Transcript PQRI Opening Session

PQRI Survey of
Pharmaceutical Excipient
Testing and Control Strategies
Used by Excipient Manufacturers,
Excipient Distributors and
Drug-Product Manufacturers
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PQRI Opening Session
Welcome
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When? The time is NOW!
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Where? The place is HERE!
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The next 2 days provide the opportunity for
you to participate!
Please be respectful of time limits.
This hotel wing will break down to 5 discussion
areas.
Your individualized, randomized topic sequence
ensures you will discuss each topic. See your
personal packet.
You will hear the thoughts of all other
participants at least once.
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Support
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The Workshop Booklet
PQRI assistance – Sylvia Gantt
Hotel maps
Phones
Facilities
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PQRI Working Group Members
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Pharmaceutical Quality Research Institute's
Excipient Working Group has organized the
survey and workshop.
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Gregory Larner, Statistics Manager with Pfizer
(Kalamazoo, MI)
David Schoneker, Chair-elect, IPEC-Americas and
Director of Global Regulatory Affairs at Colorcon (West
Point, PA).
Catherine Sheehan, Director for Excipients Group at
USP, (Rockville, MD)
Rajendra Uppoor, Pharmacist, Office of Pharmaceutical
Science, CDER/FDA (Silver Spring, MD).
Phyllis Walsh, Senior Compendial Manager with
Schering-Plough (Kenilworth, NJ).
Robert Wiens, Compendial Affairs/Global Method
Management, Eli Lilly (Indianapolis, IN).
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The Workshop
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PQRI Excipient Working Group welcomes
you to a Workshop on Excipient Control
Strategies.
Safe and Effective Excipients is our Goal
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Component Regulations and Control is critical
Global economy increases complexity
Need effective and efficient control strategies
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Objectives – PQRI Working Group
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Provide a report on the Survey of
Excipient Testing and Control
Strategies
Determine the impact of those
findings on stakeholders.
Hold discussions on the impact of
FDA regulation and guidance on
excipient control strategies and how
to use them correctly and effectively.
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Objectives - Participants
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Based on the survey information and
conference discussions the participants
will:
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Identify concerns of stakeholders - including
excipient manufacturers, drug product
manufacturers, regulators, and USP.
Communicate and clarify regulations.
Develop stakeholder recommendations and
ideas for potential changes in compendia,
guidances and regulations to minimize
regulatory burden.
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Deliverables
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Summaries of workshop discussions
A Joint Position Paper from excipient
manufacturers, drug-product
manufacturers and USP on key
excipient issues.
Possible solutions to issues currently
faced by the stakeholders.
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How the Survey was Conducted
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PQRI conducted an open, publicly
available, electronic survey
Current excipient-control strategies were
studied.
3 surveys were available:
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pharmaceutical excipient manufacturers,
excipient distributors and
drug-product manufacturers (excipient users)
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Survey Highlights - I
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Nearly all respondents (99%) stated that their
excipient specifications comply with USP-NF
monograph requirements.
Almost all drug product manufacturers (97%)
test excipients according to USP-NF
monograph/general chapter methods;
Approximately 1 in 6 excipient manufacturers and
excipient distributors do not test according to
USP-NF.
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Survey Highlights - II
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Most (79%) respondents (excipient
manufacturers, excipient distributors, and
excipient users) have been inspected by the Food
and Drug Administration (FDA); and most
distributors have been inspected by their State or
Local Authorities.
Most excipient specifications are both national
(USP-NF) and global, versus up to 15% just
national (USP-NF).
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Survey Highlights - III
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Most excipients obtained from new vendor
sources are qualified
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An excipient from a new supplier (or vendor), is
qualified
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by vendor audit (91%) and
complete testing according to compendial monograph
(96%) for the article.
approximately 35% of the time by supplier’s analytical
method,
about 50% by an in-house method,
63% of the time by process validation in the dosage
form, but
rarely (15%) accepted on Certificate of Analysis (C of A)
with identity test alone.
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Survey Highlights - IV
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Greater than 70% of all respondents
perform additional functionality or
processability testing:
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76% to determine excipient suitability,
66% always for the excipient,
little over 50% for oral solutions.
87% for solid oral dosage forms.
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Survey Highlights - V
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85% of drug product manufacturers, and
all distributors have a vendor certification
program.
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87% of drug product manufacturers audit
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excipient manufacturing sites, and
testing sites.
Greater than 90% of drug product
manufacturers’ audits are done “on-site of the
vendor” by their own company auditors
less than 20% by third party,
53% of the audits include a questionnaire.
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Background
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2003 – European Agency for the
Evaluation of Medicinal Products
issued guidance for excipients and
US Food and Drug Administration
issued guidance for CMC.
Industry believed that generally
accepted excipient control strategies
were eliminated by the guidance.
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Background, continued
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Control strategies of concern
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Drug Product Manufacturer (DPM) may apply
internal method, equivalent to Pharmacopeia.
Select single method capable of ensuring
compliance with multiple Pharmacopeia.
2006 – FDA strategically focuses on
CGMPs for 21st Century, including an
announcement that the 2003 guidance is
withdrawn.
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Surprises
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About 25% of the time drug product
manufacturers test excipient suitability for
processing, using experimental
(laboratory) scale batches, or pilot scale
manufacturing batches.
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Batches were rarely (15%) accepted on
CofA with identity test alone.
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This was higher than expected.
This is an accepted approach in the CFR, and
was lower than expected.
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Surprises, continued
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Most excipient manufacturers and distributors
that replied to the survey do label their excipients
as compendial grade.
 Excipient GMP requirements perceived as being too
restrictive generally do not impact their decision;
 Low demand for compendial grade generally does not
impact their decision;
 “Can not meet the compendial monograph” criteria
generally does not impact their decision.
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This may not be reflective of the entire excipient
manufacturers industry since the pharmaceutical
industry is often a small fraction of their
business.
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Summary of Key Survey Findings
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The majority of excipient manufacturers;
excipient distributors and drug product
manufacturers
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Manufacture their products for global
distribution.
Test their excipients according to USP-NF
monograph and general chapter methods.
97% of drug product manufacturers
perform more than an identification test
when receiving excipients from their
vendors along with Certificate of Analysis.
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Summary of Key Survey Findings
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New sources of excipients used by drug product
manufacturers are qualified by
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Nearly half (40%) of drug product manufacturers
had difficulty in finding a manufacturer of USP-NF
grade excipient.
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vendor audits, and
complete compendial testing.
In such a situation, they would use the best grade
available,
test the excipient according to compendial monograph
and
conduct the excipient manufacturer’s assessment.
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Summary of Key Survey Findings
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75% of drug product manufacturers indicated
they ensure few to all excipients they use
conform to compendial grade by testing, along
with manufacturer’s site audits.
In 80% of the cases, validated test procedures
are used to show:
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a noncompendial grade excipient conforms to a
compendial grade, or
a compendial grade conforms to a multi-compendia
grade.
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Summary of Key Survey Findings
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Majority of excipient manufacturers and
distributors are not concerned about such factors
as:
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Excipient GMP requirements being restrictive or
low demand for compendial grade, or
inability to meet compendial monograph requirement, or
potential to be inspected by FDA, or
audits by drug product manufacturers.
Nearly 80% of excipient manufacturers,
distributors and drug product manufacturers have
been inspected or visited by the FDA or State or
local authorities.
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Summary of Key Survey Findings
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89% of drug product manufacturers
stated that at least 5 of their excipients
are in a reduced testing program. They
do not perform complete monograph
testing after vendor qualification and
receipt of Certificate of Analysis.
Excipient manufacturers, distributors and
drug product manufacturers responded to
be adequately familiar with:
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FDA and compendial requirements and
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recommendations for excipients testing.
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Summary of Key Survey Findings
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>70% excipient manufacturers,
distributors, and drug product
manufacturers perform additional
functionality or processability testing that
is not part of any compendial monograph:
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87% due to processing concerns
87% for solid oral dosage forms
24% of drug product manufacturers have
products for which excipient variability is a
problem in spite of such extra-compendial
testing.
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Summary of Key Survey Findings
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Alternate international compendial methods are
used by half or more of excipient manufacturers,
distributors and drug product manufacturers to
test some, most or all of their excipients instead
of USP-NF.
Nearly 60% of excipient manufacturers and drug
product manufacturers
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conduct excipient testing per harmonized monographs;
and
reduce redundant testing by demonstrating multiple
compendial specification equivalence, or
by using the most stringent method or specification.
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Summary of Key Survey Findings
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About 50% of excipient
manufacturers and drug product
manufacturers have applied
harmonized excipient monographs
and harmonized general chapters
across all their sites.
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Workshop Topics A and B
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B.
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Clarify “continuous-flow
manufacturing” and “skip-lot
testing” used for excipients in the
context of 21 CFR Part 211.84
regulations.
Discuss how characterization of
excipient physical and chemical
properties helps build quality into
the drug product.
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Workshop Topics C, D and E
C.
D.
E.
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Highlight advantages of increased
use of third-party audits.
Discuss strategies to increase the
number of excipients labeled USP—
NF.
Discuss when reduced testing is
appropriate.
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Round Table Discussions
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Attendees will rotate through each
topic.
The topics will stay in the same
room.
Attendees will be randomized so you
will meet all attendees and attend all
topics.
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