REGISTRATION OF DMF OF PHARMACEUTICAL PACKAGING …

REGISTRATION OF DMF OF PHARMACEUTICAL PACKAGING MATERIALS IN CHINA

Dr. Suzan DavisApril 2021

Drug Master File Series

Global Regulatory Partners, Inc

Since July 2019, NMPA requires manufacturers of Pharmaceutical Packaging Materials (PPM) to register the DMF of their products using CDE platform and obtain a DMF number. Foreign manufacturers with no presence in China, should appoint local agents who can prepare and submit their DMF to CDE on their behalf. Manufacturers and their local agents are both responsible for the authenticity and integrity of information submitted in DMFs. They also need to submit to CDE an annual report during the first quarter of every year. Manufacturers should provide a Letter of Authorization (LOA) to the drugs’ applicant that they can use for their drugs’ registration with CDE.

A (PPM) that is manufactured at different manufacturing sites, or used for different routes of administration of drugs, hould be filed in a different DMF. Additionally a PPM that has different models or types should be filed in different DMFs.

Regulatory Background

The following (PPM) should get their DMFs registered in China, prior being exported to China, unless they are reviewed and approved at the same time as the drug they are used with.

D Infusion bottles ( bags, film and accessories) D Ampoules, D Pharmaceutical (oral or topical dosage form) bottles (tube caps) D Pharmaceutical stoppers, D Pharmaceutical pre-filled syringes, D Pharmaceutical eye drops, (nose, ears) bottle (tube). D Pharmaceutical hard pieces (film) D Pharmaceutical aluminum foil, D Pharmaceutical ointment tube, D Pharmaceutical desiccant, D Pharmaceutical spray (gas) aerosol pump (valves, tanks, cylinders).

Type of PPM Subject to DMF Registration in China

22DMF OF PHARMACEUTICAL PACKAGING MATERIALS IN CHINA | Drug Master File Series


NMPA classifies PPM in China to different categories based on their usage and the risk level.

Classification of PPM in China

Classification of PPM based on their usage

Classification of PPM based on their Risk

Usage Category Description

Category 1 1. Pharmaceutical packaging materials (e.g. new materials, new structure) thathave not been used with any registered domestic or foreign drug.

Category 2 2. Pharmaceutical packaging materials that have been used with domestic or foreign registered drugs, but will be used for a different route of drug administration that will increase their risk.

Category 3 3. Pharmaceutical packaging materials that have not been used with domesticor foreign registered drug, but have been used in food packaging and are indirect contact with food packaging (for oral preparations only);

Category 4 4. Pharmaceutical packaging materialsthat have been used with registered drugsand will be used with the same route of administration.

4.1 Does not have a registration for PPM

4.2 Has a registration for PPM

Category 5 5. Others

Risk category Description

High-risk High-risk pharmaceutical packaging materials generally include: primary packaging for inhalations, injections, and eye preparations

Low-risk Low-risk pharmaceutical packaging materials are the ones used for other drug presentations not included in the high-risk category


The content of DMF depends on the category of use and risk level of the PPM as explained below.

Content of DMF for PPM

Section DescriptionDescription

1 2 4.1 4.2

1. Applicant information 1.1 Name, registered address of company and manufacturing site

+ + + +

1.2 Applicant business license and certificates

+ + + +

1.3 Address of site for archiving research data

+ + + +

2. Basic information on PPM

2.1 Name of the packaging material

+ + + +

2.2 List of components (list of raw materials) with their specifications

+ + + +

2.3 Composition + + + +

2.4 Properties/function + + + +

2.5 Domestic and foreign approvals

- + + +

2.6 List of applicable standards (Chinese and foreign)

+ + + +

3. Manufacturing information

3.1 Description of manufacturing process and in-process controls

+ + + +

3.2 Raw material controls + + + +

3.3 Control of critical steps and intermediate

+ ± ± -

3.4 Manufacturing process validation and qualification

+ ± ± -

4. Quality Control 4.1 Specifications + + + +

4.2 Analytical methods + + + -

4.3 Justification of specifications + + - -

5. Batch analysis reports + + + +

6. Stability studies + + + -

7. Compatibility and safety studies

7.1 Compatibility studies + + + -

7.2 Safety studies + ± + -


Content of DMF for High-Risk PPM


Section DescriptionPPM Categories

1 2 3 4.1 4.2

1. Applicant information 1.1 Name, registered address of company and manufacturing site

+ + + + +

1.2 Applicant business license and certificates

+ + + + +

1.3 Address of site for archiving research data

+ + + + +

2. Basic information on PPM

2.1 Name of the packaging material

+ + + + +

2.2 List of components (list of raw materials) with their specifications

+ + + + +

2.3 Composition + + + + +

2.4 Properties/function + + + + +

2.5 Domestic and foreign approvals

- + - + +

2.6 List of applicable standards (Chinese and foreign)

+ + + ± -

3. Manufacturing information

3.1 Description of manufacturing process and in-process controls

+ + + + +

3.2 Materials’ controls + + + + +

3.3 Control of critical steps and intermediate

+ - - - -

3.4 Manufacturing process validation and qualification

+ - - - -

4. Quality Control 4.1 Specifications + + + + +

4.2 Analytical methods + + + + -

4.3 Justification of analytical methods

+ + + - -

5. Batch analysis reports + + + +

6. Stability studies + + + -

7. Compatibility and safety studies

7.1 Compatibility studies - - - - -

7.2 Safety studies + ± - - -


Content of DMF for Low-Risk PPM


*PPM: Pharmaceutical Packaging Material

Registration Process of DMF for PPM

PPM* manufacturer appoints a Local Agent in China

Manufacturer reviews and approves DMF dossier in English

Local Agent provides PPM manufacturer list of requirements for DMF Registration

Local Agent translates the DMF from English to Chinese

PPM Manufacturer provides technical information on PPM to Local Agent

Local Agent submits DMF to CDE ad obtains a DMF Number

Local Agent prepares and compiles the DMF dossier in English

CDE performs administrative review of DMF, and puts it under “ Inactive” Status

CDE performs a technical review of DMF at the same time as drug registration dossier

CDE receives drug application referring to PPM DMF Number

CDE approves drug application and change status of DMF to “Active “



The content of the application for DMF of pharmaceutical packaging material depends on the risk of the drug it is used for. Generally, high-risk pharmaceutical package materials includes pharmaceutical packaging material for inhalation preparations, injections, and eye preparations.

Timelines for Preparation of DMF for PPM

Activities Timelines (day)

Preparation of DMF dossier as per NPMA requirements

30

Translation of DMF from English to Chinese 30

CDE Administrative Review 15

CDE technical Review Timelines vary depending on if the review is done at the same time than drug application or not

• Drug Administration Law of the People’s Republic of China (2019 Revision);

• Provisions for Drug Registration;

• Announcement No. 146 of CFDA, 2017: Announcement of Adjustment on the Review and

Approval Procedure of APIs, Pharmaceutical Excipients and Packaging Materials;

• Announcement No. 56 of NMPA, 2019, Announcement of Improvement on the Separated

Filing and linked Review System of Drug Products and the Supervision.

References


Note: NMPA doesn’t charge a fee for the administrative review of DMF for pharmaceutical packaging materials


http://www.cde.org.cn/attachmentout.do?mothed=list&id=f1e11c9a9251ce0c






About Global Regulatory Partners, Inc

Global Regulatory Partners Inc, (GRP) is a global CRO that provides regulatory affairs, clinical, quality and safety services to medical devices and pharmaceutical companies globally. GRP headquarter is based in USA and it has four (4) affiliates , in Brazil, China, Mexico and Japan.

In the 5 countries ,USA, Brazil, China, Mexico and Japan, GRP is licensed to act as local representative of foreign companies or MAH in those countries and help them register their products in compliance with local regulations and in record time. All GRP services are provided according to company procedures and polices that comply with international requirements for protection of confidential information and data integrity.

In China, GRP team has many years of experience registering DMFs in China.

GRP Services for DMF in China include:

D Acting as local agent for DMF filing and maintenance in China, D Consulting services for DMF registration in China, D Performing gap analysis of available data and recommending DMF registration strategy and timelines, D Providing the list of documents required for DMF registration in China, D Compiling DMF based on China NMPA requirements, D Performing DMF translation from English to Chinese, D For high-risk products, providing assistance in samples’ testing by NMPA and supporting on-site NMPA

inspections if needed, D Communicating with CDE reviewers regarding submitted DMFs, D Responding to deficiency letters received during the DMF review process, D Preparing and submitting supplementary applications (DMF amendments), D Preparing and submitting annual reports to NMPA.

Dr. Suzan DavisPresident and CEO, Global Regulatory Partners, Inc

Suzan Davis is the Founder, President and CEO of Global Regulatory Partners. Inc, (GRP), which provide regulatory affairs, clinical and quality services to pharmaceutical and medical device companies globally. She led GRP since its inception in January 2010. Suzan has more than 25 years of experience in providing regulatory affairs strategy, registering drugs and biologics, including Orphan Drugs, with FDA and in international markets, managing global products’ development programs and conducting quality audits.

Before GRP, Suzan assumed many leadership and executive responsibilities in small and large pharmaceutical and biotech companies, such as GSK, Pfizer, Genzyme, EMD Sereno, Takeda, Merk, in United States and international markets as well. Suzan received a Pharm.D from pharmacy college (Université Paris 1 Panthéon-Sorbonne) in Paris, a Master in Regulatory Affairs (MRA) and an Executive Master in Business Administration (EMBA) from Northeastern University in Boston. She is also certified as a quality auditor, certified in US regulatory affairs, European regulatory affairs and international Regulatory Affairs.

About the Author



Brazil

Avenida Frei Caneca, no. 486Bairro Nossa Senhora dasGraçasUberlândia-Minas Gerais(MG)CEP: 38402-282Telephone:(+55) 34-3235-1971

Japan

Toranomon 40MT Buildings 7th floorMinato-ku, Tokyo, 105-0001 JapanTelephone: (+81)-3-4530-9824

China

Regus Hang Seng Bank Tower 9FNo.1000 Lujiazui Ring Road,Pudong District, Shanghai,200120Telephone:(+86) 021-517-27278

Mexico

Lake Alberto 442 – 5th floorTower A – Office 509Col. Anahuac 1st SectionDelegation Miguel Hidalgo, C.P. 11320Telephone: (+52) 55 7312 4169

Address: 550 Cochituate St, East Wing, Suite 25, Framingham, 01701, MA

Email: [email protected]

Website: www.globalregulatorypartners.com

Telephone: 781.672.4200

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REGISTRATION OF DMF OF PHARMACEUTICAL PACKAGING …