Material management of pharmaceutical enterprises under GMP system

Drug production is a complex system engineering, involving many links. Each link interacts and influences each other, and is closely related to the quality of drugs. Material is the source of drug production and the basis of producing products that meet quality standards.

In the last article we introduced the production management module of one of the six systems for GMP inspection. This paper will introduce the material management module from the aspects of supplier management, material acceptance, unqualified material treatment, material storage, material distribution, material use and material identification.

Purpose of material management

Establish clear management procedures for materials and products, ensure the correct reception, storage, distribution, use and delivery of materials and products, take measures to prevent contamination, cross-contamination, confusion and error, and ensure the production of qualified products.

Scope of material management

Material management refers to the purchase, storage and distribution of materials required for drug production and the management of corresponding products. Materials involved refer to raw materials, auxiliary materials, packaging materials, other auxiliary materials, intermediate products, products to be packaged and finished products.

Supplier Management

In order to do a good job of control from the source, to ensure the reliability and safety of the quality of drug production materials, we need to choose excellent suppliers.

1. Supplier approval process

Enterprises need to establish supplier evaluation, approval, withdrawal and other processes in accordance with the requirements of laws and regulations, and clarify the supplier qualification, grading standards, selection principles of suppliers at all levels, quality assessment methods, evaluation standards, approval and withdrawal procedures.

2. Critical Control points approved by suppliers

(1) Approved department: It must be approved by the quality department, and the approved supplier list shall be established and updated and checked regularly.

(2) Sample confirmation: The new supplier shall test the sample, and if necessary, conduct small batch trial production of the sample, and conduct process verification and stability inspection.

(3) Qualification documents: the documents shall be complete and meet the requirements of laws and regulations, and they shall be reviewed and updated regularly.

(4) Sign quality agreement: sign quality agreement with approved suppliers of main materials; The quality standard shall be approved by both parties before issuing the official order. Otherwise, there should be a reasonable explanation in writing.

(5) Quality audit: on-site quality audit or assessment through questionnaire, quality assessment methods and standards can be different.

(6) Use of qualified supplier materials: Materials purchased from approved suppliers can be directly used in the production of marketed products and medical research products.

3. Supplier audit

(1) The main purpose of audit: to determine the supplier's compliance with the relevant quality requirements and business requirements, to continuously provide services according to the necessary quality standards, to rectify and take preventive measures as required.

(2) Key points of audit: key materials shall be audited on site, and special reasons can be replaced by letter audit; Auditors should have relevant knowledge background and practical experience.

(3) Situations that must be audited: first audit, cause audit, follow-up inspection and re-audit.

(4) Main contents of audit: qualification certification documents, quality assurance system, personnel organization, plant facilities and equipment, production process, material management, quality control, document system, etc.

4. Supplier quality review and change

(1) Quality review

Review cycle: Periodically (such as once a year) to evaluate the quality of suppliers.

Review contents: Complaints, deviations, OOS (exceeding the standard results), unqualified rate; Audit results; Transportation, arrival of goods, after-sales service, etc.; Qualification review and update.

Review basis and application: enterprises should establish supplier quality assessment standards and corresponding CAPA (corrective and preventive measures); According to the results of supplier quality review, the supplier classification in the next year is decided.

(2) Supplier change

Type of change: changes initiated by the enterprise, changes adopted by the supplier.

The change of supplier shall go through the change evaluation and issue the change report, which shall be reviewed and approved by the quality authorized person.

Acceptance of materials

1. Basic flow of material receiving

In order to ensure the quality and quantity of materials, strict inspection and acceptance must be carried out when the materials are stored.

Material reception includes the whole process from storage to storage, sampling, inspection and release of materials.

2. Main contents of material reception

Fill in the material ledger: including material name, material number, enterprise internal number, specification, manufacturer batch number, quantity, number of pieces, manufacturer, consignee and date, storage location, etc.

Put the goods in the designated space in the storage area, and fill in the space card according to the variety and batch number. The storage location of the materials should be consistent with the description of the space card.

Inspection materials: Before mixing with stored materials, they should be inspected and inspected according to regulations, and can be released after qualified; More than one lot at a time should be sampled, inspected and released for use one by one. A lot of receiving, each time sampling, inspection and release use.

Manage goods: account, card, material three consistent. Otherwise notify the responsible department and initiate an investigation. Based on the results of the investigation, decide whether the material is finally accepted or not. If not, the material will be destroyed or returned to the supplier based on the evaluation results.

Fill in the material identification: quality status of the material (to be inspected, qualified and unqualified), date of receipt, batch number, material name, material number, expiration date and reinspection time, special storage and processing conditions, safety level and protection measures.

Handling of nonconforming materials

When nonconforming materials are found, they shall be managed according to the following requirements:

(1) Immediately isolate the nonconforming product in the specified storage area, mark it with red and hang the nonconforming plate.

(2) The product name, specification, batch number and production date must be marked on the packaging unit of each nonconforming product.

(3) Fill in the nonconforming product treatment report form, including: product name, specification, quantity, date, source, nonconforming items and reasons, inspection data and relevant personnel responsible for identifying the reasons, etc., and send it to all relevant departments.

(4) The technical department shall, together with the quality control department, find out the reasons and put forward the handling opinions in writing. The department in charge of handling shall deal with the problems within a time limit. The execution shall be carried out after the approval of the technical person in charge.

(5) All unqualified products removed from normal production must be marked with product name, specification and batch number, and properly isolated and stored. According to the specific circumstances according to the regulations.

Storage of materials

1. Basic requirements for material storage

The storage conditions of materials are determined by risk assessment based on physical and chemical properties of materials, intended purpose of use and interaction between materials. Proper storage conditions and correct storage management can ensure the correct use and distribution of materials and ensure the safety and effectiveness of products.

2. Storage conditions

(1) The storage area shall be kept clean and dry, with lighting and ventilation facilities.

(2) There are temperature and humidity measuring instruments, according to the requirements of regular monitoring and record.

(3) There should be a sampling room, and the air cleanliness level of the sampling room environment should be consistent with the production requirements.

(4) According to the physical and chemical properties of materials, the necessary facilities or warehouse should be configured. For example, materials that are easy to oxidize and deteriorate should be shielded from light and sealed; Relative humidity, ventilation or dehumidification should be controlled for materials susceptible to deliquing and mildew.

(5) The warehouse should have strict fire prevention, anti-theft and other safety measures.

3. Storage principles

(1) Warehouse storage according to different material categories and varieties.

(2) According to different quality states of materials, store them in partitions, to be inspected, qualified, unqualified, to be treated, etc.

(3) Distinguish the storage space according to the material entry number or batch number.

• The quantiles are clear and the spacing meets the requirements

• Outward facing logo for easy identification

• A space card in front of each space

4. Storage requirements

(1) According to the types and characteristics of materials, materials should be selected and stored in different warehouses as far as possible; Periodic reinspection system shall be stipulated during the material storage period.

(2) Intermediate products can be stored at the production site, but should be consistent with the nature of the material.

(3) Establish the material inventory list of the warehouse according to the principle of risk assessment.

(4) The warehouse shall have a plane diagram indicating the warehouse area, indicating the building number, storage category, etc.

5. Layout requirements

(1) The warehouse manager rationally arranges the warehouse space according to the variety, specification and batch number of materials.

(2) Only materials of the same variety, the same specification, the same batch number and the same state can be stored in one space. The materials should be placed safely, neatly and firmly.

(3) Different materials in the same warehouse should be clearly marked, and account cards should be consistent.

Distribution of Materials

1. Material Distribution principles

Follow the principles of first-in, first-out, first-in, first-in, first-in, first-in, first-in, whole-package delivery.

2. Precautions for distributing materials

(1) Establish production material distribution management procedures;

(2) Materials shall be issued and used in batches;

(3) Only materials that have been released and marked with qualified status can be issued;

(4) According to production instructions or materials extraction single-core pair release materials;

(5) When distributing production materials, the outer packaging of the materials should be checked.

3. Material Provisioning process

Use of materials

(1) Before use, it is necessary to check the name, specification, batch number, quantity and qualification certificate of the materials, and have someone review, fill in the record, check and the signature of the recheck person.

(2) For continuously used materials, they should be sealed in time after each opening, and indicate the date of use, the quantity of use, the remaining quantity, the user and the signature of the rechecker on the material label; The remaining materials are sealed, marked, returned and recorded after review.

(3) After the production of each process, the materials used in batch products should be finished, and the completion of material balance or consumption quota index should be investigated.

(4) In case of deviation in material settlement, "Deviation Treatment SMP" shall be executed.

(5) The batch number and damage label shall not be returned to the warehouse. After counting, QA shall conduct supervision and destroy, and make a good record.

(6) Special management requirements for poison, hemp, fine and other materials should be designated to supervise the use and record.

(7) When materials are stored in the workshop, no matter what kind of container is placed, there should always be a status mark that meets the requirements.

(8) Surplus materials in the workshop should be sealed and stored in time.

Material Identification

1. Purpose: The purpose of material labeling is to prevent confusion and error, so as to avoid contamination and cross-contamination of materials and products.

2. Label the material status

Type: Generally divided into four kinds, to be checked mark, qualified mark, unqualified mark, other mark.

Label to be inspected: Usually a yellow label indicating that the indicated materials and products are in the state of being inspected and cannot be used for production, delivery and sale of formal products.

Qualified label: Usually a green label indicates that the indicated materials and products are qualified materials or products and can be used in the production, use, delivery and sale of formal products.

Nonconformity mark: Usually a red mark, which indicates that the indicated materials and products are nonconforming products and shall not be used for production, shipping and sales of formal products; Need to be destroyed or reworked, reprocessed.

3. Use and control of material status labels

The enterprise shall establish a written management procedure to stipulate: the use, storage and management of regional status sign plates and cargo status sign plates; The receipt, distribution, use and destruction of warehouse status labels and material status labels shall be managed and recorded. The quality management department is responsible for establishing and implementing the management process of receiving, distributing, using and destroying qualified labels and nonconforming labels of materials and products, and deciding the transformation of the following quality states: the status to be inspected is qualified; The state to be inspected is turned into a nonconforming state; The qualified status changed to the unqualified status.

Material management seems simple, but it is full of details and very difficult to manage well. Only in strict accordance with the relevant provisions of GMP, to ensure the safety of materials in order to ensure the safe production of drugs.