QUALITY SYSTEM ASSESSMENT - SCORE CARD

Section # Section # Section # Section # Section # Section #

2 Quality Management 5 Process Equipment 7 Material Management
2.10 1 5.10 1 7.10 1 9.20 0.5 11.60 0.5 14.30 1
2.11 1 5.11 1 7.11 1 9.21 1 11.61 14.31 1 QUALITY SYSTEM - DASH BOARD
2.12 1 5.12 1 7.12 1 9.22 0 11.62 14.32 1
2.13 1 5.13 1 7.13 1 9.30 1 11.63 14.40 1 Section Target Result
2.14 1 5.14 1 7.14 1 9.31 0 11.70 14.41 1 Quality Management 12 12
2.16 1 5.15 1 7.20 1 9.32 0 11.71 14.42 1 Personnel 7 5
2.17 1 5.16 1 7.21 1 9.33 1 12.72 14.43 1 Building & Facilities 15 14
2.18 1 5.20 1 7.22 1 9.34 1 14.50 0 Process Equipment 19 17.5
2.20 1 5.21 1 7.23 1 9.35 1 12 Validation 14.51 0 Documentation & Records 22 19.5
2.21 1 5.23 1 7.24 1 9.36 0 12.10 14.52 0 Material Management 21 21
2.22 1 5.24 1 7.30 1 9.40 1 12.11 Production & IP control 20 19
2.30 1 5.25 1 7.31 1 9.41 1 12.12 15 Complaints and Recalls Packaging & Labelling 19 10
2.40 5.26 1 7.33 1 9.42 0.5 12.20 1 15.10 1 Storage and Distribution 7 4
2.41 5.30 1 7.34 1 9.43 0 12.21 0.5 15.11 1 Laboratory controls 15 14.5
2.50 5.31 1 7.35 1 9.44 0.5 12.22 1 15.12 1 Validation 10 5
2.51 5.32 1 7.40 1 9.45 0 12.23 0 15.13 0 Change control 8 8
5.33 1 7.41 1 9.46 12.30 1 15.14 0 Rejection and Re-use 14 11
3 Personnel 5.34 0.5 7.42 1 12.40 15.15 0 Complaints and Recalls 6 3
3.10 0 5.35 0 7.43 1 10 Storage and Distribution 12.41
3.11 0.5 5.4 7.44 1 10.10 1 12.42 16 Contract Manufactures/Labs TOTAL 195 163.5
3.12 1 5.40 7.50 1 10.11 0 12.42 16.10 % 100 84
3.21 0.5 5.41 10.20 1 12.44 16.11
3.22 1 5.42 8 Production & IP Controls 10.21 1 12.45 16.12
3.23 1 5.43 8.10 1 10.22 0 12.50 0.5 16.13
3.24 1 5.44 8.11 1 10.23 1 12.51 0 16.14
5.45 8.12 1 10.24 0 12.52 0 16.15
4 Building and Facilities 5.46 8.13 1 12.60 0 16.16
4.10 0.5 5.47 8.14 1 11 Laboratory Controls 12.70
4.11 1 5.48 8.15 1 11.10 1 12.71
4.13 1 8.16 1 11.11 1 12.72
4.14 1 6 Documentation & Records 8.17 1 11.12 1 12.73
4.15 1 6.10 1 8.20 0 11.13 12.74
4.16 1 6.11 1 8.21 1 11.14 1 12.75
4.20 0.5 6.12 1 8.30 1 11.15 1 12.76 1
4.21 1 6.13 1 8.31 1 11.16 1 12.80
4.22 6.14 1 8.32 1 11.17 1 12.81
4.23 1 6.15 1 8.33 1 11.18 1 12.82
4.24 1 6.17 1 8.34 1 11.19 1 12.83
4.30 6.18 8.35 1 11.20 1
4.31 6.20 1 8.36 1 11.21 1 13 Change Control
4.32 6.21 1 8.41 11.22 13.10 1
4.33 6.30 1 8.43 11.23 13.11 1
4.34 6.31 0 8.44 11.3 13.12 1
4.4 6.40 0 8.45 11.40 1 13.13 1
4.40 6.41 0 8.46 11.41 0 13.14 1
4.41 6.50 0.5 8.47 11.42 1 13.15 1
4.42 6.51 1 8.50 1 11.43 1 13.16 1
4.43 6.52 1 8.51 1 11.44 13.17 1
4.50 1 6.53 1 8.52 1 11.50
4.60 1 6.60 1 11.51 14 Rejections and Re-use
4.70 1 6.61 1 9 Packaging & Labelling 11.52 14.10 1
4.71 1 6.70 1 9.10 0.5 11.53 14.20 1
4.72 1 6.71 1 9.11 0 11.54 14.21 1
6.72 1 9.12 1 11.55 14.22 1
6.73 1
 6 SYSTEMS ASSESSMENT

S.No Task Yes No NA observations

SYSTEM 1: Quality System
1 Adequacy of staffing to ensure fulfillment of quality unit duties.

Periodic quality reviews as described in ICH Q7 Section 2.5, Product Quality Review; inspection
audit coverage should include API types that are representative of manufacturing at this site;
inspection audit should also examine some batch and data records associated with each API
quality review to verify that firm’s review was sufficiently complete; and, audit should confirm that
2 firm has identified any trends and has corrected or mitigated sources of unacceptable variation.

Complaint reviews (quality and medical): documented; evaluated; investigated in a timely

manner; includes corrective action where appropriate. Determine whether pattern of complaints
and records of internal rejection or reprocessing/reworking of API batches warrant expanding
3 the inspection.
Discrepancy and failure investigations related to manufacturing and testing: documented;
evaluated; critical deviations investigated in a timely manner and expanded to include any
4 related APIs and material; includes corrective action where appropriate.
Change Control (including “process improvements”): documented; evaluated; approved; need
5 for revalidation assessed.
6 Returns/Salvages: assessment; investigation expanded where warranted; final disposition.
7 Rejects: investigation expanded where warranted; corrective action where appropriate.
8 System to release raw materials.
Batches manufactured since last inspection to evaluate any rejections or conversions (i.e., from
9 drug to non-drug use) due to processing problems.
Reprocessing and/or reworking events are properly approved and evaluated for impact on
10 material quality.
Recalls (including any attempt to recover distributed API not meeting its specifications or
11 purported quality), determine cause and corrective actions taken.
Stability Failures: investigation expanded where warranted; disposition. Determine if stability
12 data supports API retest or expiry dates and storage conditions.
Validation: Status of validation/revalidation activities (e.g., computer, manufacturing process,
13 laboratory methods), such as reviews and approvals of validation protocols and reports.
S.No Task Yes No NA observations
14 Training/qualification of employees in quality control unit functions.
SYSTEM 2: FACILITIES AND EQUIPMENT SYSTEM
Facilities
15 Cleaning and maintenance.
Facility layout, flow of materials and personnel for prevention of cross-contamination, including
16 from processing of non-drug materials.
Dedicated areas or containment controls for highly sensitizing materials (e.g., penicillin, betalactams,
17 steroids, hormones, and cytotoxics).

Utilities such as steam, gas, compressed air, heating, ventilation, and air conditioning should be
qualified and appropriately monitored (note: this system includes only those utilities whose
output is not intended to be incorporated into the API, such as water used in cooling/heating
18 jacketed vessels).
19 Lighting, sewage and refuse disposal, washing and toilet facilities.
20 Control system for implementing changes in the building.
Sanitation of the building including use of rodenticides, fungicides, insecticides, cleaning and
21 sanitizing agents.
22 Training and qualification of personnel.
Process Equipment
23 Equipment installation, operational, performance qualification where appropriate.
24 Appropriate design, adequate size and suitably located for its intended use.
Equipment surfaces should not be reactive, additive, or absorptive of materials under process so
25 as to alter their quality.
Equipment (e.g., reactors, storage containers) and permanently installed processing lines
26 should be appropriately identified.

Substances associated with the operation of equipment (e.g., lubricants, heating fluids or
coolants) should not come into contact with starting materials, intermediates, final APIs, and
27 containers.

Cleaning procedures and cleaning validation and sanitization studies should be reviewed to
verify that residues, microbial, and, when appropriate, endotoxin contamination are removed to
28 below scientifically appropriate levels.
Calibrations using standards traceable to certified standards, preferably NIST, USP, or
29 counterpart recognized national government standard-setting authority.
S.No Task Yes No NA observations

Equipment qualification, calibration and maintenance, including computer qualification/validation

30 and security.
31 Control system for implementing changes in the equipment. Documentation of any discrepancy.
32 Training and qualification of personnel.
SYSTEM 3: MATERIALS SYSTEM
33 Training/qualification of personnel.
34 Identification of starting materials, containers.
35 Storage conditions.
Holding of all material and APIs, including reprocessed material, under quarantine until tested or
36 examined and released.
Representative samples are collected, tested or examined using appropriate means and against
37 appropriate specifications.
38 A system for evaluating the suppliers of critical materials.
Rejection of any starting material, intermediate, or container not meeting acceptance
39 requirement.
40 Appropriate retesting/reexamination of starting materials, intermediates, or containers.
41 First-in / first-out use of materials and containers.
42 Quarantine and timely disposition of rejected materials
Suitability of process water used in the manufacture of API, including as appropriate the water
43 system design, maintenance, validation and operation.
Suitability of process gas used in the manufacture of API (e.g., gas use to sparge a reactor),
44 including as appropriate the gas system design, maintenance, validation and operation.
45 Containers and closures should not be additive, reactive, or absorptive.
46 Control system for implementing changes.
47 Qualification/validation and security of computerized or automated process
48 Finished API distribution records by batch.
49 Documentation of any discrepancy
SYSTEM 4: PRODUCTION SYSTEM
50 Training/qualification of personnel
Establishment, adherence, and documented performance of approved manufacturing
51 procedures.
52 Control system for implementing changes to process.
S.No Task Yes No NA observations
53 Controls over critical activities and operations.
54 Documentation and investigation of critical deviations.
55 Actual yields compared with expected yields at designated steps
56 Where appropriate established time limits for completion of phases of production
57 Appropriate identification of major equipment used in production of intermediates and API.
58 Justification and consistency of intermediate specifications and API specification.
Implementation and documentation of process controls, testing, and examinations (e.g., pH,
59 temperature, purity, actual yields, clarity)
In-process sampling should be conducted using procedures designed to prevent contamination
60 of the sampled material.
Recovery (e.g., from mother liquor or filtrates) of reactants; approved procedures and recovered
61 materials meet specifications suitable for their intended use.
Solvents can be recovered and reused in the same processes or in different processes provided
62 that solvents meet appropriate standards before reuse or commingling.
API micronization on multi-use equipment and the precautions taken by the firm to prevent or
63 minimize the potential for cross-contamination.
64 Process validation, including validation and security of computerized or automated process.
65 Master batch production and control records.
66 Batch production and control records.
Documentation of any discrepancy (a critical discrepancy investigation is covered under the
67 Quality System).
SYSTEM 5: PACKAGING AND LABELING SYSTEM
68 Training/qualification of personnel
69 Acceptance operations for packaging and labeling materials
70 Control system for implementing changes in packaging and labeling operations
71 Adequate storage for labels and labeling, both approved and returned after issued
72 Control of labels which are similar in size, shape, and color for different APIs.
73 Adequate packaging records that will include specimens of all labels used
74 Control of issuance of labeling, examination of issued labels and reconciliation of used labels
75 Examination of the labeled finished APIs.
76 Adequate inspection (proofing) of incoming labeling.
77 Use of lot numbers, destruction of excess labeling bearing lot/control numbers
S.No Task Yes No NA observations
78 Adequate separation and controls when labeling more than one batch at a time.
79 Adequate expiration or retest dates on the label.
Validation of packaging and labeling operations including validation and security of
80 computerized process.
Documentation of any discrepancy (a critical discrepancy investigation is covered under the
81 Quality System).
SYSTEM 6: LABORATORY CONTROL SYSTEM
82 Training/qualification of personnel.
83 Adequacy of staffing for laboratory operations.
84 Adequacy of equipment and facility for intended use
85 Calibration and maintenance programs for analytical instruments and equipment.
86 Validation and security of computerized processes.
Reference standards; source, purity and assay, and tests to establish equivalency to current
87 official reference standards as appropriate.
88 System suitability checks on chromatographic systems.
89 Specifications, standards, and representative sampling plans.
90 Validation/verification of analytical methods.
Required testing is performed on the correct samples and by the approved or filed methods or
91 equivalent methods.
Documentation of any discrepancy (a critical discrepancy investigation is covered under the
92 Quality System).
93 Complete analytical records from all tests and summaries of results.
94 Quality and retention of raw data (e.g., chromatograms and spectra).
95 Correlation of result summaries to raw data; presence and disposition of unused data.
Adherence to an adequate Out of Specification (OOS) procedure which includes timely
96 completion of the investigation.
Test methods for establishing a complete impurity profile for each API process (note: impurity
97 profiles are often process-related).
98 Adequate reserve samples; documentation of reserve samples examination.
Stability testing program, including demonstration of stability indicating capability of the test
99 methods
 QUALITY SYSTEM ASSESSMENT - SCORE CARD

Section # Section # Section # Section # Section # Section #

2 Quality Management 5 Process Equipment 7 Material Management
2.10 1 5.10 1 7.10 1 9.20 1 11.60 1 14.30 1
2.11 1 5.11 1 7.11 1 9.21 1 11.61 14.31 1 QUALITY SYSTEM - DASH BOARD
2.12 1 5.12 1 7.12 1 9.22 1 11.62 14.32 1
2.13 1 5.13 1 7.13 1 9.30 1 11.63 14.40 1 Section Target Result
2.14 1 5.14 1 7.14 1 9.31 0 11.70 14.41 1 Quality Management 12 12
2.16 1 5.15 1 7.20 1 9.32 1 11.71 14.42 1 Personnel 7 7
2.17 1 5.16 1 7.21 1 9.33 1 12.72 14.43 1 Building & Facilities 15 15
2.18 1 5.20 1 7.22 1 9.34 1 14.50 0 Process Equipment 19 19
2.20 1 5.21 1 7.23 1 9.35 1 12 Validation 14.51 0 Documentation & Records 22 20
2.21 1 5.23 1 7.24 1 9.36 1 12.10 14.52 0 Material Management 22 22
2.22 1 5.24 1 7.30 1 9.40 1 12.11 Production & IP control 20 20
2.30 1 5.25 1 7.31 1 9.41 1 12.12 15 Complaints and Recalls Packaging & Labelling 19 18
2.40 5.26 1 7.32 1 9.42 1 12.20 1 15.10 1 Storage and Distribution 7 7
2.41 5.30 1 7.33 1 9.43 1 12.21 1 15.11 1 Laboratory controls 16 16
2.50 5.31 1 7.34 1 9.44 1 12.22 1 15.12 1 Validation 10 9
2.51 5.32 1 7.35 1 9.45 1 12.23 1 15.13 1 Change control 8 8
5.33 1 7.40 1 9.46 12.30 1 15.14 1 Rejection and Re-use 14 11
3 Personnel 5.34 1 7.41 1 12.40 15.15 1 Complaints and Recalls 6 6
3.10 1 5.35 1 7.42 1 10 Storage and Distribution 12.41
3.11 1 5.4 7.43 1 10.10 1 12.42 16 Contract Manufactures/Labs TOTAL 197 190
3.12 1 5.40 7.44 1 10.11 1 12.42 16.10 % 100 96
3.21 1 5.41 7.50 1 10.20 1 12.44 16.11
3.22 1 5.42 10.21 1 12.45 16.12
3.23 1 5.43 8 Production & IP Controls 10.22 1 12.50 1 16.13
3.24 1 5.44 8.10 1 10.23 1 12.51 1 16.14
5.45 8.11 1 10.24 1 12.52 1 16.15
4 Building and Facilities 5.46 8.12 1 12.60 0 16.16
4.10 1 5.47 8.13 1 11 Laboratory Controls 12.70
4.11 1 5.48 8.14 1 11.10 1 12.71
4.13 1 8.15 1 11.11 1 12.72 Indicates the improvement since December 2010
4.14 1 6 Documentation & Records 8.16 1 11.12 1 12.73
4.15 1 6.10 1 8.17 1 11.13 12.74 Indicates that yet to improve
4.16 1 6.11 1 8.20 1 11.14 1 12.75
4.20 1 6.12 1 8.21 1 11.15 1 12.76 1
4.21 1 6.13 1 8.30 1 11.16 1 12.80
4.22 6.14 1 8.31 1 11.17 1 12.81
4.23 1 6.15 1 8.32 1 11.18 1 12.82
4.24 1 6.17 1 8.33 1 11.19 1 12.83
4.30 6.18 8.34 1 11.20 1
4.31 6.20 1 8.35 1 11.21 1 13 Change Control
4.32 6.21 1 8.36 1 11.22 13.10 1
4.33 6.30 1 8.41 11.23 13.11 1
4.34 6.31 0 8.43 11.3 13.12 1
4.4 6.40 0 8.44 11.40 1 13.13 1
4.40 6.41 0 8.45 11.41 1 13.14 1
4.41 6.50 1 8.46 11.42 1 13.15 1
4.42 6.51 1 8.47 11.43 1 13.16 1
4.43 6.52 1 8.50 1 11.44 13.17 1
4.50 1 6.53 1 8.51 1 11.50
4.60 1 6.60 1 8.52 1 11.51 14 Rejections and Re-use
4.70 1 6.61 1 11.52 14.10 1
4.71 1 6.70 1 9 Packaging & Labelling 11.53 14.20 1
4.72 1 6.71 1 9.10 1 11.54 14.21 1
6.72 1 9.11 1 11.55 14.22 1
6.73 1 9.12 1