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GMP Information Handbook: General Knowledge

2022-03-29

Original

Marya

GMP General Knowledge

 1. General knowledge  .......................................................................................................................................................................

 

 

(1) Clean rooms and utilities

Sinks and drains installed in the clean room (area) shall not contaminate the drug.

There should be measures to prevent cross-contamination when personnel and materials are transferred into or out of clean rooms (areas) with different air cleanliness levels.

According to the requirements of the pharmaceutical manufacturing process, the air cleanliness level of the weighing and preparation room in the clean room (area) should be in compliance with the manufacturing requirements, and there should be facilities for collecting dust etc. to prevent cross-contamination.

Production areas are not allowed to store non-production items and personal items. Production waste should be removed in a timely manner.

The setting of changing rooms, bathrooms and toilets shall not adversely affect the clean room (area).

Aseptic work clothes used in different air cleanliness levels should be washed and sorted separately, disinfected or sterilized when necessary. And the additional particulate matter should not be brought in when washing and sterilizing the aseptic work clothes, and the cleaning cycle of work clothes should be formulated.

In a clean room (area) where a large amount of dust is generated , when the cross-contamination cannot be avoided after the dust capture treatment, the air purification shall not use the return air.

In areas with the same level of air cleanliness, the operating room with a large amount of dust should maintain a relatively negative pressure.

The cleanliness level of the exposure process in the final treatment of packaging materials directly in contact with drugs should be the same as that of the drug production environment.

 

(2) Process water

The extraction process water of Chinese herbal medicine is drinking water. Water for injection is used for the preparation of injections. The water used for the preparation of oral liquid and solid dosage form is purified water.

The preparation, storage and distribution of purified water shall prevent the growth and contamination of microorganisms. The materials used for storage tanks and conveying pipelines should be non-toxic and corrosion-resistant. Design and installation of pipelines should avoid dead ends and blind pipes. Cleaning and sterilization cycles should be specified for storage tanks and pipes.

The conductivity of purified water should be below 2μΩ.cm. If it exceeds this standard, it means that the ion exchange capacity has declined and needs to be regenerated or replaced.

Select process water according to the product process specification. In addition to the daily inspection, the process water should be inspected regularly, and the inspection cycle can be determined by the verification results.

The water used for the final washing of the equipment, utensils and packaging materials for non-sterile preparations that come into direct contact with drugs should meet the purified water quality standards. The water for the last washing of the equipment and utensils that are in direct contact with the drug for sterile preparations should be water for injection.

 

(3) Processing and storage of Chinese medicinal materials

A selection workbench should be set up in the workshop for purification of medicinal materials, and the surface of the workbench should be flat and not prone to fall off.

The workshops for steaming, frying, roasting, and calcining in the processing of Chinese medicinal materials should be adapted to their production scale, and have good ventilation, dust removal, smoke removal, cooling and other facilities.

The plants for the extraction and concentration of Chinese herbal medicines and Chinese herbal decoction pieces should be adapted to their production scale, and have good ventilation and facilities to prevent pollution and cross-contamination.

Tools and containers that are in direct contact with medicines should be clean, easy to clean and disinfect, and not easy to fall off.

Chinese herbal medicines must be selected, sorted, cut, processed, washed and other processing according to regulations before use. If you need to infiltrate, you should make the medicine permeable.

The sterilization methods of Chinese herbal medicines, intermediate products and finished products should be verified on the principle of not changing the quality.

The water used for cleaning and infiltration of Chinese herbal medicines and Chinese herbal decoction pieces should meet the drinking water standards.

Materials, intermediate products and finished products that have special requirements for temperature, humidity or other conditions should be stored in accordance with the specified conditions. Solid and liquid raw materials should be stored separately; volatile materials should be careful not to contaminate other materials; processed and processed clean medicinal materials should be packaged in clean containers and strictly separated from unprocessed and processed medicinal materials.

 

(4) GMP implementation and quality management

The implementation of GMP should take hardware as the basic condition, software as the foundation, and personnel quality as the guarantee. As long as the GMP is strictly followed, the occurrence of quality accidents can be prevented and drugs that meet the quality standards can always be produced.

GMP gives a new concept to the quality of medicines: medicines must not only meet quality standards, but also the entire production process must comply with GMP. Only medicines that meet both conditions can be released and sold as qualified medicines.

The product quality analysis meeting is divided into three levels, which are the three-level product quality analysis meeting of factory level, workshop and team. The factory-level quality analysis meeting is presided over by the general manager or deputy general manager and is generally held every three months; the workshop quality analysis meeting is presided over by the workshop director and is generally held once a month; the team quality analysis meeting is presided over by the team leader and is generally held once a week .

Medicine is a special commodity, and its quality requirements are also special. In general, it requires safety, effectiveness, stability and uniformity.

Enterprises should establish a monitoring and reporting system for adverse drug reactions, and designate specialized agencies or personnel to be responsible for management.

 

(5) GMP Definitions:

1. Drugs: refers to substances that are used to prevent, treat and diagnose human diseases, purposefully regulate human physiological functions, and specify indications or functional indications, usage and dosage, including Chinese herbal medicines, Chinese herbal decoction pieces, Chinese patent medicines, chemical APIs and their preparations, antibiotics, biochemical drugs, radiopharmaceuticals, serum, vaccines, blood products and diagnostic drugs, etc.

2. GMP: GMP is a set of systematic and scientific management practices that ensure the production of high-quality medicines with scientific, reasonable and standardized conditions and methods in the entire process of drug production. It is the basic criterion for drug production and quality management.

3. Materials: raw materials, auxiliary materials, packaging materials, etc. for the production of medicines.

4. Batch number: a group of numbers or letters plus numbers used to identify the "batch". Used to trace and review the production history of a batch of medicines (20010808, indicating the 8th batch of medicines produced in August 2001.)

5. To be inspected: the state where the material is on hold before entering the factory or before the finished product leaves the factory, waiting for the inspection result.

6. Batch production records: all production records of a batch of products to be packaged or finished products. Batch production records provide the production history and quality-related information for the batch.

7. Material balance: The comparison between the theoretical output or theoretical consumption of a product or material and the actual output or consumption, with due consideration of allowable normal deviations.

8. Standard operating procedures: General documents or management methods approved to indicate operations.

9. Production process regulations: specify the quantity of starting materials and packaging materials required to produce a certain number of finished products, as well as one or a set of documents such as process, processing instructions, precautions, including control in the production process.

10. Process water: water used in the pharmaceutical production process, including drinking water, purified water, and water for injection.

11. Purified water: water for medicinal use obtained by distillation, ion exchange, reverse osmosis or other suitable methods for drinking water, without any additives.

12. Water for injection: water obtained by distillation of purified water.

13. Drinking water: water that meets drinking standards and can be consumed by people.

14. Clean room (area): a room where the concentration of airborne particles is controlled. It should be constructed and used to reduce indoor induction and retention of particles. Other indoor parameters such as temperature, humidity, pressure, etc. are controlled as required.

15. Validation: A documented set of activities to demonstrate that any procedure, production process, equipment, material, activity or system actually achieves the intended results.

16. Batch: A certain quantity of medicines with the same nature and quality within specified limits and produced in the same production cycle.

17. Clean workshop: workshops with air cleanliness requirements in the production process.

18. Pollution: The process or state of adverse effects on the performance and function of an object or substance as a treatment object due to adhesion, mixing or generation of a certain substance is called pollution.

19. Airlock door: set at the entrance and exit of the clean room to block the outdoor or adjacent room polluted air flow and the buffer room for differential pressure control.

20. Technical interlayer: a building interlayer mainly separated by horizontal objects for installation of pipelines and other facilities.

21. Laminar flow (unidirectional flow): an air flow with equal lines, parallel streamlines along a single direction and the same wind speed on the transverse folded surface.

22. Turbulence (non-unidirectional flow): any airflow that does not meet the definition of unidirectional flow.

23. Sterile room: refers to a clean room in which the amount of suspended microorganisms in the ambient air is managed according to aseptic requirements and meets the requirements of aseptic production.

24. Air purification: The act of removing pollutants in the air through primary, medium, and high-efficiency filters to make the air clean.

25. Purification: refers to the process of removing pollutants in order to achieve the necessary cleanliness.

26. Non-sterile preparations: a certain amount of live microorganisms (bacteria) are allowed to be contained in such preparations, but the content does not exceed the provisions of hygienic standards.

27. Sterile preparation: A preparation product in which no living organisms exist.

28. Sterile: Complete absence of living organisms.

29. Sterilization: to achieve a sterile state.

30. Control point: In order to ensure that the process is in a controlled state, under a certain time and under certain conditions, the quality characteristics, key parts or weak links that need to be controlled in the product manufacturing process.

31. Validity period: Drug manufacturers or research institutions, based on the actual measurement of stability investigation, or through chemical kinetics methods to study drug stability and reaction speed, the established normal temperature storage period for the drug is the validity period.

32. Quality: The sum of characteristics that reflect the ability of an entity (a combination of products, processes, and organizations) to meet explicit and implicit needs.

33. Quality Assurance: All planned and systematic activities implemented in a quality system and demonstrated as needed in order to provide sufficient confidence that an entity can meet quality requirements.

34. Quality Control: Operational techniques and activities adopted to achieve quality requirements.

35. Quality management: All activities that determine the quality policy, objectives and responsibilities and implement all management intelligence in the quality system through such as quality planning, quality control, quality assurance and quality improvement.

36. Quality Assurance System: The organizational structure, procedures, processes and resources required to implement quality management.

37. FO value: The moist heat sterilization process gives the product the equivalent sterilization time at 121°C.

38. Clean clothes: special work clothes used in clean areas, with the characteristics of anti-static and no dust collection.

39. Static test: The facility has been built, the production equipment has been installed, and it is running in the state agreed by the owner and the supplier, but there is no production personnel, and the test is carried out in this case.

40. Dynamic test: The facility operates in a specified state, with specified personnel present, and conducts work tests under agreed conditions.

41. Documents: All the situation standards related to the production and management of drugs and the recorded results in the implementation.

42. Status signs: signs used to indicate materials, intermediate products, semi-finished products, products, containers, equipment, facilities, and production sites.

 

(6) Abbreviations and Acronyms: 

SOP

Standard Operating Procedures (Operating Standard)

POP

Process Operating Procedures

 

QOP

Quality Operating Procedure

 

EOP

Equipment Operating Procedures 

MOP

Material Operating Procedures

HOP

Hygiene Operating Procedures

CLP

cleaning protocol

SMP

Standard Management Procedures

QMP

Quality Management Procedures

DMP

Document Management Procedures

MMP

Material Management Procedures

PMP

Production Management Procedures

EMP

Equipment Management Procedures

VMP

Verification Management Procedures

OMP

Operation Management Procedures

HMP

Hygiene Management Procedures

TMP

Training Management Procedures

FMP

Facility Management Procedures

QA

Quality Assurance

QC

Quality Control (Inspection)

FO

Sterilization Guaranteed Value

HVAC

Air Purification System

 

FDA 

U.S. Drug and Food Administration

WTO

World Trade Organization

WHO

World Health Organization

 

pH

pH (measure of acidity and alkalinity)

 

CFU

Colony-Forming Unit (measure of viable bacterial or fungal cells)

ppm

parts per million(grams)

h.hr

hours

min

minutes

RH

Relative Humidity

dB

decibel

m³

cubic meter

㎡

square meter