Công văn 302/BYT-QLD của Bộ Y tế về việc triển khai thực hiện Thông tư 14/2012/TT-BYT về thực hành tốt sản xuất bao bì dược phẩm

No.

CONTENTS

1.

Quality control system

a.

A quality control system must be established, including the procedure, resources, and relevant structures.

b.

The production division and quality management division must be independent from each other.

c.

The chief of the quality assurance division may concurrently hold the position of the chief of the quality inspection division.

d.

Inspection must be maintained throughout the manufacturing process.

dd.

Internal standards of customers must be established among the divisions of the factory, including material supply, experiment, manufacture, packaging, preservation, and distribution. Adherence to such standards shall be assessed by one another to support the comprehensive quality control

2.

Personnel and training

a.

The staff of quality assurance department, quality inspection department, the workshop, and other departments (warehouses, electro mechanics, etc.) must be physically and professionally qualified.

Number of staff members:

Number of holders of bachelor’s degrees, college degrees, junior college degrees, primary degrees,

b.

Periodic health checks must be provided for the staff.

c.

Every group of staff members must have a separate work description sheet. The tasks and entitlements of the chief of the quality assurance division, the chief of the production management division, the chief of the quality inspection department, and authorized managers must be specified in writing.

d.

Training plans and training programs must be established, including external training.

dd.

The instructors must have knowledge, experience, and be trained in GMP.

e.

An examination must be carried out after every training course.

g.

Training documents must be retained in full.

3.

Workshop

a.

The workshop must be designed and built in a way that meet the requirements

b.

The restrooms must be located away from the manufacture area.

c.

The area where packages are manufactured must be isolated from the areas where other products are manufactured in a way that is compatible with other areas such as storage of raw materials, package preservation, and storage of finished products.

d.

The manufacture chambers must be arranged in conformity with one-way principles and spacious enough for placing and operating the devices.

dd.

Classes of cleanliness in manufacture chambers must be suitable for the products and the manufacture stages.

e.

Measures must be taken (such as differential pressure, ventilation, etc.) to properly maintain and control the classes of cleanliness and the manufacture conditions.

g.

The preservation areas must meet the conditions and conform to the preserved items.

h.

An overall assessment must be carried out before the workshop is put into operation. Periodic assessments must be carried out. The assessment results must be retained.

4.

Equipment

a.

Install a system of equipment that meets the requirements for manufacture and quality inspection.

b.

Assess the equipment according to its documents before use.

c.

Periodically maintain, inspect, and label the equipment.

d.

Periodically inspect and calibrate the scales, manometers, and other measurement devices to ensure the accuracy.

dd.

Use proper vehicles to transport goods and products.

5.

Hygiene

a.

Formulate a plan for cleaning the workshop, prevent contamination and cross-contamination.

b.

Introduce regulations on access to manufacture areas applicable to unauthorized persons, sick employees, or visitors.

c.

The personal protective equipment and footwear used in the factory by packaging workers and the workers in areas where classes of cleanliness are controlled must be distinguished from clothing worn outside.

d.

Establish standard operation procedures (SOPs) for personal hygiene and manufacturing equipment, use the equipment that is manufactured and assessed according to the SOPs.

dd.

Workers must dry their hands after using the restroom and before wearing personal protective equipment.

e.

Status labels must be put on manufacturing instruments or protective clothing.

g.

Manufacturing instruments and detachable parts must be cleaned and preserved in separate rooms.

h.

Only use clean water to rinse manufacturing instruments.

i.

Assess the limits on contamination of physical dust and microbiological dust of compressed air (in contact with the equipment, in the clean room, and open products).

k.

Periodically sterilize the manufacture chambers (including the air supply system).

l.

Impose regulations on collecting wastes and cleaning the common areas such as corridors, pass-boxes, etc.

6.

Materials

a.

Enumerate some primary materials and types of water used for manufacturing packages.

b.

Employ a method to assess the quality of water used for the manufacture.

c.

Establish quality standards of the materials used in the factory.

d.

Quality standards of raw materials must conform to the quality standards and purposes of the finished packages (manufactured at the facility).

dd.

Quality standards ofmaterialsand finished packagesmust conform to theVietnam’s pharmacopoeia and other common pharmacopoeias.

e.

Establish a procedure for assessing the suppliers of raw materials; assess the suppliers and retain the records.

g.

Purchased materials must be stored separately (bearing yellow labels) pending sampling, and assessed before used, and preserved in suitable conditions.

h.

Every batch of material purchased must be examined and approved by a competent person.

i.

Take appropriate measures for controlling and assessing the quality of the tests that cannot be run by the laboratory of the facility.

k.

Enumerate the tests that cannot be run by the laboratory.

l.

All testing certificates of raw materials must be retained.

m.

Specify the inks used on the primary package (level 1) used by the facility.

n.

Present documents proving the safety of such inks.

7.

Manufacture

a.

The manager of the workshop, the team leaders and workers must be sufficient in quantity, proficient, and experienced.

b.

Enumerate the employees that directly participate in the manufacture.

c.

The stages of manufacture must be located in the areas with suitable class of cleanliness and one-way principle.

d.

Raw materials may only be used when they are approved by a competent person and have green labels.

dd.

The manufacturing chamber and other devices must be cleaned and checked to be sure they are functional before the shift.

e.

Each product must follow a manufacture procedure approved by a competent person.

g.

Enumerate the assessed manufacture procedures out of the established ones.

h.

The results must be recorded in the documents of the batch.

i.

Carry out inspection during the process to ensure the manufacture procedure and GMP are adhered to.

k.

Enumerate the IPC officers and their departments.

l.

Establish SOPs describing the tasks of IPC officers and the frequency of each task.

m.

Establish SOPs for operating and cleaning manufacturing equipment.

n.

After each primary stage, the products must be stored separately pending the results or opinions of competent persons before proceeding.

o.

The release of products must be decided by a competent person after considering the documents of the batch, results of in-process inspections, testing certificates, and the relevant factors.

ρ.

The use and cleaning of primary manufacturing equipment of the line must be recorded in writing.

q.

Establish SOPs for collecting, isolating, treating refuses, and keeping records.

8.

Quality inspection

a.

Establish a laboratory to inspect the quality of raw materials, intermediary products, finished products, and assess the manufacture conditions.

b.

The chief,the team leaders andstaff members of the laboratorymust be sufficient in quantity, proficient, and experienced.

c.

Enumerate the staff of the laboratory.

d.

Thelaboratorymust meettherequirements of cleanliness and have adequate equipment to assess themanufacture conditionsand test the bacterial contamination in products.

dd.

Provide testing instruments that are able to test the quality of raw materials and products.

e.

Enumerate the existing testing instruments.

g.

The instruments must be maintained, inspected, and calibrated periodically and before use.

h.

The testing procedures must beapproved by a competent person.

i.

Enumerate the tests that cannot be run by thefacility.

k.

Enumerate some bases for certifying the conformity of preliminary material if the facility cannot run some tests.

l.

Raw materials must be sampled in a way that does not affect the test results and the representation of the samples.

m.

The quantity of samples, time and conditions of sample retention (including samples of finished products) must meet the requirements for monitoring quality and settling complaints.

n.

Study the stability and shelf life of the products manufactured by the facility.

o.

Specify the expiration dates of the products and conditions for preserving them in storage and during transportation.

9.

Assessment

a.

Make an assessment plan specifying the necessary tasks during the assessment.

b.

Establish an assessment council with suitable personnel.

c.

Enumerate the assessment contents.

d.

Give detailed description of the contents that need assessing, specifying the methods, instruments, participants, applied standards, time for reassessment, etc.

dd.

The assessment must comply with the approved plan and description.

10.

Documentation

a.

Establish SOPs for compiling, issuing, managing documents, accessing, adjusting, storing documents via computers, and other SOPs for regular tasks (personal hygiene, cleaning/operating manufacturing equipment, etc.)

b.

Documents about quality inspection must contain at least:

-The quality standards (requirements, test methods), raw materials, finished products, and semi-finished products;

-Testing documents (testers’ books, analysis sheets, testing sheets);

-Logbooks of primary analysis instruments

-Documents about inspection/calibration of analysis/testing instruments;

-Logbooks of chemicals, reagents, titans, titration solutions; sample delivery.

c.

Documents aboutmanufacturemust contain at least:

-Original manufacturing process of each product.

-Documents about the batch.

-Documents about the assessment of each manufacturing process.

-Logbooks of primary manufacturing equipment and manufacturing conditions.

d.

Make and retain other documents such as:

-Labels;

-Documents about assessment of equipment/conditions for manufacturing, testing, or preservation;

-Documents about preservation, circulation, complaint settlement, and recall;

-Documents about assessments of contracted suppliers, manufacturers, and testers;

-Personnel documents;

-Documents about occupational safety, fire safety, and environment protection;

- Documentsabout internal inspection.

11.

Contractual manufacture and testing

a.

Contractual manufacture or testing is restricted within certain stages or tests of which the contractee (the applicant for inspection of package manufacturing conditions) is not capable. Do not overuse contractual manufacture and testing.

The contractual manufacture and tests must be specified.

b.

The contract must specify both parties’ responsibilities; the contractor must not delegate their tasks to a third party without the consent of the contractee; the contractee is entitled to inspect and supervise the contractor’s compliance.

c.

The contractee must assess the capability of the contractor in terms of conformity with GMP for pharmaceutical packages to ensure product quality.

12.

Settling complaints, recalling products, handling returned products

a.

Establish procedures for receiving and processingcomplaintsabout the products, recalling products,andhandling returned products.

b.

Establish a council to handlecomplaintsand returnedproducts.

c.

Keep the documents about complaint settlement and product recall.

13.

Internal inspection

a.

Formulate a plan for periodic and unscheduled internal inspection, an internal inspection list (overall or divisional inspection); establish an internal inspection board (including quality management division and relevant divisions).

These documents must match the operation of the facility and must be periodically reviewed and updated.

b.

A report on internal inspection, assessment, classification of flaws, solutions, rectification plans, implementation of such plans; assess the accomplishment after each internal inspection.

c.

Documents about internal inspection must be retained in full and presented on request.