With the first half of the year now behind us, how has the quality of our pharmaceutical products fared?

The Drug Quality Bulletin contains a wealth of information that is highly informative and instructive for us. Carefully studying the bulletin—particularly the sections on non-compliant products and test items—can be invaluable in helping us learn from our peers’ mistakes, identify potential problems, and enhance our quality control efforts.

Accordingly, the editor has compiled and analyzed official quality announcements issued by drug regulatory authorities in various provinces and cities during the first half of 2020, in order to identify the “quality” signals reflected in these announcements and the underlying reasons for non-compliance—information that we must heed and avoid.

Since the implementation of the new Drug Administration Law, the harshest penalties have served as a “sword of Damocles” hanging over the industry, constantly reminding us to uphold quality. It can be said that, under the new regulatory framework, “preventing the occurrence of non-compliant products” has become an essential survival skill for pharmaceutical companies.

In the first half of 2020, a total of 627 batches of pharmaceutical products were found to be non-compliant (including two batches of counterfeit chemical drugs and 77 batches of traditional Chinese medicine decoction pieces for which the listed manufacturing enterprises denied having produced them). During statistical compilation and analysis, the aforementioned counterfeit or disputed batches were excluded.

In the first half of 2020, a total of 58 batches of chemical pharmaceuticals were found to be non-compliant (including 2 batches that were counterfeit), involving 48 pharmaceutical companies and 48 drug products. The most common non-compliance issue was dissolution testing (12 cases), followed by visible foreign matter (9 cases) and assay (8 cases).

Among the varieties failing the dissolution test, norfloxacin capsules account for the largest number, with all five noncompliant batches attributed to dissolution. The following table lists the specific varieties associated with each noncompliant dissolution parameter:

In the first half of 2020, a total of six batches of pharmaceutical inner packaging materials were found to be non-compliant, including two batches of composite films, two batches of polyethylene bags, one batch of pharmaceutical eye-drop bottles, and one batch of solid pharmaceutical composite rigid sheets.

In the first half of 2020, a total of two batches of pharmaceutical excipients were found to be non-compliant: black iron oxide and hydroxypropyl starch hollow capsules.

In the first half of 2020, a total of 82 batches of proprietary Chinese medicines were found to be non-compliant, involving 64 pharmaceutical companies and 72 product varieties.

Analyzing by variety:

The nonconforming varieties are relatively dispersed, with no obvious clustering of nonconforming varieties.

The top-ranked non-compliant product is Compound Danshen Tablets, with the primary failure items being assay (two batches) and weight variation (two batches). The second-ranked non-compliant product is Xiaofeng Zhitongning Capsules, with all failures attributable to moisture content (three batches) and fill-weight variation (one batch).

The top three nonconforming items, in order, were fill weight variation (22), physical characteristics (17), and microbial limits (14). Nonconformities related to fill weight and weight variation indicate that pharmaceutical manufacturers should place greater emphasis on process control and quality management during production to reduce the occurrence of such defects. As for nonconformities in microbial limits, most affected products are hospital-prepared formulations, suggesting that hospitals need to strengthen management of material hygiene and environmental sanitation throughout the manufacturing process.

In the first half of 2020, a total of 479 batches of traditional Chinese medicine decoction pieces were found to be non-compliant, with 77 of these batches being denied by the labeled manufacturing enterprises as having been produced by them.

Compared with the non-compliance rates of the two preceding years, a total of 2,260 batches of processed herbal slices were found to be non-compliant in 2019, versus 2,385 batches in 2018.

By way of comparison, if the number of non-compliant batches in the second half of the year remains at the current level, the number of non-compliant batches of traditional Chinese medicinal decoction pieces in 2020 would be halved. Of course, such a comparison is not scientifically sound—after all, it’s possible that the decline this year is simply due to a smaller number of batches being sampled for inspection.

The top five substandard traditional Chinese medicine decoction pieces in the latest inspection were yam, peucedanum praeruptorum, plantago asiatica, great burdock, and wild chrysanthemum; in 2019, the top five were yam, myrrh vinegar-soaked, peucedanum praeruptorum, pueraria lobata, and stir-fried atractylodes with bran. It is evident that yam and peucedanum praeruptorum have consistently ranked at the top of the list of non-compliant products.

Chinese yam Analysis of Nonconforming Items (Total of 17 Batches): Total Ash (10 batches), Inspection (3 batches), Sulfur Dioxide (4 batches), and Processing (2 batches). It can be seen that the primary cause of nonconformity for Chinese yam is total ash.

Peucedanum praeruptorum Analysis of Nonconforming Items (Total of 13 Batches): Assay (12 batches), Physical Characteristics (1 batch), Identification (1 batch), Thin-Layer Chromatography (1 batch); it can be seen that the primary cause of nonconformity in Peucedanum praeruptorum is failure in the assay.

Plantain Analysis of Nonconforming Items (Total of 12 Batches): Inspection (5 batches), Total Ash (5 batches), and Assay (3 batches). It can be seen that the primary reasons for nonconformity in Plantago psyllium are total ash and assay.

Great Thistle Analysis of Nonconforming Items (Total of 10 Batches): Assay (10 Batches)

Wild Chrysanthemum Analysis of Nonconforming Items (Total of 7 Batches): Assay (6 batches), Physical Characteristics (1 batch), Thin-Layer Chromatography (1 batch); it can be seen that assay is the most significant issue.

Dictamnus bark: All six batches of non-compliance were due to unsatisfactory physical characteristics (six batches) and inspection (impurities) (four batches).

Cicada slough: All five batches failed due to non-compliant characteristics.

Vinegar-processed Cyperus rotundus: All six batches failed to meet the required quality standards.

Trichosanthes fruit and Trichosanthes peel: All six batches failed to meet the required quality standards.

Hai Feng Teng: Five batches failed to meet all quality specifications, while another two batches failed the microscopic examination.

Ophiopogon: All six batches failed to meet quality standards.

In addition to the aforementioned top five—Peucedanum praeruptorum, Cirsium japonicum, and Chrysanthemum indicum—which are prone to failing quality standards for their active ingredient content, the following varieties are also susceptible to such failures:

Pueraria: Of the 7 batches that failed inspection, 5 were due to non-compliant content levels.

Kudzu root: Of the seven batches that failed inspection, all were due to non-compliant assay results.

Epimedium: Five batches, all due to non-compliant content;

Roasted Epimedium : 2 batches, all due to non-compliant content;

Unqualified pH:

Scalding leech: Four batches, all due to non-compliance with pH standards;

Aflatoxin Non-compliant inspections: One batch each of Platycladi Semen, Lotus Seed, and processed Polygala Root was found non-compliant.

Heavy Metals and Harmful Elements Non-compliant: One batch each of hawthorn and leech is non-compliant.

Sulfur dioxide Non-compliant: One batch each of Bletilla, Pueraria lobata, Pueraria root, and Prince Ginseng; two batches of Asparagus cochinchinensis, two batches of Chrysanthemum, and four batches of Chinese yam.

In general, failure in microscopic identification essentially indicates that the herbal slice is a “false drug.” As evidenced by the list of nonconforming items, varieties that fail microscopic examination often concurrently exhibit noncompliance in macroscopic characteristics, other identification tests, and assay results.

Therefore, the following varieties that fail microscopic identification require particular vigilance on the part of pharmaceutical professionals: we must ensure that “counterfeit drugs” do not leave the factory and that they are not introduced into pharmaceutical companies for use as raw materials in production.

Varieties that failed microscopic identification: 1 batch each of Pulsatilla, Amomum villosum, Stephania tetrandra, Citrus medica var. sarcodactylis, Nardostachys jatamansi, Pueraria lobata, Crocus sativus, and Magnolia officinalis; 2 batches each of Lysimachia christinae, Ophiopogon japonicus, Bletilla striata, and Celosia argentea seeds; and 3 batches each of Tetrapanax papyrifer, Tetrapanax microphyllus, and Tetracarpaea sinensis.