Analysis: "Change" and Its "Control" under the GMP System

It is normal for drugs to change during the production process.
Even in developed countries with relatively high drug research and development capabilities, it is very common for a variety to change between 5 and 10 per year, and if new products, sterile products, biological products, etc. are involved, the number will be even higher.
domestic, the current control of change can not reach the advanced level abroad, if the implementation of control is no longer effective, drug quality and safety risk factor will be greatly increased.
recent years, the domestic pharmaceutical industry explosive "drug harm" incidents, many are due to the production of change control is weak! 01 GMP system - change definition In the GMP system, change refers to the approved listed chemicals in the production, quality control, conditions of use and other aspects of the proposed sources, methods, control conditions.
that changes made to produce safe, effective and stable products in order to improve product quality can be considered changes.
these changes are proactive, pre-planned changes that may affect drug safety, effectiveness and quality control.
of the changes include changes in raw materials, packaging materials, quality standards, inspection methods, production processes, operating procedures, plant, facilities, equipment, and instruments.
02 GMP system - Change classification According to the nature of the change, scope and potential impact on product quality, and whether the change can affect registration, change time limit, etc., there are different classification methods, according to their own actual situation to choose the classification method suitable for their own enterprises, the change classification includes but is not limited to the following listed: material changes, general changes and minor changes (currently the largest number of enterprise applications) significant changes (requires) To submit documents to the drug regulatory department for approval, refers to changes that will have a significant impact on product quality, including: changes in product registration standards, changes in internal packaging materials, changes in storage conditions, labels, instructions, changes in key synthetic routes, main raw materials or solvents, key process parameters, prescription ingredients, changes in operating methods, structure changes in equipment and changes in production site.
General change (pharmaceutical department filing) refers to the change of the inline quality (safety, effectiveness) of the product, including: production, quality of the main equipment, facilities, equipment, the replacement of key components;
minor changes (no need to apply to the Drug Administration for approval or filing) are changes that have no impact on the safety and effectiveness of the product.
such changes only need to be included in the annual quality report.
mainly include: the replacement of auxiliary parts of equipment and facilities, the change of raw material suppliers where the quality standards have not changed, the change of intermediate production site, etc.
Related to changes in registration, changes not related to registration In China's existing drug production laws and regulations, such as the "Drug Production Quality Management Code" clearly stipulates that pharmaceutical production enterprises should be strictly in accordance with the registered approved production process production;
The Measures for the Administration of Drug Registration refer to the specific requirements for changes in the registration, such as changes to the documents for the development of new drugs, the production of drugs and the approval of imported drugs and the matters set out in their annexes, supplementary applications shall be made; The supplementary materials required for medicinal use, the change of the production process affecting the quality of the drug, etc., the supplementary application shall be reported, the supplementary application shall be reported for changing the name of the domestic pharmaceutical production enterprise, the change of the validity period of the domestic pharmaceutical production enterprise, the change of the pharmaceutical production site within the domestic pharmaceutical production enterprise, etc., and the change of the drug packaging label shall be reported as the supplementary application.
03 GMP System - Change Control GMP System, change control ensures that any changes to validated processes, procedures, documents, equipment, facilities, suppliers, materials and electronic software systems are recorded, evaluated and approved before execution.
The main responsible department for the change, usually by the quality management department to coordinate the entire change control process, to undertake the following work: 1, to assist the initiator to evaluate and analyze the change;
changes to a validated system are often accompanied by unpredictable risks, a detailed assessment should be made during the initiating phase of a change to determine whether the change is necessary.
assessment can be carried out in the following ways: 1, is it a requirement of the drug regulatory department? 2. Does it affect the safety of employees? 3, is it the requirements of compliance with the regulations? 4. Will the quality or productivity of the product be improved?04 Small knot / small sense in the past 2018, the domestic pharmaceutical industry occurred a series of vaccine events, a large part of the reason is due to the production process for the concealment of changes, its impact is extremely bad, not only the enterprise itself, but also the entire industry has caused a very large negative effect! Drugs, as a special commodity, is related to life, so the quality control of the whole life cycle of drugs, naturally is extremely important! And because of technological progress, quality standards continue to improve, the emergence of related changes in production, is very normal and meaningful things.
Although GMP pursues stability, the nature of change is not to challenge stability, but rather to achieve longer-term stability, and what each of us pharmaceutical people has to do is how to make change better controlled, better serve the properties of drugs!" Full text data: "Pharmaceutical Production Quality Management Code";