The Comprehensive Affairs Department of NMPA Solicits Public Comments on “Good Manufacturing Practice (GMP) – Appendix for Investigational Drugs (Draft for Comments)”

Chapter I Scope

Article 1 This Appendix applies to the preparation of drugs for clinical trials (including test drugs and placebos). This Appendix also applies to changes in packaging and labeling of marketed drugs used as control drugs or test drugs.

Chapter II Principles

Article 2 The preparation of drugs for clinical trials shall comply with the relevant basic principles of the Good Manufacturing Practice for Pharmaceuticals and the requirements for data reliability, minimize the risks introduced in the preparation process, ensure the quality of drugs used in clinical trials, and protect the safety of subjects.

Article 3 The quality management of the preparation of drugs for clinical trials shall fully consider its particularity, including:

(I) In the early clinical trial stage of new drugs, the preparation of test drugs lacks mature process procedures, and the prescriptions and processes are usually not fully confirmed and verified;

(II) The understanding of the characteristics, potential effects and toxicity of new drugs is not sufficient, and the identification of the key quality attributes of test drugs and the research on quality control indicators and methods need to be further deepened;

(III) Clinical trials may involve the preparation of placebos and changes in the packaging of control drugs. The requirements of randomization and blinding increase the risk of confusion and errors in the preparation process of drugs for clinical trials.

The preparation and inspection of drugs for clinical trials should be controlled in the quality management process based on the above particularities, the characteristics of different R&D stages and the requirements of clinical trial design.

Article 4 The quality risk management strategy of drugs for clinical trials can be adjusted accordingly according to the research and development rules on the basis of ensuring the safety of subjects and not affecting the quality of clinical trials. The preparation of drugs for prevention and control of public health emergencies should be managed in accordance with the principles of safety, reliability, scientific feasibility and emergency needs.

Chapter III Quality Management

Article 5 The preparation unit of drugs for clinical trials shall establish a quality management system based on quality risk management. The system shall cover the necessary factors affecting the quality of drugs for clinical trials, and establish a document system to ensure the effective operation of the quality management system.

Article 6 The applicant shall bear the ultimate responsibility for the quality of drugs for clinical trials. If the preparation of drugs for clinical trials is entrusted, the applicant shall audit and confirm the quality management system of the entrusted enterprise, and sign a commission agreement and a quality agreement to clearly stipulate the responsibilities of all parties to ensure that the drugs for clinical trials meet the intended use and quality requirements. The quality agreement shall clearly stipulate that the applicant may inspect or conduct on-site quality audits of the entrusted enterprise.

Article 7 If changes occur in the preparation site, prescription process, scale, quality standards, key raw materials, auxiliary materials and packaging materials of clinical trial drugs, as well as the transfer of related technologies, the safety risks of the changes to the clinical trial drugs shall be evaluated, and the changes and evaluations shall be recorded to ensure traceability. The preparation process shall investigate and evaluate the process and quality or other deviations that may affect the quality of clinical trial drugs, and keep corresponding records.

Chapter IV Personnel

Article 8 Personnel involved in the preparation and quality management of clinical trial drugs shall have appropriate qualifications and training, and have the ability to perform corresponding duties. Personnel responsible for quality management and preparation management shall not hold concurrent positions.

Article 9 The applicant shall have a person responsible for the release of clinical trial drugs, who shall be responsible for the release of each batch of clinical trial drugs.

(I) Qualifications:

The person responsible for release shall have at least a bachelor's degree or above in pharmacy or related majors, at least five years of practical experience in drug research and development and drug production quality management, including at least one year of experience in drug quality management, and have received training on product knowledge and release.

(II) Main responsibilities:

The person responsible for release shall be responsible for the release of clinical trial drugs, ensure that the preparation and inspection of each batch of released clinical trial drugs comply with relevant laws and regulations, drug registration requirements and quality standards, and issue release review records.

Chapter V Plants and Facilities

Article 10 Plants and facilities for the preparation of clinical trial drugs shall comply with the requirements of the Good Manufacturing Practice for Pharmaceuticals and the corresponding appendix. The scope of confirmation of plants, facilities and equipment shall be determined based on risk assessment.

Article 11 When clinical trial drugs are co-produced with other clinical trial drugs or marketed drugs, a risk assessment of the feasibility of co-production shall be conducted based on the toxicity, pharmacological activity and potential sensitization of the clinical trial drugs, including the evaluation of the acceptable standards for the applicable population, route of administration, risks to subjects and pharmacological and toxicological factors of the co-produced varieties. The risks of contamination and cross-contamination during the preparation process can be minimized through phased preparation.

In the early clinical trial stage, the preparation of test drugs should use dedicated or independent production facilities and equipment as much as possible.

Chapter VI Material Management

Article 12 A relatively complete quality standard for raw materials and packaging materials shall be established, and necessary re-evaluation and update shall be carried out.

The raw materials and packaging materials used in the preparation of clinical trial drugs shall be subject to corresponding inspection or examination, and they can be released for use only after they are qualified. The excipients and packaging materials used in early clinical trial drugs can be accepted based on the supplier's analysis report, but at least identification shall be carried out.

Article 13 A sample retention procedure shall be established to manage the samples of raw materials and packaging materials used in each batch of clinical trial drugs. The number of samples retained shall generally be at least enough to ensure that two full inspections are completed in accordance with the quality standards at the time. The sample retention time shall not be shorter than the sample retention time of the corresponding clinical trial drugs.

Specific news link: The General Office of the National Medical Products Administration publicly solicits opinions on the "Good Manufacturing Practice for Pharmaceuticals - Appendix for Drugs Used in Clinical Trials (Draft for Comments)"