Manufacturing Process

Control and Validation

at SMDIL

Procedure: 8.2.3.01.00 Manufacturing Process Control and

Validation
Applicable Documents source of
requirement

Monitoring and Measurement of Process

(Procedure: 8.2.3.00.00)
5.2.1. When utilizing a special process that cannot be
verified against product requirements within the
regular final inspection (sterilization, welding, gluing
etc) this process shall be validated prior to initiation.
5.2.2. For that, a special Work Instruction shall be
written, and shall include the validation protocol,
sample size, approving criteria, tools and equipment,
standards and specs, further review etc.

(As required under ISO 13485)

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Molecular Detection, Inc.

Procedure: 8.2.3.01.00 Manufacturing Process Control and

Validation
Applicable Docs - outlining
requirements
Medical Device Quality Systems Manual:
A Small Entity Compliance Guide
(section 4 - Process Validation)
GHTF/SG3/N99-10:2004 Quality
Management Systems Process Validation
Guidance January 2004

Molecular Detection, Inc.

Validation Defined
Confirmation by examination and
provision of objective evidence that the
particular requirement for a specific
intended use can be consistently
fulfilled.(1)

(1) Guideline on General Principles of Process Validation,

May 1987, FDA, CDRH/CDER
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Procedure: 8.2.3.01.00 Manufacturing Process Control and

Validation
Purpose/Scope of procedure:
Control and validation of the
Manufacturing Process for a product (and
each product component) - integral
prerequisites for ensuring quality
commercial production of SMDIL
products.
Defines the procedures for controlling
and performing process validation of
SMDIL's manufacturing processes
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Molecular Detection, Inc.

Manufacturing Process Control

and Validation Responsibilities

Molecular Detection, Inc.

Manufacturing Process Control

and Validation Responsibilities cont. 1
Production Engineering Committee shall be
responsible for:
Development and transfer of the preliminary
technical instructions for manufacturing
Determining and transferring preliminary
technical instruction tolerances
Determining and transferring preliminary
performance parameters and tolerances for
each instrument to be used in the
Manufacturing Process
Determining and transferring specifications for
materials manufactured outside of SMDIL
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Molecular Detection, Inc.

Manufacturing Process Control

and Validation Responsibilities cont. 2

Molecular Detection, Inc.

Manufacturing Process Control

and Validation Responsibilities cont. 3

Molecular Detection, Inc.

Manufacturing Process Control

and Validation responsibilities
cont. 4

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Molecular Detection, Inc.

Manufacturing Process Control

and Validation responsibilities
cont. 5

Dir. Process Engineering

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Molecular Detection, Inc.

Development of a Controlled
Manufacturing Process -1
Establish & verify through preliminary testing
collection of specifications, technical instructions for
production and variation tolerances.
Done by R&D or Process Development & Product
Characterization.
E.g., volumes, min/max drying time and temperature,
energies etc

Document as Design Transfer or OQ for particular

instruments.
Analyze Process and product data to determine normal
range of variation for the process output.
Knowing the normal variation of the output is crucial in determining the
Process Performance Qualification parameters and to determine
whether a process is operating in a state of control and is capable of
consistently producing the specified output.
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Molecular Detection, Inc.

Development of a Controlled
Manufacturing Process -2
Analyze Process and product data also to identify
any variation due to controllable causes.
Take appropriate measures to eliminate controllable
causes of variation.
Controllable causes of variation may include:

Temperature
Humidity
Variations in electrical supply
Vibration
Environmental contaminants
Purity of process water
Light
Inadequate employee training
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Molecular Detection, Inc.

Development of a Controlled
Manufacturing Process -3
The TF (and/or DMR, as applicable) lists
Specifications (e.g, Material Spec Sheets)
Process Documents (SOPs & RCs)
For each specific manufacturing process.

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Molecular Detection, Inc.

Manufacturing Process
Validation Procedure
When?
When process documents are signed-off (may be
experimental versions when necessary)

Who?
PD&PC Designs
Manufacturing manufactures as per SOP/RC and any special
controls defined
QC or PD&PC scientist performs Product Performance
Qualification (PPQ)

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Molecular Detection, Inc.

Validation
Process Performance
Qualification
Definition of PPQ:
establishing documented evidence that

the process is effective and reproducible.

Study plan incorporates PPQ through:

Performing manufacturing process by qualified production

scientists
Observation - concurrent visual inspection by a second employee to verify
performance as detailed in process Document(s).

Defining allowed range of conditions - performing Process at most

challenging limit.
If process may be challenged at both upper and lower limit, study shall repeat
process at both allowed limits.

Flaws found during process

Take action to correct the flaws

e,g, the Process Documents do not accurately describe the process, or visa
versa
updating the Process Document,
Train the production team etc.

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Molecular Detection, Inc.

Manufacturing Process
Validation
PLAN

The Validation Plan should include the following, as

applicable:

ID of process, ID of product
Criteria for a successful study
Length and duration of study
# of different operators, and type of equipment to be used
Identification of equipment to be used in the process
ID of utilities for the process equipment and quality of the utilities
Identification of operators and required operator qualifications
Reference to the Process Document(s) (complete description of
process)
Reference to DMR /TF for relevant specifications
Any special controls / conditions needed during or before the validation
Process parameters to be controlled and monitored, and how
Product characteristics to be monitored and how
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Molecular Detection, Inc.

Manufacturing Process
Validation
PLAN (contd)
ALSO:
Any subjective criteria used to evaluate the product
Definition of what constitutes nonconformance for both
measurable and subjective criteria
Statistical methods for data collection and analysis
(e.g., statistical metrics defining both intra-batch and inter-batch
variability)

Consideration of maintenance and repairs

Conditions that may indicate that the process should be
revalidated
Stages of the study where design review is required
Approval of the protocol

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Molecular Detection, Inc.

What are you USING?!?!

Materials match Specs
Equipment: Successful IQ, OQ
PQ: Performed as part of the current
process validation

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Molecular Detection, Inc.

Types of Validation
Prospective:
Manufacturing Process Validation Study Plan
shall be designed, implemented and
documented to serve as prospective validation
of a Manufacturing Process
Product components manufactured as part of
the validation study may be commercially
distributed upon successful completion of the
process validation.

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Molecular Detection, Inc.

Types of Validation

(contd)

Retrospective Validation:
Validation of a process can be partially based on accumulated
historical manufacturing, testing, control, and other data
related to a product or process. Historical manufacturing data
of a pass / fail nature is usually not adequate

Conditions required for adequate

Retrospective Validation
No changes to equipment or comprehensive
maintenance records
No changes to SOP
No changes to chemicals / reagents
Comprehensive feedback / CAPA records
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Molecular Detection, Inc.

Review and revalidation

To change a validated Manufacturing Process:
review and evaluate to determine if the change is substantial
enough that the revision may affect the product's
characteristics.
If yes, revalidation is required. Revalidation may be partial or
encompass all the Validation processes.

If a process deviation occurs:

review and evaluate the process to determine if:
revalidation is required
product components manufactured using the Manufacturing
Process prior to completion of the revalidation may be
commercially distributed.

The review and evaluation must be documented !

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Molecular Detection, Inc.

Manufacturing Process
Validation Study Plan
Dir. PD & PC shall oversee design of a
Manufacturing Process Validation Study Plan and
Manufacturing Process Validation Study Technical
Protocol Form
Dir. QM reviews and approves
A separate study may be designed for each
Manufacturing Process
OR
one study may be designed for concurrent
validation
of several Manufacturing Processes.
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Molecular Detection, Inc.

KNOW YOUR TEMPLATES:

The Manufacturing Process Validation
Study
1) MPV-Check & Approval:
approval/ cover sheet which identifies:
the Process Documents
the process to be validated
the title of the documents produced during
validation
includes the approval table which consolidates
the results of the Manufacturing Process
Validation Study

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Molecular Detection, Inc.

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Molecular Detection, Inc.

KNOW YOUR TEMPLATES :

The Manufacturing Process Validation
Study
2) Manufacturing Process Validation Study Plan
includes product performance qualification by QC /Scientist from
the PD & PC Dept.
performance testing of the finished product components
manufactured during the validation study to establish that they
meet all release performance requirements.

refers to the IQ, OQ and PQ of each piece of equipment used in

the process, PPQ, and product performance qualification
The equipment review is to be conducted once and not repeated for
each manufacturing process unless additional equipment is used.
If the Manufacturing Process includes use of the instrument in a
manner for which it has not been previously qualified, PQ of the
instrument shall be included in the study plan and considered
successfully completed upon successful completion of the validation.

Plan the study carefully to ensure that the

process is adequately validated!
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Molecular Detection, Inc.

KNOW YOUR TEMPLATES :

The Manufacturing Process Validation
Study
3) Manufacturing Process Validation
Study Technical Protocol Form

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Molecular Detection, Inc.

KNOW YOUR TEMPLATES:

The Manufacturing Process Validation
Study
4) MPOR Manufacturing Process
Observation Report
produced during the validation process
details and records the observation phase of
the manufacturing process

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And NOW what?!?

Approve and save study plan and results in
COMPLY when completed
Place an electronic copy of the study plan,
technical protocols (forms), MPORs and
MPV-Check & Approval in the DHF of each
product manufactured using the specific
Manufacturing Process

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Molecular Detection, Inc.

Thank you!

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Molecular Detection, Inc.