GMP Inspection Trends

GMP Inspection Trends
Karen Wallace-Graner, Compliance Officer

Drug GMP Inspection Unit
Compliance Coordination and Licencing Division (CCLD), Ottawa, ON
Health Products and Food Program – Inspectorate
GMP Inspection Trends
Overview
• Introduction
–About GMP Inspections (slide3-10)
–Observation Risk Classification and Ratings (slide 11)
–Distribution of Licenced Establishments – A National Perspective (slide12-15)
• Trends in GMP Inspections and Observations (slide16-18)
–Rating (slide 19)
–Risk 1 observations and examples (slide20-25)
–Overview of key areas of GMP deficiencies and examples (slide26-46)
• On the Horizon (slide 47-51)
Health Products and Food Branch

Inspectorate
L’Inspectorat de la Direction générale 2
des produits de santé et des aliments
www.healthcanada.gc.ca/gmp
Introduction – National Locations
Human and Veterinary Drug GMP #
~25 staff
inspectors Compliance Coordination and Licencing 5.9

Division (CCLD) - Ottawa, ON
in the field Western Operational Centre (WOC) – 3.79
Burnaby, BC; Edmonton, AB
Manitoba and Saskatchewan Operational 2.46
Centre (MSOC) – Winnipeg, MB
Ontario Operational Centre (OOC) – 11.63

Toronto, ON
Quebec Operational Centre (QOC) – 5.37
Longueuil, QC
Atlantic
Atlantic Operational Centre (AOC) – 1.81
Western
Manitoba & Quebec Halifax, NS; St. John’s NFLD
Saskatchewan
Laboratories -Toronto, ON (more than GMP) 12.5
CCLD
Ontario
Laboratories - Longueuil, QC (more than GMP) 12.61

Inspectorate
GMP Inspections – Scope
GMP inspection program applies to Human and

Veterinary drugs under Division 2 and Division 1A of
the Food and Drug Regulations:
• Pharmaceuticals
• Biologics
• Radiopharmaceuticals
• Natural Health Products exported to a MRA jurisdiction

Inspectorate
Introduction – Primary Drivers for GMP Inspection
Drug Establishment Licences (DEL)

• Part C, Division 1A of the Food and Drug Regulations (FDR)
• Required for licenceable activities:
▪ 1. Fabricate
▪ 2. Package/label
▪ 3. Perform the tests, including any examinations,
required under Division 2
▪ 4. Distribute
▪ 5. Import
▪ 6. Wholesale

Inspectorate
Inspection Strategy and Enforcement Approach for
GMP Inspections
POL-0001: Compliance and Enforcement Policy (May 31, 2005)*

POL-0004: Drug Good Manufacturing Practices (GMP) and
Establishment Licencing (EL) Enforcement
Directive (January 1, 2004)
POL-0011: GMP Inspection Policy for Canadian Drug
Establishments (January 31, 2008)
GUI-0001: Good Manufacturing Practices (GMP) Guidelines

- 2009 Edition (released May 8, 2009)

Inspectorate
GMP Inspection Types – Definitions
(POL-0011)
Regular: An inspection during which all of the applicable requirements of the

FDA and its associated Regulations are assessed.
Initial: An inspection conducted prior to the issuance of an establishment

licence where not all applicable requirements of the FDA and its
associated Regulations are assessed. This is not considered to be a
regular inspection.
Partial: An inspection of an historically compliant non-sterile fabricator that is

focused on selected GMP sections. A partial inspection should be changed
to a regular inspection when a risk 1 observation is found or when an NC
inspection rating is considered. All GMP sections are assessed after two
partial inspections for a site. The Plant Tour and the Documentation
Review stages are adapted for each partial inspection.

Inspectorate
GMP Inspection Types – Definitions cont’d
(POL-0011)
Re-assessment: A follow-up inspection carried out in situations where the
establishment was assigned an overall C rating on the previous inspection
but the number or type of observations contained in the previous
Inspection Exit Notice are such that correction action is required within a
timely manner. The inspection is focussed on, but not restricted to those
GMP sections where violations were observed and the implementation of
appropriate corrective actions
Re-inspection: A follow-up inspection carried out in response to the

assignment of an NC rating. The inspection is focussed on , but is not
restricted to those GMP sections where violations were observed and the
implementation of appropriate corrective action.

Inspectorate
GMP Inspections – Cycle
(POL-0011)
The type and cycle for Inspections is outlined in POL-0011:

GMP Inspection Policy for Canadian Drug Establishments
Targets for Regular Inspections:
Fabricators, Packagers/Labellers, Testing Laboratories 24 months
Importers, Distributors, Wholesalers 36 months

Inspectorate
GMP Inspections – Cycle cont’d
(POL-0011)
Initial Inspections:
- Commitment by Inspectorate to perform an initial inspection within 3
months following date of EL application/request
- Initial Inspections are followed by Regular Inspection within 1 year
Notice of upcoming inspection may or may not be provided

- inspections are generally announced as a courtesy
- Changes to dates of scheduled inspections will only be done at the
discretion of the Inspectorate and upon receipt of sufficient justification
from the establishment

Inspectorate
GMP Inspections – Observation Risk Classification
and Ratings (GUI-0023)
Observations are rated according to the “Risk Classification of GMP Compliance
Observations” (GUI-0023) (April 4, 2003)*
- Critical -> RISK 1
- Major -> RISK 2
- Other -> RISK 3
Possible inspection ratings are:
C (Compliant) = recommended for the continuation or issuance of an establishment licence

At the time of the inspection, the regulated party has demonstrated that the activities it
conducts are in compliance with the Food and Drugs Act and its associated Regulations.
*A C rating does not mean that there are no observations or corrective actions required.
NC (Non-compliant) = not recommended for the continuation or issuance of an establishment

licence
At the time of the inspection, the regulated party has not demonstrated that the activities it
conducts are in compliance with the Food and Drugs Act and its associated Regulations.

Inspectorate
National Distribution of Licenced Establishments –
by Activity Type
National Distribution of Licenced Firms
Current total= 1070

Fabricators 22% Fabricator,
Wholesaler,
Packagers/Labellers 17% 228 232
Testing Laboratories 7%
Importers 21%
Distributors 12%
Wholesalers 21%
Packager,
Distributor, 181
129 Importer, Tester, 72
228
As of March 31, 2009.

Does not remove overlap of activities factor

Inspectorate
Once the
date of
by Activity Type and
303
DropYear (2004
Page Fields Here to 2008)
inspection
350
has been
303
300 251
240
251
250 240
201 Year (Start Date)
Year (Start Date)
183188
(1029)
# of Inspections
201 2004
2004
200 170 183188 168 2005 (1020)
170
165 2005
165 168 2006
155 153 (729)
155 153 2006
142 140
142 140 136 2007 (735)
150 136 2007
129132 128
128124
122122 122122123 123
117 124 121
121 2008
2008 (928)
117 111 107
111
101 107
95 101
100 89
95 81 84
81 84
50
0
Count of Count of Count of Testing Count of Count of Count of
Fabricators Distributors Laboratories Packagers Importers Wholesalers
of Count of Count of Testing

Canada
Count of Count of Importers Count of
Activity
tors Distributors Laboratories Packagers Wholesalers
CanadaCountry Data Health Products and Food Branch
Activity Inspectorate
Country Data des produits de santé et des aliments
by Operational Centre (2008-2009)
Western
154
Region (WOC)
WOC - 14%
Manitoba &
Saskatchewan 64
(MSOC) MSOC - 6%
Ontario Region
596
(OOC)
OOC - 56%
Quebec Region
225
(QOC)
QOC – 21%
Atlantic Region
31
(AOC)
AOC – 3%
0 100 200 300 400 500 600
As of March 31, 2009

Inspectorate
National Distribution of Licenced Establishments–
by Region and Activity (2008-2009)
Wes tern Region
27 34 15 17 9 52
(WOC)
Manitoba &
Sas katchewan 9 13 3 4 35
(MSOC)
Ontario Region
125 90 32 206 47 96
(OOC)
Quebec Region
66 35 21 73 30
(QOC)
Atlantic Region
5 9 11 15
(AOC)
0% 100%
Fabricator Packager Tester

Importer Distributor Wholesaler

Inspectorate
Trends in GMP Inspections and

Observations

Inspectorate
GMP Inspection Trends – Overall Results (Ratings)
Fiscal Year Number of C rated NC rated

(Apr 1st – Mar 31st) Inspections
2004-2005 433 93% 7%
2005-2006 454 95% 5%
2006-2007 320 98% 2%
2007-2008 446 98% 2%
2008-2009 434 98% 2%

Inspectorate
GMP Inspection Trends – by Inspection Type
Fiscal Initial Regular Re- Re- Partial
Year Inspection assessment
2004- 22% 72% 3% 3% 0.2%
2005
2005- 19% 73% 2% 5% 2%
2006
2006- 24% 67% 3% 4% 1%
2007
2007- 19% 76% 2% 1% 2%
2008
2008- 15% 79% 2% 3% 0.8%
2009
Inspectorate
GMP Observations – Overall Results (Observations/Risk)
Fiscal Year Total # Inspections Total # Observations Percentage Risk
Noted
2004-2005 433 3529 Risk 1: 0.9%

Risk 2: 66%
Risk 3: 24%
2005-2006 454 3643 Risk 1: 0.7%
Risk 2: 62%
Risk 3: 37%
2006-2007 320 2442 Risk 1: <0.1%
Risk 2: 61%
Risk 3: 39%
2007-2008 446 3289 Risk 1: 0.2%
Risk 2: 57%
Risk 3: 42%
2008-2009 434 3649 Risk 1: 0.3%
Risk 2: 56%
Risk 3: 43%

Inspectorate
Inspection Trends – Risk 1 Observations
Fiscal Year # Risk 1 Observations
2004-2005 29
2005-2006 23
2006-2007 2
2007-2008 7
2008-2009 12

Inspectorate
Fiscal 2004 to 2008
Eq
Ra uip
w m
P e
M Ma er nt C
an te so
uf ria nn .02
0
2
4
6
8
10
12
M actu l Te el C .005
an
uf ring sting .02
ac .
tur Con C.0 006
ing tro 2.
0
Q Co l C.0 09
C n 2
D tro .01
Q epa l C.0 1
C r
D tme 2.01
Q ep nt 2
Fi C D artm C.0
nP e 2.0
r ep n 1
Fi odu artm t C.0 3
n P ct e 2
ro Tes nt C .014
du
ct tin .0
Inspectorate
Te g C 2.01
sti .02 5
ng .0
1
Inspection Trends – Risk 1 Observations
Re C.0 8
co 2.01
r
Re ds C 9
co .0
r 2
Re ds C .02
co .02 0
r
St ds C .021
ab .0
St ilit 2.
L’Inspectorat de la Direction générale
er Sta y C 022
ile b .0
Pr ility 2.0
od 2
uc C.0 7
ts 2.0
C.
02 28
.02
9
21
Inspection Trends – Risk 1 Observation Examples
C.02.018, C.02.019: Finished Product Testing

“Finished products were not fully tested for compliance with applicable
specifications by the DIN holding fabricator….Some lots of XXX were
released for sale without assay results of the active ingredient”

Inspectorate
Inspection Trends – Risk 1 Observation Examples cont’d
C.02.020: Records
Batch records for XXX presented on DATE were fabricated. The true records
for the product were presented on DATE. Manufacturing manager provided
the records on DATE. The QC Manager responsible for the GMP records
was not available on that day.
C.02.022: Records
“During the opening meeting on…the Director of Operations for the company
stated that the company had not conducted any licenceable activities since
first obtaining its licence in XXXX. It was further stated that there were no
records including distribution records, to review as part of the inspection.
Records were obtained by the Inspectorate indicating that sales were made
under Company X….Additionally, sale invoices indicated that the company
had not revealed the full extent of its wholesaling activities.”

Inspectorate
C.02.027: Stability
“There was no data available supporting the expiry date of any products
sold by the company”
“In absence of an expiry date on Product XXX there was no stability data
to support the shelf life beyond 3 years”

Inspectorate
C.02.029: Sterile Products
Eg.#1 Aseptic process validation for XXX injection had not been
performed. No media fill was performed to demonstrate the validity of the
aseptic filling operations. There was no written standard designed to test
the efficiency of the overall aseptic filling operations.
There was no monitoring for viable microorganisms and for non-viable
particulates in the XXX where the product was aseptically filled and
dispensed. There was no written environmental monitoring program in
place for particulates and viable microorganisms in grade A, B, C, and D
areas.
Eg. #2 Between January and June 200X eight finished products released
for sale failed the sterility test. Investigations were carried out but the
conclusion drawn did not invalidate the initial test. In each case, the
investigation concluded as a false positive.

Inspectorate
Inspection Trends – By Regulation
Top 3 Regulations Cited
Regulation 2004- 2005- 2006- 2007- 2008-

2005 2006 2007 2008 2009
Manufacturing 14% 12% 10% 11% 9%

Control C.02.011
Manufacturing 9% 9% 11% 10% 9%

Control C.02.012
#1 QC Department 25% 27% 31% 26% 28%

C.02.015

Inspectorate
Inspection Trends – By Regulation
• Examination and categorization of GMP observations

from:
– Fiscal 2007-2008
– Fiscal 2008-2009

Inspectorate
Inspection Trends – Regulation
C.02.015 Quality Control Department (most cited)
Regulation:
(1) All fabrication, packaging/labelling, testing, storage, and
transportation methods and procedures that may affect the quality
of a drug shall be examined and approved by the person in
charge of the quality control department.
(2) The person in charge of the quality control department shall
cause to be investigated every complaint on quality that is
received and cause corrective action to be taken where
necessary.
(3) The person in charge of the quality control department shall
cause all tests or examinations required persuant to this Division
to be performed by a competent laboratory.

Inspectorate
For Fiscal 2007-2008 & 2008-2009:

• 56% Risk 2, 44% Risk 3
• 2 prominent categories of observations cited against
this regulation relating to:
– Inappropriate procedures for handling, storage and
shipment of drug products with respect to temperature
requirements
(~50% observations cited to wholesalers)
– Laboratory operations
Inspectorate
Inappropriate procedures for handling, storage and

shipment of drug products with respect to
temperature requirements
• accounts for 23% of observations cited under this regulation
• Requirements and expectations are outlined in GUI-0069:

“Guidelines for Temperature Control of Drug Products
during Storage and Transportation” (October 17, 2005)*

Inspectorate
Some Examples…..
Inappropriate procedures handling, storage and shipment of

drug products with respect to temperature requirements
“There was no procedure in place and implemented to monitor storage and
transportation conditions such as temperature, humidity, stock rotation and other
precautions necessary to maintain quality and safe distribution of drugs.”
“There was no written transportation procedure to ensure that products lacking freeze
thaw stability studies are transported in heated carriers during winter months and
verification of adequate transport conditions is conducted upon receipt of shipment…”
“Shipping cooler configurations and sizes utilized for shipping temperature sensitive
drugs to end users were not validated to demonstrate that label storage conditions
would be maintained for the drugs during worst case weather conditions and for
logistical distance/transit time extremes.”

Inspectorate
Examples cont’d…..
Absence or inadequate temperature control, monitoring,
mapping & thermometer calibration
“Review of temperature records revealed incidences of lack of data as well as

excursion without any noted corrective and preventative action initiated as a result.
Impact assessment of affected drug products had not been performed by quality
control. In fact, as per procedure, there was no requirement for QC/QA to be involved
or notified in the event of excursion…”
“Coolers used to store drug products requiring refrigeration had not been mapped to
ensure that worst case areas are blocked from product storage. Coolers were also
not continuously being monitored to ensure that the requirements for products stored
within the cooler were continuously being met.”

Inspectorate
Laboratory Operations
• accounts for 24% of observations cited under this regulation

– 57% of these observations Risk 2
• Key areas: Qualification, calibration of laboratory

instrumentation/equipment, control of reagents, cultures, culture
media, procedures (inadequate or not followed)

Inspectorate
Examples….
“There was insufficient and/or lack of traceability within analytical records to pertinent
procedures, lots of reagents, prepared working solutions, pertinent physical checks, etc.,
applied to facilitate an audit trail during the review of a methodological test process.
Examples: 1. Test record for heavy metal analysis of formaldehyde by the ACS standard
failed to identify or cross reference the preparation or lot of the ammonium acetate pH 3.5
buffer solution and the standard control solution. 2. Test record for the assay of
monosodium glutamate via FCC standard did not cross reference the lot of acetic acid
used.”
“ There was no evidence that media used in-house for environmental monitoring, testing of
raw materials and finished products was tested for their growth promotion capability”

Inspectorate
Examples cont’d….
“Annual OQ on the HPLC instrument did not include a test for drift and lamp intensity of
the detector and did not include test for carry-over of the auto-injector.”
“The following comments pertain to reference materials:

1. A formal qualification program for house standards had been established, however it
had not been implemented within the chemistry laboratory.
2. Data was not available to support the blanket 3 year expiry/usage period for house
standards which did not possess an expiry by the manufacturer.”

Inspectorate
C.02.011 - Manufacturing Control (tied for 2nd most cited)
Regulation:
(1) Every fabricator, packager/labeller, distributor referred to in
paragraph C.01A.003(b) and importer of a drug shall have
written procedures prepared by qualified personnel, in respect of
the drug to ensure that the drug meets the specifications for use
of that drug.
(2) Every person required to have written procedures referred to in

subsection (1) shall ensure that each lot or batch of the drug is
fabricated, packaged/labelled and tested in compliance with
those procedures.

Inspectorate
For Fiscal 2007-2008 & 2008-2009:

• 58% Risk 2, 42% Risk 3
• Observations made at all types of facilities to which the

regulation applies (i.e., fabricators, packager/labellers,
importers, distributors)
• Prominent themes:
– Process validation
– Incomplete manufacturing procedures/batch documents
– Incomplete packaging documents
Inspectorate
Process Validation for critical production processes
not conducted or incomplete.
– 17% of all observations
– All Risk 2
Example:
“Powder filling validation protocol requirements for low, target and high speed runs
were deficient in that samples tested for potency were not appropriately representative
of the beginning and end of the runs i.e low and high speed run samples tested were
representative of the 30% and 90% run time sampling points; target speed run
samples tested were representative of the 10 % and
97% run time sampling points.”

Inspectorate
Incomplete manufacturing procedures/ batch
documents; failure to follow manufacturing
procedures
– 14% of observations, all Risk 2
Example:
“The master production document for XXX tablets (Formula XXX) did not specify the
validated paddle speed or whether pre-compression is to be used.”
“The bulk reconciliation for XXX, lot XXX was outside the acceptable limit of 98-
102% and no investigation was performed. The actual yield of the batch was
recorded as 89.6%.”

Inspectorate
Incomplete Packaging Documents; incomplete

packaging procedures
– 10% of observations, all Risk 2
Examples:
“There was no system in place to ensure that line clearance of packaging lines was
performed, documented and approved by a responsible person before the product
and packaging components were brought on the line.”
“ Incoming labels were not quarantined upon receipt. Unused labels were not counted
following their return to label storage from the packaging line or prior to re-issuance to
another batch.”
Inspectorate
Regulation
(1) Every fabricator, packager/labeller or distributor referred to in section

C.01A.003, importer, and wholesaler of a drug shall maintain
(a) a system of control that permits complete and rapid recall of any lot or
batch of the drug that is on the market; and
(b) a program of self-inspection.
(2) Every fabricator and packager/labeller and subject to subsections (3) and
(4), every distributor referred to in section C.01A.003(b) and importer of a
drug shall maintain a system designed to ensure that any lot or batch of
the drug fabricated and packaged/labelled on premises other than their
own is fabricated and packaged/labelled in accordance with the
requirements of this Division.

Inspectorate
Regulation cont’d…..
(3) The distributor referred to in paragraph C.01A.003(b) of a drug that is

fabricated, packaged/labelled, and tested in Canada by a person who
holds an establishment licence that authorizes those activities is not
required to comply with the requirements of subsection (2) in respect of
that drug.
(4) If a drug is fabricated or packaged/labelled in an MRA country at a

recognized building, the distributor referred to in paragraph C.01A.003(b)
or importer of the drug is not required to comply with the requirements of
subsection (2) in respect of that activity for that drug if
(a) the address of the building is set out in that person’s
establishment licence; and
(b) that person retains a copy of the batch certificate for each lot
or batch of the drug received by that person.

Inspectorate
For Fiscal 2007-2008 and 2008-2009:

• 51% Risk 2, 49% Risk 3
• only one Risk 1 cited
• Observations made at all types of facilities to which the

regulation applies (i.e., fabricators, packager/labellers,
importers, distributors, wholesalers).
• Prominent Themes:
– Lack of Quality Agreements
– Inadequate or lack of recall system/procedure
– Inadequate or lack of self inspection program
Inspectorate
Inadequate/Lack of Quality Agreements
•35% of observations, mostly risk 2
Examples:
“ A technical agreement covering matters pertinent to Canadian GMPs had not been
established between the importer and their foreign supplier of drug products.”
“The quality agreement between the firm and the foreign supplier was deficient in that it
did not address the following:
-change control;
-documentation;
-the purchase of raw material and packaging components;
-the reporting of OOS results;
-test method validation and method transfer;
-the use of sub-contractors;
-re-working/re-processing;
-transportation of finished goods.”

Inspectorate
Inadequate/Lack of Recall system/procedure

• 18% of observations – mostly risk 2
Examples:
“The written recall procedure was deficient in that : 1) Health Canada would not be
notified if a recall was initiated by XXX. 2) the responsible person for initiating and
coordinating a recall was not identified.”

Inspectorate
Absence of/inadequate Self Inspection Program

• 33% of observations – mostly risk 2
Examples:
“i) There was no documentation to demonstrate that corrective action had been taken
to address Self Inspection Observation of XXXX pertaining to inadequate control of
XXXX. This self inspection observation was still open.
ii) The fabricator’s self inspection did not include activities related to import and /or
distribution of third party products.”
“There was no written self inspection program outlining the criteria and frequency of a
self inspection. There were no evidence that a self inspection had been conducted to
ensure compliance with sections of Part C, Division 2 of the Food and Drug
Regulations.”

Inspectorate
On the Horizon….

Inspectorate
Inspection Trends: On the Horizon...
Final documents planned for release in 2009-2010:
• GUI-0001 - Good Manufacturing Practices (GMP) Guidelines, 2008 Edition / Lignes

directrices des Bonnes pratiques de fabrication (BPF), édition 2008 (RELEASED May 8/09)
• GUI-0029 - Validation Guidelines for Pharmaceutical Dosage Forms / Directives sur la
validation des formes posologiques pharmaceutiques (will be final, not for comment)
• GUI-0036 - Annex 2 to GMP: Manufacture of drugs for Clinical Trials / Annex 2 aux BPF :
fabrication des drogues pour essais cliniques
• GUI-0063 - Risk Classification of Post-Market Reporting Compliance Observations /
Classification des observations liées à la conformité aux exigences de déclaration après
commercialisation en fonction du risque (will be final, not for comment)
• GUI-0080 - Guidance on Evidence to Demonstrate Drug GMP Compliance of Foreign Sites -
Guide sur les preuves de conformité aux BPF des médicaments provenant de sites
étrangers + related forms (FRM-0211, 0212, 0213, 0214)
• FRM-0211 - GMP Audit Report Form - Formulaire de rapport d’audit
• FRM-0212 - GMP Foreign Site Submission - Présentation d’un site étranger
• FRM-0213 - GMP Request for an Inspection of a Foreign Site - Demande d’inspection d’un
site étranger
• FRM-0214 - GMP Foreign Site Inspection Services Agreement - Accord pour l'exécution de
services d'inspection dans un établissement étranger
• Updates to GMP Q&A, as needed

Inspectorate
Inspection Trends: On the Horizon...
Draft documents planned for release in 2009-2010 for comment from
Stakeholders:
? GUI-0006 - Process Validation: Aseptic Processes for Pharmaceuticals / Validation de

procédés: Procédés aseptiques pour les produits pharmaceutiques
• GUI-0012 - Annex 4 to the Current Edition of the Good Manufacturing Practices Guidelines -
Veterinary Drugs - Annexe 4 à l’édition actuelle des Lignes directrices sur les Bonnes
pratiques de fabrication - Médicaments vétérinaires
• GUI-0014 - Alternate Sample Retention Site Guidelines - Lignes directrices concernant les
sites alternatifs pour la rétention d'échantillons
• GUI-0023 - Risk Classification of GMP Observations (GUI-0023) - 2009 Edition -
Classification des observations BPF en fonction du risque (GUI -0023) - Édition 2009
• GUI-0026 - Annex to the GMP Guidelines- Schedule C Drugs/ Annexe aux lignes directrices
sur les BPF- drogues visées à l'annexe C
• GUI-0027 - Annex to the GMP Guidelines-Schedule D Drugs part 1: Biological Drugs
including fractionated blood products - Annexe aux lignes directrices sur les BPF-drogues
visées à l'annexe D partie 1: drogues biologiques incluant les produits de fractionnement du
sang

Inspectorate
Inspection Trends: On the Horizon….
Draft documents planned for release in 2009-2010 for comment from
Stakeholders cont’d:
• GUI-0066 - Annex 1 to the Current Edition of the Good Manufacturing Practices Guidelines -
Selected Category IV Monograph Drugs - Annexe 1 à l’édition actuelle des Lignes directrices
sur les Bonnes pratiques de fabrication - Certains médicaments de la monographie de la
catégorie IV
• GUI-0069 - Guidelines for Temperature Control of Drug Products during Storage and
Transportation / Lignes directrices concernant le contrôle de la température des
médicaments pendant l'entreposage ou le transport
? GUI-0071 - Annex to GMP Guidelines - GMP for Positron Emitting Radiopharmaceu- ticals -
Annexe aux Lignes directrices sur les BPF - BPF concernant les Produits
radiopharmaceutiques émetteurs de positrons
? GUI-0074 - Process validation: Terminal Sterilization Processes for Pharmaceutical Products
/ Validation de procédés : Procédés de strérilisation terminal des produits pharmaceutiques

Inspectorate
Inspection Trends: On the Horizon…
Things for the future:
• GMP Program Review
• API Inspection Program
• “GUI-0001 Roadshow”

Inspectorate
Karen Wallace-Graner, Compliance Officer

Drug GMP Inspection Unit,
Compliance Coordination and Licencing Division (CCLD) - Ottawa
Phone: 613-952-5216
Fax: 613-
E-mail: karen_wallace-graner@hc-sc.gc.ca
Compliance and Enforcement Website:

http://www.hc-sc.gc.ca/dhp-mps/compli-conform/index-
eng.php
Presentation content prepared by Patricia Moretti (Compliance Specialist, OOC) and Karen Wallace -Graner

Inspectorate

GMP Inspection Trends

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

GMP Inspection Trends

Uploaded by

Copyright:

Available Formats

GMP Inspection Trends

Karen Wallace-Graner, Compliance Officer

–Observation Risk Classification and Ratings (slide 11)

–Distribution of Licenced Establishments – A National Perspective (slide12-15)

• Trends in GMP Inspections and Observations (slide16-18)

–Rating (slide 19)

–Risk 1 observations and examples (slide20-25)

–Overview of key areas of GMP deficiencies and examples (slide26-46)

• On the Horizon (slide 47-51)

Health Products and Food Branch

inspectors Compliance Coordination and Licencing 5.9

Ontario Operational Centre (OOC) – 11.63

Health Products and Food Branch

GMP inspection program applies to Human and

Health Products and Food Branch

Drug Establishment Licences (DEL)

Health Products and Food Branch

POL-0001: Compliance and Enforcement Policy (May 31, 2005)*

GUI-0001: Good Manufacturing Practices (GMP) Guidelines

Health Products and Food Branch

Regular: An inspection during which all of the applicable requirements of the

Initial: An inspection conducted prior to the issuance of an establishment

Partial: An inspection of an historically compliant non-sterile fabricator that is

Health Products and Food Branch

Re-inspection: A follow-up inspection carried out in response to the

Health Products and Food Branch

The type and cycle for Inspections is outlined in POL-0011:

Targets for Regular Inspections:

Fabricators, Packagers/Labellers, Testing Laboratories 24 months

Importers, Distributors, Wholesalers 36 months

Health Products and Food Branch

Notice of upcoming inspection may or may not be provided

Health Products and Food Branch

Possible inspection ratings are:

C (Compliant) = recommended for the continuation or issuance of an establishment licence

NC (Non-compliant) = not recommended for the continuation or issuance of an establishment

Health Products and Food Branch

Current total= 1070

As of March 31, 2009.

Health Products and Food Branch

of Count of Count of Testing

Health Products and Food Branch

Fabricator Packager Tester

Health Products and Food Branch

Trends in GMP Inspections and

Health Products and Food Branch

Fiscal Year Number of C rated NC rated

2005-2006 454 95% 5%

2006-2007 320 98% 2%

2007-2008 446 98% 2%

2008-2009 434 98% 2%

Health Products and Food Branch

2004-2005 433 3529 Risk 1: 0.9%

Health Products and Food Branch

Fiscal Year # Risk 1 Observations

Health Products and Food Branch

C.02.018, C.02.019: Finished Product Testing

Health Products and Food Branch

Health Products and Food Branch

Health Products and Food Branch

Health Products and Food Branch

Regulation 2004- 2005- 2006- 2007- 2008-

Manufacturing 14% 12% 10% 11% 9%

Manufacturing 9% 9% 11% 10% 9%