Doc #: ALXN-QD-0079710 Version: 1.

3 Status: In Coordination
Ravulizumab OBDS using SmartDose Gen I Hazard Analysis - Pediatric Clinical

Table of Contents
1.0 Purpose................................................................................................................................. 2
2.0 Scope .................................................................................................................................... 2
3.0 Definitions............................................................................................................................ 2
4.0 Intended Use ........................................................................................................................ 2
5.0 Severity ................................................................................................................................ 2
6.0 Hazard Analysis ................................................................................................................... 2
7.0 References ............................................................................................................................ 3
8.0 Attachments ......................................................................................................................... 4

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9.0 Revision History…………………………………………………………………………....4

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 Doc #: ALXN-QD-0079710 Version: 1.3 Status: In Coordination
Ravulizumab OBDS using SmartDose Gen I Hazard Analysis - Pediatric Clinical

1.0 Purpose
1.1. This Hazard Analysis document determines and analyzes the hazards that could
potentially impact end-user safety that are associated with the subcutaneous (SC) injection
of Ravulizumab 70 mg/mL (ravulizumab SC formulation drug product hereafter referred
to as Ravulizumab) via the single-use, On-body Delivery System (OBDS) using the West
SmartDose® Gen. I 3.5mL Drug Delivery Platform.
1.2. From hereafter, “OBDS” shall refer to the device constituent of the Drug Delivery
Platform with prefilled cartridge containing Ravulizumab (the complete co-packaged
combination product) and “On-body injector” shall refer to only the device constituent
(the OBDS without the prefilled cartridge).
2.0 Scope

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2.1. Potential hazards related to intended users, intended use, characteristics related to safety,
and reasonably foreseeable misuse, and disposal of the Ravulizumab OBDS in both
normal and fault conditions were considered.

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2.2. This hazard analysis applies to Pediatric Clinical Ravulizumab OBDS and is written
according to ALXN-SOP-0006230, Device Risk Management Procedure.
3.0 Definitions
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3.1. HA – Hazard Analysis
3.2. ISO – International Organization for Standardization
3.3. OBDS – On-Body Delivery System
3.4. PHA – Preliminary Hazard Analysis
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4.0 Intended Use

4.1. See ALXN-QD-0008413, Ravulizumab OBDS using SmartDose Gen I Intended
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Use/Use Specification Commercial

5.0 Severity
5.1. The Severity of Harm Classification Table is defined in ALXN-QD-0008414,
Attachment 3, Ravulizumab OBDS using SmartDose Gen I Risk Management Plan
Commercial. This table is used to classify the severity levels of the harms in Attachment
In

1.
6.0 Hazard Analysis
6.1. The Hazard Analysis in Attachment 1 was created per FDA Guidance on Infusion Pumps
Total Product Life Cycle: 2014. FDA has identified infusion pump system hazards as
follows: infusion delivery error, incorrect therapy*, biological/chemical contamination,
and traumatic injury. Additional hazards and harms have been identified as part of ALXN-
QD-0008118, Ravulizumab OBDS using SmartDose Gen I Preliminary Hazard
Analysis-Commercial, beyond the requirements outlined in the FDA guidance document.
Those additional hazards have been accounted for in the individual risk assessments and
summarized as part of ALXN-QD-0079696, Ravulizumab OBDS using SmartDose
Gen I Risk Management Report Pediatric Clinical. The Hazard Analysis (Attachment
1) focus the supporting evidence on those hazards, harms, and associated failure modes
linked to the top-level system hazards and described in the FDA guidance document.

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 Doc #: ALXN-QD-0079710 Version: 1.3 Status: In Coordination
Ravulizumab OBDS using SmartDose Gen I Hazard Analysis - Pediatric Clinical

*Note: FDA System Hazard “Incorrect therapy” is not included in the Hazard Analysis
(Attachment 1) because it does not apply to Ravulizumab OBDS. The OBDS is
intended for use with one (1) drug only (i.e., the user is provided with only the one
intended drug for use with the OBDS).

6.2. In addition, this hazard analysis refers to risk assessments which have identified hazards
and their associated risks. The following risk assessments have been used as a part of
Attachment 1: ALXN-QD-0008398, Ravulizumab OBDS using SmartDose Gen I
System Failure Mode and Effects Analysis (sFMEA) Commercial, ALXN-QD-
0077801, Ravulizumab OBDS using SmartDose Gen I Use Failure Mode and Effects
Analysis Pediatric, ALXN-QD-0079215, Ravulizumab OBDS using SmartDose Gen

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I - Pediatrics Clinical pFMEA, WP05RSK00001, SmartDose 3.5 Risk Analysis
DFMEA for CM-1405 Commercial, and WP05RSK00038, Risk Assessment and
Process Failure Mode and Effects Analysis (FMEA) for the Commercial
Configuration of SmartDose Injector, CM-1405. The inclusion of the risk assessment

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line items concludes that the Hazard Analysis has been utilized as a top-down risk
document to ensure system level hazards and associated risks have been addressed and
controlled per FDA Guidance on Infusion Pumps Total Product Life Cycle: 2014. The
referenced risk assessments have been included in Section 7.0 below.
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7.0 References
7.1. ALXN-SOP-0006230, Device Risk Management Procedure
7.2. ALXN-QD-0008413, Ravulizumab OBDS using SmartDose Gen I Intended Use/Use
Specification Commercial
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7.3. ALXN-QD-0008414, Ravulizumab OBDS using SmartDose Gen I Risk Management

Plan Commercial
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7.4. ALXN-QD-0008118, Ravulizumab OBDS using SmartDose Gen I Preliminary Hazard

Analysis – Commercial
7.5. ALXN-QD-0008398, Ravulizumab OBDS using SmartDose Gen I System Failure Mode
and Effects Analysis (sFMEA) Commercial
7.6. ALXN-QD-0077801, Ravulizumab OBDS using SmartDose Gen I User Failure Mode
In

and Effects Analysis Pediatric

7.7. ALXN-QD-0079215, Ravulizumab OBDS using SmartDose Gen I - Pediatrics Clinical
pFMEA
7.8. WP05RSK00001, SmartDose 3.5 Risk Analysis DFMEA for CM-1405 Commercial
7.9. WP05RSK00038, Risk Assessment and Process Failure Mode and Effects Analysis
(FMEA) for the Commercial Configuration of SmartDose Injector, CM-1405
7.10. (EN) ISO 14971:2019, Medical devices – Application of risk management to medical
devices
7.11. FDA Guidance on Infusion Pumps Total Product Life Cycle: 2014 (i.e., Infusion Pumps
Total Product Life Cycle, Guidance for Industry and FDA Staff)
7.12. ALXN-QD-0079696, Ravulizumab OBDS using SmartDose Gen I Risk Management
Report - Pediatric Clinical

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 Doc #: ALXN-QD-0079710 Version: 1.3 Status: In Coordination
Ravulizumab OBDS using SmartDose Gen I Hazard Analysis - Pediatric Clinical

8.0 Attachments
8.1. Attachment 1 – Ravulizumab OBDS using SmartDose Gen I Hazard Analysis
Spreadsheet

9.0 Revision History

Change
Version Type
Revision Summary Justification
No. (New, Revise, or
Admin)

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1.0 New Initial release Initial release
a) Attachment 1, HA #H-1-1, H-1-2, H-1-3,
H-1-4, H-1-5, H-1-7, H-1-8, H-2-3, H-2-
5, H-5-1, H-5-2, H-5-6, H-5-8, H-6-1, H-

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6-3, H-6-6, H-6-7, H-6-9, H-6-10, H-6-
14, H-7-1, H-7-2, H-7-3, H-7-4, H-8-1,
H-8-2, H-8-3, H-8-4, H-8-6, H-8-7, H-8-
8, H-8-13, H-8-15, H-8-17, H-8-18, H-8-
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19: Revised “Harm” column to align
with harm in the FMEA Harm column
(Single underdose (no/partial). Revised
“Severity” scores from 3 to 1
b) Attachment 1, HA #H-1-7: Moved
a. through d. To align with
Alexion pFMEA risk ID’s 22.1, 18.4,
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2.0 Revise latest FMEAs (ref. PR

18.5, 18.3, 18.1, 15.3, 13.4, 27.1, 27.2,
117587)
27.4, 28.3, 28.4, 27.3, 28.6, 16.14, to H-
1-2 since they are linked to the highest-
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severity harm (Minor Injury) in the

pFMEA
c) Attachment 1, HA #H-5-2: Added
section to capture the highest severity
harm (Minor Infection) in the pFMEA
that dictates the severity score of
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Alexion pFMEA 16.2

d) Attachment 1, HA #H-8-20: Added line
item to include new line item u1-3.4 in
uFMEA

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