Understanding the Impact of FDA's TPMP Regulations

Editor's note: This article is the first in a series interpreting the new TPMP regulations. For the second article, please click here to read "Experts Explain in Detail the Potential Approval of Multi-Flavored E-Cigarette Products According to FDA Regulations.

On March 10th, 2023, the FDA released a draft of the Tobacco Product Manufacturing Practice (TPMP) requirements on its official website. This set of regulations is set to have a significant impact on the global tobacco industry. 2FIRSTS spoke with PMTA expert Zheng Zhi to break down the basic contents of the TPMP draft and to provide an analysis of the future market development trends for electronic cigarettes. Zheng, who previously oversaw the PMTA certification project for products at Shenzhen McKerwell, later founded Ziyuan Technology, which specializes in research on PMTA regulations and has many years of experience in pharmaceuticals and electronic cigarette inspection.

TPMP will be the final piece of PMTA.

On October 4, 2021, the FDA announced two final rules regarding pre-market review of new tobacco products on its official website, stating that products that have not passed PMTA certification are not allowed to be sold in the United States. However, due to the low efficiency of the FDA's sub-agency, CTP (Center for Tobacco Products), it is expected that only 23 electronic cigarette products will have passed PMTA by March 2023.

The PMTA review consists of two components: documentation evaluation and factory inspection. In 2021, the FDA provided nearly 500 pages of guidance as the basis for the documentation evaluation. This aspect is overseen by the Office of Science within the CTP, which is responsible for reviewing the written materials and testing data provided to demonstrate that the product meets the quality and safety requirements set forth by the FDA.

Zheng Zhi accompanied the inspector to participate in the Launch of the Factory Inspection Meeting | Source: Zheng Zhi

In addition, some factories undergo on-site inspections where not only the scientific and safety aspects of their products must meet the required standards, but also their production environment must comply with certain criteria and regulations, such as TPMP. However, there has been a lack of corresponding regulations for this aspect of on-site inspections.

After facing criticism from various stakeholders regarding measures introduced in late February, CTP released a new document titled "Requirements for Tobacco Product Manufacturing Practices" on March 10th. After reviewing the latest draft, industry expert Zheng Zhi, who previously participated in FDA inspections, expressed to 2FIRSTS that TPMP has significant significance and fills the final gap in PMTA.

Standard globalization is now unavoidable.

According to Zheng Zhi's analysis, the FDA has adopted a similar framework and terminology for regulating tobacco product manufacturing as they do for pharmaceuticals. "In fact," says Zhi, "the FDA has a set of standards for managing various industries under its purview, with only slight variations in terminology. For the pharmaceutical industry, this is referred to as Good Manufacturing Practice (GMP).

The terms used in this draft, such as pollution, cross-contamination, MMR, and CAPA, are commonly used in the pharmaceutical system. However, terms commonly used in electronic cigarette assembly factories, such as ECN, ECR, and 8D, are not mentioned. This indicates the background and expertise of the document's authors are more inclined towards the pharmaceutical or pharmaceutical industry.

This also means that manufacturers of products such as electronic cigarettes will face new challenges, while those using pharmaceutical production standards for e-liquids may be more readily accepted.

According to Zheng Zhi, "It can be said that the current version of TPMP is almost identical in terms of content and requirements to GMP, the predecessor of the former. Of course, there are also references and learnings from ISO9001 and ISO13485.

Based on the past influence of GMP worldwide, if this version of TPMP is confirmed, it will inevitably inspire other countries to emulate and reference the standard. Consequently, "the globalization of electronic cigarette production standards is inevitable.

Inspection team verifies equipment | Source: Inspection process by Zhengzhi TPMP.

Zheng Zhi was involved in the FDA's inspection of the Smoore factory. Based on his extensive experience with FDA and EU audits, it is common practice for the FDA to notify the factory being inspected two months in advance. The inspection team typically consists of a leader and two assistants, and the inspection of an e-cigarette factory can typically be completed in two to three days. With clearly defined roles for different teams responsible for quality, production, and inspection, factories preparing for PMTA applications should have no problems with efficiency.

According to Zheng Zhi, the last time SiMore was inspected was three days ago, and HeYuan technology was inspected two days ago. This timeframe is adequate as our factory is not too complicated," he mentioned.

The inspection requires that the factory must be in operation and covers all aspects of the overall production process, including personnel, equipment and facilities, materials, document records, quality management and control, production environment, among others. When confronted with more obvious issues on site, the FDA inspection team will directly pinpoint the problems and confirm with the factory's responsible personnel.

He is afraid that you won't acknowledge it.

As for the details, within one to two months after the inspection is completed, the factory will receive a factory inspection report. The factory is required to complete the necessary corrections within two months. Once the factory completes the corrections, the FDA will inspect the corrective report.

If approved, typically a confirmation letter from the FDA will be received within two to three months.

On-Site Assessment Conducted by Inspection Team | Source: Zheng Zhi

The FDA previously imposed a limit on the number of times a factory could be required to undertake corrective action, typically two instances for pharmaceutical plants. If compliance requirements were not met after this, the factory had to reapply for inspection. However, with regards to tobacco, Zheng Zhi believes that "the FDA needs to have a new understanding of the e-cigarette industry. I believe it should not be limited to just two chances, and we are also paying close attention to this restriction on the number of times.

According to the FDA's dynamic regulatory model, factories will undergo inspections again in 3-4 years after passing an initial inspection. "Future regulations are evolving, technology in e-cigarette products is changing, and personnel inside factories are also changing, so inspections are typically periodic," Zheng Zhi added.

Within the industry, this type of periodic inspection is referred to as "routine," but subsequent checks are relatively relaxed compared to the first time. Unless there is a major safety incident at the factory, the FDA will reassess the overall safety of the factory.

The advantage of TPMP lies in the fact that once a factory passes an inspection that fully meets the requirements of TPMP, it is unlikely that any further on-site inspections will be required when the factory applies for any future products, unless significant changes such as the introduction of new workshops or factories are made. Therefore, applicants only need to focus on the scientific reports of data review, which saves electronic cigarette brand factories or OEM factories the cost of re-evaluation.

Zheng emphasized that if two brands use the same production line in a factory, they only need to go through one inspection. However, if they are in different factory areas or on different production lines, they will need to be inspected again. Production line updates and adjustments can be handed over to the inspection group during periodic inspections, as long as the changes are in accordance with the process.

Zheng Zhi

Lin X graduated from Shenyang Pharmaceutical University with a Bachelor's degree in Chemical Pharmaceuticals and later obtained a Master's degree in Pharmaceutical Science from the University of Pretoria in South Africa.

WHO has hired external consultants for the PQ International Certification Program for Medicines.

Translator for the United Nations Population Fund's (UNFPA) Good Manufacturing Practice (GMP) inspection.

Auditor of domestic active ingredient pharmaceutical factories in the EU EMEA region.

With 18 years of experience in international pharmaceutical certification and 4 years of experience in electronic cigarette product certification through the U.S. PMTA process.

In August 2019, [Person or Company Name] joined Shenzhen Mcwell and assumed full responsibility for the FDA PMTA certification project.

Shenzhen Ziyuan Technology was founded in February 2021.

Specialized in international certification, registration, non-clinical and clinical trial design, environmental assessment, and TPMP system for electronic cigarettes.

2FIRSTS will continue to report and analyze TPMP regulations. Stay tuned for updates.