Asean Guideline on

Process Validation

Objectives of Presentation
To provide update on outstanding
issues arising from last meeting
To discuss proposed changes (for
fine-tuning)
To seek concurrence on proposed
amendments and adoption as the
final guideline

Outline of Presentation
Background
Proposed Changes & Rationale
Industrys feedback and Comments by
member countries
Discussion

Background
Part of ACTD and ICH CTD
6th PPWG meeting - Adopted as Asean
working guideline
Follow up action consider
a) the use of retrospective data as a basis for
validation requirement for site changes, if
equivalent equipment and process is
maintained
b) to review the applicability of EU Validation
Scheme for the ACTD
Revised guideline was sent to other member
countries for comment in mid May

Matters Arising from last

meeting
Follow up action consider
a) the use of retrospective data as a basis for
validation requirement for site changes, if equivalent
equipment and process is maintained
Change control seek approval from DRA with
appropriate data. Flexibility for manufacturers to
justify.
b) to review the applicability of EU Validation Scheme
for the ACTD
Validation protocol will be changed to Validation
Scheme
Content of Validation scheme will be as specified in
CPMP guidance notes

Proposed changes &

Rationale
Rationale of changes:
Clarification
Streamlining the requirements
Alignment to international
requirements
Flexibility to cater for a wider range of
circumstances and future possible
development

Proposed changes &

Rationale
1. Editorial changes to Sec 2. Scope
To clarify that
(a) the scope refers to requirements that
falls under the remit of DR
(b) requirements are intended to validate
manufacturing process of commercial
dosage form
(c) the general principles are applicable to
biotechnological and biological pdts but
more extensive data may be required.

Proposed changes &

Rationale
1. Editorial changes to Sec 2. Scope (contd)
This guideline is intended to outline the regulatory
requirements with respect to the manufacturing
process validation studies which falls under the remit
of drug registration and to guide the applicant in
preparing the dossiers for the product licence
application. These requirements are not intended for
regulating the manufacture of active substance and
other starting materials, but intended to apply the data
generated to evaluate or validate the manufacturing
process of the commercial dosage form. nor for
biotechnological and biological products that may
require more extensive data. For biotechnological and
biological products, more extensive data may be
required.

Proposed changes &

Rationale
2. Streamline the submission requirements
Sec 3. Data Submission requirements
Option 1 : When 3 Production Batches are ready
Original : Validation report, summary &
protocol
Proposed : Only validation report is required.
Separate summary and protocol (or scheme)
are not necessary.
(Note : Validation scheme is document to be
submitted to regulatory agency, stating how
the validation study will be conducted.)

Proposed changes &

Rationale
Some critical information in
validation summary & protocol will
be incorporated in the report
Validation report content is revised.

Proposed changes & Rationale

Sec 3. Data Submission requirements
Option 2 : when 3 Production Batches
are not ready
Original: Development pharmaceutics,
Validation report on 1 pilot batch &
validation protocol
Proposed:Development Pharmaceutics
Validation report on 1 pilot batch or
Validation Scheme

Proposed changes &

Rationale
[contd] Option 2 : when 3 Production
Batches are not ready

Standard commitment:
Commitment (a)
To undertake that 3 consecutive full production
batches are successfully validated before the
product is marketed and to submit the report to
the DRA upon request within a specified time
frame or to make the information from these
studies available post authorisation for
verification by DRA , according to the national
procedure.
procedure

Proposed changes &

Rationale

[contd] Option 2 : when 3 Production

Batches are not ready
Standard commitment:
Commitment (b)
Original: To inform the DRA within 30 days if
any batch covered under the process
validation studies is not successful
Proposed : To delete . No longer applicable
Concerns already addressed by commitment
(a).

Proposed changes &

Rationale
3. Fine-tune the requirements
Sec 2. Option 3: When the product has
been approved by a reference agency
Same set of data to be submitted
Validation scheme or report may be
required when validation documents do
not form the pre-approval dossiers.

Other feedback
Industry
Concurrent Validations for generic
products
Prospective validation is preferred.
Member countries
Laos, Malaysia agreeable to the
changes

Other feedback
Member countries (contd)
Indonesia `A validated manufacturing process is one that has been proven to
do that (what) it purports or is presented to do .
`commercial dosage form to be changed to `finished product
`commercial scale batches to be changed to `production scale
batches
[sec 5 (b)] A summary of the critical processes and control variable
to be studied during validation and justification for their
selection.
[sec 8] change of new equipment
[sec 6 (a)] Summary, (including approval signature from authorised
person/persons)
[sec 6 (k)]Evaluation of (data including comparison against )
acceptance criteria
[sec 6 (m)] Results and discussion to be deleted as it is already

Other feedback
Member countries (contd)
Thailand Agreeable to proposed editorial changes to section 2
Agreed to waive summary but retain validation protocol
for Option 1.
Validation report to be discussed in the meeting
Prefer the original submission requirement under option
2 i.e. development pharmaceutics report, Validation
report on 1 pilot batch and (vs `or in revised guideline)
Validation scheme.
Prefer the original commitment (a) stipulated under
option 2 I.e to submit the report upon request
Agreeable to deletion of commitment (b)

Other feedback
Member countries (contd)
Philippines To revise the commitment (a) to
To undertake that 3 consecutive full production batches are
successfully validated (post authorisation) before the
product is marketed and to submit the report to the DRA
within a specified time frame or to make the information
from these studies available post authorisation for
verification by DRA, according to the national procedure
(while the product is marketed).
To revise statement under option 3.
Under certain circumstance where validation documents
may not form part of the pre-approval dossiers, the DRA
may request for Validation Report or Validation Scheme.
applicant should submit all the validation

Other feedback
Member countries (contd)
Philippines To revise the statement under sec on concurrent validation
In the case of orphan drugs, (For products where ) when the
number of production batches per year is expected to be low,
concurrent validation is acceptable.
Modified :
In the case of orphan drugs, when the number of production batches ..
concurrent validation is acceptable. The applicant should seek prior
consent on this from DRA before submitting the application to register
any such drug product that uses concurrent validation approach.
To delete the term `Industrial Scale Batch from the glossary as it is
not mentioned in the guidelines.
`Industrial Scale Batch to be changed to `production scale batches
`Laboratory scale batch to be deleted, `Finished pdt to be
incorporated

Summary
Agreement to

editorial changes to section 2

deletion of commitment (b) for submission option
2
Unresolved issues for discussion
Inclusion of approval signature in the validation
report (Indonesia)
Concurrent validation -to broaden the scope
(Philippines)
Submission option 1 - (report & scheme) (vs
proposed - only report) (Thailand)

Summary

Unresolved issues for discussion (contd)

Submission option 2 -retain the original one (dev pharm , 1
pilot batch and scheme) (proposed - dev phar, 1 pilot batch
or scheme) (Thailand)
Commitment (a) for option 2 - retain the original one
(submit report upon request) (vs proposed - submit report
within specified time or make available for verification)
(Thailand)
To undertake that 3 consecutive full production batches are
successfully validated (post authorisation) before the
product is marketed and to submit the report to the DRA
within a specified time frame or to make the information
from these studies available post authorisation for
verification by DRA, according to the national procedure
(while the product is marketed) (Philippine)
Submission option 3 (products approved by reference
agencies) -when no validation docs submitted to ref

Thank you for

your kind attention