NMPA Allows Conditional Extensions for Generic Drug Consistency Evaluation

On December 28, the National Medical Products Administration (NMPA) issued a notice stating that quality takes precedence over timelines. For drugs listed in the National Essential Medicines List that have failed to complete the consistency evaluation within the prescribed period, enterprises may apply for an extension to their provincial-level drug regulatory authorities if, after assessment, the drugs are deemed clinically essential and in short supply in the market.

Previously, in February 2016, the China Food and Drug Administration (CFDA) issued the “Opinions on Consistency Evaluation,” which set requirements for the scope and timeline of the evaluation. The scope included generic drugs approved for marketing before the implementation of the new chemical drug registration classification, provided they had not been approved in accordance with the principle of consistency in quality and efficacy with the original reference listed drugs. All such products were required to undergo consistency evaluation. (A total of 289 drug varieties were involved.)

The time requirements are as follows: For generic chemical drug oral solid dosage forms approved for marketing before October 1, 2007, and included in the National Essential Medicines List (2012 Edition), consistency evaluation shall be completed by the end of 2018. Among these, varieties requiring clinical efficacy trials and those under special circumstances shall complete consistency evaluation by the end of 2021; those failing to meet the deadline will not be granted re-registration.

According to a research report by the Shanghai Stock Exchange, as of November 2018, 109 approval numbers had passed the consistency evaluation (including those deemed equivalent), among which 78 passed the consistency evaluation and 31 were generic drugs approved under the new registration classification for chemical drugs. In terms of product specifications, five specifications had three or more enterprises passing the consistency evaluation, 13 specifications had two enterprises passing, and 65 specifications had one enterprise passing.

In this supplementary guidance on the consistency evaluation, the deadline has been extended in light of implementation progress, but the requirements remain stringent.

Conducting consistency evaluations for generic drugs already approved for market is a remedial measure to address historical gaps. In the past, there were no mandatory requirements for consistency evaluation against originator drugs for medications approved in China, leading to certain discrepancies in efficacy between some generics and their originator counterparts. Historically, countries such as the United States and Japan have undergone similar processes; Japan, for instance, spent over a decade advancing its consistency evaluation program for generic drugs.

Conducting consistency evaluations for generic drugs ensures that generics match originator drugs in quality and efficacy, allowing them to serve as clinical substitutes. This not only reduces medical costs but also enhances the quality of China’s generic drugs and the overall development level of its pharmaceutical industry, thereby ensuring safe and effective medication for the public. In China, the consistency evaluation of generic drugs represents both a remedial measure and an innovation. Achieving equivalence in quality and efficacy with originator drugs brings us closer to developing novel drugs.

The NMPA’s interpretive document posits that consistency evaluation is a matter of survival for pharmaceutical companies, representing a process of natural selection where the number of approval numbers holds little significance; only products whose quality and efficacy are consistent with those of the originator drugs will possess market value. Companies should select products with a high likelihood of success, conduct robust foundational research on crystal forms, excipients, and manufacturing processes, perform in vitro dissolution testing, and then proceed to bioavailability clinical trials to avoid unnecessary detours. By having several products pass consistency evaluation, coupled with the implementation of the Marketing Authorization Holder (MAH) system, a company can gain a competitive edge.

China faces severe overcapacity in pharmaceutical production, with an excessive number of enterprises; it is therefore normal for some companies to fail the consistency evaluation. Pharmaceutical companies that pass the consistency evaluation can act as Marketing Authorization Holders (MAHs) and commission other enterprises to manufacture their products. Those that fail the evaluation can leverage their respective strengths to engage in contract manufacturing. The key lies in companies accurately identifying their strategic positioning.

Certainly, the consistency evaluation is also an important way for enterprises to seize the market. At present, multiple local governments have successively introduced relevant policies on tender procurement and pricing for products that have passed the consistency evaluation. These mainly include priority procurement and use by medical institutions, as well as support in terms of medical insurance payment. Among them, from August to November 2018, some regions successively issued documents to further implement the policy that "when three companies producing the same variety pass the consistency evaluation, the online procurement qualification of manufacturers that have not passed the consistency evaluation will be suspended."

With the improvement in the quality of generic drugs, achieving clinical interchangeability with originator drugs will drive structural reforms in the pharmaceutical manufacturing sector. This will change the current situation where originator drugs account for up to 80% of drug sales in some large hospitals, help reduce total healthcare expenditures, facilitate the elimination of outdated production capacity, and enhance the competitiveness of generic drugs. Furthermore, conducting bioequivalence evaluations for generic drugs also benefits innovation by pharmaceutical companies. As a formulation is an organic combination of active ingredients, excipients, and packaging materials, bioequivalence evaluations will encourage companies to conduct more comprehensive research on manufacturing processes, excipients, and packaging materials, thereby comprehensively improving formulation standards.

The following is the original policy text:

In recent years, relevant departments have earnestly implemented the Opinions of the State Council on Reforming the Review and Approval System for Drugs and Medical Devices (Guo Fa [2015] No. 44), the Opinions of the General Office of the State Council on Carrying Out the Consistency Evaluation of Quality and Efficacy of Generic Drugs (Guo Ban Fa [2016] No. 8), and other regulations, adopting practical and effective measures to advance the consistency evaluation work. Enterprises have continuously increased their R&D investment and actively conducted evaluations. To further improve the consistency evaluation work, and with the approval of the State Council, the following matters are hereby announced:

I. Strictly Evaluate Standards and Strengthen Post-Marketing Supervision

Strictly implement the review and approval process for consistency evaluation, adhere to the principle that generic drugs must be equivalent in quality and efficacy to originator drugs, maintain rigorous standards, and conduct technical reviews in accordance with the currently issued technical guidelines for drug development. Strengthen post-marketing supervision and inspection of pharmaceuticals; drugs that have passed the consistency evaluation shall be included in the national drug sampling and testing plan for the following year, and the intensity of supervision and inspection of relevant enterprises shall be increased.

II. Prioritize Quality Over Timelines, and Reasonably Adjust Relevant Work Deadlines and Requirements

(I) The National Essential Medicines List (2018 Edition) has been in effect since November 1, 2018, and a dynamic adjustment mechanism has been established to align with the consistency evaluation. Varieties that have passed the consistency evaluation are given priority for inclusion in the List, while those that have not passed will be gradually removed. For varieties included in the National Essential Medicines List, no uniform time limits for evaluation shall be imposed.

(II) For generic drugs, including those containing essential medicines, that were approved for marketing before the implementation of the new registration classification system for chemical drugs, other manufacturers of the same varieties shall, in principle, complete the consistency evaluation within three years after the first manufacturer of such variety passes the evaluation. If the evaluation is not completed within the specified period, enterprises may apply for an extension to the provincial-level drug regulatory authority where they are located, provided that, upon assessment, the varieties are deemed clinically necessary and in short supply. An appropriate extension may be granted following review and determination by the provincial-level drug regulatory authority in conjunction with the health administrative department. Failure to complete the evaluation within the extended period will result in non-renewal of the drug registration.

III. Strengthen service guidance and fully advance the consistency evaluation work

Thoroughly implement the State Council’s requirements for the reform of “streamlining administration, delegating power, improving regulation, and upgrading services,” adhering to an equal emphasis on guidance, supervision, and service. Based on the specific circumstances of each drug subject to evaluation, adopt classified management and tailored measures to further strengthen service and guidance. Establish a green channel to ensure immediate review of consistency evaluation applications upon submission, thereby accelerating the review process. If enterprises encounter significant technical issues during research and development, they may communicate and consult with the drug evaluation agency in accordance with the relevant provisions of the Administrative Measures for Communication and Consultation in Drug Research and Development and Technical Review. Further strengthen guidance for key drugs and key enterprises by organizing on-site investigations and consultations to help enterprises resolve critical challenges.

IV. Strengthen Supporting Policy Measures to Stimulate Enterprises’ Enthusiasm for Evaluation

Fully leverage market mechanisms to stimulate enterprises’ enthusiasm for conducting consistency evaluations. For drug varieties that have passed the consistency evaluation, the drug regulatory authorities shall permit their inclusion in the package inserts and labels, and include them in the Catalogue of Marketed Drugs in China. Where three or more pharmaceutical manufacturers have obtained consistency evaluation approval for the same drug variety, unapproved varieties shall, in principle, no longer be selected for centralized drug procurement and other related purposes. Localities shall improve centralized procurement policies based on actual conditions, while ensuring drug quality and supply. The National Health Commission shall provide policy support for low-priced, clinically essential drugs listed in the National Essential Medicines List (2018 Edition) to ensure clinical medication needs are met.