Circular 35/2018/TT-BYT: GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICAL PRODUCTS AND PHARMACEUTICAL STARTING MATERIALS

THE MINISTRY OF HEALTH
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THE SOCIALIST REPUBLIC OF VIETNAM
Independence - Freedom - Happiness
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No. 35/2018/TT-BYT Hanoi, November 22, 2018
CIRCULAR
GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICAL PRODUCTS AND
PHARMACEUTICAL STARTING MATERIALS
Pursuant to the Law on Pharmacy No. 105/2016/QH13 dated April 06, 2016;
Pursuant to the Government’s Decree No. 54/2017/ND-CP dated May 08, 2017 on guidelines for
implementation of the Law on Pharmacy;
Pursuant to the Government’s Decree No. 155/2018/ND-CP dated November 12, 2018 on amendments
to some Articles related to business conditions under state management of the Ministry of Health;
Pursuant to the Government’s Decree No. 75/2017/ND-CP dated June 20, 2017 defining functions,
tasks, entitlements and organizational structure of the Ministry of Health;
At the request of the General Director of the Drug Administration of Vietnam and the General Director of
the Traditional Medicine Administration of Vietnam,
The Minister of Health hereby promulgates a Circular on Good Manufacturing Practices for
pharmaceutical products and pharmaceutical starting materials.
Chapter I
GENERAL PROVISIONS
Article 1. Scope
This Circular provides for application and promulgation of Good Manufacturing Practices for
pharmaceutical products and pharmaceutical starting materials (hereinafter referred to as “GMP”) and
inspection of GMP compliance.
Article 2. Definitions
For the purposes of this Circular, the terms below shall be construed as follows:
1. “Good Manufacturing Practices” (GMP) means a set of principles and standards for manufacture of
pharmaceutical products and pharmaceutical starting materials to ensure that pharmaceutical products
and pharmaceutical starting materials are consistently manufactured and controlled to the quality
standards appropriate to their intended use and as required by the certificate of pharmaceutical product
and pharmaceutical starting material registration.
2. “manufacturer” (including manufacturers of chemical pharmaceutical products, herbal pharmaceutical
products, vaccines, biologicals, traditional pharmaceutical products, traditional pharmaceutical products,
prepared traditional pharmaceutical materials, pharmaceutical starting materials) means a pharmacy
establishment that is required or not required to obtain Certificates of eligibility for pharmacy business
and enters one, some or all stages of the process of manufacturing pharmaceutical products and
pharmaceutical starting materials.
3. “deficiency” means a deviation from GMP principles or other applicable regulations on pharmacy
management.
4. “GMP” stands for Good Manufacturing Practices.
5. “WHO” stands for World Health Organization.
6. “WHO - GMP” means Good Manufacturing Practices of World Health Organization.
7. “PIC/S” stands for Pharmaceutical Inspection Co-operation Scheme.
8. “PIC/S - GMP” means Good Manufacturing Practices of Pharmaceutical Inspection Co-operation
Scheme.
9. “EU” stands for European Union.
10. “EU - GMP” means Good Manufacturing Practices of European Union.
11. “US” stands for United States.
MEDGATE TECHNOLOGY AND
INVESTMENT JOINT STOCK COMPANY
Hotline: 098.546.1894
Website: medgate.vn

12. “SRA” stands for Stringent Regulatory Agency.
Chapter II
APPLICATION AND PROMULGATION OF GMP
Article 3. Documents about GMP principles
1. The following GMP principles shall be applied:
a) WHO GMP principles provided in the Appendix I hereof and updated documents specified in Clause 3
of this Article;
b) Principles of WHO - GMP for biological medicinal products derived from Human Blood or Plasma
provided in the Appendix II hereof and updated documents specified in Clause 3 of this Article;
c) GMP principles of Pharmaceutical Inspection Co-operation Scheme provided in the Appendix I hereof
and updated documents specified in Clause 3 of this Article;
d) EU - GMP principles provided in the Appendix IV hereof and updated documents specified in Clause 3
of this Article.
2. The following GMP principles shall be promulgated:
a) Principles of GMP for herbal pharmaceutical products provided in the Appendix V hereof;
b) Principles of GMP for traditional pharmaceutical products provided in the Appendix VI hereof;
c) Principles of GMP for prepared traditional medicinal materials provided in the Appendix VII hereof.
3. In addition to the GMP principles specified Clauses 1 and 2 of this Article, other GMP principles
proved equivalent to EU - GMP principles promulgated by pharmacy authorities of SRA countries shall
be applied. Manufacturers of pharmaceutical products and pharmaceutical starting materials that apply
GMP shall translate and certify translations as prescribed by the law on notarization and authentication
and submit them to the Drug Administration of Vietnam to be posted on the web portal of the Ministry of
Health and website of the Drug Administration of Vietnam.
4. In the cases where WHO, PICS, EU or pharmacy authorities of SRA countries make any revision to
GMP principles (hereinafter referred to as “updated documents) specified in Clause 1 of this Article,
within 06 months from the date on which updated documents are published on websites of such
authorities, the Drug Administration of Vietnam shall translate and publish the revisions on the web portal
of the Ministry of Health and websites of the Drug Administration of Vietnam and Traditional Medicine
Administration of Vietnam.
Article 4. Application of GMP principles
1. Manufacturers of pharmaceutical products and pharmaceutical starting materials shall apply GMP
principles specified in the Appendix I or Appendix III or Appendix IV hereof and updated documents
specified in Clause 4 Article 3 hereof.
2. Manufacturers of biological medicinal products derived from human blood or plasma shall apply GMP
principles specified in the Appendix II hereof and updated documents specified in Clause 4 Article 3
hereof.
3. Manufacturers of herbal pharmaceutical products shall apply GMP in accordance with regulations
specified in Appendix V hereof.
4. Manufacturers of traditional pharmaceutical products in the form of extractions, pills, pellets or powder
shall apply GMP principles specified in Part I - Appendix VI hereof.
5. Manufacturers of traditional pharmaceutical products in modern dosage forms (capsules, tablets,
granules, liquid medicines and other modern dosage forms) other than those specified in Clause 4 of this
Article shall apply GMP principles specified in Part II - Appendix VI hereof.
6. Manufacturers of prepared traditional medicinal materials shall apply GMP principles specified in
Appendix VII hereof.
7. Manufacturers of pharmaceutical products and pharmaceutical starting materials are entitled to apply
other GMP principles proved equivalent to EU - GMP principles promulgated by pharmacy authorities of
SRA countries and updated documents specified in Clause 4 Article 3 hereof.
8. Manufacturers of herbal pharmaceutical products, traditional pharmaceutical products and prepared
traditional medicinal materials shall apply GMP principles specified in the Appendix I or Appendix III or
Appendix IV hereof and updated documents specified in Clause 4 Article 3 hereof.
9. Manufacturers of traditional pharmaceutical products and prepared traditional pharmaceutical
materials are permitted to apply GMP principles specified in Part II Appendix VI or Appendix I or
Appendix III or Appendix IV hereof and updated documents specified in Clause 4 Article 3 hereof.

10. In addition to being manufactured by the manufacturer applying corresponding GMP specified in this
Article, pharmaceutical products and pharmaceutical starting materials containing beta-lactam antibiotics
(Penicillins, Cephalosporins, Penems and equivalent), cytotoxics/cytostatics, contraceptive sex
hormones, vaccines, biologicals and pharmaceutical products with special requirements specified in
GMP must be manufacturered at separate facilities using separate equipment, and measures should be
in place to prevent the release of such pharmaceutical products, which is likely to affect the environment
and other pharmaceutical products manufactured in the same area.
11. Manufacturers of chemical pharmaceutical products in the form of soft capsules, oral liquids and
external medicines (creams, gels, ointments and lotions) are entitled to manufacture herbal
pharmaceutical products from herbal extract, glue and granule which have been standardized on
production lines capable of producing the same dosage forms, and must apply GMP principles specified
in the Appendix I or Appendix III or Appendix IV hereof and updated documents specified in Clause 4
Article 3 hereof.
12. Manufacturers of herbal pharmaceutical products are entitled to manufacture herbal pharmaceutical
products with added pure ingredients extracted from essential oils, vitamins and minerals, and must
apply GMP principles specified in the Appendix V hereof.
13. Manufacturers of traditional pharmaceutical products are entitled to manufacture traditional
pharmaceutical products with added pure ingredients extracted from essential oils, vitamins and
minerals, and must apply GMP principles specified in the Appendix VI hereof.
14. Manufacturers entering one or some stages of the process of manufacturing pharmaceutical products
and pharmaceutical starting materials shall apply and comply with corresponding GMP principles
mentioned in Clauses 1, 2, 3, 4 and 5 of this Article.
15. Manufacturers of pharmaceutical products and pharmaceutical starting materials shall apply updated
documents specified in Clause 3 Article 3 hereof within:
a) 12 months in case of any change of premises or manufacturing equipment, from the date on which
updated documents are published on the website of the Ministry of Health and web portal of the Drug
Administration of Vietnam;
b) 06 months in case of updates other than those specified in Point a of this Clause, from the date on
which updated documents are published on the website of the Ministry of Health and web portal of the
Drug Administration of Vietnam.
Chapter III
INSPECTION OF GMP COMPLIANCE
Article 5. Documents used as basis for inspection of GMP compliance
1. Documents used as basis for inspection of GMP compliance by a pharmacy business establishment
are those included in its application for certificate of eligibility for pharmacy business (the establishment
is not required to submit these documents because they have been submitted when it applies for the
certificate of eligibility for pharmacy business) prescribed in Article 38 of the Law on Pharmacy and
Article 32 of the Government’s Decree No. 54/2017/ND-CP dated May 08, 2017 on guidelines for the
implementation of the Law on Pharmacy (hereinafter referred to as “the Decree No. 54/2017/ND-CP”).
Manufacturers of special-controlled pharmaceutical products must have the documents prescribed in
Article 38 of the Law on Pharmacy and Clause 31 Article 5 of the Government’s Decree No.
155/2018/ND-CP dated November 12, 2018 on amendments to some Articles related to business
conditions under state management of the Ministry of Health (hereinafter referred to as “the Decree
No.155/2018/ND-CP”).
Technical documents about a manufacturer shall be prepared in accordance with guidelines for the site
master file provided in the Appendix VIII hereof or the site master file that is updated in the case of
change of scope of operation.
2. If a manufacturer applies for both certificate of GMP compliance and certificate of eligibility for
pharmacy business, this content and applied GMP principles must be clearly specified in its application
form for certificate of eligibility for pharmacy business.
3. If the manufacturer applying for certificate of eligibility for pharmacy business sells pharmaceutical
products and pharmaceutical starting materials to wholesalers, retailers or health facilities, documents
about its technologies and personnel according to Clause 2 Article 32 of the Decree No. 54/2017/ND-CP
are required when it applies for both certificate of GDP compliance and certificate of eligibility for
pharmacy business. The receiving authority shall inspect its compliance with both GDP and GMP in
accordance with regulations on GDP.
Article 6. Sequence of inspection of GMP compliance
1. Receipt of applications:

The manufacturer shall submit an application, which includes the documents specified in Article 5 herein,
accompanied by the application fees in accordance with regulations of the Minister of Finance to:
a) the Traditional Medicine Administration of Vietnam if the manufacturer applies for the certificate for
eligibility for pharmacy business that allows manufacture of herbal materials, traditional pharmaceutical
products and prepared traditional medicinal materials at the time of submission;
b) the Drug Administration of Vietnam if the manufacturer applies for the certificate for eligibility for
pharmacy business that allows manufacture of pharmaceutical starting materials (excluding herbal
materials), chemical pharmaceutical products, herbal pharmaceutical products, vaccines and biologicals;
c) the Drug Administration of Vietnam if the manufacturer applies for the certificate for eligibility for
pharmacy business that allows manufacture of both one of the pharmaceutical products and
pharmaceutical starting materials specified in Point a of this Clause and one of the pharmaceutical
products and pharmaceutical starting materials specified in Point b of this Clause at the time of
submission.
2. Sequence of receiving and processing applications is prescribed in Clauses 2 and 5 Article 33 of the
Decree No. 54/2017/ND-CP and Clause 12 Article 5 of the Decree No. 155/2018/ND-CP.
3. Within 05 days from the receipt of the satisfactory application, the receiving authority shall establish an
inspectorate and send the manufacturer the decision on inspectorate establishment specifying expected
date of the site inspection.
Within 15 days from the date of issuing the decision, the inspectorate shall carry out a site inspection of
the manufacturer.
Article 7. Procedures for inspection and classification of GMP compliance
1. Principles of using GMP documents for inspection of GMP compliance:
a) GMP documents are applied by the manufacturer and specified in the application form for certificate of
eligibility for pharmacy business.
b) EU - GMP or PIC/S - GMP or GMP documents specified in Clause 3 Article 3 of this Article are applied
if the manufacturer has undergone GMP inspection by SRA and been recommended by SRA to make
the declaration of compliance with GMP.
c) WHO - GMP or GMP documents specified in Clauses 2, 3, 4, 5 and 6 Article 4 of this Circular are
applied if the manufacturer does not specify applied GMP principles in the application form for certificate
of eligibility for pharmacy business.
2. Inspection procedures:
a) Step 1. The inspectorate shall publish the decision on inspectorate establishment, purposes, contents
and plan for the inspection at the manufacturer;
b) Step 2. The manufacturer shall make a brief introduction of its organizational structure, personnel and
implementation or application of GMP, or specific contents in conformity with the inspected contents;
c) Step 3. The inspectorate shall carry out a site inspection of the application of GMP at the
manufacturer. If the manufacturer enters one or some stages of the manufacturing process, only GMP
applied to such stages is inspected.
d) Step 4. The inspectorate shall have a talk with the manufacturer about deficiencies found during the
inspection (if any) and assess the level of each deficiency; discuss with the manufacturer in case the
manufacturer does not agree with the inspectorate about the assessment of each deficiency or level of
GMP compliance;
dd) Step 5. An inspection record is prepared and signed as follows:
After the site inspection, the inspectorate shall make an inspection record using the Form No. 03 in the
Appendix X hereof. It shall clearly specify members of the inspectorate and the manufacturer, location,
date and scope of the inspection and disagreements (if any) between the inspectorate and the
manufacturer. It shall be signed by the head of the manufacturer and chief of the inspectorate. The
record shall be made into 03 copies, among which one is kept by the manufacturer and the others are
kept by the receiving authority.
e) Step 6. The inspection record is completed as follows:
The inspectorate shall make a GMP inspection report using the Form No. 04 in the Appendix X hereof,
list, analyze and classify deficiencies that need to be rectified by the manufacturer, make a comparison
of corresponding regulations specified in legal documents and GMP, and assess the level of GMP
compliance. The deficiency classification and assessment of level of GMP compliance (applied to each
production line) are prescribed in the Appendix IX hereof.
3. Level of GMP compliance:

The inspection of manufacturer's compliance with GMP specified in Appendix IX hereof shall be carried
out according to the following 04 levels:
a) GMP level 1 manufacturer;
b) GMP level 2 manufacturer;
c) GMP level 3 manufacturer;
d) GMP level 4 manufacturer.
Article 8. Processing results of inspection of GMP compliance
1. If the GMP inspection report indicates that the manufacturer complies with GMP at level 1 as
prescribed in Point a Clause 3 Article 7 of this Circular:
Within 10 working days from the date of signing the inspection record, the receiving authority shall
request the Minister of Health to issue the certificate of eligibility for pharmacy business and issue the
Certificate of GMP compliance according to Form No. 05 in the Appendix X hereof if the manufacturer
applies for both certificate of GMP compliance and certificate of eligibility for pharmacy business.
prescribed in Point b Clause 3 Article 7 of this Circular:
a) Within 05 working days from the date of signing the inspection record, the receiving authority shall
send the GMP inspection report to the manufacturer as prescribed in Point b Clause 6 Article 33 of the
Decree No. 54/2017/ND-CP.
b) Upon completion of deficiency rectification, the manufacturer shall submit a rectification report
including a plan and evidences (such as documents, images, videos, certificates or other documentary
evidences) for completion of rectification of deficiencies specified in the GMP inspection report;
c) Within 20 days from the receipt of the rectification report, the receiving authority shall assess result of
deficiency rectification by the manufacturer and conclude the level of its GMP compliance. To be specific:
- If the result of deficiency rectification makes the manufacturer comply with GMP, the receiving authority
shall request the Minister of Health to issue the certificate of eligibility for pharmacy business and the
certificate of GMP compliance according to the Form No. 05 in the Appendix X hereof if the manufacturer
applies for both certificate of GMP compliance and certificate of eligibility for pharmacy business;
- If the result of deficiency rectification shows that the manufacturer still fails to comply with GMP, the
receiving authority shall respond and provide explanation in writing.
d) Within 06 months from the date on which additional documents are requested in writing by the
receiving authority, the manufacturer shall submit them as requested. If the manufacturer fails to satisfy
such request by the aforementioned deadline or the application is not satisfactory within 12 months from
the first time it is submitted, the application will be rejected.
prescribed in Point c Clause 3 Article 7 of this Circular:
Sequence and time of processing result of inspection of GMP compliance are specified in Clause 2 of
this Article.
Within 20 days from the receipt of the rectification report, the receiving authority shall carry out a site
inspection of deficiency rectification at the manufacturer before concluding the level of GMP compliance
as prescribed in Point c Clause 2 of this Article.
prescribed in Point d Clause 3 Article 7 of this Circular:
Within 05 working days from the date of signing the inspection record, the receiving authority shall send
a notification of failure to comply with GMP enclosed with a GMP inspection report to the manufacturer
and shall not issue the certificate of eligibility for pharmacy business.
5. In the cases where the manufacturer does not agree with the deficiency stated by the inspectorate,
within 30 days from the date on which the inspectorate sends GMP inspection report or rectification
report, the manufacturer shall submit a written recommendation enclosed with evidences (such as
documents, images, videos and certificates) related to such deficiency to the receiving authority.
Within 10 working days from the receipt of the written recommendation, the receiving authority shall
review GMP inspection report and written recommendation submitted by the manufacturer, if necessary,
consult relevant exports and respond to the manufacturer in writing. The written response must clearly
specify agreements and disagreements with the written recommendation submitted by the manufacturer
and reasons for disagreements. The abovementioned length of time shall not add to the time limit for
inspection.

6. Within 05 working days from the date of issuing the certificate of eligibility for pharmacy business, the
receiving authority shall publish the following information on its website and web portal of the Ministry of
Health:
a) Name and address of the manufacturer;
b) Full name of the person in charge of pharmacy, person in charge of quality assurance and number of
his/her pharmacy practicing certificate;
c) Number of the certificate of eligibility for pharmacy business and Certificate of GMP compliance (if
any);
d) Expiry date of inspection of GMP compliance;
dd) Scope of operation of the manufacturer;
e) EU - GMP certificate number, validity period and issuing authority if the manufacturer has its
compliance with EU - GMP or equivalent inspected by SRA.
Chapter IV
INSPECTION OF GMP COMPLIANCE AND MAINTENANCE THEREOF
Article 9. Periodic inspection of GMP compliance
1. GMP compliance by a manufacturer shall be periodically inspected every 03 year from the date of
signing the previous inspection record (except surprise inspections or audits by the Ministry of Health or
the Provincial Department of Health).
2. In November, every receiving authority shall publish the plan for periodic inspection of GMP
compliance by manufacturers in the succeeding year on its website and send it to manufacturers that are
mentioned in the plan. Regarding the manufacturer specified in Point c Clause 1 Article 6 of this Circular,
the Drug Administration of Vietnam shall publish and implement the periodic inspection plan, except in
the cases where the manufacturer applies for a particular inspection.
3. At least 30 days prior to the date of carrying out periodic inspection of GMP compliance according to
the published plan, the manufacturer shall submit a report on its manufacture of pharmaceutical products
and pharmaceutical starting materials and GMP compliance (hereinafter referred to as “operation and
GMP compliance report”) according to the Form No. 2 in the Appendix X hereof enclosed with updated
technical documents about infrastructure, technologies and personnel of the manufacturer (in case any
change is made) to the receiving authority.
E.g.: If the estimated date of periodic inspection of the manufacturer A is on August 18, 2018, the
manufacturer A is required to submit an operation and GMP compliance report to the receiving authority
by July 18, 2018.
4. If the manufacturer fails to submit the operation and GMP compliance report within the time limit
prescribed in Clause 3 of this Article, within 15 days from the deadline for submission of the report, the
receiving authority shall request the manufacturer in writing to submit the operation and GMP compliance
report as prescribed.
5. Within 45 days from the date on which the operation and GMP compliance report is requested in
writing by the receiving authority, the manufacturer shall submit the report enclosed with a written
explanation for its delay in submission. By the aforementioned deadline, if the manufacturer fails to
submit the report, the receiving authority shall carry out an surprise inspection or audit of GMP
compliance by the manufacturer as prescribed in Article 12 of this Circular.
6. After submitting the operation and GMP compliance report within the prescribed time limit, the
manufacturer is entitled to keep manufacturing pharmaceutical products and pharmaceutical starting
materials within the scope specified in the certificate for eligibility for pharmacy business until the result of
periodic inspection of GMP compliance is available and shall ensure its maintenance of GMP
compliance.
7. Sequence of inspecting and procedures for inspecting and classifying results of inspection of GMP
compliance are prescribed in Articles 6 and 7 of this Circular.
Article 10. Processing of results of periodic inspection of GMP compliance
prescribed in Point a Clause 3 Article 7 of this Circular:
Within 10 working days from the date of signing the inspection record, the receiving authority shall
update information about the maintenance of GMP compliance by the manufacturer on its website and
web portal of the Ministry of Health as prescribed in Clause 6 Article 8 of this Circular and issue the
applies for the certificate of GMP compliance.

prescribed in Point b Clause 3 Article 7 of this Circular:
a) Within 05 working days from the date of signing the inspection record, the receiving authority shall
send the GMP inspection report to the manufacturer so that it can rectify deficiencies and send a
rectification report to the receiving authority;
b) Within 45 days from the date on which the receiving authority sends the GMP inspection report, the
manufacturer shall submit a rectification report including a plan and evidences (such as documents,
images, videos, certificates or other documentary evidences) for completion of rectification of
deficiencies specified in the GMP inspection report;
c) Within 20 days from the receipt of the rectification report, the receiving authority shall assess result of
deficiency rectification by the manufacturer and conclude the level of its GMP compliance. To be specific:
shall update information about the maintenance of GMP compliance by the manufacturer on its website
and web portal of the Ministry of Health as prescribed in Clause 6 Article 8 of this Circular and issue the
applies for the certificate of GMP compliance;
- If the result of deficiency rectification shows that the manufacturer still fails to comply with GMP, the
receiving authority shall request the manufacturer in writing to take more corrective actions against
deficiencies and submit an additional report. The manufacturer shall have 45 days from the receipt of the
written request to complete corrective actions and send report thereof as requested.
d) Within 90 days from the date of signing the inspection record, if the manufacturer fails to submit the
rectification report or still fails to comply with GMP after rectifying deficiencies, the receiving authority
shall send a notification of failure to comply with GMP and impose one or some measures prescribed in
Points and b Clause 4 of this Clause depending on the nature and level of non-compliance with GMP.
prescribed in Point c Clause 3 Article 7 of this Circular:
Sequence and time of processing result of inspection of GMP compliance are specified in Clause 2 of
this Article.
Within 20 days from the receipt of the rectification report, the receiving authority shall carry out a site
inspection and supervision of deficiency rectification at the manufacturer before concluding the level of
GMP compliance as prescribed in Point c Clause 2 of this Article.
prescribed in Point d Clause 3 Article 7 of this Circular:
Within 05 working days from the date of signing the inspection record, according to the assessment of
risks of deficiencies in the quality of pharmaceutical products and pharmaceutical starting materials, and
pharmaceutical product user safety, the receiving authority shall send a notification of failure to comply
with GMP enclosed with a GMP inspection report. Depending on the nature and level of non-compliance
with GMP, the receiving authority shall impose one or some of the following measures:
a) Impose penalties for administrative violations in accordance with regulations of the Law on penalties
for administrative violations;
b) Request the Minister of Health to issue a decision on revocation of the certificate of eligibility for
pharmacy business as prescribed in Clause 2 Article 40 of the Law on Pharmacy and revoke the
certificate of GMP compliance (if any).
c) If the manufacturer is ineligible for one or several business activities specified in its certificate of
eligibility for pharmacy business, the receiving authority shall:
- request the Minister of Health to issue a decision on revocation of the certificate of eligibility for
pharmacy business to remove the business activity for which the manufacturer is ineligible and issue a
new certificate of eligibility for pharmacy business which is conformable with the business activity for
which the manufacturer is eligible;
- issue the certificate of GMP compliance which is conformable with the business activity for which the
manufacturer is eligible if it so wishes.
5. Within 05 working days from the date of concluding that the manufacturer maintains its compliance
with GMP or issuing the decision on revocation of the issued certificate of eligibility for pharmacy
business because of the manufacturer’s failure to maintain GMP compliance, the receiving authority shall
update GMP compliance status on its website as prescribed in Clause 6 Article 8 of this Circular if the
manufacturer complies with GMP or information about the revocation of the certificate of eligibility for
pharmacy business or Certificate of GMP compliance (if any) if the manufacturer fails to maintain its
GMP compliance.

6. If it is concluded that a sample of pharmaceutical product or pharmaceutical starting material collected
by the inspectorate during the inspection violates quality regulations, the receiving authority shall handle
it in accordance with applicable regulations.
Article 11. Control of changes
1. Before making one of the changes specified in Points a and b of this Clause, a vaccine manufacturer
shall send a notification including the result of assessment of risks and effect of changes expected to be
made on the product quality and safety:
a) Changes specified in Points d, dd, e and g Clause 2 of this Article;
b) Manufacture or trial manufacture of vaccines or other pharmaceutical products on the vaccine
production line that has been certified;
Within 15 days, the Drug Administration of Vietnam shall respond in writing in case it does not agree with
the changes proposed by the vaccine manufacturer.
2. After making any change, the manufacturer shall apply for the certificate of eligibility for pharmacy
business or submit a report on its change using the Form No. 06 in the Appendix X hereof if:
a) making one of the changes specified in Point b Clause 1 Article 36 of the Law on Pharmacy; or
b) changing the location of a factory at the same business location; or
c) opening a new factory at the same business location; or
d) expanding existing factory; or
dd) repairing or having significant changes in structure and floor plan of the premises and production line,
which results in changes to environmental conditions and manufacturing process; or
e) changing important manufacturing equipment, thereby affecting manufacturing process and quality of
pharmaceutical products and pharmaceutical starting materials; or
g) changing auxiliary system or principle of designing and operating utility systems, thereby affecting
manufacturing environment; or
h) changing applied GMP and undergoing inspection of compliance with EU - GMP or equivalent (Japan
- GMP, US - Current GMP, PIC/S -GMP) by an SRA and being recommended by an SRA to make the
declaration of compliance with GMP.
3. In case of changes specified in Point a Clause 2 of this Article, the manufacturer shall submit an
application for the certificate of eligibility for pharmacy business as prescribed in Clause 2 and Clause 4
Article 38 of the Law on Pharmacy.
Sequence of inspecting, classifying and processing the result of inspection of GMP compliance is
specified in Articles 6, 7 and 8 of this Circular.
4. If the manufacturer has one of the changes prescribed in Points b, c, d or h Clause 2 of this Article or
the manufacturer of sterile pharmaceutical products and pharmaceutical starting materials has the
change specified in Point dd Clause 2 of this Article, the manufacturer is required to submit a report on
its changes, accompanied by relevant technical documents, to the receiving authority.
a) The receiving authority shall carry out an inspection at the manufacturing site. If the manufacturer
complies with GMP, the receiving authority shall grant a written consent to its changes;
b) Sequence of inspecting, classifying and processing the result of inspection of GMP compliance in
case of the change specified in Point b Clause 2 of this Article is prescribed in Articles 6, 7 and 10 of this
Circular;
c) Sequence of inspecting, classifying and processing the result of inspection of GMP compliance by the
manufacturer that makes the change specified in Point c or d Clause 2 of this Article or the manufacturer
of sterile pharmaceutical products and pharmaceutical starting materials that makes the change specified
in Point dd Clause 2 of this Article is prescribed in Articles 6, 7 and 8 of this Circular.
5. In case of the change specified in Point h Clause 2 of this Article, the manufacturer shall send a
notification of change of applied GMP and inspection by SRA at the manufacturer (name of SRA, date of
inspection, content/scope of inspection and inspection result) enclosed with relevant technical
documents, certificate of GMP compliance or GMP inspection report issued by SRA.
a) The receiving authority shall review the notification and enclosed documents and add/update
information about compliance with EU - GMP or equivalent by the manufacturer as prescribed in Clause
6 Article 8 of this Circular.
b) The receiving authority shall inspect compliance with EU - GMP or equivalent by the manufacturer as
prescribed in Article 12 of this Circular.

6. In case of one of the changes prescribed in Point dd, e or g Clause 2 of this Article (except in the
cases specified in Clauses 4 and 6 of this Article), the manufacturer shall submit a report on its change,
accompanied by relevant technical documents, to the receiving authority. The receiving authority shall
assess the manufacturer’s report on changes.
a) Within 10 working days from the receipt of the report on changes, the receiving authority shall notify
the manufacturer in writing of approval for its changes if they meet requirements or issue a notification of
deficiencies that need rectifying if its changes fail to meet with requirements;
b) Within 45 days from the receipt of the notification, the manufacturer shall complete deficiency
rectification and send a rectification report enclosed with documentary evidences (such as documents,
images, videos, certificates and other documentary evidences) for completion of rectification of
deficiencies specified in the notification;
c) Within 10 days from the receipt of the rectification report enclosed with documentary evidences (such
as documents, images, videos, certificates and other documentary evidences), the receiving authority
shall assess result of deficiency rectification by the manufacturer and conclude the level of its GMP
compliance. To be specific:
shall notify the manufacturer in writing of approval for its changes;
- If the result of deficiency rectification shows the manufacturer still fails to comply with GMP, the
receiving authority shall carry out an surprise inspection and process inspection result as prescribed in
Article 12 of this Circular.
7. If the manufacturer of non-sterile pharmaceutical products and pharmaceutical starting materials for
external use has one of the changes prescribed in Points dd, e and g Clause 2 of this Article, the
manufacturer is required to submit a report on its change, accompanied by relevant technical documents,
to the receiving authority. The manufacturer shall keep carrying out manufacturing operations in
accordance with principles of GMP.
Article 12. Unexpected inspection of GMP compliance or audit of GMP compliance and
maintenance thereof
1. Audit of GMP compliance and maintenance thereof by manufacturers shall be conducted as
prescribed by law.
2. An surprise inspection of GMP compliance and maintenance thereof shall be carried out at the
manufacturer in one of the following cases:
a) The result of deficiency rectification by the manufacturer shows it still fails to comply with GMP
according to Sub-point 2 Point c Clause 6 Article 11 of this Circular;
b) The manufacturer that complies with GMP at level 3 or level 4 according to Points c and d Clause 3
Article 7 of this Circular shall undergo an surprise inspection at least once within 03 (three) years from
the end of the previous inspection;
c) The manufacturer has at least 01 batch of pharmaceutical products which is recalled because of first-
degree violations;
d) The manufacturer has a pharmaceutical product that is reported to have adverse effects, including
serious ones;
dd) The inspecting authority concludes that the manufacturer seriously violates GMP;
e) There is any complaint or denunciation that the manufacturer seriously violates GMP;
g) The manufacturer fails to submit the operation and GMP compliance report according to Clause 5
3. The head of the receiving authority shall decide on members of the inspectorate as prescribed in
4. Sequence of conducting surprise inspections at a manufacturer is mentioned in Article 7 of this
Circular.
5. Results of surprise inspections or audits conducted at a manufacturer shall be processed as
prescribed by law.
Chapter V
INSPECTION OF GMP COMPLIANCE BY MANUFACTURERS NOT REQUIRED TO
OBTAIN CERTIFICATES OF ELIGIBILITY FOR PHARMACY BUSINESS AND
OVERSEAS MANUFACTURERS WHEN THEY APPLY FOR REGISTRATION OF

PHARMACEUTICAL PRODUCTS AND PHARMACEUTICAL STARTING
MATERIALS IN VIETNAM
Article 13. Inspection of GMP compliance by manufacturers not required to obtain certificates of
eligibility for pharmacy business
1. A manufacturer not required to obtain the certificate of eligibility for pharmacy business (non-
commercial pharmacy establishment) must comply with GMP as prescribed in Point a Clause 2 Article 35
of the Law on Pharmacy.
2. The manufacturer not required to obtain the certificate of eligibility for pharmacy business (except the
health facility’s division in charge of pharmaceutical product preparation) shall submit an application form
for inspection of GMP compliance using the Form No. 1 in the Appendix X hereof and technical
documents about the manufacturer, which shall be prepared in accordance with guidelines for the site
master file in the Appendix VIII hereof in case of first inspection or manufacturing operation and GMP
compliance report enclosed with updated technical documents about the manufacturer (if any change is
made) according Clause 2 of Article 9 in case of periodic inspection.
3. Sequence of inspection and procedures for inspection and classification of results of inspection of
GMP compliance, control of changes and surprise inspection of GMP compliance by manufacturers of
pharmaceutical products and pharmaceutical starting materials not required to obtain certificates of
eligibility for pharmacy business are mentioned in Articles 6, 7, 9, 11 and 12 of this Circular.
4. Results of first inspection of GMP compliance by a manufacturer of pharmaceutical products and
pharmaceutical starting materials not required to obtain the certificate of eligibility for pharmacy business
shall be processed as follows:
a) Sequence and time of processing result of first inspection of GMP compliance by the manufacturer are
mentioned in Article 8 of this Circular.
b) The receiving authority shall send a notification of status of GMP compliance by the manufacturer and
publish it on its website and web portal of the Ministry of Health as prescribed in Clause 6 of this Article.
5. Results of surprise and periodic inspections of GMP compliance by a manufacturer of pharmaceutical
products and pharmaceutical starting materials not required to obtain the certificate of eligibility for
pharmacy business shall be processed as follows:
a) If the inspection result shows that the manufacturer complies with GMP at level 1 or level 2 or level 3
as prescribed in Points a, b and c Clause 3 Article 7 of this Circular, the receiving authority shall carry out
inspection as prescribed in Clauses 1, 2 and 3 Article 10 of this Circular.
b) If the inspection result shows that the manufacturer complies with GMP at level 4 as prescribed in
Point d Clause 3 Article 7 of this Circular, the receiving authority shall carry out an inspection and issue a
decision on suspension of all manufacturing operations or manufacturing operations that fail to comply
with GMP until the result of deficiency rectification by the manufacturer rectifies is satisfactory.
c) If it is concluded that a sample of pharmaceutical product or pharmaceutical starting material collected
by the inspectorate during the inspection violates quality regulations, the receiving authority shall handle
it in accordance with applicable regulations on management of quality of pharmaceutical products and
pharmaceutical starting materials. The head of the manufacturer shall be responsible to law for such
violation.
6. Within 05 working days from the date of concluding that the GMP compliance or maintenance of GMP
compliance by a manufacturer of pharmaceutical products and pharmaceutical starting materials not
required to obtain the certificate of eligibility for pharmacy business, the receiving authority shall publish
the following information on its website and web portal of the Ministry of Health:
b) Full name of the person in charge of pharmacy, person in charge of quality assurance and number of
his/her pharmacy practicing certificate;
c) Number of certificate of GMP compliance;
d) Expiry date of inspection of GMP compliance;
dd) Scope of operation of the manufacturer.
e) EU - GMP certificate number, validity period and issuing authority if the manufacturer has its
compliance with EU - GMP or equivalent (if any) inspected by SRA.
Article 14. Inspection of GMP compliance by overseas manufacturers when they apply for
registration of pharmaceutical products and pharmaceutical starting materials in Vietnam

1. Before submitting an application for inspection of GMP compliance to the Ministry of Health (the
receiving authority specified in Clause 1 Article 6 of this Circular) shall have its GMP compliance
inspected and certified by a competent pharmacy authority of the home country.
2. Methods, contents, documentation, sequence, procedures and power for inspection of GMP
compliance by overseas manufacturers are mentioned in Articles 96, 97, 98 and 99 of the Decree No.
54/2017/ND-CP.
In the cases where the inspection of GMP compliance is conducted using the method for conducting a
inspection at the manufacturer, procedures for inspecting, classifying and processing inspection results
and controlling changes is prescribed in Articles 6, 7, 8, 9, 10, 11 and 12 of this Circular.
3. Within 10 working days from the date on which the result of inspection of GMP compliance by a
manufacturer is obtained, the receiving authority shall publish the following information on its website and
web portal of the Ministry of Health:
b) Number of certificate of GMP compliance, GMP documents applied, validity period of certificate of
GMP compliance and name of the competent pharmacy authority in the cases specified in Points a and b
Clause 5 Article 54 of the Law on Pharmacy or date of GMP compliance inspection by the Vietnam
Ministry of Health, GMP documents applied and validity period of result of inspection of GMP compliance
in the case specified in Point c Clause 5 Article 54 of the Law on Pharmacy;
c) Scope of operation of the inspected manufacturer.
Chapter VI
INSPECTORATE CONDUCTING INSPECTIONS OF GMP COMPLIANCE
Article 15. Members and standards to be satisfied by members of an inspectorate
1. An inspectorate includes:
a) the chief and 01 or 02 members of the receiving authority. 01 or 02 members of the Traditional
Medicine Administration of Vietnam, regarding the manufacturer specified in Point c Clause 1 Article 6 of
this Circular;
b) 01 member: the representative of the National Institute of Drug Quality Control or Institute of Drug
Quality Control - Ho Chi Minh City or National Institute for Control of Vaccine and Biologicals (regarding
the manufacturer of vaccines and biologicals);
c) 01 member: the representative of the Department of Health of a province or central-affiliated city
(hereinafter referred to as “the Department of Health”) where the factory is located.
d) Members of relevant authorities where necessary.
2. A member of the inspectorate must satisfy the following standards:
a) He/she must obtain at least a bachelor’s degree and has been provided with training medicine,
pharmacy, biology, pharmaceutical product quality management and pharmacy management;
b) He/she has been trained in GMP and inspection of GMP compliance, and has a thorough grasp of
GPP principles. Members joining the inspectorate conducting inspections of manufacturers of traditional
pharmaceutical products and herbal materials must be trained in GMP for traditional pharmaceutical
products and herbal materials.
c) He/she must be honest, objective strictly comply with regulations during the inspection and must not
create any conflict of interest with the inspected manufacturer as prescribed in Clause 3 of this Article;
d) The chief must have at least 03 (three) years’ experience in pharmacy management.
3. Rules for assessing the conflict of interest: A member of the inspectorate shall be deemed to involve a
conflict of interest with the inspected manufacturer in one of the following cases:
a) He/she has worked or participated in providing consulting services for the inspected manufacturer in
the past 05 years;
b) He/she is receiving financial benefits associated with the inspected manufacturer;
c) His/her spouse, child, parent, sibling or parent-in-law is working for the inspected manufacturer.
Article 16. Rights and responsibilities of an inspectorate
1. The inspectorate has the responsibility to:
a) inspect all operations of a manufacture according to corresponding GMP prescribed in Article 3 of this
Circular, updated versions of GMP principles and relevant legislative documents and regulations; clearly
record inspection contents and deficiencies found, prepare GMP inspection records and reports;

b) report inspection results or provide explanation for the GMP inspection report if the manufacturer has
any disagreements with the report;
c) maintain confidentiality of all information about the inspection and manufacturing operations,
inspection of quality, storage and distribution of pharmaceutical products (manufacturing, testing and
cleaning process, technological secrets, etc.) unless otherwise agreed upon by the manufacturer or
requested by the competent authority.
2. The inspectorate has the right to:
a) inspect all areas and premises of the manufacturer and request inspection of other areas related to
the manufacture, storage and testing of pharmaceutical products and pharmaceutical starting materials.
Regarding manufacture of prepared traditional pharmaceutical materials, inspect the prepared traditional
pharmaceutical material processing and manufacturing process.
b) request the manufacturer to provide documents concerning its quality management, manufacture,
testing and storage of pharmaceutical products and pharmaceutical starting materials;
c) collect documentary evidences (by copying documents, taking pictures or recording videos) of
deficiencies found during the inspection;
d) take samples of pharmaceutical products, semi-finished products and herbal materials to test their
quality as regulated by law;
dd) make inspection records and request the manufacturer to suspend one, some or all of its
manufacturing operations related to violations. During the inspection, if the inspectorate finds that the
manufacturer commits a violation which seriously affects quality of one or multiple pharmaceutical
products and pharmaceutical starting materials, it is required to notify the competent person thereof.
Chapter VII
IMPLEMENTATION CLAUSE
Article 17. Effect
1. This Circular comes into force from January 10, 2019.
2. The following documents and regulations are null and void from the effective date of this Circular:
a) Decision No. 3886/2004/QD-BYT dated November 03, 2004 of the Minister of Health;
b) Regulations on GMP specified in the Decision No. 27/2007/QD-BYT dated April 19, 2007 of the
Minister of Health;
c) Regulations on GMP specified in the Circular No. 45/2011/TT-BYT dated December 21, 2011 of the
Minister of Health; Decision No. 2701/2001/QD-BYT dated June 29, 2001 of the Minister of Health;
Circular No. 06/2004/TT-BYT dated May 28, 2004; Decision No. 3886/2004/QD-BYT dated November
03, 2004 of the Ministry of Health; Circular No. 13/2009/TT-BYT September 01, 2009 of the Ministry of
Health; Circular No. 22/2009/TT-BYT dated November 24, 2009 of the Ministry of Health; Circular No.
2010/TT-BYT dated December 29, 2010.
d) Regulations on conditions for processing herbal materials in the Circular No. 03/2016/TT-BYT dated
January 21, 2016 of the Minister of Health shall remain effective until December 31, 2020 according to
Clause 4 Article 19 of this Circular.
dd) Regulation: “If the test facility fails to submit the application as prescribed, the Ministry of Health shall
revoke its certificate of eligibility for pharmacy business as prescribed in Clause 2 Article 40 of the Law
on Pharmacy” specified in Clause 5 Article 9 of the Circular No. 04/2018/TT-BYT of the Minister of Health
dated February 09, 2018.
Article 18. Reference clause
In the cases where any of the legislative documents and regulations referred to in this Circular is
amended or replaced, the newest one shall apply.
Article 19. Transitional clauses
1. Any manufacturer of pharmaceutical products and pharmaceutical starting materials that has been
issued with the certificate for eligibility for pharmacy business that allows manufacture of pharmaceutical
products and pharmaceutical starting materials or certificate of GMP compliance before the effective date
of this Circular is entitled to manufacture pharmaceutical products and pharmaceutical starting materials
until the expiry date of such certificate.
If the certificate of eligibility for pharmacy business expires, the manufacturer shall apply for the
certificate of eligibility for pharmacy business as prescribed by law.

If the certificate of GMP compliance expires before the expiry date of the certificate of eligibility for
pharmacy business, the manufacturer shall apply for inspection of GMP compliance and maintenance
thereof according to Chapter IV of this Circular in order to keep operating as prescribed.
2. Regarding the manufacturer of pharmaceutical products and pharmaceutical starting materials that
has been issued with the indefinite term certificate for eligibility for pharmacy business that allows
manufacture of pharmaceutical products and pharmaceutical starting materials, it shall, upon the expiry
date of the certificate of GMP compliance, apply for inspection of GMP compliance and follow relevant
procedures as prescribed by law.
3. Regarding applications for certificate of eligibility for pharmacy business or applications for periodic
inspection of GMP compliance submitted to the receiving authority before the effective date of this
Circular, the receiving authority shall keep inspecting the manufacturer according to GMP promulgated
together with the Decision No. 3886/2004/QD-BYT dated November 03, 2004 of the Minister of Health
or regulations of this Circular if the manufacturer so requests.
4. If an herbal material trading establishment that processes herbal materials has had its GMP
compliance inspected and published by the Traditional Medicine Administration of Vietnam on the web
portal as prescribed in the Circular No. 03/2016/TT-BYT dated January 21, 2016 of the Minister of Health
shall keep operating until December 31, 2020. By January 01, 2021, every establishment manufacturing
and processing herbal materials and prepared traditional pharmaceutical materials shall submit an
application for the certificate of eligibility for pharmacy business that allows processing of herbal
materials and manufacture of and prepared traditional pharmaceutical materials as prescribed in Article 5
of this Circular and comply with manufacturing conditions prescribed in Articles 13, 14, 15, 16, 17, 18, 19
and 20 of the Circular No. 03/2016/TT-BYT dated January 21, 2016 of the Minister of Health.
Documentation and procedures for conducting inspections and processing inspection results are
mentioned in Articles 5, 6, 7 and 8 of this Circular.
Article 20. Responsibility for implementation
1. The Drug Administration of Vietnam shall:
a) take charge and cooperate with relevant units in organizing the dissemination of this Circular. Take
charge of compiling a list of GMP criteria relevant to each type of manufacturing according to the
principle of transparency, clarity and accuracy and request the Ministry of Health to promulgate it to form
a basis for application of GMP to manufacturers of pharmaceutical products and pharmaceutical starting
materials and inspection by pharmacy authorities.
b) within its jurisdiction, instruct Provincial Departments of Health, health authorities and manufacturers
of pharmaceutical products and pharmaceutical starting materials to implement this Circular;
c) consolidate and publish the list of manufacturers that have been granted the certificate of eligibility for
pharmacy business and/or Certificate of GMP compliance, status of such certificates, status of GMP
compliance and other information on its website according to Clause 6 Article 8 of this Circular within its
jurisdiction;
d) publish updated GMP documents on its website and the web portal of the Ministry of Health;
dd) take charge or cooperate with the Ministry Inspectorate in inspecting and auditing GMP compliance
and take actions against violations within its power.
2. The Traditional Medicine Administration of Vietnam shall:
a) within its jurisdiction, instruct Provincial Departments of Health, health authorities and manufacturers
of pharmaceutical products and pharmaceutical starting materials to implement this Circular;
b) consolidate and publish the list of manufacturers that have been granted the certificate of eligibility for
pharmacy business or Certificate of GMP compliance, status of such certificates, status of GMP
compliance and other information on its website according to Clause 6 Article 8 of this Circular within its
jurisdiction;
c) take charge or cooperate with the Ministry Inspectorate in inspecting and auditing GMP compliance
and take actions against violations within its power.
3. Provincial Departments of Health shall:
a) cooperate with relevant units in organizing the dissemination of this Circular and instruct units within
provinces to implement this Circular;
b) join the inspectorate conducting inspections of GMP compliance; within their power, supervise and
takes actions against violations against regulations on GMP compliance by manufacturers of
pharmaceutical products and pharmaceutical starting materials within provinces.
4. The National Institute of Drug Quality Control, Institute of Drug Quality Control - Ho Chi Minh City and
National Institute for Control of Vaccine and Biologicals shall join the inspectorate conducting inspections
of GMP compliance upon request.

5. Manufacturers of pharmaceutical products and pharmaceutical starting materials shall:
a) organize the implementation of this Circular;
b) ensure their compliance with GMP during their operation;
c) carry out manufacturing operations within the inspected and licensed scope according to regulations of
law.
Difficulties that arise during the implementation of this Circular should be reported to the Ministry of
Health (Drug Administration of Vietnam or Traditional Medicine Administration of Vietnam) for
consideration./.
PP. THE MINISTER
THE DEPUTY MINISTER
Truong Quoc Cuong
APPENDIX I
WHO GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICAL PRODUCTS: MAIN
PRINCIPLES
(Enclosed with the Circular No. 35/2018/TT-BYT dated November 22, 2018 of the Minister of Health)
PART I. GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICAL PRODUCTS - MAIN
PRINCIPLES
General considerations
Glossary
Quality management in the medicines industry: philosophy and essential elements
1. Pharmaceutical quality system
2. Good manufacturing practices for pharmaceutical products
3. Sanitation and hygiene
4. Qualification and validation
5. Complaints
6. Product recalls
7. Contract production, analysis and other activities
8. Self-inspection, quality audits and suppliers’ audits and approval
9. Personnel
10. Training
11. Personal hygiene
12. Premises
13. Equipment
14. Materials
15. Documentation
16. Good practices in production
17. Good practices in quality control
PART II. GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICAL STARTING MATERIALS
1. Introduction
2. Quality management
3. Personnel

4. Buildings and facilities
5. Process equipment
6. Documentation and records
7. Materials management
8. Production and in-process controls
9. Packaging and identification labeling of APIs and intermediates
10. Storage and distribution
11. Laboratory controls
12. Validation
13. Change control
14. Rejection and re-use of materials
15. Complaints and recalls
16. Contract manufacturers (including laboratories)
17. Agents, brokers, traders, distributors, repackers, and relabellers
18. Specific guidance for APIs manufactured by cell culture/fermentation
19. APIs for use in clinical trials
20. Glossary
PART III. GOOD MANUFACTURING PRACTICES FOR BIOLOGICAL PRODUCTS
1. Introduction
2. Scope
3. Terminology
4. Principles and general considerations
5. Pharmaceutical quality system and quality risk management
6. Personnel
7. Starting materials
8. Seed lots and cell banks
9. Premises and equipment
10. Containment
11. Clean rooms
12. Production
13. Campaign production
14. Labelling
15. Validation
16. Quality control
17. Documentation (batch processing records)
18. Use of animals
PART I
GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICAL PRODUCTS - MAIN PRINCIPLES
General considerations
Licensed pharmaceutical products (marketing authorization) should be manufactured only by licensed
manufacturers (holders of a manufacturing authorization) whose activities are regularly inspected by
competent national authorities. This guide to GMP shall be used as a standard to justify GMP status,
which constitutes one of the elements of the WHO Certification Scheme on the quality of pharmaceutical
products moving in international commerce, through the assessment of applications for manufacturing
authorizations and as a basis for the inspection of manufacturing facilities. It may also be used as

training material for government medicines inspectors, as well as for production, QC and QA personnel
in the industry.
The guide is applicable to operations for the manufacture of medicines in their finished dosage forms,
including large-scale processes in hospitals and the preparation of supplies for use in clinical trials.
The good practices outlined below are to be considered general guides, and they may be adapted to
meet individual needs. The equivalence of alternative approaches to QA, however, should be validated.
The guide as a whole does not cover safety aspects for the personnel engaged in manufacture, or
environmental protection: these are normally governed by national legislation. A new concept of hazard
analysis related to the risks in production and personnel safety has also been recently recommended
(WHO Technical Report Series, No. 961, Annex 7). The manufacturer should assure the safety of
workers and take the necessary measures to prevent pollution of the external environment.
International Nonproprietary Names (INN) for pharmaceutical substances designated by WHO should be
used when available, together with other designated names.
Glossary
The definitions given below apply to the terms used in this guide. They may have different meanings in
other contexts.
active pharmaceutical ingredient (API)
Any substance or mixture of substances intended to be used in the manufacture of a pharmaceutical
dosage form and that, when so used, becomes an active ingredient of that pharmaceutical dosage form.
Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis,
cure, mitigation, treatment, or prevention of disease or to affect the structure and function of the body.
airlock
An enclosed space with two or more doors, which is interposed between two or more rooms, e.g. of
differing classes of cleanliness, for the purpose of controlling the airflow between those rooms when they
need to be entered. An airlock is designed for use either by people or for goods and/or equipment.
authorized person
The person recognized by the national regulatory authority as having the responsibility for ensuring that
each batch of finished product has been manufactured, tested and approved for release in compliance
with the laws and regulations in force in that country.
batch (or lot)
A defined quantity of starting material, packaging material, or product processed in a single process or
series of processes so that it is expected to be homogeneous. It may sometimes be necessary to divide
a batch into a number of sub-batches, which are later brought together to form a final homogeneous
batch. In the case of terminal sterilization, the batch size is determined by the capacity of the autoclave.
In continuous manufacture, the batch must correspond to a defined fraction of the production,
characterized by its intended homogeneity. The batch size can be defined either as a fixed quantity or as
the amount produced in a fixed time interval.
batch number
A distinctive combination of numbers and/or letters which uniquely identifies a batch on the labels, its
batch records and corresponding certificates of analysis, etc.
batch records
All documents associated with the manufacture of a batch of bulk product or finished product. They
provide a history of each batch of product and of all circumstances pertinent to the quality of the final
product.
bulk product
Any product that has completed all processing stages up to, but not including, final packaging.
calibration
The set of operations that establish, under specified conditions, the relationship between values
indicated by an instrument or system for measuring (especially weighing), recording, and controlling, or
the values represented by a material measure, and the corresponding known values of a reference
standard. Limits for acceptance of the results of measuring should be established.
clean area
An area with defined environmental control of particulate and microbial contamination, constructed and
used in such a way as to reduce the introduction, generation, and retention of contaminants within the
area.

consignment (or delivery)
The quantity of a pharmaceutical or pharmaceuticals, made by one manufacturer and supplied at one
time in response to a particular request or order. A consignment may comprise one or more packages or
containers and may include material belonging to more than one batch.
contamination
The undesired introduction of impurities of a chemical or microbiological nature, or of foreign matter, into
or on to a starting material or intermediate during production, sampling, packaging or repackaging,
storage or transport.
critical operation
An operation in the manufacturing process that may cause variation in the quality of the pharmaceutical
product.
cross-contamination
Contamination of a starting material, intermediate product or finished product with another starting
material or product during production.
finished product
A finished dosage form that has undergone all stages of manufacture, including packaging in its final
container and labelling.
in-process control
Checks performed during production in order to monitor and, if necessary, to adjust the process to
ensure that the product conforms to its specifications. The control of the environment or equipment may
also be regarded as a part of in-process control.
intermediate product
Partly processed product that must undergo further manufacturing steps before it becomes a bulk
product.
large-volume parenterals
Sterile solutions intended for parenteral application with a volume of 100 ml or more in one container of
the finished dosage form.
manufacture
All operations of purchase of materials and products, production, quality control (QC), release, storage
and distribution of pharmaceutical products, and the related controls.
manufacturer
A company that carries out operations such as production, packaging, repackaging, labelling and
relabelling of pharmaceuticals.
marketing authorization (product licence, registration certificate)
A legal document issued by the competent medicines regulatory authority that establishes the detailed
composition and formulation of the product and the pharmacopoeial or other recognized specifications of
its ingredients and of the final product itself, and includes details of packaging, labelling and shelf-life.
master formula
A document or set of documents specifying the starting materials with their quantities and the packaging
materials, together with a description of the procedures and precautions required to produce a specified
quantity of a finished product as well as the processing instructions, including the in-process controls.
master record
A document or set of documents that serve as a basis for the batch documentation (blank batch record).
packaging
All operations, including filling and labelling, that a bulk product has to undergo in order to become a
finished product. Filling of a sterile product under aseptic conditions or a product intended to be
terminally sterilized, would not normally be regarded as part of packaging.
packaging material
Any material, including printed material, employed in the packaging of a pharmaceutical, but excluding
any outer packaging used for transportation or shipment. Packaging materials are referred to as primary
or secondary according to whether or not they are intended to be in direct contact with the product.
pharmaceutical product

Any material or product intended for human or veterinary use presented in its finished dosage form, or as
a starting material for use in such a dosage form, that is subject to control by pharmaceutical legislation
in the exporting state and/or the importing state.
production
All operations involved in the preparation of a pharmaceutical product, from receipt of materials, through
processing, packaging and repackaging, labelling and relabelling, to completion of the finished product.
qualification
Action of proving that any premises, systems and items of equipment work correctly and actually lead to
the expected results. The meaning of the word “validation” is sometimes extended to incorporate the
concept of qualification.
quality assurance
See Part 1 (6).
quality unit(s)
An organizational unit independent of production which fulfils both quality assurance (QA) and quality
control (QC) responsibilities. This can be in the form of separate QA and QC units or a single individual
or group, depending upon the size and structure of the organization.
quarantine
The status of starting or packaging materials, intermediates, or bulk or finished products isolated
physically or by other effective means while a decision is awaited on their release, rejection or
reprocessing.
reconciliation
A comparison between the theoretical quantity and the actual quantity.
recovery
The introduction of all or part of previous batches (or of redistilled solvents and similar products) of the
required quality into another batch at a defined stage of manufacture. It includes the removal of
impurities from waste to obtain a pure substance or the recovery of used materials for a separate use.
reprocessing
Subjecting all or part of a batch or lot of an in-process medicine, bulk process intermediate (final
biological bulk intermediate) or bulk product of a single batch or lot to a previous step in the validated
manufacturing process due to failure to meet predetermined specifications. Reprocessing procedures are
foreseen as occasionally necessary for biological medicines and, in such cases, are validated and pre-
approved as part of the marketing authorization.
reworking
Subjecting all or part of a batch or lot of an in-process medicine, bulk process intermediate (final
biological bulk intermediate) or bulk product of a single batch or lot to a previous step in the validated
manufacturing process due to failure to meet predetermined specifications. Reworking is an unexpected
occurrence and is not pre-approved as part of the marketing authorization.
self-contained area
Premises which provide complete and total separation of all aspects of an operation, including personnel
and equipment movement, with well established procedures, controls and monitoring. This includes
physical barriers as well as separate air-handling systems, but does not necessarily imply two distinct
and separate buildings.
specification
A list of detailed requirements with which the products or materials used or obtained during manufacture
have to conform. They serve as a basis for quality evaluation.
standard operating procedure (SOP)
An authorized written procedure giving instructions for performing operations not necessarily specific to a
given product or material (e.g. equipment operation, maintenance and cleaning; validation; cleaning of
premises and environmental control; sampling and inspection). Certain SOPs may be used to
supplement product-specific master and batch production documentation.
starting material
Any substance of a defined quality used in the production of a pharmaceutical product, but excluding
packaging materials.

validation
Action of proving, in accordance with the principles of GMP, that any procedure, process, equipment,
material, activity or system actually leads to the expected results.
Quality management in the medicines industry: philosophy and essential elements
In the medicines industry at large, quality management is usually defined as the aspect of the
management function that determines and implements the “quality policy”, i.e. the overall intention and
direction of an organization regarding quality, as formally expressed and authorized by top management.
The basic elements of quality management are:
- an appropriate infrastructure or “quality system”, encompassing the organizational structure,
procedures, processes and resources;
- systematic actions necessary to ensure adequate confidence that a product (or service) will satisfy
given requirements for quality.
The totality of these actions is termed “QA”. Within an organization, QA serves as a management tool. In
contractual situations, QA also serves to generate confidence in the supplier. The concepts of QA, GMP,
QC and quality risk management (QRM) are interrelated aspects of quality management and should be
the responsibility of all personnel. They are described here in order to emphasize their relationship and
their fundamental importance to the production and control of pharmaceutical products.
1. Pharmaceutical quality system
1.1. Principle: The manufacturer must assume responsibility for the quality of the pharmaceutical
products to ensure that they are fit for their intended use, comply with the requirements of the marketing
authorization and do not place patients at risk due to inadequate safety, quality or efficacy. The
attainment of this quality objective is the responsibility of senior management and requires the
participation and commitment of staff in many different departments and at all levels within the company,
the company’s suppliers and the distributors. To achieve this quality objective reliably there must be a
comprehensively designed and correctly implemented pharmaceutical quality system (PQS)
incorporating GMP and QRM.
1.2. Senior management has the ultimate responsibility to ensure an effective PQS is in place, is
adequately resourced, and that roles, responsibilities, and authorities are defined, communicated and
implemented throughout the organization. Senior management’s leadership and active participation in
the PQS is essential. This leadership should ensure the support and commitment of staff at all levels and
sites within the organization to the PQS.
1.3. Quality management is a wide-ranging concept covering all matters that individually or collectively
influence the quality of a product. It is the totality of the arrangements made with the object of ensuring
that pharmaceutical products are of the quality required for their intended use. Quality management,
therefore, incorporates GMP and other factors, including those outside the scope of this guide, such as
product design and development.
1.4. GMP applies to the life-cycle stages from the manufacture of investigational medicinal products,
technology transfer, and commercial manufacturing, through to product discontinuation. The PQS can
extend to the pharmaceutical development life-cycle stage and should facilitate innovation and continual
improvement and strengthen the link between pharmaceutical development and manufacturing activities.
All parts of the PQS should be adequately resourced and maintained, including being provided with
sufficient competent personnel, suitable premises, equipment and facilities.
1.5. The PQS appropriate to the manufacture of pharmaceutical products should ensure that:
a) product realization is achieved by designing, qualifying, planning, implementing, maintaining and
continuously improving a system that allows the consistent delivery of products with appropriate quality
attributes;
b) product and process knowledge is managed throughout all lifecycle stages;
c) pharmaceutical products are designed and developed in a way that takes account of the requirements
of GMP and other associated codes such as those of good laboratory practice (GLP) and good clinical
practice (GCP);
d) production and control operations are clearly specified in a written form and GMP requirements are
adopted;
e) managerial responsibilities are clearly specified in job descriptions;
f) arrangements are made for the manufacture, supply and use of the correct starting and packaging
materials, the selection and monitoring of suppliers and for verifying that each delivery is the correct
material from the approved supply chain;
g) all necessary controls on starting materials, intermediate products, and bulk products and other in-

process controls, calibrations and validations are carried out;
h) the finished product is correctly processed and checked, according to the defined procedures;
i) pharmaceutical products are not sold or supplied before the authorized persons (see also sections 9.11
and 9.12) have certified that each production batch has been produced and controlled in accordance with
the requirements of the marketing authorization and any other regulations relevant to the production,
control and release of pharmaceutical products;
j) processes are in place to assure the management of outsourced activities;
k) satisfactory arrangements exist to ensure, as far as possible, that the pharmaceutical products are
stored, distributed and subsequently handled so that quality is maintained throughout their shelf-life;
l) there is a procedure for self-inspection and/or quality audit that regularly appraises the effectiveness
and applicability of the PQS;
m) product and processes are monitored and the results taken into account in batch release, in the
investigation of deviations and, with a view to taking preventive action to avoid potential deviations
occurring in the future;
n) arrangements are in place for the prospective evaluation and approval of planned changes and their
approval prior to implementation taking into account regulatory notification and approval where required.
After implementation of any change, an evaluation is undertaken to confirm that the quality objectives
were achieved and that there was no unintended adverse impact on product quality.
o) regular reviews of the quality of pharmaceutical products are conducted with the objective of verifying
the consistency of the process and identifying where there is a need for improvement;
p) a state of control is established and maintained by developing and using effective monitoring and
control systems for process performance and product quality;
q) continual improvement is facilitated through the implementation of quality improvements appropriate to
the current level of process and product knowledge;
r) there is a system for QRM;
s) deviations, suspected product defects and other problems are reported, investigated and recorded. An
appropriate level of root cause analysis is applied during such investigations. The most likely root
cause(s) should be identified and appropriate corrective actions and/or preventive actions (CAPAs)
should be identified and taken. The effectiveness of CAPAs should be monitored.
1.6. There should be periodic management reviews, with the involvement of senior management, of the
operation of the PQS to identify opportunities for continual improvement of products, processes and the
system itself. Unless otherwise justified, such reviews should be conducted at least annually
1.7. The PQS should be defined and documented. A quality manual or equivalent documentation should
be established and should contain a description of the quality management system including
management responsibilities.
Quality risk management
1.8. QRM is a systematic process for the assessment, control, communication and review of risks to the
quality of the medicinal product. It can be applied both proactively and retrospectively.
1.9. QRM should ensure that:
- the evaluation of the risk to quality is based on scientific knowledge, experience with the process and
ultimately links to the protection of the patient;
- the level of effort, formality and documentation of the QRM process is commensurate with the level of
risk.
Product quality review
1.10. Regular, periodic or rolling quality reviews of all pharmaceutical products, including export-only
products, should be conducted with the objective of verifying the consistency of the existing process and
the appropriateness of current specifications for both starting materials and finished product, to highlight
any trends and to identify product and process improvements. Such reviews should normally be
conducted and documented annually, taking into account previous reviews, and should include at least:
a) review of starting materials and packaging materials used for the product, especially those from new
sources and in particular the review of supply chain traceability of active substances;
b) a review of critical in-process controls, and finished product results;
c) a review of all batches that failed to meet established specification(s) and their investigation;
d) a review of all significant deviations or non-conformances, the related investigations and the

effectiveness of resultant CAPAs taken;
e) a review of all changes made to the processes or analytical methods;
f) a review of dossier variations submitted, granted or refused;
g) a review of the results of the stability monitoring programme and any adverse trends;
h) a review of all quality-related returns, complaints and recalls and the investigations performed at the
time;
i) a review of adequacy of any other previous corrective actions on product processes or equipment;
j) post-marketing commitments for new dossiers and variations to the dossiers;
k) the qualification status of relevant equipment and utilities, e.g. heating, ventilation and air-conditioning
(HVAC), water or compressed gases and a review of the results of monitoring the output of such
equipment and utilities;
l) a review of technical agreements to ensure that they are up to date.
The manufacturer and, where different, marketing authorization holder, should evaluate the results of the
review and an assessment should be made as to whether CAPA or any revalidation should be
undertaken, under the PQS. CAPAs should be completed in a timely and effective manner, according to
documented procedures. There should be procedures for the ongoing management and review of these
actions, and the effectiveness of these procedures should be verified during self-inspection. Quality
reviews may be grouped by product type, e.g. solid dosage forms, liquid dosage forms, or sterile
products, where scientifically justified. Where the marketing authorization holder is not the manufacturer,
there should be a technical agreement in place between the various parties that defines their respective
responsibilities in producing the quality review. The authorized person responsible for final batch
certification, together with the marketing authorization holder, should ensure that the quality review is
performed in a timely manner and is accurate.
2. Good manufacturing practices for pharmaceutical products
2.1 GMP is that part of quality management which ensures that products are consistently produced and
controlled according to the quality standards appropriate to their intended use and as required by the
marketing authorization, clinical trial authorization or product specification. GMP is concerned with both
production and QC. GMP is concerned with both production and QC. GMP is aimed primarily at
managing and minimizing the risks inherent in pharmaceutical manufacture to ensure the quality, safety
and efficacy of products: Under GMP:
a) all manufacturing processes are clearly defined, systematically reviewed for associated risks in the
light of scientific knowledge and experience, and shown to be capable of consistently manufacturing
pharmaceutical products of the required quality that comply with their specifications;
b) qualification and validation are performed;
c) all necessary resources are provided, including:
(i) sufficient and appropriately qualified and trained personnel;
(ii) adequate premises and space;
(iii) suitable equipment and services;
(iv) appropriate materials, containers and labels;
(v) approved procedures and instructions;
(vi) suitable storage and transport; and
(vii) adequate personnel, laboratories and equipment for in-process controls.
d) instructions and procedures are written in clear and unambiguous language, specifically applicable to
the facilities provided;
e) procedures are carried out correctly and personnel are trained to do so;
f) records are made (manually and/or by recording instruments) during manufacture to show that all the
steps required by the defined procedures and instructions have in fact been taken and that the quantity
and quality of the product are as expected. Any significant deviations are fully recorded and investigated
with the objective of determining the root cause and appropriate corrective and preventive action is
implemented;
g) records covering manufacture and distribution, which enable the complete history of a batch to be
traced, are retained in a comprehensible and accessible form;
h) the proper storage and distribution of the products minimizes any risk to their quality and takes
account of good distribution practices (GDP);

i) a system is available to recall any batch of product from sale or supply;
j) complaints about marketed products are examined, the causes of quality defects investigated and
appropriate measures taken in respect of the defective products to prevent recurrence.
3. Sanitation and hygiene
3.1. A high level of sanitation and hygiene should be practised in every aspect of the manufacture of
medicines. The scope of sanitation and hygiene covers personnel, premises, equipment and apparatus,
production materials and containers, products for cleaning and disinfection, and anything that could
become a source of contamination to the product. Potential sources of contamination should be
eliminated through an integrated comprehensive programme of sanitation and hygiene. (For Personal
hygiene see section 11, and for sanitation see section 12, “Premises”.)
4. Qualification and validation
4.1. In accordance with GMP, each pharmaceutical company should identify what qualification and
validation work is required to prove that the critical aspects of their particular operation are controlled.
4.2. The key elements of a qualification and validation programme of a company should be clearly
defined and documented in a validation master plan.
4.3. Qualification and validation should establish and provide documentary evidence that:
a) the premises, supporting utilities, equipment and processes have been designed in accordance with
the requirements for GMP (design qualification or DQ);
b) the premises, supporting utilities and equipment have been built and installed in compliance with their
design specifications (installation qualification or IQ);
c) the premises, supporting utilities and equipment operate in accordance with their design specifications
(operational qualification or OQ);
d) a specific process will consistently produce a product meeting its predetermined specifications and
quality attributes (process validation or PV, also called performance qualification or PQ).
4.4. Any aspect of operation, including significant changes to the premises, facilities, equipment or
processes, which may affect the quality of the product, directly or indirectly, should be qualified and
validated.
4.5. Qualification and validation should not be considered as one-off exercises. An ongoing programme
should follow their first implementation and should be based on an annual review.
4.6. The commitment to maintain continued validation status should be stated in the relevant company
documentation, such as the quality manual or validation master plan.
4.7. The responsibility for performing validation should be clearly defined.
4.8. Validation studies are an essential part of GMP and should be conducted in accordance with
predefined and approved protocols.
4.9. A written report summarizing the results recorded and the conclusions reached should be prepared
and stored.
4.10. Processes and procedures should be established on the basis of the results of the validation
performed.
4.11. Particular attention should be paid to the validation of analytical test methods, automated systems
and cleaning procedures.
5. Complaints
5.1. Principle. All complaints and other information concerning potentially defective products should be
carefully reviewed according to written procedures and the corrective action should be taken.
5.2. A person responsible for handling the complaints and deciding the measures to be taken should be
designated, together with sufficient supporting staff to assist him or her. If this person is different from the
authorized person, the latter should be made aware of any complaint, investigation or recall.
5.3. There should be written procedures describing the action to be taken, including the need to consider
a recall, in the case of a complaint concerning a possible product defect.
5.4. Special attention should be given to establishing that the product that gave rise to a complaint was
defective.
5.5. Any complaint concerning a product defect should be recorded with all the original details and
thoroughly investigated. The person responsible for QC should normally be involved in the review of
such investigations.
5.6. If a product defect is discovered or suspected in a batch, consideration should be given to whether

other batches should be checked in order to determine whether they are also affected. In particular, other
batches that may contain reprocessed product from the defective batch should be investigated.
5.7. Where necessary, appropriate follow-up action, possibly including product recall, should be taken
after investigation and evaluation of the complaint.
5.8. All decisions made and measures taken as a result of a complaint should be recorded and
referenced to the corresponding batch records.
5.9. Complaints records should be regularly reviewed for any indication of specific or recurring problems
that require attention and might justify the recall of marketed products.
5.10. The competent authorities should be informed if a manufacturer is considering action following
possibly faulty manufacture, product deterioration, a suspect product or any other serious quality
problems with a product.
6. Product recalls
6.1. Principle. There should be a system to recall from the market, promptly and effectively, products
known or suspected to be defective.
6.2. The authorized person should be responsible for the execution and coordination of recalls. He or she
should have sufficient staff to handle all aspects of the recalls with the appropriate degree of urgency.
6.3. There should be established written procedures, which are regularly reviewed and updated, for the
organization of any recall activity. Recall operations should be capable of being initiated promptly down
to the required level in the distribution chain.
6.4. An instruction should be included in the written procedures to store recalled products in a secure
segregated area while their fate is decided.
6.5. All competent authorities of all countries to which a given product has been distributed should be
promptly informed of any intention to recall the product because it is, or is suspected of being, defective.
6.6. The distribution records should be readily available to the authorized person, and they should
contain sufficient information on wholesalers and directly supplied customers (including, for exported
products, those who have received samples for clinical tests and medical samples) to permit an effective
recall.
6.7. The progress of the recall process should be monitored and recorded. Records should include the
disposition of the product. A final report should be issued, including a reconciliation between the
delivered and recovered quantities of the products.
6.8. The effectiveness of the arrangements for recalls should be tested and evaluated from time to time.
7. Contract production, analysis and other activities
7.1. Principle. Contract production, analysis and any other activity covered by GMP must be correctly
defined, agreed and controlled in order to avoid misunderstandings that could result in a product, or work
or analysis, of unsatisfactory quality.
General
7.2. All arrangements for contract production and analysis, including technology transfer and any
proposed changes in technical or other arrangements, should be in accordance with the marketing
authorization for the product concerned.
7.3. The contract should permit the contract giver to audit the facilities and activities of the contract
acceptor or mutually agreed subcontractors.
7.4. In the case of contract analysis, the final approval for release must be given by the authorized
person in accordance with GMP and the marketing authorization as specified in the contract.
The contract giver
7.5. The PQS of the contract giver should include the control and review of any outsourced activities. The
contract giver is responsible for assessing the legality, suitability and competence of the contract
acceptor to successfully carry out the work or tests required, for approval for contract activities, and for
ensuring by means of the contract that the principles of GMP incorporating QRM principles are followed.
7.6. The contract giver should provide the contract acceptor with all the information necessary to carry
out the contracted operations correctly in accordance with the marketing authorization and any other
legal requirements. The contract giver should ensure that the contract acceptor is fully aware of any
hazards associated with the product, work or tests that might pose a risk to premises, equipment,
personnel, other materials or other products.
7.7. The contract giver should review and assess the records and results related to the outsourced
activities. The contract giver should ensure that all products and materials delivered by the contract

acceptor have been processed in accordance with GMP and the marketing authorization; comply with
their specifications and that the product has been released by the authorized person in accordance with
GMP and the marketing authorization.
7.8. The contract giver should monitor and review the performance of the contract acceptor including the
implementation of any needed improvements and their effectiveness.
7.9. The contract giver is responsible for ensuring that the contract acceptor understands that his or her
activities may be subject to inspection by competent authorities.
The contract acceptor
7.10. The contract acceptor must have adequate premises, equipment, knowledge, experience and
competent personnel to satisfactorily carry out the work ordered by the contract giver. Contract
manufacture may be undertaken only by a manufacturer who holds a valid manufacturing authorization.
7.11. The contract acceptor should not pass to a third party any of the work entrusted to him or her under
the contract without the contract giver’s prior evaluation and approval of the arrangements.
Arrangements made between the contract acceptor and any third party should ensure that information
and knowledge, including that from assessments of the suitability of the third party, are made available in
the same way as between the original contract giver and contract acceptor.
7.12. The contract acceptor should refrain from any activity (including unauthorized changes outside the
terms of the contract) that may adversely affect the quality of the product manufactured and/or analysed
for the contract giver.
The contract
7.13. There must be a written contract between the contract giver and the contract acceptor which clearly
establishes the responsibilities of each party, covering the outsourced activities, the products or
operations to which they are related, communication processes relating to the outsourced activities and
any technical arrangements made in connection with it.
7.14. The contract must clearly state the way in which the authorized person, in releasing each batch of
product for sale or issuing the certificate of analysis, exercises his or her full responsibility and ensures
that each batch has been manufactured in, and checked for, compliance with the requirements of the
marketing authorization.
7.15. Technical aspects of the contract should be drawn up by competent persons with suitable
knowledge of pharmaceutical technology, analysis and GMP.
7.16. All arrangements for production and analysis must be in accordance with the marketing
authorization and agreed by both parties.
7.17. The contract should clearly describe who is responsible for contracted activities, e.g. knowledge
management, technology transfer, supply chain, subcontracting, testing and releasing materials and
undertaking production and QC, including in-process controls, and who has responsibility for sampling
and analysis. In the case of contract analysis, the contract should state whether or not the contract
acceptor should take samples at the premises of the manufacturer.
7.18. Manufacturing, analytical and distribution records, and reference samples, should be kept by, or be
available to, the contract giver. Any records relevant to assessing the quality of a product in the event of
complaints or a suspected defect, or to investigating in the case of a suspected falsified product or
laboratory fraud, must be accessible and specified in the procedures of the contract giver.
7.19. The contract should describe the handling of starting materials, intermediate, bulk and finished
products, if they are rejected. It should also describe the procedure to be followed if the contract analysis
shows that the tested product must be rejected.
8. Self-inspection, quality audits and suppliers’ audits and approval
8.1. Principle. The purpose of self-inspection is to evaluate the manufacturer’s compliance with GMP in
all aspects of production and QC. The selfinspection programme should be designed to detect any
shortcomings in the implementation of GMP and to recommend the necessary corrective actions. Self-
inspections should be performed routinely, and may be, in addition, performed on special occasions, e.g.
in the case of product recalls or repeated rejections, or when an inspection by the health authorities is
announced. The team responsible for self-inspection should consist of personnel who can evaluate the
implementation of GMP objectively. All recommendations for corrective action should be implemented.
The procedure for self-inspection should be documented, and there should be an effective follow-up
programme.
Items for self-inspection
8.2. Written instructions for self-inspection should be established to provide a minimum and uniform
standard of requirements. These may include questionnaires on GMP requirements covering at least the
following items:

Circular 35/2018/TT-BYT: GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICAL PRODUCTS AND PHARMACEUTICAL STARTING MATERIALS

Circular 35/2018/TT-BYT: GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICAL PRODUCTS AND PHARMACEUTICAL STARTING MATERIALS

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Circular 35/2018/TT-BYT: GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICAL PRODUCTS AND PHARMACEUTICAL STARTING MATERIALS