From the role of QP under the framework of EU regulations to see the performance of QP responsibility under China's MAH system.

With the development of the European single market, various EU regulations have been gradually established.
in 2001, many drug directives were consolidated into two new directives: 2001/83 /EC on human medicines and 2001/82 /EC on veterinary drugs.
directive sought to require member States to ensure that they have at least one QP for their own and manufacturers of imported medicines produced in third countries.
QP is appointed by the Pharmaceutical Administration to perform specific duties and operations to ensure that each batch of medicines is produced, packaged or imported in accordance with relevant regulations.
QP must sign a register or other records to demonstrate that each batch meets the criteria for release, sale, supply or(in some cases) further processing.
and these rules and regulations are beneficial to China's pharmaceutical industry and regulators for the rapid implementation of MAH.
the author does not venture, for all readers to introduce the details of the EU QP system and guide you to think about our China MAH system under the QP responsibility to fulfill the problem.
The first part: EU QP regulations, responsibilities and roles 1, eu QP roles and responsibilities According to article 41 (c) of EU Directive 2001/83/EC and article 45 (c) of Directive 2001/82/EC, the applicant for a production licence should have at least one QP available.
articles 49 and 50 of 2001/83/EC and articles 53 and 54 of 2001/82/EC provide for academic and empirical standards relating to QP.
The QP designated under the permanent provisions of these Directives is eligible to be designated as AQP in any Member State.
eu QP experience criteria should be at least two years of qualitative analysis of drugs in one or more licensed manufacturers, quantitative analysis of active ingredients, and necessary testing and inspection experience to ensure drug quality.
experience gained by third-country manufacturers usually does not contribute to the required duration of experience.
each batch must be confirmed by the QP of the European Community or the European Economic Area before it can be sold or supplied in the European Community/EEA, or exported.
this is to ensure that the production and control of each batch complies with the relevant on-the-market and production licensing requirements and ec GMP principles and guidelines.
when the product is produced in a third country, QP should consider the country's GMP standards and whether they are recognized in the same way as the EC (e.g. there is an agreement on mutual recognition between the country and the EC) or whether there are other relevant legal provisions.
before approval, QP should ensure that the relevant licensing requirements are met, that GMP principles and guidelines are integrated throughout the manufacturing, assembly and testing processes and that key processes in these areas are validated.
QP should also ensure that all relevant inspections and tests are carried out, including process control and environmental monitoring.
If there is a change or deviation in production or quality control, QP should assess whether these changes will have an impact on product quality and, if necessary, ensure that these changes are notified to the relevant regulatory authority and approved by the relevant regulatory authority.
should consider any other checks that are required as a result of the change.
quality assurance plan should ensure that all relevant documents have been completed and that the necessary checks have been carried out and there is no reason to be concerned.
if the various stages of the production and assembly of a drug are carried out by different companies, there should be a written contract describing the contractual arrangements for the identification of QP.
QP representing the ultimate manufacturer in the supply chain must be able to access all relevant information at previous stages in order to fulfil its responsibilities.
QP may also rely on one or more quality assurance procedures to confirm compliance with the requirements in the intermediate stages of batch production.
if the listing licensee is different from the production licensee and wishes to be responsible for the release, the organization's QP must also be able to access all relevant information about the manufacturer.
further information on batch QPs responsibilities performed at different locations or by different agencies at different stages of production, please refer to Appendix 16 of the EU GMP Guidelines.
QP does not need to perform all duties related to the release themselves.
he/she can delegate tests and inspections to trained, experienced, and competent employees.
in this case, qP has a responsibility to ensure that the necessary work has been completed and documented.
QP should also ensure that an effective, audited quality management system is in place to provide a degree of assurance in support of such authorization.
QP must also work on the production site long enough to familiarize itself with production conditions and perform delegated duties.
Although QP may delegate some responsibilities, he/she is still responsible for the confirmation and execution of the release.
there should be a formal written agreement between the entrusted QP, QP and the organization detailing the various responsibilities.
contract should also specify the expected time for the QP on site.
2, the EU QP responsible for clinical trial products and API management In accordance with EU Directive 2001/20/EC, member states are required to ensure that the manufacturer of clinical trial products (IMP) has an appropriate license for production and that the manufacturer should have at least one fixed QP perform the relevant duties.
QP is responsible for ensuring that each batch of IMP produced in EC/EEA is produced and inspected in accordance with the GMP principles and guidelines set out in Directive 2003/94/EC.
in addition, QP should ensure that the product has been manufactured and tested in accordance with product standards and that the initiator of the product's use for clinical trial has applied for the necessary regulatory permission for the trial.
if the product is produced in a third country, QP must ensure that each batch of product is produced and inspected in accordance with GMP standards, at least the same as ec/EEA standards.
If IMP is a controlled drug produced in a third country and is not available for the above guarantees, QP must be satisfied that each production batch has been analysed and subjected to the necessary checks and tests to confirm its quality.
the role of IMP's QP is described in Appendix 13 of the EC GMP Guide.
EU Directive 2001/83/EC, 46 (f), stipulates that manufacturers must only use active substances that have been produced in accordance with the detailed GMP guidelines for raw materials as starting materials. the production of active substances
as starting materials includes the total production and partial production, or the import ation of active substances.
requires the manufacturer of the active substance to declare that the active substance manufacturer meets the appropriate GMP standards, supports the product's listing permit application, and supports the listing license change request for the change of the manufacturer of the starting material.
does not require API manufacturers to be equipped with QP, but there should be a separate quality department whose responsibilities include releasing or rejecting APIs.
3, the role of the EU QP in the distribution activities QP's responsibilities do not end with the confirmation of the approval.
QP plays an important role in ensuring the quality of the entire distribution chain and ensuring that activities are in line with GDP.
with the increasing globalization of drug distribution, supply chains can be complex, involving many storage sites, transshipment locations and transport systems.
Under EC GMPs, manufacturers' quality assurance systems should ensure that they are well organized for the storage, distribution and subsequent treatment of medicines, so that quality is maintained throughout the shelf life.
the system should also ensure that all necessary facilities, including proper storage and transport, are provided for GMP.
4, QP's legal and professional responsibilities The following content mainly from the perspective of the UK drug regulatory discussion QP legal and professional aspects.
it is largely confined to the production and control of human-use drugs, much of the discussion relates to veterinary and other QP sectors.
each member state incorporates EU directives into national legislation and interprets its requirements.
it is clear that the way a person is considered fit to perform his or her duties in a joint QP is different among member States.
provide a brief overview of the history of the relevant EU directives in order to place the UK's procedures in the context of articles 48 and 49 of EU Directive 2001/83/EC and its relationship with Article 51. At the heart of the
document is a discussion of the UK's decision to implement QP requirements in three areas: 1) Ways to meet qualifications, knowledge and experience 2) Qualifications and Training 3) Professional Code of Conduct 4.1 Uk Law Outlines the UK has a history of controlling drug production and release prior to EU Directive 75/318/EEC and 75/319/EEC and its EU member states.
The Drug Act (1968) was a direct product of the thalidomide tragedy in the early 1960s and was the core legislation of the United Kingdom.
introduced a product and production licensing system.
drug production license is the legal basis for regulating and controlling the quality of drugs.
during this period, this provision has been amended and extended through the mechanism of the statutory instrument.
in fact, it is the same mechanism used today to issue EU directives within British law. The GMP Guide was first published in the UK in 1971 and is affectionately known as the "Orange Guide".
the guide has evolved over the years and is the basis of the 1987 EU GMP Guidelines.
the ROLE OF QP is explained by the UK Drug Enforcement Administration (MCA) through two Drug Law Information (MAL 45 and 69).
these documents have since been withdrawn and will be replaced in the existing cases with guidance note 9.
in practice, they have been replaced by a set of codes of practice for The Pharmaceutical Industry QP contained in the Drug Manufacturers and Distributors Guidelines 2002 (Fda) (now the Drug and Health Products Regulatory Authority, MHRA). The role of professional bodies in this and other areas of the
and elsewhere will be discussed later in the UK.
4.2 EU Directive EU Directives are complex, but evolved from a single founding Directive 65/65/EEC.
this complexity makes it useful to track the basic aspects of their development in the simplified form shown in Figure 1.
chose Codification Directive 2001/83/EC as the focus of the chart because it provides a fixed point of historical requirements from 65/65/EEC and provides a natural path to the current extension and modification of instructions.
for QPs that are "on-the-job" and affected by the 75/319/EC and its 75/318/EC transitional arrangements, the regulations are the basis for the QP responsibilities arrangements.
article 48 of 2001/83/EC is essential to the current discussion of legal and professional responsibilities, as it relates both to the eligibility requirements (article 49) and to the statutory duties of the QP (article 51).
5, QP delegation and responsibility distinction Seiny Usually a batch has different production stages or tests performed at different locations or by different manufacturers.
an intermediate production batch or a mass production batch can be divided into more than one finished batch.
in these cases, the delegation of responsibility for qP is necessary, primarily based on quality agreements between different production locations/QPs.
APPENDIX 16 OF THE EU GMP GUIDELINES DEFINES IN DETAIL THE RESPONSIBILITIES OF THE QP IN THIS CASE.
Special requirements must be met if the product is imported from a third country outside the EC/EC.
If there is an mutual recognition agreement (MRA), it is much easier to import from that country.
5.1, describing appendix 16 "QP confirmation and batch release" of the EU GMP Guide, is particularly applicable to batches at different locations or at different stages of production or testing by different manufacturers.
it also describes how an intermediate or mass production batch can be divided into more than one finished batch.
, in addition, it includes the release of batches imported into the EC/EC in the absence of mutual recognition agreements (MRA) between the Community and third countries.
possible scenario: 1) EC/EEA-produced products batch testing and release 2) bulk testing and release from third countries imports 3) Bulk testing and release of products from third countries with MRA in the duties of the QP in Directive 2001/83/EC 51 The description is described in detail, as follows: a) For medicines produced in the Ec, QP ensures that production and testing are carried out in accordance with directives and market-to-market permits b) For medicines produced outside the EC, QP shall ensure that each shipment of imported products is tested in the importing country under article 51, paragraph 1 (b).
QP must meet the eligibility requirements set out in Directive 49 of Directive 2001/83/EC.
manufacturer should have a fixed QP to carry out its duties on an ongoing basis.
QP responsibilities can be delegated, but only to other eligible people.
5.2, batch testing and release of products produced in EC/EEA There are several different situations for batch testing and release of products produced in ec/EC as described in Article 5 of Appendix 16.
can be divided into the following situations: 5.2.1, all production is carried out in a separate licensing site This is qP on the production site quality system has a direct impact on the simplest scenario (Figure 1).
within the prescribed system, the QP that provides the release signature for the finished batch is usually personally responsible for this.
some inspections and controls can be delegated to others within the quality organization.
specially trained quality personnel can conduct batch records audits on the workshop and sign environmental monitoring reports and critical system reports.
analysis testing protocols can be signed by a laboratory supervisor.
deviation investigation report can be signed by quality assurance personnel.
QP only needs to execute the last signature of the batch release.
the last signature cannot be delegated.
5.2.2, the QP of the listing licenseholder at different production stages in different locations within the same company is responsible for the signature and release of the finished batch for all stages (Figure 2).
he could consider the confirmation of the early stages of the relevant QP responsible for these phases.
even if the production is in the same company, each production site should have QP to ensure the release of the relevant intermediate products.
last, Q.