Sterilization Cycle Process Capability

Best Practices Washing & Sterilization of PPMs

A Case

The temperature and duration required for the heat sterilization method will damage the
elastomeric closures and render them unusable.

Best Practices Washing & Sterilization of PPMs

A Case
Vial Washing Process Validation is Based on Capability to Remove:

Salt

Charcoal

Not a Risk Based Approach !!!

Packaging Best Practices Trends & Drivers

Quality Expectations Visible Particulate Matter

Regulatory Requirements

Regulatory Scrutiny Approval Delays

Cost Pressure Margins (Cost of Components Processing Capex & Opex)

Drug Requirements Complexity (Custom Component Preparation Equipment)

Self-Injection Technology Patient Focused Care

Supply Chain Need for Risk Mitigation

Best Practices Filling, Sealing & Visual Inspection

Reduction of Interventions & Aseptic Manipulations Sterility
Assurance, Particulates Matter, and Dose Accuracy
CPPs: (1) Design & Selection of PPMs PPQ Studies, PST (2)
Trending of Incoming CC items for Defects/ Dimensions, (3)
Change Control, (4) Management Reviews
CQAs: Continuous Verification: (1) PPM Specifications
Established Specifications, (2) Aseptic Interventions Frequency
Basis: (1) PPQ Studies Engineering/ Material Feasibility, (2) IP
Checks Fill Accuracy
Establishes: (1) Incoming Material Controls, (2) Routine Inprocess Checks, and (3) Process Capability Index

Best Practices Filling, Sealing & Visual Inspection

Future Trends Injectable Packaging Line

Reducing Contamination During Processing

(Pre)washed, sterilized, de-pyrogenated
containers and closures
Reducing Cost (capex & opex) Avoiding
multiple unit operations, such as washing,
sterilization & de-pyrogenation
Reducing Regulatory Review Time
Approval Delays

Future Trends Injectable Packaging Line

Open

Close

Future Trends Injectable Packaging Line

Blow/ Form Fill & Seal

Future Trends Injectable Packaging Line

Limited

Versatile

Future Trends Injectable Packaging

Growth and competition in injectable markets

Use of biologics drugs
Global demand for vaccines
Need of drug delivery in non-medical settings
Focus on more efficient drug administration
Ease of Administration
Compliance patient as well as regulatory
Differentiaion

Future Trends Injectable Packaging

Formulation

Device

Future Trends Injectable Packaging (Ease of Administration)

Vetters dual chamber technology, LyoJect syringe and

dual chamber VLK cartridge allows the differing
ingredients and solvents to be prefilled and stored
separately, then easily mixed and administered as needed
just prior to administration. This help mitigate the residual
risk of needle stick injuries allowing non professionals like
patients and family members to safely use the device, in
non-clinical setting.
Watson Pharmaceuticals + West Pharmaceutical Services,
Inc. developed a safe and convenient Wests MixJect
drug transfer device. This device provides ease of
reconstitution with a diluent prior to injection by syringe. The
entire process makes administration and disposal
significantly easier and safer for patients and caregivers.

Future Trends Injectable Packaging (Human Factor, Convenience)

Integrating Human Factor in the Device

Development
Aptar Pharma ProJect is a novel auto
injector
Confirmed benefits of ProJect in terms of
ease of use, ergonomics, and design
Features include push on skin activation,
slow injection, hidden needle, highly visible
indicator window, and audible feedback

Future Trends Injectable Packaging (Human Factor, Needle Safety)

Credence Companion offers the bio-pharm product

manufacturers a new option to differentiate their
products by delivering to their patients and caregivers
the best technologies available.
The cover allows easy attachment by dexteritychallenged users as well. Needle can be attached by
holding the cover in a fist or in a thumb/forefinger
wedge.
Once attached the user receives audible, tactile, and
visual feedback of a successful needle to syringe
connection.
At the completion of the injection, the needle
automatically retracts into the syringe barrel and the
syringe is automatically disabled.

Future Trends Injectable Packaging (Patient Compliance & Self-use)

West SmartDose electronic wearable bolus injector.

The single use, disposable system cGMP
manufactured.
Utilizies a Daikyo Crystal Zenith polymer cartridge
along with Flurotec barrier filmcoated elastomers as
the primary container.
Designed for high volume (>1mL) and/or high
viscosity protein formulations for subcutaneous bolus
administration.
The SmartDose injector can extend the time between
dosing and may improve patient compliance (versus
daily injections).

Thank You...