Analysis of the composition of the drug quality risk factors, set up a scientific evaluation index, the pharmaceutical production enterprises to carry out the risk assessment of the quality of
products in the hope that the risk of the quality of medicines in advance, so as to adopt an effective means of supervision from the
Source Eliminate the risk or minimize the risk loss.
I. Composition of pharmaceutical quality risk
Pharmaceutical quality risk is the possible danger to patients and society in the process of drug use.
The product quality risk of drug manufacturers mainly comes from two aspects: inherent risk and management risk, both of which
will cause the potential danger of drugs in the process of use.
1, inherent risk is inherent in the drug, including quality standard risk and adverse reaction risk.
Quality standard risk is caused by the lack of perfect standardization, non-clinical research and clinical research information is not complete
Face, approval is not strict enough, is the drugs listed on the market has been born before.
Since last year, the state bureau has begun to address the problem by verifying recently declared varieties and re-registering existing varieties
. With the implementation of the new Measures for the Administration of Drug Registration on October 1, 2007
, the information on drug development and registration declaration will be more truthful, scientific and standardized, the evaluation system of drug technology
will be more perfect, and the inspection of raw data of drug development and the production site will be intensified, and
will crack down on all kinds of falsification in the process of drug development and registration declaration in accordance with the law.
The quality standards for newly approved drugs will be improved.
The risk of adverse drug reactions is inherent in any kind of medicine, as the saying goes:
"A medicine is three times as poisonous as any other".
The State Bureau and the Ministry of Health promulgated and implemented the Measures for the Administration of Adverse Drug Reaction Reporting and Monitoring
on March 4, 2004, which established a routine working system for monitoring and reporting adverse drug reactions between drug manufacturers, business units, medical units and adverse drug reaction monitoring organizations at all levels nationwide,
Through the medical staff to the patient after the use of drugs occurring after the suspected adverse drug reactions reported to the drug supervision and management
management departments to organize the relevant experts on a variety of cases of adverse drug reactions to carry out causality analysis and evaluation and drug flow
practice pathology investigations, and will be the results of timely feedback, to take measures to stop the use of, modify the instructions to prevent adverse drug reactions
repeat. Repeat occurrence.
The inherent risk of drugs is inherent in drugs, and the National Board is working to minimize this risk through the standardization of the drug registration process, registration
special rectification work, and the gradual development of adverse drug reaction monitoring
. What enterprises can do is to report the registration declaration materials truthfully and standardized, formulate practical and feasible quality-controlled
drug quality standards, and actively do the monitoring of adverse drug reactions in order to effectively reduce the inherent risks of their
products.
2, management risk is the enterprise from the purchase of raw and auxiliary materials to the finished product factory in the whole process due to management problems and
generated potential dangers of the quality of drugs, mainly from three aspects: hardware, software, people.
Hardware factors include the environment around the plant, production workshop and auxiliary plant, production and auxiliary equipment facilities
Supplies, inspection equipment and environment. Since the mandatory implementation of GMP in China, manufacturers in the hardware facilities
investment is relatively large, relatively in place, but with the new version of the "Drug GMP certification inspection and evaluation standards" in
January 1, 2008 implementation, some of the design ideas at that time is not in line with the current "evaluation standards", will inevitably be
to the product quality risk, these risks Through the GMP certification inspection can be reflected.
Software factors include whether the enterprise's various licenses are complete, whether the file system (management file system
system, standard file system, record file system) to support each other to form a closed system
system. Software factors for an enterprise is very important, what needs to be done, how to do, in accordance with what standards to do,
how to connect between the various departments of the mutual constraints rely on the document system, there is no software system, a
enterprise is a plate of loose sand. So whether the software system is in line with national laws and regulations, in line with the actual enterprise, with
Operability of product quality risk plays a decisive role. Anhui Huayuan Bio-pharmaceutical Co., Ltd. arbitrarily changed
process procedures, change the key sterilization process parameters, resulting in serious consequences of the "Xinfu" incident.
Document
Whether the system is perfect, whether the enterprise management in accordance with the provisions of the document, the key to the daily production of the enterprise
Execution of the process, relying on the GMP certification can not be fully reflected, the need to follow up on inspections, flight inspections, special
inspections and a variety of causal inspections to be supplemented.
The human factor is the most easily overlooked of the three factors, all personnel should be in strict accordance with the various
Management regulations in compliance with the requirements of the hardware environment using the prescribed equipment to complete the prescribed work, truthful records of their own
The work done, all personnel should have the appropriate educational qualifications, professional knowledge, and practice
The post experience. All work is done by people, and the human factor is crucial. "Qiji drug" incident if any of the two
inspectors, or laboratory director a little stronger sense of responsibility, if all levels of management
management, purchasing staff a little stronger awareness of the law, it will not cause that tragic consequences, so that the enterprise to pay a
hurtful price! The company's business is a very important part of the company's success. Certification inspection, tracking inspection, special inspection, flight inspection of personnel aspects of the inspection have
has its limitations, only on the surface factors and on-site practice inspection, lack of people and people, departments and
departments between the ability to communicate and coordinate the ability to test, which should be
considered in the process of risk assessment of the enterprise.
Scientific determination of risk evaluation indicators
To achieve a fair and comprehensive evaluation of an enterprise, it is necessary to determine the scientific risk evaluation indicators, in order to
Can be as comprehensive as possible to reflect the risk of drug quality of the various components, to facilitate the correct prediction of the drug quality risk
Risk, combined with the supervision of the practice in recent years, to determine the following evaluation indicators:
1, safety supervision information
GMP certification, tracking and inspection, flight inspection, special inspection, daily supervision
, stationed in the factory supervision, the frequency of changes in important positions and training
2, drug testing information
evaluative sampling failed, supervision sampling failed
3, adverse reaction monitoring information
Adverse reaction monitoring, the state announced the situation of adverse reaction varieties
4, drug inspection information
National quality announcements, the public reported cases, the verification of cases in foreign provinces
5, drug registration information
drug registration on-site verification of the situation, the authenticity of the declared data The situation, illegal use of labeling instructions
status, illegal use of packaging materials
6, market supervision information
drug advertising, market feedback on the quality of drugs within the jurisdiction of the enterprise
The above indicators can basically reflect the risk factors that may exist in the enterprise, these indicators according to the different results
quantitative Scoring, each score is summarized to form a total score, according to the score will be divided into low-risk enterprises, general
risk enterprises and high-risk enterprises three grades.
Third, to take effective measures to actively prevent
1, for the identification of low-risk enterprises
in addition to special inspections and reporting inspections, can be appropriately reduced in the content of the daily supervision and inspection;
in the scope permitted by law, regulations, may be appropriate to give priority to the administrative examination and approval procedures;
2, for the identification of the general risk of Enterprises
Check back after closing the case;
Increase the frequency of daily supervision and inspection, and increase the content of supervision and inspection in the factory;
3. For the enterprises identified as high-risk
Check back after closing the case;
Increase the frequency of daily supervision and inspection, and increase the content of supervision and inspection in the factory;
Listed as the object of key supervision and inspection, and Conduct key special supervision and inspection;
Interview the person in charge of the enterprise;
Fourth, the need to further solve the problem
1, the difference between product dosage forms
A better managed injectable manufacturer and a poorly managed oral solid preparation manufacturer
Compared to the former injectable products inherent risk is greater, management The latter has less inherent risk and more management risk for its solid dosage products
. The two companies are less comparable and need to be differentiated when conducting risk
evaluations.
2, the difference between the business situation
Business situation is good business production, sales coverage, the emergence of unqualified test reports and adverse information
base is large; business situation is poor business production is small, only in the local area of the sale of medicines, not to be sampling or
there is no adverse reaction report. This does not mean that the latter is less risky and the former is more risky, so it is necessary to further
improve the evaluation methodology so that our evaluation results more truly reflect the actual situation of the enterprise.