Requirements of the hottest solid preparation prod

Requirements of solid preparation production and product quality on pharmaceutical equipment

I. GMP requirements for validation in the U.S. pharmaceutical industry

principles:

● key processes in the process of product manufacturing, packaging, inspection and distribution, as well as relevant plants, air conditioners, equipment, analysis methods, etc., need to be validated

● all confirmations of relevant plants and equipment should consider meeting and meeting the requirements of product verification

equipment:

● the equipment used in the production and packaging process should be qualified

● confirm the utility/air conditioning system

● equipment requiring verification/validation of solid oral preparations (but not limited to the following): granulator, sifter, powder mixer, tablet press, coating machine, cleaning equipment, elevator, weighbridge packaging equipment, air conditioning system, compressed air system, water system

II. Requirements for equipment verification/validation

1. Pharmaceutical enterprises must consider various principles and specific requirements of GMP in the design stage of factories, including the requirements for validation

2. Because pharmaceutical equipment is the special equipment of drug manufacturing enterprises, GMP has special requirements for equipment, and continues to expand the utilization of domestic aluminum alloy materials with high strength, high toughness and low quenching sensitivity in new aircraft and aerospace vehicles. Main principles for equipment supplier selection:

● whether the supplier's previous experience in providing such equipment can ensure comprehensive support in installation, training and commissioning

● supplier's reputation

● the level of technical training provided by the supplier

● whether the equipment performance test can be carried out at the location of the supplier

● comparison of similar equipment from different manufacturers

● know GMP

● cost, delivery time, etc

3. The confirmation/verification of equipment is usually carried out according to the set scheme with the participation of suppliers, installation units and relevant personnel of the factory

● preparation of confirmation/verification scheme (document work)

● IQ - Installation confirmation: the installation of machinery and equipment meets GMP requirements, safety requirements and relevant requirements of the supplier, and the corresponding technical instructions and maintenance manuals are complete and archived

● OQ - operation confirmation: if the equipment operation reaches the specified technical indicators, the corresponding management procedures should be established

● PQ - - HVAC (heating ventilation and air conditioning system), compressed air system (compressed air system), water system (water system)

● process validation - - all equipment related to the manufacturing process, through the process validation results to verify the practicality and feasibility of the technical indicators of the equipment

4. Take tablet press as an example:

● IQ Objective: the purpose of installation confirmation is to ensure that the installation of tablet press meets the requirements of suppliers and users. (equipment identification, manufacturer's specifications, procurement standards, installation and positioning requirements)

● OQ Objective: the purpose of operation confirmation is to prove that all functions of the tablet press meet the technical indicators and use requirements, and the operation and control system will be evaluated according to the established technical indicators and standards

● preparation of relevant documents - SOP, maintenance manual, etc.

● equipment repair, maintenance, correction

● operation test requirements:

A, safety system test formulate safety test requirements according to the characteristics of each equipment

b, under normal conditions of transmission device test, test low speed, medium speed, high speed

C, power off for 5-10 seconds, restart, observe and record the tablet pressing control system

D The pressure control device confirms the ability of automatically adjusting the filling depth, chipping and tablet pressing machine to exceed the specified range in a short time

e, set the low speed, medium speed and high speed for blank tablet test run, and take samples to detect the weight difference, hardness and thickness of tablets

5. Take the powder mixer as an example:

installation confirmation: confirm according to the approved scheme

● equipment identification data

● installation requirements

● manufacturer's technical specifications

● user's order requirements

● confirm the main components of the equipment

● utility requirements through installation confirmation, SOP operation confirmation must be drafted

● scheme of operation confirmation

● necessary data of equipment, maintenance and correction manual, etc.

● formulated standard operating procedures

● operation test

a, safety system test - formulate safety test requirements according to the conditions of each equipment

b, control board function test - operate the normal operation, slow down, stop, etc. of the powder mixer

c Transmission system test - record the no-load running speed, repeat the normal loading operation, formulate the acceptable standard

d, feeding system test - confirm whether it meets the design index

e one by one according to the document requirements, blank material test run - evaluate the equipment with the operation of blank materials

III. production process verification flow chart

● formulate the verification scheme 1, drafted by a department of our factory, Quality assurance and relevant departments countersign, and the factory director approves. 2. The verification scheme includes the following contents: 2-1 Objective 2-2 Range 2-3 Reference 2-4 Relevant equipment, process parameters and inspection methods 2-5 Production process 2-6 The following main factors should be considered when formulating the validation scheme for stability test:

● the influence of raw and auxiliary material crystal form/particle size/process route on product quality and process stability to avoid electrostatic induction

● influence of equipment model/performance on quality and process stability

● the effectiveness and repeatability should be considered in the setting of production process conditions. Take the validation of tablet production process as an example:

I Objective

II Range sqrt (n+1)

Ⅲ Equipment IV Detailed production process description

v Validation procedure

1. granulation sampling: 5 points inspection: moisture, particle size distribution, acceptable indicators, according to the process requirements. 2. Powder mixing (to verify the rationality of powder mixing time): 5 points

(or sampling) inspection items: moisture, content uniformity, particle size distribution or color uniformity, etc. Acceptable standard: depending on specific requirements. (if the mixing conditions are designed, sampling at different mixing times can be considered)

3. tablet pressing (set the conditions required for tablet pressing) sampling: Method 1) - set the sampling from every 15 minutes to 300 minutes method 2) - start, 1/4, 2/4, 3/4, end point inspection items: appearance, tablet weight difference, hardness, thickness, disintegration, brittleness, content acceptable indicators: according to the specific process and quality standards

4. coating (set coating conditions)

sampling: it depends on the process. Inspection items: appearance AQL disintegration, loss on drying, hardness tablet weight difference acceptable indicators: internal

5. The analysis of finished products is in accordance with the requirements of quality standards. Validation report, conclusion

validation report Conclusion

● overview

● verification and evaluation

- acceptable standards

- Data Statistics (relevant statistics were carried out on all data according to the verification scheme to see whether they could meet the acceptable indicators)

● AQL inspection

● finished product analysis report

● conclusion RSD calculation: (slice weight difference, content uniformity needs to calculate RSD, relative standard deviation)

revalidation procedure

☆ when the main factors affecting product quality, such as process, quality control methods, main raw and auxiliary materials, main production equipment, etc., change, and after a certain production cycle, revalidation

☆ changes in major raw material suppliers

☆ validation scheme

☆ retrospective validation of validation report

☆ collect sufficient information and data from TXV aerospace composites, a joint venture between Victrex and tri Mack, to make a retrospective summary of the production process and production quality:

1. Evaluate at least 20 batches

2. Statistical analysis of all components and data

3. Compare the differences of the main steps

4. Stability

5. Calculate the control limit and draw a diagram

6. Summary