Red line or shackles Talk about the impact of MAH commissioned production quality agreement guidelines.

Background Given that many experts in the pharmaceutical industry have already expressed their views on this document, the author did not want to ignore it.
but with the warm invitation of friends, I will be under the heavy pressure of chasing drama and stock speculation at the same time, to talk about their own shallow views.
is not the first of its many quality agreements on commissioned production.
the FDA issued a guide, Contract Manufacturing Arrangements for Drugs: Quality Agreements, in November 2016.
, in addition to the FDA guidelines, there are APIC quality agreement guidelines, the industry can refer to.
the domestic agreement to regulate the relationship between MAH and the entrusted production enterprises, the Shanghai Bureau, Zhejiang Bureau, Jiangsu Bureau and other local drug administration agencies have issued similar agreement guidelines when the MAH system pilot was launched in 2016.
, the author talks about the impact of this agreement document on the pharmaceutical industry according to the shallow understanding of the individual.
of course, if your comrades indulge in mountains and rivers, no intention of rivers and lakes, this document will not have any impact on you.
1. The Drug Administration Law, which came into effect on December 1, 2019, clearly stipulates that the Drug Administration Department of the State Council shall formulate guidelines for quality agreements for the commissioned production of drugs, and guide and supervise drug market license holders and entrusted production enterprises to fulfill their drug quality assurance obligations.
therefore, the development and implementation of this quality agreement guide is also an initiative of the NMPA to implement the Drug Administration Act.
1.2, the title of the document is named after a guide, indicating that the document is not mandatory and provides reference and reference to the pharmaceutical industry.
but the official guide is, after all, an official guide, and the document reflects the latest official views on the issue, which the industry should try to comply with.
mah and trustees are subject to other regulations and their own business agreements for other issues not covered by this guide.
1.3 This guide, despite drafting and follow-up feedback in early March 2020, follows the shortcomings of China's pharmaceutical regulatory documents in terms of format.
such as no clear numbering system, no file version history section.
would be a blessing for people in the pharmaceutical industry if a document history similar to the following, as well as a coding system similar to the EMA file number, could appear on China's pharmaceutical regulatory documents.
II. The coordination and partial omission of the guidelines and the templates that follow included two annexes to the document issued by NMPA on 9 October 2020, namely, the Guidelines for Quality Agreements for The Commissioned Production of Drugs (2020 edition) and the Template for the Agreement on the Quality of Pharmaceutical Commissioned Productions (2020).
NMPA must have coordinated the writing and publication of the two annexes by the organization's experts, as there was some coordination in terms of the guidelines and subsequent templates.
2.1 The Quality Agreement Guidelines and Templates Coordination section, for example, whether commissioned production quality agreement guidelines or subsequent templates, includes the main impact aspects of pharmaceutical production: personnel management, plant facilities and equipment management, material and product management, validation and verification management, document management, production management, quality control and quality assurance, product storage shipments and recalls, on-site audit work, compliance support, regulatory supervision and inspection, quality dispute resolution.
2.2 The Quality Agreement Guide and Template omissions section Although we see the co-ordination of most of the contents of the two documents, we can also see that there are some incompociencys between the previous Quality Agreement Guide and the templates that follow.
--- for the personnel and organization requirements of the entrusted enterprise, the quality agreement template requirements are low.
only mentioned the training section, not the professional experience, job skills, medical examination and other requirements.
--- the common-line assessment section, although the main content is written, it is hoped to attract the attention of the pharmaceutical industry in view of the new international guidelines on common-line assessment.
is also being drafted, both MAH and the trustees need attention.
--- and verification parts, lack of storage facilities verification, transportation verification requirements.
--- specific operating time limits given in the template are not appropriate for certain specific files.
e.g., the template mentions that "for deviations and OOS that may affect product safety, effectiveness and quality control, the trustee shall notify the holder in writing within X days and complete the investigation within X days from the date of the deviation or OOS and report it to the holder for approval."
" obviously, for deviations, changes, OOS, OOT, CAPA and other matters, should not be specified in the agreement template specific completion time, but should be specified in the relevant procedures of MAH and the trustees.
After all, a trustee may accept multiple MAH delegates, and if each MAH sends similar instructions to the trustee, which is conflicting, the trustee's technicians will surely have a headache.
--- similar to the above, this template in product quality review analysis, complaints and adverse reactions treatment, etc. , in the template body to give a specific operating date.
clearly, this is not reasonable or operational.
the author strongly recommends that MAH and the trustees set these dates in specific procedures and leave room for reasonable operation.
III. The distribution of authority and responsibility in dealing with issues such as deviation/OOS/OOT, when it comes to drug production and quality management, cannot but address topics such as deviation, OOS/OOT, and similar issues are described and specified in this guide.
comprehensive quality agreement guidelines and quality protocol templates, NMPA also requires MAH to participate in the entire bias and OOS/OOT investigation, but emphasizes that MAH should review and approve the deviation and OOS/OOT investigation report.
is reasonable because deviations and OOS/OOT investigations cannot be conducted off-site, which is often far from MAH.
, however, the author here to solemnly remind MAH: must be in the first audit and follow-up audit, for deviation and OOS / OOT investigation capacity to fully assess, especially the invalid OOS treatment level.
because these capabilities and experiences are eddy from the long hard work of the technical team and have a critical impact on the products commissioned by MAH.
4. The issue of the distribution of powers and responsibilities in the area of change, which came into force on 1 December 2019, has been the subject of a ground-breaking talk of change management requirements, which have not been seen in previous versions of the Drug Administration Act.
with the publication and implementation of the Measures for the Supervision and Administration of Drug Production and the Measures for the Administration of Drug Registration, the pace of regulatory management changes has come a step closer.
industry is looking forward to supporting the technical guidelines, hope to be finalized quickly.
Above the quality agreement guidelines, the change is also clearly defined: the holder, as the subject of responsibility, shall, in accordance with the provisions of the State Drug Administration, fully assess and verify the impact of the change on the safety, effectiveness and quality control of the drug.
and trustees shall make changes in accordance with the laws, regulations and technical norms of drug administration.
any party to make changes that may affect the quality of the drug should be communicated to the other party in writing in a timely manner.
The quality agreement shall stipulate that both parties shall establish change control procedures to clarify the work measures in the event of a change, that the degree of risk associated with the change of the commissioned production product shall be determined by the holder's assessment, and that the trustee shall be approved by the holder before the change is implemented.
for the commissioned product, if a change involving a process or prescription occurs, MAH is certainly responsible for the principal responsibility.
However, changes to the public systems of the trustees that affect the products entrusted also require MAH's attention and participation in audits, such as compressed air systems, process water systems, HVAC systems, and electronic data control systems.
5. A new change in MAH's guidelines for new commissioned production quality agreements, which are responsible for the evaluation and approval of material suppliers, is to make it clear that quality agreements should provide for the selection, management and auditing of material suppliers by the holder, and that suppliers should comply with the production quality management practices established by the State Drug Administration and the relevant requirements for related review and approval.
The author speculates that there should be two reasons for this provision: fear that the trustees will relax the management of suppliers in order to save audit costs, and, as EHS costs continue to rise, it will be more difficult for suppliers to manage, requiring MAH to take personal responsibility for this.
MAH, after completing supplier screening, evaluation and approval, needs to hand over the qualified supplier catalog to the trustee and incorporate it into the trustee's procurement system.
work related to the material can be delegated by MAH to the trustee.
. The quality agreement guide on product inspection and release issues clearly stipulates that the quality agreement shall clearly state that the entrusted party is responsible for the inspection of the finished product and must ensure the completion of the complete inspection of the finished product.
the inspection report shall be handed over to the holder by a copy or other means after the completion of the inspection.
But the full inspection here should mean that the product needs to complete the full test according to the registration criteria before it is released from the factory, rather than requiring the trustee to have the full detection capability.
Because, as mentioned later, the quality agreement should stipulate that any party involved in the original accessories, packaging materials, intermediate products and finished products of the commissioned inspection must comply with drug laws and regulations and GMP and other requirements, the trustee will be entrusted to a third party inspection project, should be approved by the holder.
on the release of products to market, as this is the core expression of MAH's powers and responsibilities, as the Quality Agreement Guidelines clearly state that MAH is responsible for commissioning the release of drugs on the market.
to remind MAH and trustees here, consider the following questions: How does the --- factory release and release SOP write and what pre-conditions are set? --- you specify a specific contact? Which is the contact mailbox? --- does MAH get product information? How do I demonstrate a full audit? How do I ensure that the listing and release instructions are accurately issued to the trustees? Seven. The quality agreement guide on document approval is listed for the documents of cooperation between the two parties, and the examination and approval of relevant documents is carefully stipulated.
eight. What kind of team can effectively implement this agreement When the article wrote this paragraph, the author felt that whether it is MAH's technical team, or the technical team of the entrusted unit, should carefully study the NMPA quality agreement guidelines, and their boss to talk about life and ideals.
NMPA regardless of whether pharmaceutical industry practitioners drank the first cup of milk tea in the fall, but in the guide began to mention the requirement that the two sides should establish an effective communication mechanism, in the quality agreement to determine the technical quality of direct contact, timely communication on the quality agreement in the implementation of the problems encountered.
to demonstrate my understanding of effective communication, I give the following table: Nine. Red line or shackles--- future infinite vast in fact, write down the last subheading, the author's heart also has no answer.
But since you pharmaceutical colleagues have happily started the MAH road, I still want to carefully, euphemistically inform you, if you have rich work experience, and their products are popular, technology stability, and lucky to find like-spirited partners, this quality agreement guide and the template behind you to start a happy journey of the red line, for both sides are good.
, it is expected that quarrels and tears will continue to occur.
in order to avoid the infinite pain of the subsequent, it is recommended that you be prepared for a quarrel during the trustee screening evaluation phase and the quality agreement signing phase.
so in advance to make the quarrel, the follow-up will be smoother.
above is the author's "unsymonsmic" good wishes, I hope you can understand.
thank you. Introduction to
Authors: Zhulikou431, Senior Engineer, PDA Member, ISPE Member, ECA Member, PQRI Member, Senior Sterile GMP Specialist, with deep knowledge in the fields of sterile process development and verification, drug research and development and registration, CTD document writing and auditing, regulatory audit, international certification, international registration, quality system construction and maintenance, as well as sterile inspection, environmental monitoring and other fields.
recent years, we have focused on the analysis of trends in the macro-field of pharmaceutical companies and the risk management of mergers and acquisitions projects of pharmaceutical companies.
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