Manufacturer

Qualification
Jakarta, Nov` 13th 2013

R. Sosialin

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Manufacturer/ Supplier
Qualification

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 Guidelines On Indonesia – GMP 2012 Edition :

6.18 6.19 8.7 8.8

The purchase of Starting materials QA should have A list of
starting materials should only be responsibility with
is an important
approved
purchased from relevant
operation which approved suppliers departments for pp
suppliers
should involve where possible approving should be
staff who have a directly from the suppliers who can established
particular and producer). reliably supply
thorough
and reviewed.
Specifications and starting and
knowledge of the other aspects are packaging
supplier. discussed to compose materials.
QAA

89
8.9 8 10
8.10
Suppliers are evaluated, including All established
history and nature of materials. If audit suppliers should
is required, it should determine the be evaluated
ability of suppliers to confirm with regularly.
GMP standards.

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COST – QUALITY PERSPECTIVE

Examples:
- Qualification, Calibration,
Examples:
- Validation
- Preventive Maintenance - Sampling
- Cleaning - Testing (chemicals, etc)
- Environmental Monitoring - IPC
- GMP Training - Stability Study
- Self Inspection
- Change & Deviation Control - Supplier Certification
- Supplier Qualification
& GMP Audit

•PREVENTIVE COSTS
QUALITY
VS •APPRAISAL COSTS
COST
•INTERNAL FAILURE COSTS
•EXTERNAL FAILURE COSTS
Example:
- O O S/ Retesting Example:
- Re
Re--sampling / re inspection - Product Complaint
- Low yield – sorting out - Product Recall
- Reprocess / Reworking
- Rejection

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 Purpose of Manufacturer/ Supplier Qualification

Provide assurance to patients/ customers on

safety and efficacy of products

P id assurance th
Provide thatt variables
i bl off manufacturing
f t i
are under control

Enhance a better bargaining position and build an

established relationship with manufacturer ÆQAA

Shopping is fun ... ... but should meet the user requirements!

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Manufacturer & Supplier Qualification

ACTIVE PHARMA INGRIDIENTS (API)

Including vitamins, minerals nutrients

EXCIPIENTS
Including flavour, dyestuff, etc.
•SCOPE

PACKAGING MATERIALS
Including primary & secondary packing
materials

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 Manufacturer & Supplier Qualification

Historical data, if available

Asssessment Criteria
a

Quality of the material and the ability to meet specific requirements

Effectiveness of the quality system and of the processes taking

place at the supplier’s and/or manufacturer’s facilities

Delivery reliability and adherence to committed timelines

Cooperation and service readiness

Health, safety and environmental protection (HSE) aspects as well

whenever p
as social / ethical aspects
Applicable
Whenever possible, the material is procured directly from the
manufacturer

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Categorization of manufacturers
a. Reduction of
analytical tests (other
a. First time of than identity test) by
deliveries permitting to refer
results of C of A
b. Not used for the b. C of A of indicates
production of compendial compliant
marketed or as per registered
products specifications
c. Complete testing is
c. Full analysis on performed at least
receipt once a year

Provisional Qualified Certified Disqualified

Qualification is withdrawn
a. identified significant
a. routinely used deficiencies ( quality ,
for marketed HSE and or other
social/ethical issues.
products b. termination of the
b. full analysis on business relationship (e.g.
receipt. no purchase for more
than 5 years).

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 Manufacturer & Supplier Qualification

Provisional Qualified Certified Disqualified

Recommence sourcing from manufacturers who

were disqualified due to no purchasing for more
than 5 years via reassessment
New assessment of the qualification status which is
disqualified due to quality .

a complete risk assessment is done.

Note :
The trade name / article number of raw material is referenced in the internal quality specification (Material No.)

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Provisional

Primary Secondary
Requirement APIs Excipient PM PM

TSE-Statement
TSE Statement √ √ √ X

Residual solvent statement √ √ X X

Metal catalyst statement √ √ X X

Certificate of analysis / product

specification (incl. testing √ √ √ √
methods, testing frequency)
IInformation
f ti as tto ki
kind
d off
packaging & packaging size
√ √ X X

Material Safety Data Sheet √ √ X X

Technical Specifications/ drawing X X √ √

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 Qualified

Requirement APIs Excipient Primary PM Secondary PM

TSE-Statement √ √ X X
Residual solvent & Metal catalyst statement √ √ X X
C of A , Product Specifications, Test methods,
Testing Frequency √ √ √ √

Information as to kind of packaging

and packaging size √ √ X X

Manufacturer Questionnaire √ √ √ √
Supplier/Vendor Questionnaire √ √ √ √
Stability information (storage condition
condition,
re-test period and/or shelf life) √ √ X X
Confirmation that the material will meet agreed
specifications √ √ √ √
Certification of GMP- status √ X X X
Certification (Quality System, e.g. ISO, HACCP) NA √ √ √

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Qualified

continued
Requirement APIs Excipient Primary PM Secondary PM

Regulatory Documentation (e.g. production flow

√ √ X
chart, DMF, CEP – complete CTD required (for novel √
d
documents)
t ) excipients)
i i t )

Remark:
Novel excipients are all “new chemical entities”, used for the first time in a drug product or by new route of
administration.

Audit report √ √* √ √

Quality Assurance Agreement (QAA) √ √* √ √

* Based on Risk Assessment (Sterile Parenteral Product)

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 Certified

Requirement APIs Excipient Primary PM Secondary PM

TSE-Statement √ √ √ X
Residual solvent statement √ √ X X
Metal catalyst statement √ √ X X
Certificate of analysis / product specification (incl.
√ √ √ √
testing methods, testing frequency)
Information as to kind of packaging and
√ √ X X
packaging size
Material safety datasheet √ √ X X
Supplier questionnaire
√ √ X X
(if the supplier is not the manufacturer)
Manufacturer questionnaire √ √ √ √
Stability information (storage condition,
re-test period and/or shelf life)
√ √ √ √
Confirmation of the supplier / manufacturer that
the material will meet the respective quality √ √ √ √
specification(s)
Certification of GMP - status √ X X X

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Certified

Requirement APIs Excipient Primary PM Secondary PM

Certification (Quality system) (e.g. ISO, HACCP) X √ √ √

Regulatory Documentation (e.g. production flow √
chart, DMF, CEP – complete CTD required √ (for novel √ X
documents excipients)
* Novel excipients are all “new chemical entities”, used for the first time in a drug product or by new route of
administration.

Audit report √ √ √ √

Complete testing is performed

Test procedures of supplier/manufacturer for
release testing are identical or successful cross-at least
√ once a year
√ X X
validated.

Comparable analysis results & report for at least 3

batches incl. an assessment of individual quality √ √ √ √
relevant testing parameters and test procedures

Quality Assurance Agreement (QAA) √ √ √ √

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 Form for Assessment and Qualification
of Manufacturer of Materials

T.01
Suppliers / manufacturers’ data and reason for application:

- Material`s
Material s Name
Name, Trade Name
Name, Specifications
- Route of administration
- API or excipients
- Container type & size
- Name & address of manufacturer
(not office, marketing or HQ)
- Name and address of supplier
- Reason for application:
new material, new manufacturer, change, etc.

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Form for Assessment and Qualification of

Manufacturer of Materials - continued

T.02 Planned Actions – QC Function

- Number and type of samples to be evaluated

- Pl
Planned
d tests
t t on the
th material
t i l to
t be
b evaluated
l t d

- Stability study (materials, product) ÆTest results to be evaluated

T.03 Planned Actions – QA Function

Stability Audit necessary: ‰ yes ‰ no (specify reason)

Study Audit of: ‰ Supplier ‰ Manufacturer

Trial Scheduled date: 1 Supplier
1. Date:
Batches 2. Manufacturer Date:
GMP
Audit

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 Form for Assessment and Qualification of
Manufacturer of Materials - continued
T.04 Evaluation

• container and size acceptable in production

• Results of trial batches – process validation
• Results of stability study

T.05 Approval

• Development
• Procurement
• Production
• Quality
y

Supporting documentations are reviewed following check list

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Supporting documentations are reviewed

following check list.
- Material`s Name, Trade Name,
Specifications, Identification number
A. Product-related - Route of administration : oral, parenteral, etc.
Information
- API or excipient
- Container type & size
- Storage Condition & Best Before period
- Name & address of manufacturer
((not the office,, marketing
g or HQ))
- Name and address of supplier
- Reason for application:
new material, new manufacturer, change, etc.

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 Supporting documentations are reviewed
following check list - continued

B. Quality status of
Manufacturer
• GMP Certificate
• CEP API` s
• DMF (US DMF, others)

• ISO certification
• Other Certification Other
C GMP Certificate
C. • No certification Materials

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Supporting documentations are reviewed

following check list - continued

• Production Flowchart, system (e.g.

batch numbering system)
D. Questionnaires • Organization Chart
• QA Agreement

‰ Are the documents satisfied (?)

E. Evaluation
l i received
i d
documents ‰ Is weakness or lack identified to follow up ?

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 Questionnaires for Manufacturer

A Manufacturer of materials : Y / N

B General Company Information

C Contact Person

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Manufacturing Information - Questionnaires

ation
Recrystallization - purifica
Manufacture - reaction

API Manufacturing
Final Packing

Warehouse

QC Testing

Input – Process – Output

Milling

Filling

Any process by other site or third party?

Responsible person (Name/ function)

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 Quality Assurance - Questionnaires

GMP Certification:
Do the operations conform to GMP regulations – API ?
- Is there any supervisory authority
- If yes, which GMPs (e.g. EC GMP Guide, National Guideline, etc.)

Do the operations follow a Quality System – other than API`s ?

- Is a certificate according to the EN/ISO 9001 series available for
the manufacturing site.
- Is there any supervisory certification body
- Is QA System/ manual available

Change Control:
• Do you inform your customer of changes of the production
process, starting materials, GMP status, etc.?
• Do you inform your customer of changes of the
production site?

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General Information - Questionnaires

9 Total number of employees at production facility

9 Is
I there
th a generall training
t i i program, conducted
d t d by
b QA?

9 Is there a training program for new employees/ documented

9 Are periodic internal inspections performed according to a self-

inspection program and documented:
production quality control,
production, control warehouse,
warehouse QA.
QA

9 Materials produced and shifts or not

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 Production - Questionnaires

• Is access to production areas restricted?

• How long are batch documents archived?

• Are raw materials of animal origin processed (incl. microbiology) anywhere?

• Are specifications available for all raw materials?

• Are all containers of raw materials identified before usage?

• Is the quantity of all raw materials used documented?

• Is every production step documented?

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Production - Questionnaires

• Are validation data for all critical production steps available?

• If no: for which production steps are validation data available?

• Is a flow chart (please attach) of production available?

• A continuous or batch production ?

• Batch definition and batch numbering system – traceability

• Is the homogeneity of the batches documented (validated)?

• Is there a written sampling procedure?

• Where are the manufacturing date and/or expiry date of a batch

indicated? (labels, C of A)

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 Certificate of Analysis
• Name of manufacturer/ producer
• Address of manufacturer
• Item/ article Number
• M t i l Description
Materials D i ti
• Pack Size/ type
• Batch number
• MFD
• Best Before
• Reference of specifications – current edition (?)
• Parameters, acceptance criterions/ limits, test procedure and test results
• Date of testing
• Responsible person for batch disposition

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Supplier Audits
Audits are performed during the qualification process for the
following materials:
ct e p
9Active pharmaceutical
a aceut ca ingredients
g ed e ts - API
9Excipients used for the production of sterile/ parenteral
drug products
9Manufacturers intended to be certified:
- excipients
- primary packing primary materials
materials,
- secondary packing materials,
- other any critical materials.

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 Regular Supplier / Manufacturer Assessment

9This assessment results in a

documented decision about the
necessary steps to be taken:
manufacturer has to be disqualified,
change in qualification status,
maintenance of qualification status.

9Regular quality review for materials is

performed according to SOP. The
assessmentt considers
id th
the evaluation
l ti off
quality-related events (e.g. complaints,
rejections, process ability, hidden
defects) and changes.

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