Sample Inventory Control and Risk Management - …1).pdf · This procedure applies to all...

Sample Inventory Control and

Risk ManagementEvald Muraj

Stability Manager

Ironwood Pharmaceuticals

10-Dec-2015

Email: [email protected]

Key Questions

What is risk?

How do we spot risk?

How do we avoid risk?

What makes it so risky?

How do these questions apply to Product Stability

and Stability Studies?

Risk

Risk: The combination of the probability of

occurrence of harm and the severity of that harm

(ISO/IEC Guide 51)

Quality Risk Management: A systematic process for

the assessment, the control, the communication

and the review of risks to quality of the drug

across the product lifecycle.

Stability Risk Management: …across the product

lifecycle.

Question

How do we spot risk?

In order to spot Stability-related risk, we must first

understand the quality systems within Stability.

Afterward, we must understand what Stability entails and,

in doing so, locate the weakest links.

What group does Stability belong to?

What does Stability generally entail?

Risk & Stability

Stability has its roots in Quality (control).

Sum up quality in six letters:

GMP

GDP

Sum up stability in six words:

Identify

Store

Test

Review

Trend

Report

Sample Control and Stability Terms

Identify: product, duration, condition, location

Store: GMP, 5S, Contingency

Test: Logout, Assay,

Review: Sample Results, Annual inventory

Trend: Sample Metrics, Chamber Performance

Report: Results, Metrics, Disposition

For auditors, stability inventory control is low-hanging fruit.

GDP Backup to LIMS

Sample Tracking SOP

Reserve Sample SOP

Stability Chamber SOPs

Stability Set Down SOP

Routine Testing Location

Sample Request Form

Stability Inventory Form

Stability Set-Down Form

Sample Tracking Form/Book

Stability Chamber Form

Stability Chamber Housekeeping Form

Sample Disposition Form

Sample Tracking SOP

Purpose:

To identify all samples in circulation that will require

testing and/or storage within a GMP facility.

To provide a tracking system that will catalog said

samples throughout their lifecycle.

Scope:

This procedure applies to all manufacturing samples

that are to be tested and/stored in Quality Labs.

A stability section can define the zones that are

reserved for stability samples.

Sample Tracking SOP

How are stability samples requested?

Stability sample request form.

How are samples labeled?

What are the sample delivery methods to Stability Dept.?

MFG can deliver samples at a designated time.

Samples can be shipped from external facility.

Who has the authority to receive Stability samples?

Stability personnel? Quality personnel?

Do samples undergo preliminary inspection?

Is handling time recorded?

Sample Request Form

Does not have to be Stability Specific if requesting

samples from within same facility.

For Stability Purposes - Covers:

Who is requesting e.g. Name, Department?

What sample e.g. Batch #, DS, intermediate?

What time/date?

Are labels provided/attached

Signatures e.g. Requestor, MFG manager

Archived with MFG docs and Copy with Stability

Sample Request Form

If being shipped from external facility.

Form should be Stability Specific

Covers:

Shipper information

Time/Day of shipment

Type/Quantity of Samples e.g. Lot #4321, 75 lyo vials

Receiver Information

Receiver Inspection

Can double as Set Down Form/Inventory Form

Stability Set-Down Form

A form that outlines the specifics of sample-lifecycle.

What the study protocol # is

When the batch was manufactured (attached COA/Disposition)

What the specific testing panel is with specific calendar dates

When the material was placed in its chamber/condition

What the chambers/conditions are

The quantity/container of samples and % overage

Signature of individual that stores and Stability manager

When does study begin? When is T=0? Does condition matter?

Stability Inventory Form

Information:

Batch/Lot/study number

Date of initial sample entry

Quantity/description of samples

Additional blank rows for future documentation of sample withdrawal and final disposition.

Two possible locations for form:

Study-specific Binder

Chamber-specific Inventory Binder

Stability Test Request Form

Form that outlines the required testing per Time Point.

Covers:

Sample #s from Routine Tracking System:

Time Point/Study Info

Requester Info/Date

Volume of Product per test

Quantity of Aliquots per Sample

Test Requested per Sample

Attribute Specification

Assay Reference Number

Analyst Entry signature/date

Reviewer signature/date

Sample Tracking Book (Routine)

QC Routine Sample Tracking Book

Tracks all samples received by QC.

Book has continuous blank rows of preassigned numbers.

Sample # Sample Description Received by Logged in by Logged out by

CAM-75089Batch: BOS-1120 Nanofiltrate

Vol: 1mL Test: Purity by SDS-PAGEEM 02 DEC 2015 EM 02 DEC 2015 OB 04 DEC 2015

CAM-75090Stability Batch: BOS-1121 Drug Substance

Vol: 1mL Test: Potency by PLA T=12M (5ºC)EM 02 DEC 2015 EM 02 DEC 2015 OB 04 DEC 2015






Vol: 1mL Test: Appearance/pH T=12M (5ºC)EM 02 DEC 2015 EM 02 DEC 2015 AD 05 DEC 2015

Stability Chambers

Key Details

Size

Tolerance required

Qualification

Calibration

Maintenance

Monitoring

Access

Dedicated to Stability Purposes

Reach-In Chambers

Range in size up to 33 cu.ft. and often larger.

Up to ten adjustable shelves

System mechanics built into cabinet

Less expensive

Often used for small inventory control

Less risk of failure

Walk-in Chambers

Any size – client specific

Mechanics locates above or inside

More expensive than reach in chambers

Used when larger space is needed

More efficient to install one than a room full of reach-ins

But backup for excursion or failure should be considered

Will require same GMP activities

Qualification

Calibration

Preventative maintenance

Monitoring

Chamber Specifications

Set-Point Tolerance

Any temperature above refrigerated ± 2°C

Refrigerated ± 3°C

Freezer ± 5°C

Ultra-low freezer ± 10°C

Relative Humidity ± 5%RH

Chamber Specifications

Example

25°C/60%RH chamber has set point 23-27°C and a relative humidity

tolerance of 55-65% RH.

Each facility must determine the number of significant figures in the

tolerance e.g. does 22.5°C round to 23°C? If not then spec is 23.0°C.

Chamber Qualification

Stability chambers are GMP Equipment

IQ

OQ

PQ

Must have approved qualification protocols.

Combining is allowed for efficiency e.g. IQ/OQ OQ/PQ

DQ sometimes performed.

Precedes IQ

Installation Qualification (IQ)

Parameter Specification

Chamber ID Documented

Chamber Size Documented

Chamber Location Documented

Chamber description/design Documented

Spare parts Documented

Preventative Maintenance Documented

Environmental Conditions Meets Criteria

Electrical Requirements Meets Criteria

Water (if applicable Meets Criteria

Monitoring, back up and alarm systems in place Documented

Test Equipment Documented

Corresponding SOPs Documented

Stability Chamber IQ - Attributes

Operation Qualification (OQ)


IQ has been approved Documented

Chamber turns on Documented

Chamber set-point Programmed and Documented

Control Variables Programmed and Documented

Calibration Meets Criteria

Distribution study Meets Criteria



15 temp/RH probes – 5 top, 5 middle, 5 bottom - corners/center

1 probe placed in proximity to chamber probe

24 hour timeframe with 5 minute readings

Performance Qualification

A full load e.g. trays, boxes, vials is recommended to mimic stability storage

Probe placed within each vial/bottle is preferred.


OQ has been approved Documented

Program Variables Set/Documented

Distribution Study Meets Criteria

Open Door Study Results Documented

Failure Study Results Documented

Recovery Study Results Documented



Chamber SOP and Maintenance

Calibration should be ongoing by facilities department.

6 month intervals directed by SOP

Preventative Maintenance

Backup power

Redundant compressors

Alternate water source

Secondary chamber

Housekeeping SOP

Monthly check

Quarterly cleaning activities

Monitoring and Alarm Systems

Chart recorder

Human listener close by to hear alarm.

Automated system

Equipment probes wired into computer

Emails and phone #s programmed into computer

Computer automatically emails/calls

Quickest response to chamber excursion

Needs own qualification when installed

Preferred is Stability Chambers follow 5S e.g. clearly labeled/mapped contents

Preferred if only Stability personnel and site management has access.

Presentation and Access to Stability Samples

Sample Inventory Control and Risk Management - …1).pdf · This procedure applies to all...

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